A GSC Global Genome Census (GSC8 Meeting)

ScienceCinema

Kyrpides, Nikos

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Nikos Kyrpides of the DOE Joint Genome Institute discusses the notion of a global genome census at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Gene Calling Standards (GSC8 Meeting)

ScienceCinema

Kyrpides, Nikos

2018-04-27

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Nikos Kyrpides of the DOE Joint Genome Institute discusses gene calling standards at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 10, 2009.

Annotations in Refseq (GSC8 Meeting)

ScienceCinema

Tatusova, Tatiana

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Tatiana Tatusova of NCBI discusses "Annotations in Refseq" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 10, 2009.

Towards a Consensus Annotation System (GSC8 Meeting)

ScienceCinema

White, Owen

2018-02-01

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Towards Consensus Annotation at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 10, 2009.

Draft Genome Sequence of Achromobacter sp. Strain AR476-2, Isolated from a Cellulolytic Consortium

PubMed Central

Kurth, Daniel; Romero, Cintia M.; Fernandez, Pablo M.; Ferrero, Marcela A.

2016-01-01

Achromobacter sp. AR476-2 is a noncellulolytic strain previously isolated from a cellulolytic consortium selected from samples of insect gut. Its genome sequence could contribute to the unraveling of the complex interaction of microorganisms and enzymes involved in the biodegradation of lignocellulosic biomass in nature. PMID:27340069

Genome-Centric Analysis of a Thermophilic and Cellulolytic Bacterial Consortium Derived from Composting

PubMed Central

Lemos, Leandro N.; Pereira, Roberta V.; Quaggio, Ronaldo B.; Martins, Layla F.; Moura, Livia M. S.; da Silva, Amanda R.; Antunes, Luciana P.; da Silva, Aline M.; Setubal, João C.

2017-01-01

Microbial consortia selected from complex lignocellulolytic microbial communities are promising alternatives to deconstruct plant waste, since synergistic action of different enzymes is required for full degradation of plant biomass in biorefining applications. Culture enrichment also facilitates the study of interactions among consortium members, and can be a good source of novel microbial species. Here, we used a sample from a plant waste composting operation in the São Paulo Zoo (Brazil) as inoculum to obtain a thermophilic aerobic consortium enriched through multiple passages at 60°C in carboxymethylcellulose as sole carbon source. The microbial community composition of this consortium was investigated by shotgun metagenomics and genome-centric analysis. Six near-complete (over 90%) genomes were reconstructed. Similarity and phylogenetic analyses show that four of these six genomes are novel, with the following hypothesized identifications: a new Thermobacillus species; the first Bacillus thermozeamaize genome (for which currently only 16S sequences are available) or else the first representative of a new family in the Bacillales order; the first representative of a new genus in the Paenibacillaceae family; and the first representative of a new deep-branching family in the Clostridia class. The reconstructed genomes from known species were identified as Geobacillus thermoglucosidasius and Caldibacillus debilis. The metabolic potential of these recovered genomes based on COG and CAZy analyses show that these genomes encode several glycoside hydrolases (GHs) as well as other genes related to lignocellulose breakdown. The new Thermobacillus species stands out for being the richest in diversity and abundance of GHs, possessing the greatest potential for biomass degradation among the six recovered genomes. We also investigated the presence and activity of the organisms corresponding to these genomes in the composting operation from which the consortium was built, using compost metagenome and metatranscriptome datasets generated in a previous study. We obtained strong evidence that five of the six recovered genomes are indeed present and active in that composting process. We have thus discovered three (perhaps four) new thermophillic bacterial species that add to the increasing repertoire of known lignocellulose degraders, whose biotechnological potential can now be investigated in further studies. PMID:28469608

The High-Throughput Protein Sample Production Platform of the Northeast Structural Genomics Consortium

PubMed Central

Xiao, Rong; Anderson, Stephen; Aramini, James; Belote, Rachel; Buchwald, William A.; Ciccosanti, Colleen; Conover, Ken; Everett, John K.; Hamilton, Keith; Huang, Yuanpeng Janet; Janjua, Haleema; Jiang, Mei; Kornhaber, Gregory J.; Lee, Dong Yup; Locke, Jessica Y.; Ma, Li-Chung; Maglaqui, Melissa; Mao, Lei; Mitra, Saheli; Patel, Dayaban; Rossi, Paolo; Sahdev, Seema; Sharma, Seema; Shastry, Ritu; Swapna, G.V.T.; Tong, Saichu N.; Wang, Dongyan; Wang, Huang; Zhao, Li; Montelione, Gaetano T.; Acton, Thomas B.

2014-01-01

We describe the core Protein Production Platform of the Northeast Structural Genomics Consortium (NESG) and outline the strategies used for producing high-quality protein samples. The platform is centered on the cloning, expression and purification of 6X-His-tagged proteins using T7-based Escherichia coli systems. The 6X-His tag allows for similar purification procedures for most targets and implementation of high-throughput (HTP) parallel methods. In most cases, the 6X-His-tagged proteins are sufficiently purified (> 97% homogeneity) using a HTP two-step purification protocol for most structural studies. Using this platform, the open reading frames of over 16,000 different targeted proteins (or domains) have been cloned as > 26,000 constructs. Over the past nine years, more than 16,000 of these expressed protein, and more than 4,400 proteins (or domains) have been purified to homogeneity in tens of milligram quantities (see Summary Statistics, http://nesg.org/statistics.html). Using these samples, the NESG has deposited more than 900 new protein structures to the Protein Data Bank (PDB). The methods described here are effective in producing eukaryotic and prokaryotic protein samples in E. coli. This paper summarizes some of the updates made to the protein production pipeline in the last five years, corresponding to phase 2 of the NIGMS Protein Structure Initiative (PSI-2) project. The NESG Protein Production Platform is suitable for implementation in a large individual laboratory or by a small group of collaborating investigators. These advanced automated and/or parallel cloning, expression, purification, and biophysical screening technologies are of broad value to the structural biology, functional proteomics, and structural genomics communities. PMID:20688167

Draft Genome Sequence of Achromobacter sp. Strain AR476-2, Isolated from a Cellulolytic Consortium.

PubMed

Kurth, Daniel; Romero, Cintia M; Fernandez, Pablo M; Ferrero, Marcela A; Martinez, M Alejandra

2016-06-23

Achromobacter sp. AR476-2 is a noncellulolytic strain previously isolated from a cellulolytic consortium selected from samples of insect gut. Its genome sequence could contribute to the unraveling of the complex interaction of microorganisms and enzymes involved in the biodegradation of lignocellulosic biomass in nature. Copyright © 2016 Kurth et al.

Clinical utilization of genomics data produced by the international Pseudomonas aeruginosa consortium

PubMed Central

Freschi, Luca; Jeukens, Julie; Kukavica-Ibrulj, Irena; Boyle, Brian; Dupont, Marie-Josée; Laroche, Jérôme; Larose, Stéphane; Maaroufi, Halim; Fothergill, Joanne L.; Moore, Matthew; Winsor, Geoffrey L.; Aaron, Shawn D.; Barbeau, Jean; Bell, Scott C.; Burns, Jane L.; Camara, Miguel; Cantin, André; Charette, Steve J.; Dewar, Ken; Déziel, Éric; Grimwood, Keith; Hancock, Robert E. W.; Harrison, Joe J.; Heeb, Stephan; Jelsbak, Lars; Jia, Baofeng; Kenna, Dervla T.; Kidd, Timothy J.; Klockgether, Jens; Lam, Joseph S.; Lamont, Iain L.; Lewenza, Shawn; Loman, Nick; Malouin, François; Manos, Jim; McArthur, Andrew G.; McKeown, Josie; Milot, Julie; Naghra, Hardeep; Nguyen, Dao; Pereira, Sheldon K.; Perron, Gabriel G.; Pirnay, Jean-Paul; Rainey, Paul B.; Rousseau, Simon; Santos, Pedro M.; Stephenson, Anne; Taylor, Véronique; Turton, Jane F.; Waglechner, Nicholas; Williams, Paul; Thrane, Sandra W.; Wright, Gerard D.; Brinkman, Fiona S. L.; Tucker, Nicholas P.; Tümmler, Burkhard; Winstanley, Craig; Levesque, Roger C.

2015-01-01

The International Pseudomonas aeruginosa Consortium is sequencing over 1000 genomes and building an analysis pipeline for the study of Pseudomonas genome evolution, antibiotic resistance and virulence genes. Metadata, including genomic and phenotypic data for each isolate of the collection, are available through the International Pseudomonas Consortium Database (http://ipcd.ibis.ulaval.ca/). Here, we present our strategy and the results that emerged from the analysis of the first 389 genomes. With as yet unmatched resolution, our results confirm that P. aeruginosa strains can be divided into three major groups that are further divided into subgroups, some not previously reported in the literature. We also provide the first snapshot of P. aeruginosa strain diversity with respect to antibiotic resistance. Our approach will allow us to draw potential links between environmental strains and those implicated in human and animal infections, understand how patients become infected and how the infection evolves over time as well as identify prognostic markers for better evidence-based decisions on patient care. PMID:26483767

Systems Biology Knowledgebase (GSC8 Meeting)

ScienceCinema

Cottingham, Robert W.

2018-01-04

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Robert W. Cottingham of Oak Ridge National Laboratory discusses the DOE Knowledge Base at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

The Biocurator Society (GSC8 Meeting)

ScienceCinema

Gaudet, Pascal

2018-01-10

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Pascal Gaudet of Northwestern University talks about "The Biocurator Society" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 11, 2009.

Connecting genomic alterations to cancer biology with proteomics: the NCI Clinical Proteomic Tumor Analysis Consortium.

PubMed

Ellis, Matthew J; Gillette, Michael; Carr, Steven A; Paulovich, Amanda G; Smith, Richard D; Rodland, Karin K; Townsend, R Reid; Kinsinger, Christopher; Mesri, Mehdi; Rodriguez, Henry; Liebler, Daniel C

2013-10-01

The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative of the NCI and the National Human Genome Research Institute. By providing a fully integrated accounting of DNA, RNA, and protein abnormalities in individual tumors, these datasets will illuminate the complex relationship between genomic abnormalities and cancer phenotypes, thus producing biologic insights as well as a wave of novel candidate biomarkers and therapeutic targets amenable to verification using targeted mass spectrometry methods. ©2013 AACR.

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine.

PubMed

Green, Robert C; Goddard, Katrina A B; Jarvik, Gail P; Amendola, Laura M; Appelbaum, Paul S; Berg, Jonathan S; Bernhardt, Barbara A; Biesecker, Leslie G; Biswas, Sawona; Blout, Carrie L; Bowling, Kevin M; Brothers, Kyle B; Burke, Wylie; Caga-Anan, Charlisse F; Chinnaiyan, Arul M; Chung, Wendy K; Clayton, Ellen W; Cooper, Gregory M; East, Kelly; Evans, James P; Fullerton, Stephanie M; Garraway, Levi A; Garrett, Jeremy R; Gray, Stacy W; Henderson, Gail E; Hindorff, Lucia A; Holm, Ingrid A; Lewis, Michelle Huckaby; Hutter, Carolyn M; Janne, Pasi A; Joffe, Steven; Kaufman, David; Knoppers, Bartha M; Koenig, Barbara A; Krantz, Ian D; Manolio, Teri A; McCullough, Laurence; McEwen, Jean; McGuire, Amy; Muzny, Donna; Myers, Richard M; Nickerson, Deborah A; Ou, Jeffrey; Parsons, Donald W; Petersen, Gloria M; Plon, Sharon E; Rehm, Heidi L; Roberts, J Scott; Robinson, Dan; Salama, Joseph S; Scollon, Sarah; Sharp, Richard R; Shirts, Brian; Spinner, Nancy B; Tabor, Holly K; Tarczy-Hornoch, Peter; Veenstra, David L; Wagle, Nikhil; Weck, Karen; Wilfond, Benjamin S; Wilhelmsen, Kirk; Wolf, Susan M; Wynn, Julia; Yu, Joon-Ho

2016-06-02

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine. Copyright © 2016 American Society of Human Genetics. All rights reserved.

Accelerating target discovery using pre-competitive open science-patients need faster innovation more than anyone else.

PubMed

Low, Eric; Bountra, Chas; Lee, Wen Hwa

2016-01-01

We are experiencing a new era enabled by unencumbered access to high quality data through the emergence of open science initiatives in the historically challenging area of early stage drug discovery. At the same time, many patient-centric organisations are taking matters into their own hands by participating in, enabling and funding research. Here we present the rationale behind the innovative partnership between the Structural Genomics Consortium (SGC)-an open, pre-competitive pre-clinical research consortium and the research-focused patient organisation Myeloma UK to create a new, comprehensive platform to accelerate the discovery and development of new treatments for multiple myeloma.

78 FR 47674 - Genome in a Bottle Consortium-Progress and Planning Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

... quantitative performance metrics for confidence in variant calling. These standards and quantitative..., reproducible research and regulated applications in the clinic. On April 13, 2012, NIST convened the workshop... consortium. No proprietary information will be shared as part of the consortium, and all research results...

Structural genomics reveals EVE as a new ASCH/PUA-related domain

PubMed Central

Bertonati, Claudia; Punta, Marco; Fischer, Markus; Yachdav, Guy; Forouhar, Farhad; Zhou, Weihong; Kuzin, Alexander P.; Seetharaman, Jayaraman; Abashidze, Mariam; Ramelot, Theresa A.; Kennedy, Michael A.; Cort, John R.; Belachew, Adam; Hunt, John F.; Tong, Liang; Montelione, Gaetano T.; Rost, Burkhard

2014-01-01

Summary We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE. Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links. PMID:19191354

Structural Genomics Reveals EVE as a New ASCH/PUA-Related Domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertonati, C.; Punta, M; Fischer, M

2008-01-01

We report on several proteins recently solved by structural genomics consortia, in particular by the Northeast Structural Genomics consortium (NESG). The proteins considered in this study differ substantially in their sequences but they share a similar structural core, characterized by a pseudobarrel five-stranded beta sheet. This core corresponds to the PUA domain-like architecture in the SCOP database. By connecting sequence information with structural knowledge, we characterize a new subgroup of these proteins that we propose to be distinctly different from previously described PUA domain-like domains such as PUA proper or ASCH. We refer to these newly defined domains as EVE.more » Although EVE may have retained the ability of PUA domains to bind RNA, the available experimental and computational data suggests that both the details of its molecular function and its cellular function differ from those of other PUA domain-like domains. This study of EVE and its relatives illustrates how the combination of structure and genomics creates new insights by connecting a cornucopia of structures that map to the same evolutionary potential. Primary sequence information alone would have not been sufficient to reveal these evolutionary links.« less

Standards and the INSDC: Submission of MIGS, MIMS, MIENS (GSC8 Meeting)

ScienceCinema

Mizrachi, Ilene

2017-12-21

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding. Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Ilene Mizrachi of the NCBI talks about submission of MIGS/MIMS/MIENS information at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.

Oceanic Communities in a Changing Planet - The Tara Oceans Project (GSC8 Meeting)

ScienceCinema

Raes, Jeroen

2018-01-10

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Jeroen Raes of the University of Brussels discusses the Tara-Oceans expedition at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Defining Genome Project Standards in a New Era of Sequencing

ScienceCinema

Chain, Patrick

2018-01-16

Patrick Chain of the DOE Joint Genome Institute gives a talk on behalf of the International Genome Sequencing Standards Consortium on the need for intermediate genome classifications between "draft" and "finished".

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

PubMed Central

Pope, Welkin H; Bowman, Charles A; Russell, Daniel A; Jacobs-Sera, Deborah; Asai, David J; Cresawn, Steven G; Jacobs, William R; Hendrix, Roger W; Lawrence, Jeffrey G; Hatfull, Graham F; Abbazia, Patrick; Ababio, Amma; Adam, Naazneen

2015-01-01

The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery. DOI: http://dx.doi.org/10.7554/eLife.06416.001 PMID:25919952

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity.

PubMed

Pope, Welkin H; Bowman, Charles A; Russell, Daniel A; Jacobs-Sera, Deborah; Asai, David J; Cresawn, Steven G; Jacobs, William R; Hendrix, Roger W; Lawrence, Jeffrey G; Hatfull, Graham F

2015-04-28

The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery.

Overview | Office of Cancer Genomics

Cancer.gov

The Human Cancer Model Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models with associated genomic and clinical data. The HCMI consortium includes the US-National Cancer Institute, part of the National Institutes of Health, Cancer Research UK, foundation Hubrecht Organoid Technology, and Wellcome Sanger Institute. The goal of HCMI is to create up to one thousand cancer models from patient tumors.

Functional Insights from Structural Genomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forouhar,F.; Kuzin, A.; Seetharaman, J.

2007-01-01

Structural genomics efforts have produced structural information, either directly or by modeling, for thousands of proteins over the past few years. While many of these proteins have known functions, a large percentage of them have not been characterized at the functional level. The structural information has provided valuable functional insights on some of these proteins, through careful structural analyses, serendipity, and structure-guided functional screening. Some of the success stories based on structures solved at the Northeast Structural Genomics Consortium (NESG) are reported here. These include a novel methyl salicylate esterase with important role in plant innate immunity, a novel RNAmore » methyltransferase (H. influenzae yggJ (HI0303)), a novel spermidine/spermine N-acetyltransferase (B. subtilis PaiA), a novel methyltransferase or AdoMet binding protein (A. fulgidus AF{_}0241), an ATP:cob(I)alamin adenosyltransferase (B. subtilis YvqK), a novel carboxysome pore (E. coli EutN), a proline racemase homolog with a disrupted active site (B. melitensis BME11586), an FMN-dependent enzyme (S. pneumoniae SP{_}1951), and a 12-stranded {beta}-barrel with a novel fold (V. parahaemolyticus VPA1032).« less

Genomic standards consortium projects.

PubMed

Field, Dawn; Sterk, Peter; Kottmann, Renzo; De Smet, J Wim; Amaral-Zettler, Linda; Cochrane, Guy; Cole, James R; Davies, Neil; Dawyndt, Peter; Garrity, George M; Gilbert, Jack A; Glöckner, Frank Oliver; Hirschman, Lynette; Klenk, Hans-Peter; Knight, Rob; Kyrpides, Nikos; Meyer, Folker; Karsch-Mizrachi, Ilene; Morrison, Norman; Robbins, Robert; San Gil, Inigo; Sansone, Susanna; Schriml, Lynn; Tatusova, Tatiana; Ussery, Dave; Yilmaz, Pelin; White, Owen; Wooley, John; Caporaso, Gregory

2014-06-15

The Genomic Standards Consortium (GSC) is an open-membership community that was founded in 2005 to work towards the development, implementation and harmonization of standards in the field of genomics. Starting with the defined task of establishing a minimal set of descriptions the GSC has evolved into an active standards-setting body that currently has 18 ongoing projects, with additional projects regularly proposed from within and outside the GSC. Here we describe our recently enacted policy for proposing new activities that are intended to be taken on by the GSC, along with the template for proposing such new activities.

Glycan array data management at Consortium for Functional Glycomics.

PubMed

Venkataraman, Maha; Sasisekharan, Ram; Raman, Rahul

2015-01-01

Glycomics or the study of structure-function relationships of complex glycans has reshaped post-genomics biology. Glycans mediate fundamental biological functions via their specific interactions with a variety of proteins. Recognizing the importance of glycomics, large-scale research initiatives such as the Consortium for Functional Glycomics (CFG) were established to address these challenges. Over the past decade, the Consortium for Functional Glycomics (CFG) has generated novel reagents and technologies for glycomics analyses, which in turn have led to generation of diverse datasets. These datasets have contributed to understanding glycan diversity and structure-function relationships at molecular (glycan-protein interactions), cellular (gene expression and glycan analysis), and whole organism (mouse phenotyping) levels. Among these analyses and datasets, screening of glycan-protein interactions on glycan array platforms has gained much prominence and has contributed to cross-disciplinary realization of the importance of glycomics in areas such as immunology, infectious diseases, cancer biomarkers, etc. This manuscript outlines methodologies for capturing data from glycan array experiments and online tools to access and visualize glycan array data implemented at the CFG.

Personal Genome Sequencing in Ostensibly Healthy Individuals and the PeopleSeq Consortium

PubMed Central

Linderman, Michael D.; Nielsen, Daiva E.; Green, Robert C.

2016-01-01

Thousands of ostensibly healthy individuals have had their exome or genome sequenced, but a much smaller number of these individuals have received any personal genomic results from that sequencing. We term those projects in which ostensibly healthy participants can receive sequencing-derived genetic findings and may also have access to their genomic data as participatory predispositional personal genome sequencing (PPGS). Here we are focused on genome sequencing applied in a pre-symptomatic context and so define PPGS to exclude diagnostic genome sequencing intended to identify the molecular cause of suspected or diagnosed genetic disease. In this report we describe the design of completed and underway PPGS projects, briefly summarize the results reported to date and introduce the PeopleSeq Consortium, a newly formed collaboration of PPGS projects designed to collect much-needed longitudinal outcome data. PMID:27023617

Illustrative case studies in the return of exome and genome sequencing results

PubMed Central

Amendola, Laura M; Lautenbach, Denise; Scollon, Sarah; Bernhardt, Barbara; Biswas, Sawona; East, Kelly; Everett, Jessica; Gilmore, Marian J; Himes, Patricia; Raymond, Victoria M; Wynn, Julia; Hart, Ragan; Jarvik, Gail P

2015-01-01

Whole genome and exome sequencing tests are increasingly being ordered in clinical practice, creating a need for research exploring the return of results from these tests. A goal of the Clinical Sequencing and Exploratory Research (CSER) consortium is to gain experience with this process to develop best practice recommendations for offering exome and genome testing and returning results. Genetic counselors in the CSER consortium have an integral role in the return of results from these genomic sequencing tests and have gained valuable insight. We present seven emerging themes related to return of exome and genome sequencing results accompanied by case descriptions illustrating important lessons learned, counseling challenges specific to these tests and considerations for future research and practice. PMID:26478737

Breast and Prostate Cancer Cohort Consortium (BPC3)

Cancer.gov

Breast and Prostate Cancer Cohort Consortium collaborates with three genomic facilities, epidemiologists, population geneticists, and biostatisticians from multiple institutions to study hormone-related gene variants and environmental factors in breast and prostate cancers.

Preparation of Protein Samples for NMR Structure, Function, and Small Molecule Screening Studies

PubMed Central

Acton, Thomas B.; Xiao, Rong; Anderson, Stephen; Aramini, James; Buchwald, William A.; Ciccosanti, Colleen; Conover, Ken; Everett, John; Hamilton, Keith; Huang, Yuanpeng Janet; Janjua, Haleema; Kornhaber, Gregory; Lau, Jessica; Lee, Dong Yup; Liu, Gaohua; Maglaqui, Melissa; Ma, Lichung; Mao, Lei; Patel, Dayaban; Rossi, Paolo; Sahdev, Seema; Shastry, Ritu; Swapna, G.V.T.; Tang, Yeufeng; Tong, Saichiu; Wang, Dongyan; Wang, Huang; Zhao, Li; Montelione, Gaetano T.

2014-01-01

In this chapter, we concentrate on the production of high quality protein samples for NMR studies. In particular, we provide an in-depth description of recent advances in the production of NMR samples and their synergistic use with recent advancements in NMR hardware. We describe the protein production platform of the Northeast Structural Genomics Consortium, and outline our high-throughput strategies for producing high quality protein samples for nuclear magnetic resonance (NMR) studies. Our strategy is based on the cloning, expression and purification of 6X-His-tagged proteins using T7-based Escherichia coli systems and isotope enrichment in minimal media. We describe 96-well ligation-independent cloning and analytical expression systems, parallel preparative scale fermentation, and high-throughput purification protocols. The 6X-His affinity tag allows for a similar two-step purification procedure implemented in a parallel high-throughput fashion that routinely results in purity levels sufficient for NMR studies (> 97% homogeneity). Using this platform, the protein open reading frames of over 17,500 different targeted proteins (or domains) have been cloned as over 28,000 constructs. Nearly 5,000 of these proteins have been purified to homogeneity in tens of milligram quantities (see Summary Statistics, http://nesg.org/statistics.html), resulting in more than 950 new protein structures, including more than 400 NMR structures, deposited in the Protein Data Bank. The Northeast Structural Genomics Consortium pipeline has been effective in producing protein samples of both prokaryotic and eukaryotic origin. Although this paper describes our entire pipeline for producing isotope-enriched protein samples, it focuses on the major updates introduced during the last 5 years (Phase 2 of the National Institute of General Medical Sciences Protein Structure Initiative). Our advanced automated and/or parallel cloning, expression, purification, and biophysical screening technologies are suitable for implementation in a large individual laboratory or by a small group of collaborating investigators for structural biology, functional proteomics, ligand screening and structural genomics research. PMID:21371586

10KP: A phylodiverse genome sequencing plan.

PubMed

Cheng, Shifeng; Melkonian, Michael; Smith, Stephen A; Brockington, Samuel; Archibald, John M; Delaux, Pierre-Marc; Li, Fay-Wei; Melkonian, Barbara; Mavrodiev, Evgeny V; Sun, Wenjing; Fu, Yuan; Yang, Huanming; Soltis, Douglas E; Graham, Sean W; Soltis, Pamela S; Liu, Xin; Xu, Xun; Wong, Gane Ka-Shu

2018-03-01

Understanding plant evolution and diversity in a phylogenomic context is an enormous challenge due, in part, to limited availability of genome-scale data across phylodiverse species. The 10KP (10,000 Plants) Genome Sequencing Project will sequence and characterize representative genomes from every major clade of embryophytes, green algae, and protists (excluding fungi) within the next 5 years. By implementing and continuously improving leading-edge sequencing technologies and bioinformatics tools, 10KP will catalogue the genome content of plant and protist diversity and make these data freely available as an enduring foundation for future scientific discoveries and applications. 10KP is structured as an international consortium, open to the global community, including botanical gardens, plant research institutes, universities, and private industry. Our immediate goal is to establish a policy framework for this endeavor, the principles of which are outlined here.

The Genome 10K Project: a way forward.

PubMed

Koepfli, Klaus-Peter; Paten, Benedict; O'Brien, Stephen J

2015-01-01

The Genome 10K Project was established in 2009 by a consortium of biologists and genome scientists determined to facilitate the sequencing and analysis of the complete genomes of 10,000 vertebrate species. Since then the number of selected and initiated species has risen from ∼26 to 277 sequenced or ongoing with funding, an approximately tenfold increase in five years. Here we summarize the advances and commitments that have occurred by mid-2014 and outline the achievements and present challenges of reaching the 10,000-species goal. We summarize the status of known vertebrate genome projects, recommend standards for pronouncing a genome as sequenced or completed, and provide our present and future vision of the landscape of Genome 10K. The endeavor is ambitious, bold, expensive, and uncertain, but together the Genome 10K Consortium of Scientists and the worldwide genomics community are moving toward their goal of delivering to the coming generation the gift of genome empowerment for many vertebrate species.

The Genome 10K Project: A Way Forward

PubMed Central

Koepfli, Klaus-Peter; Paten, Benedict; O’Brien, Stephen J.

2017-01-01

The Genome 10K Project was established in 2009 by a consortium of biologists and genome scientists determined to facilitate the sequencing and analysis of the complete genomes of 10,000 vertebrate species. Since then the number of selected and initiated species has risen from ~26 to 277 sequenced or ongoing with funding, an approximately tenfold increase in five years. Here we summarize the advances and commitments that have occurred by mid-2014 and outline the achievements and present challenges of reaching the 10,000-species goal. We summarize the status of known vertebrate genome projects, recommend standards for pronouncing a genome as sequenced or completed, and provide our present and future vision of the landscape of Genome 10K. The endeavor is ambitious, bold, expensive, and uncertain, but together the Genome 10K Consortium of Scientists and the worldwide genomics community are moving toward their goal of delivering to the coming generation the gift of genome empowerment for many vertebrate species. PMID:25689317

The Genomes and Metagenomes (GEM) Catalogue (first presentation) and The ISA-GCDML Workshop (second presentation) (GSC8 Meeting)

ScienceCinema

Field, Dawn; Sansone, Susanna

2018-01-24

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding ''Research Coordination Network'' from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology & Hydrology briefly introduces the GEM Catalogue, followed by Susanna Sansone of the European Bioinformatics Institute who talks about the ISA-GCDML workshop at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Quality control and conduct of genome-wide association meta-analyses.

PubMed

Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth J F

2014-05-01

Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.

Metabolomics as a Hypothesis-Generating Functional Genomics Tool for the Annotation of Arabidopsis thaliana Genes of “Unknown Function”

PubMed Central

Quanbeck, Stephanie M.; Brachova, Libuse; Campbell, Alexis A.; Guan, Xin; Perera, Ann; He, Kun; Rhee, Seung Y.; Bais, Preeti; Dickerson, Julie A.; Dixon, Philip; Wohlgemuth, Gert; Fiehn, Oliver; Barkan, Lenore; Lange, Iris; Lange, B. Markus; Lee, Insuk; Cortes, Diego; Salazar, Carolina; Shuman, Joel; Shulaev, Vladimir; Huhman, David V.; Sumner, Lloyd W.; Roth, Mary R.; Welti, Ruth; Ilarslan, Hilal; Wurtele, Eve S.; Nikolau, Basil J.

2012-01-01

Metabolomics is the methodology that identifies and measures global pools of small molecules (of less than about 1,000 Da) of a biological sample, which are collectively called the metabolome. Metabolomics can therefore reveal the metabolic outcome of a genetic or environmental perturbation of a metabolic regulatory network, and thus provide insights into the structure and regulation of that network. Because of the chemical complexity of the metabolome and limitations associated with individual analytical platforms for determining the metabolome, it is currently difficult to capture the complete metabolome of an organism or tissue, which is in contrast to genomics and transcriptomics. This paper describes the analysis of Arabidopsis metabolomics data sets acquired by a consortium that includes five analytical laboratories, bioinformaticists, and biostatisticians, which aims to develop and validate metabolomics as a hypothesis-generating functional genomics tool. The consortium is determining the metabolomes of Arabidopsis T-DNA mutant stocks, grown in standardized controlled environment optimized to minimize environmental impacts on the metabolomes. Metabolomics data were generated with seven analytical platforms, and the combined data is being provided to the research community to formulate initial hypotheses about genes of unknown function (GUFs). A public database (www.PlantMetabolomics.org) has been developed to provide the scientific community with access to the data along with tools to allow for its interactive analysis. Exemplary datasets are discussed to validate the approach, which illustrate how initial hypotheses can be generated from the consortium-produced metabolomics data, integrated with prior knowledge to provide a testable hypothesis concerning the functionality of GUFs. PMID:22645570

Life in the fast lane for protein crystallization and X-ray crystallography

NASA Technical Reports Server (NTRS)

Pusey, Marc L.; Liu, Zhi-Jie; Tempel, Wolfram; Praissman, Jeremy; Lin, Dawei; Wang, Bi-Cheng; Gavira, Jose A.; Ng, Joseph D.

2005-01-01

The common goal for structural genomic centers and consortiums is to decipher as quickly as possible the three-dimensional structures for a multitude of recombinant proteins derived from known genomic sequences. Since X-ray crystallography is the foremost method to acquire atomic resolution for macromolecules, the limiting step is obtaining protein crystals that can be useful of structure determination. High-throughput methods have been developed in recent years to clone, express, purify, crystallize and determine the three-dimensional structure of a protein gene product rapidly using automated devices, commercialized kits and consolidated protocols. However, the average number of protein structures obtained for most structural genomic groups has been very low compared to the total number of proteins purified. As more entire genomic sequences are obtained for different organisms from the three kingdoms of life, only the proteins that can be crystallized and whose structures can be obtained easily are studied. Consequently, an astonishing number of genomic proteins remain unexamined. In the era of high-throughput processes, traditional methods in molecular biology, protein chemistry and crystallization are eclipsed by automation and pipeline practices. The necessity for high-rate production of protein crystals and structures has prevented the usage of more intellectual strategies and creative approaches in experimental executions. Fundamental principles and personal experiences in protein chemistry and crystallization are minimally exploited only to obtain "low-hanging fruit" protein structures. We review the practical aspects of today's high-throughput manipulations and discuss the challenges in fast pace protein crystallization and tools for crystallography. Structural genomic pipelines can be improved with information gained from low-throughput tactics that may help us reach the higher-bearing fruits. Examples of recent developments in this area are reported from the efforts of the Southeast Collaboratory for Structural Genomics (SECSG).

Life in the Fast Lane for Protein Crystallization and X-Ray Crystallography

NASA Technical Reports Server (NTRS)

Pusey, Marc L.; Liu, Zhi-Jie; Tempel, Wolfram; Praissman, Jeremy; Lin, Dawei; Wang, Bi-Cheng; Gavira, Jose A.; Ng, Joseph D.

2004-01-01

The common goal for structural genomic centers and consortiums is to decipher as quickly as possible the three-dimensional structures for a multitude of recombinant proteins derived from known genomic sequences. Since X-ray crystallography is the foremost method to acquire atomic resolution for macromolecules, the limiting step is obtaining protein crystals that can be useful of structure determination. High-throughput methods have been developed in recent years to clone, express, purify, crystallize and determine the three-dimensional structure of a protein gene product rapidly using automated devices, commercialized kits and consolidated protocols. However, the average number of protein structures obtained for most structural genomic groups has been very low compared to the total number of proteins purified. As more entire genomic sequences are obtained for different organisms from the three kingdoms of life, only the proteins that can be crystallized and whose structures can be obtained easily are studied. Consequently, an astonishing number of genomic proteins remain unexamined. In the era of high-throughput processes, traditional methods in molecular biology, protein chemistry and crystallization are eclipsed by automation and pipeline practices. The necessity for high rate production of protein crystals and structures has prevented the usage of more intellectual strategies and creative approaches in experimental executions. Fundamental principles and personal experiences in protein chemistry and crystallization are minimally exploited only to obtain "low-hanging fruit" protein structures. We review the practical aspects of today s high-throughput manipulations and discuss the challenges in fast pace protein crystallization and tools for crystallography. Structural genomic pipelines can be improved with information gained from low-throughput tactics that may help us reach the higher-bearing fruits. Examples of recent developments in this area are reported from the efforts of the Southeast Collaboratory for Structural Genomics (SECSG).

MIENS Minimum Information about an ENvironmental Sequence and The GSC's Not-for-Profit (GSC8 Meeting)

ScienceCinema

Yilmaz, Pelin; Kolker, Eugene

2018-01-24

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Pelin Yilmaz of the Max Planck Institute-Bremen talks about the MIENS specification and Eugene Kolker of Seattle Children's Hospital discusses the GSC's non-for-profit at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5b. GRANT NUMBER... therapy resistance/sensitivity, identification of new therapeutic targets through high quality genomic analyses, providing access to the highest quality

Extensive sequencing of seven human genomes to characterize benchmark reference materials

PubMed Central

Zook, Justin M.; Catoe, David; McDaniel, Jennifer; Vang, Lindsay; Spies, Noah; Sidow, Arend; Weng, Ziming; Liu, Yuling; Mason, Christopher E.; Alexander, Noah; Henaff, Elizabeth; McIntyre, Alexa B.R.; Chandramohan, Dhruva; Chen, Feng; Jaeger, Erich; Moshrefi, Ali; Pham, Khoa; Stedman, William; Liang, Tiffany; Saghbini, Michael; Dzakula, Zeljko; Hastie, Alex; Cao, Han; Deikus, Gintaras; Schadt, Eric; Sebra, Robert; Bashir, Ali; Truty, Rebecca M.; Chang, Christopher C.; Gulbahce, Natali; Zhao, Keyan; Ghosh, Srinka; Hyland, Fiona; Fu, Yutao; Chaisson, Mark; Xiao, Chunlin; Trow, Jonathan; Sherry, Stephen T.; Zaranek, Alexander W.; Ball, Madeleine; Bobe, Jason; Estep, Preston; Church, George M.; Marks, Patrick; Kyriazopoulou-Panagiotopoulou, Sofia; Zheng, Grace X.Y.; Schnall-Levin, Michael; Ordonez, Heather S.; Mudivarti, Patrice A.; Giorda, Kristina; Sheng, Ying; Rypdal, Karoline Bjarnesdatter; Salit, Marc

2016-01-01

The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry. The data come from 12 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCode WGS, and Illumina exome and WGS paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly. PMID:27271295

CIDR

Science.gov Websites

CIDR Skip navigation Home About CIDR General Highlights Newsletter Staff Employment Opportunities Genotyping General Information Genome Wide Association Custom FFPE Sample Options Methylation Linkage Consortium Developed Mouse Whole Genome Sequencing General Information Whole Genome Whole Exome Custom

CIDR

Science.gov Websites

Initiation Application Schedule Service Information and Pricing Services Sample Requirements Pricing SNP Genotyping General Information Genome Wide Association Custom FFPE Sample Options Methylation Linkage Consortium Developed Mouse Whole Genome Sequencing General Information Whole Genome Whole Exome Custom

Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.

PubMed

Wang, Jun; Kurilshikov, Alexander; Radjabzadeh, Djawad; Turpin, Williams; Croitoru, Kenneth; Bonder, Marc Jan; Jackson, Matthew A; Medina-Gomez, Carolina; Frost, Fabian; Homuth, Georg; Rühlemann, Malte; Hughes, David; Kim, Han-Na; Spector, Tim D; Bell, Jordana T; Steves, Claire J; Timpson, Nicolas; Franke, Andre; Wijmenga, Cisca; Meyer, Katie; Kacprowski, Tim; Franke, Lude; Paterson, Andrew D; Raes, Jeroen; Kraaij, Robert; Zhernakova, Alexandra

2018-06-08

In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture. Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories. We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

Using Markov chains of nucleotide sequences as a possible precursor to predict functional roles of human genome: a case study on inactive chromatin regions.

PubMed

Lee, K-E; Lee, E-J; Park, H-S

2016-08-30

Recent advances in computational epigenetics have provided new opportunities to evaluate n-gram probabilistic language models. In this paper, we describe a systematic genome-wide approach for predicting functional roles in inactive chromatin regions by using a sequence-based Markovian chromatin map of the human genome. We demonstrate that Markov chains of sequences can be used as a precursor to predict functional roles in heterochromatin regions and provide an example comparing two publicly available chromatin annotations of large-scale epigenomics projects: ENCODE project consortium and Roadmap Epigenomics consortium.

The Encyclopedia of Systems Biology and OMICS (first presentation) and The ISA Infrastructure for Multi-omics Data (second presentation) (GSC8 Meeting)

ScienceCinema

Kolker, Eugene; Sansone, Susanna

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Eugene Kolker from Seattle Children's Hospital briefly discusses "The Encyclopedia of Systems Biology and OMICS," followed by Susanna Sansone from the EBI on "The ISA Infrastructure for multi-omics data" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA. on Sept. 11, 2009.

Flash Updates of GSC projects (GSC8 Meeting)

ScienceCinema

Glockner, Frank Oliver; Markowitz, Victor; Kyrpides, Nikos; Meyer, Folker; Amaral-Zettler, Linda; Cole, James

2018-01-25

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. In quick succession Frank Oliver Glockner (MPI-Bremen), Victor Markowitz (LBNL), Nikos Kyripides (JGI), Folker Meyer (ANL), Linda Amaral-Zettler (Marine Biology Lab), and James Cole (Michigan State University) provide updates on a number of topics related to GSC projects at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

Flash Updates of GSC projects (GSC8 Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glockner, Frank Oliver; Markowitz, Victor; Kyrpides, Nikos

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. In quick succession Frank Oliver Glockner (MPI-Bremen), Victor Markowitz (LBNL), Nikos Kyripides (JGI), Folker Meyer (ANL), Linda Amaral-Zettler (Marine Biology Lab), and James Colemore » (Michigan State University) provide updates on a number of topics related to GSC projects at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.« less

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

USDA-ARS?s Scientific Manuscript database

We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the minimum information about any (x) sequence (MIxS). The standards are the minimum information about a single amplified genome (MISAG) and the ...

Epigenome data release: a participant-centered approach to privacy protection.

PubMed

Dyke, Stephanie O M; Cheung, Warren A; Joly, Yann; Ammerpohl, Ole; Lutsik, Pavlo; Rothstein, Mark A; Caron, Maxime; Busche, Stephan; Bourque, Guillaume; Rönnblom, Lars; Flicek, Paul; Beck, Stephan; Hirst, Martin; Stunnenberg, Henk; Siebert, Reiner; Walter, Jörn; Pastinen, Tomi

2015-07-17

Large-scale epigenome mapping by the NIH Roadmap Epigenomics Project, the ENCODE Consortium and the International Human Epigenome Consortium (IHEC) produces genome-wide DNA methylation data at one base-pair resolution. We examine how such data can be made open-access while balancing appropriate interpretation and genomic privacy. We propose guidelines for data release that both reduce ambiguity in the interpretation of open-access data and limit immediate access to genetic variation data that are made available through controlled access.

A bacterial pioneer produces cellulase complexes that persist through community succession

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolinko, Sebastian; Wu, Yu-Wei; Tachea, Firehiwot

Cultivation of microbial consortia provides low-complexity communities that can serve as tractable models to understand community dynamics. Time-resolved metagenomics demonstrated that an aerobic cellulolytic consortium cultivated from compost exhibited community dynamics consistent with the definition of an endogenous heterotrophic succession. The genome of the proposed pioneer population, 'Candidatus Reconcilibacillus cellulovorans', possessed a gene cluster containing multidomain glycoside hydrolases (GHs). Purification of the soluble cellulase activity from a 300litre cultivation of this consortium revealed that ~70% of the activity arose from the 'Ca. Reconcilibacillus cellulovorans' multidomain GHs assembled into cellulase complexes through glycosylation. These remarkably stable complexes have supramolecular structures formore » enzymatic cellulose hydrolysis that are distinct from cellulosomes. The persistence of these complexes during cultivation indicates that they may be active through multiple cultivations of this consortium and act as public goods that sustain the community. Thus, the provision of extracellular GHs as public goods may influence microbial community dynamics in native biomass-deconstructing communities relevant to agriculture, human health and biotechnology.« less

A bacterial pioneer produces cellulase complexes that persist through community succession

DOE PAGES

Kolinko, Sebastian; Wu, Yu-Wei; Tachea, Firehiwot; ...

2017-11-06

Cultivation of microbial consortia provides low-complexity communities that can serve as tractable models to understand community dynamics. Time-resolved metagenomics demonstrated that an aerobic cellulolytic consortium cultivated from compost exhibited community dynamics consistent with the definition of an endogenous heterotrophic succession. The genome of the proposed pioneer population, 'Candidatus Reconcilibacillus cellulovorans', possessed a gene cluster containing multidomain glycoside hydrolases (GHs). Purification of the soluble cellulase activity from a 300litre cultivation of this consortium revealed that ~70% of the activity arose from the 'Ca. Reconcilibacillus cellulovorans' multidomain GHs assembled into cellulase complexes through glycosylation. These remarkably stable complexes have supramolecular structures formore » enzymatic cellulose hydrolysis that are distinct from cellulosomes. The persistence of these complexes during cultivation indicates that they may be active through multiple cultivations of this consortium and act as public goods that sustain the community. Thus, the provision of extracellular GHs as public goods may influence microbial community dynamics in native biomass-deconstructing communities relevant to agriculture, human health and biotechnology.« less

A bacterial pioneer produces cellulase complexes that persist through community succession.

PubMed

Kolinko, Sebastian; Wu, Yu-Wei; Tachea, Firehiwot; Denzel, Evelyn; Hiras, Jennifer; Gabriel, Raphael; Bäcker, Nora; Chan, Leanne Jade G; Eichorst, Stephanie A; Frey, Dario; Chen, Qiushi; Azadi, Parastoo; Adams, Paul D; Pray, Todd R; Tanjore, Deepti; Petzold, Christopher J; Gladden, John M; Simmons, Blake A; Singer, Steven W

2018-01-01

Cultivation of microbial consortia provides low-complexity communities that can serve as tractable models to understand community dynamics. Time-resolved metagenomics demonstrated that an aerobic cellulolytic consortium cultivated from compost exhibited community dynamics consistent with the definition of an endogenous heterotrophic succession. The genome of the proposed pioneer population, 'Candidatus Reconcilibacillus cellulovorans', possessed a gene cluster containing multidomain glycoside hydrolases (GHs). Purification of the soluble cellulase activity from a 300litre cultivation of this consortium revealed that ~70% of the activity arose from the 'Ca. Reconcilibacillus cellulovorans' multidomain GHs assembled into cellulase complexes through glycosylation. These remarkably stable complexes have supramolecular structures for enzymatic cellulose hydrolysis that are distinct from cellulosomes. The persistence of these complexes during cultivation indicates that they may be active through multiple cultivations of this consortium and act as public goods that sustain the community. The provision of extracellular GHs as public goods may influence microbial community dynamics in native biomass-deconstructing communities relevant to agriculture, human health and biotechnology.

FANTOM5 CAGE profiles of human and mouse reprocessed for GRCh38 and GRCm38 genome assemblies.

PubMed

Abugessaisa, Imad; Noguchi, Shuhei; Hasegawa, Akira; Harshbarger, Jayson; Kondo, Atsushi; Lizio, Marina; Severin, Jessica; Carninci, Piero; Kawaji, Hideya; Kasukawa, Takeya

2017-08-29

The FANTOM5 consortium described the promoter-level expression atlas of human and mouse by using CAGE (Cap Analysis of Gene Expression) with single molecule sequencing. In the original publications, GRCh37/hg19 and NCBI37/mm9 assemblies were used as the reference genomes of human and mouse respectively; later, the Genome Reference Consortium released newer genome assemblies GRCh38/hg38 and GRCm38/mm10. To increase the utility of the atlas in forthcoming researches, we reprocessed the data to make them available on the recent genome assemblies. The data include observed frequencies of transcription starting sites (TSSs) based on the realignment of CAGE reads, and TSS peaks that are converted from those based on the previous reference. Annotations of the peak names were also updated based on the latest public databases. The reprocessed results enable us to examine frequencies of transcription initiations on the recent genome assemblies and to refer promoters with updated information across the genome assemblies consistently.

Guided Exploration of Genomic Risk for Gray Matter Abnormalities in Schizophrenia Using Parallel Independent Component Analysis with Reference

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Pearlson, Godfrey D.; Perrone-Bizzozero, Nora; Sui, Jing; Turner, Jessica A.; Bustillo, Juan R; Ehrlich, Stefan; Sponheim, Scott R.; Cañive, José M.; Ho, Beng-Choon; Liu, Jingyu

2013-01-01

One application of imaging genomics is to explore genetic variants associated with brain structure and function, presenting a new means of mapping genetic influences on mental disorders. While there is growing interest in performing genome-wide searches for determinants, it remains challenging to identify genetic factors of small effect size, especially in limited sample sizes. In an attempt to address this issue, we propose to take advantage of a priori knowledge, specifically to extend parallel independent component analysis (pICA) to incorporate a reference (pICA-R), aiming to better reveal relationships between hidden factors of a particular attribute. The new approach was first evaluated on simulated data for its performance under different configurations of effect size and dimensionality. Then pICA-R was applied to a 300-participant (140 schizophrenia (SZ) patients versus 160 healthy controls) dataset consisting of structural magnetic resonance imaging (sMRI) and single nucleotide polymorphism (SNP) data. Guided by a reference SNP set derived from ANK3, a gene implicated by the Psychiatric Genomic Consortium SZ study, pICA-R identified one pair of SNP and sMRI components with a significant loading correlation of 0.27 (p = 1.64×10−6). The sMRI component showed a significant group difference in loading parameters between patients and controls (p = 1.33×10−15), indicating SZ-related reduction in gray matter concentration in prefrontal and temporal regions. The linked SNP component also showed a group difference (p = 0.04) and was predominantly contributed to by 1,030 SNPs. The effect of these top contributing SNPs was verified using association test results of the Psychiatric Genomic Consortium SZ study, where the 1,030 SNPs exhibited significant SZ enrichment compared to the whole genome. In addition, pathway analyses indicated the genetic component majorly relating to neurotransmitter and nervous system signaling pathways. Given the simulation and experiment results, pICA-R may prove a promising multivariate approach for use in imaging genomics to discover reliable genetic risk factors under a scenario of relatively high dimensionality and small effect size. PMID:23727316

Submitting MIGS, MIMS, MIENS Information to EMBL and Standards and the Sequencing Pipelines of the Gordon and Betty Moore Foundation (GSC8 Meeting)

ScienceCinema

Vaughan, Bob; Kaye, Jon

2018-01-24

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Bob Vaughan of EMBL on submitting MIGS/MIMS/MIENS information to EMBL-EBI's system, followed by a brief talk from Jon Kaye of the Gordon and Betty Moore Foundation on standards and the foundation's sequencing pipelines at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

The Human Microbiome Project (HMP) and the Data Analysis and Coordination Center (DAAC) Portal to the HMP (GSC8 Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weinstock, George; Wortman, Jennifer

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. George Weinstock from Washington University School of Medicine talks about the Human Microbiome Project (HMP) followed briefly by Jennifer Wortman from the University ofmore » Maryland School of Medicine on the Data Analysis and Coordination Center (DACC) portal to the HMP at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.« less

"A New Arm of the GSC: the RCN4GSC" and "Curation of MIGS-compliant Data" (GSC 8 Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Field, Dawn; Sterk, Peter

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology & Hydrology briefly describes RCN4GSC and Peter Sterk of the NERC Centre for Ecology & Hydrologymore » follows with a talk on curation of MIGS-compliant data at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.« less

A New Arm of the GSC: The RCN4GSC and Curation of MIGS-compliant Data (GSC8 Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Field, Dawn; Sterk, Peter

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology and Hydrology briefly describes RCN4GSC and Peter Sterk of the NERC Centre for Ecology and Hydrologymore » follows with a talk on curation of MIGS-compliant data at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.« less

Submitting MIGS, MIMS, MIENS Information to EMBL and Standards and the Sequencing Pipelines of the Gordon and Betty Moore Foundation (GSC8 Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaughan, Bob; Kaye, Jon

2009-09-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Bob Vaughan of EMBL on submitting MIGS/MIMS/MIENS information to EMBL-EBI's system, followed by a brief talk from Jon Kaye of the Gordon and Bettymore » Moore Foundation on standards and the foundation's sequencing pipelines at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.« less

The Human Microbiome Project (HMP) and the Data Analysis and Coordination Center (DAAC) Portal to the HMP (GSC8 Meeting)

ScienceCinema

Weinstock, George; Wortman, Jennifer

2018-01-22

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. George Weinstock from Washington University School of Medicine talks about the Human Microbiome Project (HMP) followed briefly by Jennifer Wortman from the University of Maryland School of Medicine on the Data Analysis and Coordination Center (DACC) portal to the HMP at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA on Sept. 9, 2009.

The Encyclopedia of Systems Biology and OMICS (first presentation) and The ISA Infrastructure for Multi-omics Data (second presentation) (GSC8 Meeting)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolker, Eugene; Sansone, Susanna

2011-09-11

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding "Research Coordination Network" from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Eugene Kolker from Seattle Children's Hospital briefly discusses "The Encyclopedia of Systems Biology and OMICS," followed by Susanna Sansone from the EBI on "Themore » ISA Infrastructure for multi-omics data" at the Genomic Standards Consortium's 8th meeting at the DOE JGI in Walnut Creek, CA. on Sept. 11, 2009.« less

A New Arm of the GSC: The RCN4GSC and Curation of MIGS-compliant Data (GSC8 Meeting)

ScienceCinema

Field, Dawn; Sterk, Peter

2018-01-09

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego. Dawn Field of the NERC Centre for Ecology and Hydrology briefly describes RCN4GSC and Peter Sterk of the NERC Centre for Ecology and Hydrology follows with a talk on curation of MIGS-compliant data at the Genomic Standards Consortium 8th meeting at the DOE JGI in Walnut Creek, Calif. on Sept. 9, 2009.

Assembly: a resource for assembled genomes at NCBI

PubMed Central

Kitts, Paul A.; Church, Deanna M.; Thibaud-Nissen, Françoise; Choi, Jinna; Hem, Vichet; Sapojnikov, Victor; Smith, Robert G.; Tatusova, Tatiana; Xiang, Charlie; Zherikov, Andrey; DiCuccio, Michael; Murphy, Terence D.; Pruitt, Kim D.; Kimchi, Avi

2016-01-01

The NCBI Assembly database (www.ncbi.nlm.nih.gov/assembly/) provides stable accessioning and data tracking for genome assembly data. The model underlying the database can accommodate a range of assembly structures, including sets of unordered contig or scaffold sequences, bacterial genomes consisting of a single complete chromosome, or complex structures such as a human genome with modeled allelic variation. The database provides an assembly accession and version to unambiguously identify the set of sequences that make up a particular version of an assembly, and tracks changes to updated genome assemblies. The Assembly database reports metadata such as assembly names, simple statistical reports of the assembly (number of contigs and scaffolds, contiguity metrics such as contig N50, total sequence length and total gap length) as well as the assembly update history. The Assembly database also tracks the relationship between an assembly submitted to the International Nucleotide Sequence Database Consortium (INSDC) and the assembly represented in the NCBI RefSeq project. Users can find assemblies of interest by querying the Assembly Resource directly or by browsing available assemblies for a particular organism. Links in the Assembly Resource allow users to easily download sequence and annotations for current versions of genome assemblies from the NCBI genomes FTP site. PMID:26578580

Researcher Interview: Tom Hudson

Cancer.gov

Tom Hudson, M.D., President and Scientific Director of the Ontario Institute for Cancer Research, describes the International Cancer Genome Consortium (ICGC), which brings together cancer genomic data and research from across the world.

A snapshot of the emerging tomato genome sequence

USDA-ARS?s Scientific Manuscript database

The genome of tomato (Solanum lycopersicum) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, the Netherlands, France, Japan, Spain, Italy and the United States) as part of a larger initiative called the ‘International Solanaceae Genome Proje...

Meeting Report: Genomics in the Undergraduate Curriculum--Rocket Science or Basic Science?

ERIC Educational Resources Information Center

Campbell, A. Malcolm

2002-01-01

At the 102nd annual meeting of the American Society for Microbiology (ASM) in Salt Lake City, Utah, members of the Genome Consortium for Active Teaching and faculty from around the world gathered to discuss educational genomics. The focus of the gathering was a series of presentations by faculty who have successfully incorporated genomics and…

Sequencing the genome of the Burmese python (Python molurus bivittatus) as a model for studying extreme adaptations in snakes.

PubMed

Castoe, Todd A; de Koning, Jason A P; Hall, Kathryn T; Yokoyama, Ken D; Gu, Wanjun; Smith, Eric N; Feschotte, Cédric; Uetz, Peter; Ray, David A; Dobry, Jason; Bogden, Robert; Mackessy, Stephen P; Bronikowski, Anne M; Warren, Wesley C; Secor, Stephen M; Pollock, David D

2011-07-28

The Consortium for Snake Genomics is in the process of sequencing the genome and creating transcriptomic resources for the Burmese python. Here, we describe how this will be done, what analyses this work will include, and provide a timeline.

RCN4GSC workshop report: managing data at the interface of biodiversity and (meta)genomics, March 2011

USDA-ARS?s Scientific Manuscript database

The Genomic Standards Consortium (GSC) is an international working body with the mission of working towards richer descriptions of genomic and metagenomic data through the development of standards and tools for supporting the consistent documentation of contextual information about sequences. Becaus...

Genome wide association analyses based on a multiple trait approach for modeling feed efficiency

USDA-ARS?s Scientific Manuscript database

Genome wide association (GWA) of feed efficiency (FE) could help target important genomic regions influencing FE. Data provided by an international dairy FE research consortium consisted of phenotypic records on dry matter intakes (DMI), milk energy (MILKE), and metabolic body weight (MBW) on 6,937 ...

DangerTrack: A scoring system to detect difficult-to-assess regions.

PubMed

Dolgalev, Igor; Sedlazeck, Fritz; Busby, Ben

2017-01-01

Over recent years, multiple groups have shown that a large number of structural variants, repeats, or problems with the underlying genome assembly have dramatic effects on the mapping, calling, and overall reliability of single nucleotide polymorphism calls. This project endeavored to develop an easy-to-use track for looking at structural variant and repeat regions. This track, DangerTrack, can be displayed alongside the existing Genome Reference Consortium assembly tracks to warn clinicians and biologists when variants of interest may be incorrectly called, of dubious quality, or on an insertion or copy number expansion. While mapping and variant calling can be automated, it is our opinion that when these regions are of interest to a particular clinical or research group, they warrant a careful examination, potentially involving localized reassembly. DangerTrack is available at https://github.com/DCGenomics/DangerTrack.

Legal Agreements and the Governance of Research Commons: Lessons from Materials Sharing in Mouse Genomics

PubMed Central

Mishra, Amrita

2014-01-01

Abstract Omics research infrastructure such as databases and bio-repositories requires effective governance to support pre-competitive research. Governance includes the use of legal agreements, such as Material Transfer Agreements (MTAs). We analyze the use of such agreements in the mouse research commons, including by two large-scale resource development projects: the International Knockout Mouse Consortium (IKMC) and International Mouse Phenotyping Consortium (IMPC). We combine an analysis of legal agreements and semi-structured interviews with 87 members of the mouse model research community to examine legal agreements in four contexts: (1) between researchers; (2) deposit into repositories; (3) distribution by repositories; and (4) exchanges between repositories, especially those that are consortium members of the IKMC and IMPC. We conclude that legal agreements for the deposit and distribution of research reagents should be kept as simple and standard as possible, especially when minimal enforcement capacity and resources exist. Simple and standardized legal agreements reduce transactional bottlenecks and facilitate the creation of a vibrant and sustainable research commons, supported by repositories and databases. PMID:24552652

Inferring genome-wide interplay landscape between DNA methylation and transcriptional regulation.

PubMed

Tang, Binhua; Wang, Xin

2015-01-01

DNA methylation and transcriptional regulation play important roles in cancer cell development and differentiation processes. Based on the currently available cell line profiling information from the ENCODE Consortium, we propose a Bayesian inference model to infer and construct genome-wide interaction landscape between DNA methylation and transcriptional regulation, which sheds light on the underlying complex functional mechanisms important within the human cancer and disease context. For the first time, we select all the currently available cell lines (>=20) and transcription factors (>=80) profiling information from the ENCODE Consortium portal. Through the integration of those genome-wide profiling sources, our genome-wide analysis detects multiple functional loci of interest, and indicates that DNA methylation is cell- and region-specific, due to the interplay mechanisms with transcription regulatory activities. We validate our analysis results with the corresponding RNA-sequencing technique for those detected genomic loci. Our results provide novel and meaningful insights for the interplay mechanisms of transcriptional regulation and gene expression for the human cancer and disease studies.

Sequencing of 15,622 gene-bearing BACs clarifies the gene-dense regions of the barley genome

USDA-ARS?s Scientific Manuscript database

Barley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole-genome shotgun sequences with a physical and genetic framework....

CPTAC Releases Largest-Ever Breast Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

Cancer.gov

National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have released a dataset of proteins and  phosphopeptides identified through deep proteomic and phosphoproteomic analysis of breast tumor samples, previously genomically analyzed by The Cancer Genome Atlas (TCGA).

The tomato genome

USDA-ARS?s Scientific Manuscript database

The tomato genome sequence was undertaken at a time when state-of-the-art sequencing methodologies were undergoing a transition to co-called next generation methodologies. The result was an international consortium undertaking a strategy merging both old and new approaches. Because biologists were...

New Funding Opportunity Announcements (FOAs): Reissuance of Clinical Proteomic Tumor Analysis Consortium (CPTAC) | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute is soliciting applications for the reissuance of its Clinical Proteomic Tumor Analysis Consortium (CPTAC) program.   CPTAC will support broad efforts focused on several cancer types to explore further the complexities of cancer proteomes and their connections to abnormalities in cancer genomes.

The SGC beyond structural genomics: redefining the role of 3D structures by coupling genomic stratification with fragment-based discovery.

PubMed

Bradley, Anthony R; Echalier, Aude; Fairhead, Michael; Strain-Damerell, Claire; Brennan, Paul; Bullock, Alex N; Burgess-Brown, Nicola A; Carpenter, Elisabeth P; Gileadi, Opher; Marsden, Brian D; Lee, Wen Hwa; Yue, Wyatt; Bountra, Chas; von Delft, Frank

2017-11-08

The ongoing explosion in genomics data has long since outpaced the capacity of conventional biochemical methodology to verify the large number of hypotheses that emerge from the analysis of such data. In contrast, it is still a gold-standard for early phenotypic validation towards small-molecule drug discovery to use probe molecules (or tool compounds), notwithstanding the difficulty and cost of generating them. Rational structure-based approaches to ligand discovery have long promised the efficiencies needed to close this divergence; in practice, however, this promise remains largely unfulfilled, for a host of well-rehearsed reasons and despite the huge technical advances spearheaded by the structural genomics initiatives of the noughties. Therefore the current, fourth funding phase of the Structural Genomics Consortium (SGC), building on its extensive experience in structural biology of novel targets and design of protein inhibitors, seeks to redefine what it means to do structural biology for drug discovery. We developed the concept of a Target Enabling Package (TEP) that provides, through reagents, assays and data, the missing link between genetic disease linkage and the development of usefully potent compounds. There are multiple prongs to the ambition: rigorously assessing targets' genetic disease linkages through crowdsourcing to a network of collaborating experts; establishing a systematic approach to generate the protocols and data that comprise each target's TEP; developing new, X-ray-based fragment technologies for generating high quality chemical matter quickly and cheaply; and exploiting a stringently open access model to build multidisciplinary partnerships throughout academia and industry. By learning how to scale these approaches, the SGC aims to make structures finally serve genomics, as originally intended, and demonstrate how 3D structures systematically allow new modes of druggability to be discovered for whole classes of targets. © 2017 The Author(s).

Enhancing Psychosis-Spectrum Nosology Through an International Data Sharing Initiative.

PubMed

Docherty, Anna R; Fonseca-Pedrero, Eduardo; Debbané, Martin; Chan, Raymond C K; Linscott, Richard J; Jonas, Katherine G; Cicero, David C; Green, Melissa J; Simms, Leonard J; Mason, Oliver; Watson, David; Ettinger, Ulrich; Waszczuk, Monika; Rapp, Alexander; Grant, Phillip; Kotov, Roman; DeYoung, Colin G; Ruggero, Camilo J; Eaton, Nicolas R; Krueger, Robert F; Patrick, Christopher; Hopwood, Christopher; O'Neill, F Anthony; Zald, David H; Conway, Christopher C; Adkins, Daniel E; Waldman, Irwin D; van Os, Jim; Sullivan, Patrick F; Anderson, John S; Shabalin, Andrey A; Sponheim, Scott R; Taylor, Stephan F; Grazioplene, Rachel G; Bacanu, Silviu A; Bigdeli, Tim B; Haenschel, Corinna; Malaspina, Dolores; Gooding, Diane C; Nicodemus, Kristin; Schultze-Lutter, Frauke; Barrantes-Vidal, Neus; Mohr, Christine; Carpenter, William T; Cohen, Alex S

2018-05-16

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural equation modeling approaches. In the last 50 years, efforts in both psychiatry and psychological science have moved toward (1) a dimensional model of psychopathology (eg, the current Hierarchical Taxonomy of Psychopathology [HiTOP] initiative), (2) an integration of methods and measures across traits and units of analysis (eg, the RDoC initiative), and (3) powerful, impactful study designs maximizing sample size to detect subtle genomic variation relating to complex traits (the Psychiatric Genomics Consortium [PGC]). These movements are important to the future study of the psychosis spectrum, and to resolving heterogeneity with respect to instrument and population. The International Consortium of Schizotypy Research is composed of over 40 laboratories in 12 countries, and to date, members have compiled a body of schizotypy- and psychosis-related phenotype data from more than 30000 individuals. It has become apparent that compiling data into a protected, relational database and crowdsourcing analytic and data science expertise will result in significant enhancement of current research on the structure and biological substrates of the psychosis spectrum. The authors present a data-sharing infrastructure similar to that of the PGC, and a resource-sharing infrastructure similar to that of HiTOP. This report details the rationale and benefits of the phenotypic data collective and presents an open invitation for participation.

The peanut genome consortium and peanut genome sequence: Creating a better future through global food security

USDA-ARS?s Scientific Manuscript database

The competitiveness of peanuts in domestic and global markets has been threatened by losses in productivity and quality that are attributed to diseases, pests, environmental stresses and allergy or food safety issues. The U.S. Peanut Genome Initiative (PGI) was launched in 2004, and expanded to a gl...

Consortium biology in immunology: the perspective from the Immunological Genome Project.

PubMed

Benoist, Christophe; Lanier, Lewis; Merad, Miriam; Mathis, Diane

2012-10-01

Although the field has a long collaborative tradition, immunology has made less use than genetics of 'consortium biology', wherein groups of investigators together tackle large integrated questions or problems. However, immunology is naturally suited to large-scale integrative and systems-level approaches, owing to the multicellular and adaptive nature of the cells it encompasses. Here, we discuss the value and drawbacks of this organization of research, in the context of the long-running 'big science' debate, and consider the opportunities that may exist for the immunology community. We position this analysis in light of our own experience, both positive and negative, as participants of the Immunological Genome Project.

Bioinformatics data distribution and integration via Web Services and XML.

PubMed

Li, Xiao; Zhang, Yizheng

2003-11-01

It is widely recognized that exchange, distribution, and integration of biological data are the keys to improve bioinformatics and genome biology in post-genomic era. However, the problem of exchanging and integrating biology data is not solved satisfactorily. The eXtensible Markup Language (XML) is rapidly spreading as an emerging standard for structuring documents to exchange and integrate data on the World Wide Web (WWW). Web service is the next generation of WWW and is founded upon the open standards of W3C (World Wide Web Consortium) and IETF (Internet Engineering Task Force). This paper presents XML and Web Services technologies and their use for an appropriate solution to the problem of bioinformatics data exchange and integration.

Omics-based interpretation of synergism in a soil-derived cellulose-degrading microbial community

PubMed Central

Zhou, Yizhuang; Pope, Phillip B.; Li, Shaochun; Wen, Bo; Tan, Fengji; Cheng, Shu; Chen, Jing; Yang, Jinlong; Liu, Feng; Lei, Xuejing; Su, Qingqing; Zhou, Chengran; Zhao, Jiao; Dong, Xiuzhu; Jin, Tao; Zhou, Xin; Yang, Shuang; Zhang, Gengyun; Yang, Huangming; Wang, Jian; Yang, Ruifu; Eijsink, Vincent G. H.; Wang, Jun

2014-01-01

Reaching a comprehensive understanding of how nature solves the problem of degrading recalcitrant biomass may eventually allow development of more efficient biorefining processes. Here we interpret genomic and proteomic information generated from a cellulolytic microbial consortium (termed F1RT) enriched from soil. Analyses of reconstructed bacterial draft genomes from all seven uncultured phylotypes in F1RT indicate that its constituent microbes cooperate in both cellulose-degrading and other important metabolic processes. Support for cellulolytic inter-species cooperation came from the discovery of F1RT microbes that encode and express complimentary enzymatic inventories that include both extracellular cellulosomes and secreted free-enzyme systems. Metabolic reconstruction of the seven F1RT phylotypes predicted a wider genomic rationale as to how this particular community functions as well as possible reasons as to why biomass conversion in nature relies on a structured and cooperative microbial community. PMID:24924356

Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: A Genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls.

PubMed

Preuss, Michael; König, Inke R; Thompson, John R; Erdmann, Jeanette; Absher, Devin; Assimes, Themistocles L; Blankenberg, Stefan; Boerwinkle, Eric; Chen, Li; Cupples, L Adrienne; Hall, Alistair S; Halperin, Eran; Hengstenberg, Christian; Holm, Hilma; Laaksonen, Reijo; Li, Mingyao; März, Winfried; McPherson, Ruth; Musunuru, Kiran; Nelson, Christopher P; Burnett, Mary Susan; Epstein, Stephen E; O'Donnell, Christopher J; Quertermous, Thomas; Rader, Daniel J; Roberts, Robert; Schillert, Arne; Stefansson, Kari; Stewart, Alexandre F R; Thorleifsson, Gudmar; Voight, Benjamin F; Wells, George A; Ziegler, Andreas; Kathiresan, Sekar; Reilly, Muredach P; Samani, Nilesh J; Schunkert, Heribert

2010-10-01

Recent genome-wide association studies (GWAS) of myocardial infarction (MI) and other forms of coronary artery disease (CAD) have led to the discovery of at least 13 genetic loci. In addition to the effect size, power to detect associations is largely driven by sample size. Therefore, to maximize the chance of finding novel susceptibility loci for CAD and MI, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed. CARDIoGRAM combines data from all published and several unpublished GWAS in individuals with European ancestry; includes >22 000 cases with CAD, MI, or both and >60 000 controls; and unifies samples from the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology study, CADomics, Cohorts for Heart and Aging Research in Genomic Epidemiology, deCODE, the German Myocardial Infarction Family Studies I, II, and III, Ludwigshafen Risk and Cardiovascular Heath Study/AtheroRemo, MedStar, Myocardial Infarction Genetics Consortium, Ottawa Heart Genomics Study, PennCath, and the Wellcome Trust Case Control Consortium. Genotyping was carried out on Affymetrix or Illumina platforms followed by imputation of genotypes in most studies. On average, 2.2 million single nucleotide polymorphisms were generated per study. The results from each study are combined using meta-analysis. As proof of principle, we meta-analyzed risk variants at 9p21 and found that rs1333049 confers a 29% increase in risk for MI per copy (P=2×10⁻²⁰). CARDIoGRAM is poised to contribute to our understanding of the role of common genetic variation on risk for CAD and MI.

Publisher Correction: Whole genome sequencing in psychiatric disorders: the WGSPD consortium.

PubMed

Sanders, Stephan J; Neale, Benjamin M; Huang, Hailiang; Werling, Donna M; An, Joon-Yong; Dong, Shan; Abecasis, Goncalo; Arguello, P Alexander; Blangero, John; Boehnke, Michael; Daly, Mark J; Eggan, Kevin; Geschwind, Daniel H; Glahn, David C; Goldstein, David B; Gur, Raquel E; Handsaker, Robert E; McCarroll, Steven A; Ophoff, Roel A; Palotie, Aarno; Pato, Carlos N; Sabatti, Chiara; State, Matthew W; Willsey, A Jeremy; Hyman, Steven E; Addington, Anjene M; Lehner, Thomas; Freimer, Nelson B

2018-03-16

In the version of this article initially published, the consortium authorship and corresponding authors were not presented correctly. In the PDF and print versions, the Whole Genome Sequencing for Psychiatric Disorders (WGSPD) consortium was missing from the author list at the beginning of the paper, where it should have appeared as the seventh author; it was present in the author list at the end of the paper, but the footnote directing readers to the Supplementary Note for a list of members was missing. In the HTML version, the consortium was listed as the last author instead of as the seventh, and the line directing readers to the Supplementary Note for a list of members appeared at the end of the paper under Author Information but not in association with the consortium name itself. Also, this line stated that both member names and affiliations could be found in the Supplementary Note; in fact, only names are given. In all versions of the paper, the corresponding author symbols were attached to A. Jeremy Willsey, Steven E. Hyman, Anjene M. Addington and Thomas Lehner; they should have been attached, respectively, to Steven E. Hyman, Anjene M. Addington, Thomas Lehner and Nelson B. Freimer. As a result of this shift, the respective contact links in the HTML version did not lead to the indicated individuals. The errors have been corrected in the HTML and PDF versions of the article.

The Single Nucleotide Polymorphism Consortium

NASA Technical Reports Server (NTRS)

Morgan, Michael

2003-01-01

I want to discuss both the Single Nucleotide Polymorphism (SNP) Consortium and the Human Genome Project. I am afraid most of my presentation will be thin on law and possibly too high on rhetoric. Having been engaged in a personal and direct way with these issues as a trained scientist, I find it quite difficult to be always as objective as I ought to be.

The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.

PubMed

Thompson, Paul M; Stein, Jason L; Medland, Sarah E; Hibar, Derrek P; Vasquez, Alejandro Arias; Renteria, Miguel E; Toro, Roberto; Jahanshad, Neda; Schumann, Gunter; Franke, Barbara; Wright, Margaret J; Martin, Nicholas G; Agartz, Ingrid; Alda, Martin; Alhusaini, Saud; Almasy, Laura; Almeida, Jorge; Alpert, Kathryn; Andreasen, Nancy C; Andreassen, Ole A; Apostolova, Liana G; Appel, Katja; Armstrong, Nicola J; Aribisala, Benjamin; Bastin, Mark E; Bauer, Michael; Bearden, Carrie E; Bergmann, Orjan; Binder, Elisabeth B; Blangero, John; Bockholt, Henry J; Bøen, Erlend; Bois, Catherine; Boomsma, Dorret I; Booth, Tom; Bowman, Ian J; Bralten, Janita; Brouwer, Rachel M; Brunner, Han G; Brohawn, David G; Buckner, Randy L; Buitelaar, Jan; Bulayeva, Kazima; Bustillo, Juan R; Calhoun, Vince D; Cannon, Dara M; Cantor, Rita M; Carless, Melanie A; Caseras, Xavier; Cavalleri, Gianpiero L; Chakravarty, M Mallar; Chang, Kiki D; Ching, Christopher R K; Christoforou, Andrea; Cichon, Sven; Clark, Vincent P; Conrod, Patricia; Coppola, Giovanni; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Deary, Ian J; de Geus, Eco J C; den Braber, Anouk; Delvecchio, Giuseppe; Depondt, Chantal; de Haan, Lieuwe; de Zubicaray, Greig I; Dima, Danai; Dimitrova, Rali; Djurovic, Srdjan; Dong, Hongwei; Donohoe, Gary; Duggirala, Ravindranath; Dyer, Thomas D; Ehrlich, Stefan; Ekman, Carl Johan; Elvsåshagen, Torbjørn; Emsell, Louise; Erk, Susanne; Espeseth, Thomas; Fagerness, Jesen; Fears, Scott; Fedko, Iryna; Fernández, Guillén; Fisher, Simon E; Foroud, Tatiana; Fox, Peter T; Francks, Clyde; Frangou, Sophia; Frey, Eva Maria; Frodl, Thomas; Frouin, Vincent; Garavan, Hugh; Giddaluru, Sudheer; Glahn, David C; Godlewska, Beata; Goldstein, Rita Z; Gollub, Randy L; Grabe, Hans J; Grimm, Oliver; Gruber, Oliver; Guadalupe, Tulio; Gur, Raquel E; Gur, Ruben C; Göring, Harald H H; Hagenaars, Saskia; Hajek, Tomas; Hall, Geoffrey B; Hall, Jeremy; Hardy, John; Hartman, Catharina A; Hass, Johanna; Hatton, Sean N; Haukvik, Unn K; Hegenscheid, Katrin; Heinz, Andreas; Hickie, Ian B; Ho, Beng-Choon; Hoehn, David; Hoekstra, Pieter J; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hoogman, Martine; Hong, L Elliot; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Hwang, Kristy S; Jack, Clifford R; Jenkinson, Mark; Johnston, Caroline; Jönsson, Erik G; Kahn, René S; Kasperaviciute, Dalia; Kelly, Sinead; Kim, Sungeun; Kochunov, Peter; Koenders, Laura; Krämer, Bernd; Kwok, John B J; Lagopoulos, Jim; Laje, Gonzalo; Landen, Mikael; Landman, Bennett A; Lauriello, John; Lawrie, Stephen M; Lee, Phil H; Le Hellard, Stephanie; Lemaître, Herve; Leonardo, Cassandra D; Li, Chiang-Shan; Liberg, Benny; Liewald, David C; Liu, Xinmin; Lopez, Lorna M; Loth, Eva; Lourdusamy, Anbarasu; Luciano, Michelle; Macciardi, Fabio; Machielsen, Marise W J; Macqueen, Glenda M; Malt, Ulrik F; Mandl, René; Manoach, Dara S; Martinot, Jean-Luc; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mattingsdal, Morten; Meyer-Lindenberg, Andreas; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Milaneschi, Yuri; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Moses, Eric K; Mueller, Bryon A; Muñoz Maniega, Susana; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Mwangi, Benson; Nauck, Matthias; Nho, Kwangsik; Nichols, Thomas E; Nilsson, Lars-Göran; Nugent, Allison C; Nyberg, Lars; Olvera, Rene L; Oosterlaan, Jaap; Ophoff, Roel A; Pandolfo, Massimo; Papalampropoulou-Tsiridou, Melina; Papmeyer, Martina; Paus, Tomas; Pausova, Zdenka; Pearlson, Godfrey D; Penninx, Brenda W; Peterson, Charles P; Pfennig, Andrea; Phillips, Mary; Pike, G Bruce; Poline, Jean-Baptiste; Potkin, Steven G; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rietschel, Marcella; Rijpkema, Mark; Risacher, Shannon L; Roffman, Joshua L; Roiz-Santiañez, Roberto; Romanczuk-Seiferth, Nina; Rose, Emma J; Royle, Natalie A; Rujescu, Dan; Ryten, Mina; Sachdev, Perminder S; Salami, Alireza; Satterthwaite, Theodore D; Savitz, Jonathan; Saykin, Andrew J; Scanlon, Cathy; Schmaal, Lianne; Schnack, Hugo G; Schork, Andrew J; Schulz, S Charles; Schür, Remmelt; Seidman, Larry; Shen, Li; Shoemaker, Jody M; Simmons, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soares, Jair C; Sponheim, Scott R; Sprooten, Emma; Starr, John M; Steen, Vidar M; Strakowski, Stephen; Strike, Lachlan; Sussmann, Jessika; Sämann, Philipp G; Teumer, Alexander; Toga, Arthur W; Tordesillas-Gutierrez, Diana; Trabzuni, Daniah; Trost, Sarah; Turner, Jessica; Van den Heuvel, Martijn; van der Wee, Nic J; van Eijk, Kristel; van Erp, Theo G M; van Haren, Neeltje E M; van 't Ent, Dennis; van Tol, Marie-Jose; Valdés Hernández, Maria C; Veltman, Dick J; Versace, Amelia; Völzke, Henry; Walker, Robert; Walter, Henrik; Wang, Lei; Wardlaw, Joanna M; Weale, Michael E; Weiner, Michael W; Wen, Wei; Westlye, Lars T; Whalley, Heather C; Whelan, Christopher D; White, Tonya; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Zilles, David; Zwiers, Marcel P; Thalamuthu, Anbupalam; Schofield, Peter R; Freimer, Nelson B; Lawrence, Natalia S; Drevets, Wayne

2014-06-01

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Traditional Chinese medicine research in the post-genomic era: good practice, priorities, challenges and opportunities.

PubMed

Uzuner, Halil; Bauer, Rudolf; Fan, Tai-Ping; Guo, De-An; Dias, Alberto; El-Nezami, Hani; Efferth, Thomas; Williamson, Elizabeth M; Heinrich, Michael; Robinson, Nicola; Hylands, Peter J; Hendry, Bruce M; Cheng, Yung-Chi; Xu, Qihe

2012-04-10

GP-TCM is the 1st EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. This paper aims to summarise the objectives, structure and activities of the consortium and introduces the position of the consortium regarding good practice, priorities, challenges and opportunities in TCM research. Serving as the introductory paper for the GP-TCM Journal of Ethnopharmacology special issue, this paper describes the roadmap of this special issue and reports how the main outputs of the ten GP-TCM work packages are integrated, and have led to consortium-wide conclusions. Literature studies, opinion polls and discussions among consortium members and stakeholders. By January 2012, through 3 years of team building, the GP-TCM consortium had grown into a large collaborative network involving ∼200 scientists from 24 countries and 107 institutions. Consortium members had worked closely to address good practice issues related to various aspects of Chinese herbal medicine (CHM) and acupuncture research, the focus of this Journal of Ethnopharmacology special issue, leading to state-of-the-art reports, guidelines and consensus on the application of omics technologies in TCM research. In addition, through an online survey open to GP-TCM members and non-members, we polled opinions on grand priorities, challenges and opportunities in TCM research. Based on the poll, although consortium members and non-members had diverse opinions on the major challenges in the field, both groups agreed that high-quality efficacy/effectiveness and mechanistic studies are grand priorities and that the TCM legacy in general and its management of chronic diseases in particular represent grand opportunities. Consortium members cast their votes of confidence in omics and systems biology approaches to TCM research and believed that quality and pharmacovigilance of TCM products are not only grand priorities, but also grand challenges. Non-members, however, gave priority to integrative medicine, concerned on the impact of regulation of TCM practitioners and emphasised intersectoral collaborations in funding TCM research, especially clinical trials. The GP-TCM consortium made great efforts to address some fundamental issues in TCM research, including developing guidelines, as well as identifying priorities, challenges and opportunities. These consortium guidelines and consensus will need dissemination, validation and further development through continued interregional, interdisciplinary and intersectoral collaborations. To promote this, a new consortium, known as the GP-TCM Research Association, is being established to succeed the 3-year fixed term FP7 GP-TCM consortium and will be officially launched at the Final GP-TCM Congress in Leiden, the Netherlands, in April 2012. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group.

PubMed

Gray, Stacy W; Martins, Yolanda; Feuerman, Lindsay Z; Bernhardt, Barbara A; Biesecker, Barbara B; Christensen, Kurt D; Joffe, Steven; Rini, Christine; Veenstra, David; McGuire, Amy L

2014-10-01

The routine use of genomic sequencing in clinical medicine has the potential to dramatically alter patient care and medical outcomes. To fully understand the psychosocial and behavioral impact of sequencing integration into clinical practice, it is imperative that we identify the factors that influence sequencing-related decision making and patient outcomes. In an effort to develop a collaborative and conceptually grounded approach to studying sequencing adoption, members of the National Human Genome Research Institute's Clinical Sequencing Exploratory Research Consortium formed the Outcomes and Measures Working Group. Here we highlight the priority areas of investigation and psychosocial and behavioral outcomes identified by the Working Group. We also review some of the anticipated challenges to measurement in social and behavioral research related to genomic sequencing; opportunities for instrument development; and the importance of qualitative, quantitative, and mixed-method approaches. This work represents the early, shared efforts of multiple research teams as we strive to understand individuals' experiences with genomic sequencing. The resulting body of knowledge will guide recommendations for the optimal use of sequencing in clinical practice.

On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE.

PubMed

Graur, Dan; Zheng, Yichen; Price, Nicholas; Azevedo, Ricardo B R; Zufall, Rebecca A; Elhaik, Eran

2013-01-01

A recent slew of ENCyclopedia Of DNA Elements (ENCODE) Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 - 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these "functional" regions or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly by employing the seldom used "causal role" definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as "affirming the consequent," by failing to appreciate the crucial difference between "junk DNA" and "garbage DNA," by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and by emphasizing statistical significance rather than the magnitude of the effect. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten.

Genome Consortium for Active Teaching: Meeting the Goals of BIO2010

PubMed Central

Ledbetter, Mary Lee S.; Hoopes, Laura L.M.; Eckdahl, Todd T.; Heyer, Laurie J.; Rosenwald, Anne; Fowlks, Edison; Tonidandel, Scott; Bucholtz, Brooke; Gottfried, Gail

2007-01-01

The Genome Consortium for Active Teaching (GCAT) facilitates the use of modern genomics methods in undergraduate education. Initially focused on microarray technology, but with an eye toward diversification, GCAT is a community working to improve the education of tomorrow's life science professionals. GCAT participants have access to affordable microarrays, microarray scanners, free software for data analysis, and faculty workshops. Microarrays provided by GCAT have been used by 141 faculty on 134 campuses, including 21 faculty that serve large numbers of underrepresented minority students. An estimated 9480 undergraduates a year will have access to microarrays by 2009 as a direct result of GCAT faculty workshops. Gains for students include significantly improved comprehension of topics in functional genomics and increased interest in research. Faculty reported improved access to new technology and gains in understanding thanks to their involvement with GCAT. GCAT's network of supportive colleagues encourages faculty to explore genomics through student research and to learn a new and complex method with their undergraduates. GCAT is meeting important goals of BIO2010 by making research methods accessible to undergraduates, training faculty in genomics and bioinformatics, integrating mathematics into the biology curriculum, and increasing participation by underrepresented minority students. PMID:17548873

Genome Consortium for Active Teaching: meeting the goals of BIO2010.

PubMed

Campbell, A Malcolm; Ledbetter, Mary Lee S; Hoopes, Laura L M; Eckdahl, Todd T; Heyer, Laurie J; Rosenwald, Anne; Fowlks, Edison; Tonidandel, Scott; Bucholtz, Brooke; Gottfried, Gail

2007-01-01

The Genome Consortium for Active Teaching (GCAT) facilitates the use of modern genomics methods in undergraduate education. Initially focused on microarray technology, but with an eye toward diversification, GCAT is a community working to improve the education of tomorrow's life science professionals. GCAT participants have access to affordable microarrays, microarray scanners, free software for data analysis, and faculty workshops. Microarrays provided by GCAT have been used by 141 faculty on 134 campuses, including 21 faculty that serve large numbers of underrepresented minority students. An estimated 9480 undergraduates a year will have access to microarrays by 2009 as a direct result of GCAT faculty workshops. Gains for students include significantly improved comprehension of topics in functional genomics and increased interest in research. Faculty reported improved access to new technology and gains in understanding thanks to their involvement with GCAT. GCAT's network of supportive colleagues encourages faculty to explore genomics through student research and to learn a new and complex method with their undergraduates. GCAT is meeting important goals of BIO2010 by making research methods accessible to undergraduates, training faculty in genomics and bioinformatics, integrating mathematics into the biology curriculum, and increasing participation by underrepresented minority students.

International network of cancer genome projects

PubMed Central

2010-01-01

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumors from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of over 25,000 cancer genomes at the genomic, epigenomic, and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically-relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies. PMID:20393554

Defining Genome Project Standards in a New Era of Sequencing (GSC8 Meeting)

ScienceCinema

Chain, Patrick

2018-01-15

The Genomic Standards Consortium was formed in September 2005. It is an international, open-membership working body which promotes standardization in the description of genomes and the exchange and integration of genomic data. The 2009 meeting was an activity of a five-year funding Research Coordination Network from the National Science Foundation and was organized held at the DOE Joint Genome Institute with organizational support provided by the JGI and by the University of California - San Diego.

CPTAC Releases Largest-Ever Ovarian Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

Cancer.gov

National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have just released a comprehensive dataset of the proteomic analysis of high grade serous ovarian tumor samples, previously genomically analyzed by The Cancer Genome Atlas (TCGA).  This is one of the largest public datasets covering the proteome, phosphoproteome and glycoproteome with complementary deep genomic sequencing data on the same tumor.

PeanutBase and other bioinformatic resources for peanut

USDA-ARS?s Scientific Manuscript database

Large-scale genomic data for peanut have only become available in the last few years, with the advent of low-cost sequencing technologies. To make the data accessible to researchers and to integrate across diverse types of data, the International Peanut Genomics Consortium funded the development of ...

Comparative Metagenomics of the Polymicrobial Black Band Disease of Corals

PubMed Central

Meyer, Julie L.; Paul, Valerie J.; Raymundo, Laurie J.; Teplitski, Max

2017-01-01

Black Band Disease (BBD), the destructive microbial consortium dominated by the cyanobacterium Roseofilum reptotaenium, affects corals worldwide. While the taxonomic composition of BBD consortia has been well-characterized, substantially less is known about its functional repertoire. We sequenced the metagenomes of Caribbean and Pacific black band mats and cultured Roseofilum and obtained five metagenome-assembled genomes (MAGs) of Roseofilum, nine of Proteobacteria, and 12 of Bacteroidetes. Genomic content analysis suggests that Roseofilum is a source of organic carbon and nitrogen, as well as natural products that may influence interactions between microbes. Proteobacteria and Bacteroidetes members of the disease consortium are suited to the degradation of amino acids, proteins, and carbohydrates. The accumulation of sulfide underneath the black band mat, in part due to a lack of sulfur oxidizers, contributes to the lethality of the disease. The presence of sulfide:quinone oxidoreductase genes in all five Roseofilum MAGs and in the MAGs of several heterotrophs demonstrates that resistance to sulfide is an important characteristic for members of the BBD consortium. PMID:28458657

Role and goals of the EUR-OCEANS Consortium - Bringing marine scientists priorities and strategies to the European research planning agenda.

NASA Astrophysics Data System (ADS)

Cury, Philippe; Baisnée, Pierre-François

2010-05-01

The EUR-OCEANS Consortium is the follow-up structure of the homonym European Network of Excellence (NoE; 2005-2008, FP6 contract number 511106). It is a scientific network, benefiting from and relying upon the institutional commitment of the 27 research performing organisations forming its core (paying) membership. It aims at the long-term harmonization of European research efforts related to ocean ecosystems undergoing anthropogenic and natural forcing. More specifically, its objectives are to facilitate and promote: (1) top-level scientific research on the impacts of anthropogenic and natural forcing on ocean ecosystems, fostering collaborations across the European Research Area; (2) the optimal use of any shared technical infrastructures and scientific facilities; and (3) activities to spread excellence, such as the training of scientific personnel and students, or knowledge dissemination towards the general public and socio-economic users. A particular focus is put during the first scientific coordination mandate on the building of scenarios for marine ecosystems under anthropogenic and natural forcing in the XXI Century, and on the improvement of the science-policy interface. Through calls for projects and networking activities, the Consortium seeks to favour the emergence of coordinated projects on key hot topics on one hand, and the crystallisation of scientific priorities and strategies that could serve as input to ERA-NETs, ESFRI, Joint Programming Initiatives and European Research Planning actors in general. While being an active standalone structure, the Consortium is also engaged in the Euromarine FP7 project (submitted) aiming at the definition of a common coordinating or integrating structure for the three follow-up entities of FP6 marine science NoEs (Marine Genomics Europe, MarBEF, EUR-OCEANS). The 2009-2011 strategy and activity plan of EUR-OCEANS will be presented and the involvement of EUR-OCEANS members in other key projects or programmes will be summarized.

Design and implementation of a database for Brucella melitensis genome annotation.

PubMed

De Hertogh, Benoît; Lahlimi, Leïla; Lambert, Christophe; Letesson, Jean-Jacques; Depiereux, Eric

2008-03-18

The genome sequences of three Brucella biovars and of some species close to Brucella sp. have become available, leading to new relationship analysis. Moreover, the automatic genome annotation of the pathogenic bacteria Brucella melitensis has been manually corrected by a consortium of experts, leading to 899 modifications of start sites predictions among the 3198 open reading frames (ORFs) examined. This new annotation, coupled with the results of automatic annotation tools of the complete genome sequences of the B. melitensis genome (including BLASTs to 9 genomes close to Brucella), provides numerous data sets related to predicted functions, biochemical properties and phylogenic comparisons. To made these results available, alphaPAGe, a functional auto-updatable database of the corrected sequence genome of B. melitensis, has been built, using the entity-relationship (ER) approach and a multi-purpose database structure. A friendly graphical user interface has been designed, and users can carry out different kinds of information by three levels of queries: (1) the basic search use the classical keywords or sequence identifiers; (2) the original advanced search engine allows to combine (by using logical operators) numerous criteria: (a) keywords (textual comparison) related to the pCDS's function, family domains and cellular localization; (b) physico-chemical characteristics (numerical comparison) such as isoelectric point or molecular weight and structural criteria such as the nucleic length or the number of transmembrane helix (TMH); (c) similarity scores with Escherichia coli and 10 species phylogenetically close to B. melitensis; (3) complex queries can be performed by using a SQL field, which allows all queries respecting the database's structure. The database is publicly available through a Web server at the following url: http://www.fundp.ac.be/urbm/bioinfo/aPAGe.

Quality control and conduct of genome-wide association meta-analyses

PubMed Central

Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth JF

2014-01-01

Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for [1] organizational aspects of GWAMAs, and for [2] QC at the study file level, the meta-level across studies, and the meta-analysis output level. Real–world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for use of a powerful and flexible software package called EasyQC. For consortia of comparable size to the GIANT consortium, the present protocol takes a minimum of about 10 months to complete. PMID:24762786

The bioleaching potential of a bacterial consortium.

PubMed

Latorre, Mauricio; Cortés, María Paz; Travisany, Dante; Di Genova, Alex; Budinich, Marko; Reyes-Jara, Angélica; Hödar, Christian; González, Mauricio; Parada, Pilar; Bobadilla-Fazzini, Roberto A; Cambiazo, Verónica; Maass, Alejandro

2016-10-01

This work presents the molecular foundation of a consortium of five efficient bacteria strains isolated from copper mines currently used in state of the art industrial-scale biotechnology. The strains Acidithiobacillus thiooxidans Licanantay, Acidiphilium multivorum Yenapatur, Leptospirillum ferriphilum Pañiwe, Acidithiobacillus ferrooxidans Wenelen and Sulfobacillus thermosulfidooxidans Cutipay were selected for genome sequencing based on metal tolerance, oxidation activity and bioleaching of copper efficiency. An integrated model of metabolic pathways representing the bioleaching capability of this consortium was generated. Results revealed that greater efficiency in copper recovery may be explained by the higher functional potential of L. ferriphilum Pañiwe and At. thiooxidans Licanantay to oxidize iron and reduced inorganic sulfur compounds. The consortium had a greater capacity to resist copper, arsenic and chloride ion compared to previously described biomining strains. Specialization and particular components in these bacteria provided the consortium a greater ability to bioleach copper sulfide ores. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sequence Analysis and Characterization of Active Human Alu Subfamilies Based on the 1000 Genomes Pilot Project.

PubMed

Konkel, Miriam K; Walker, Jerilyn A; Hotard, Ashley B; Ranck, Megan C; Fontenot, Catherine C; Storer, Jessica; Stewart, Chip; Marth, Gabor T; Batzer, Mark A

2015-08-29

The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic "young" Alu insertion events, absent from the human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths. All the sequenced Alu loci were derived from the AluY lineage with no evidence of retrotransposition activity involving older Alu families (e.g., AluJ and AluS). AluYa5 is currently the most active Alu subfamily in the human lineage, followed by AluYb8, and many others including three newly identified subfamilies we have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Defining Linkages between the GSC and NSF's LTER Program: How the Ecological Metadata Language (EML) Relates to GCDML and Other Outcomes

Treesearch

Inigo San Gil; Wade Sheldon; Tom Schmidt; Mark Servilla; Raul Aguilar; Corinna Gries; Tanya Gray; Dawn Field; James Cole; Jerry Yun Pan; Giri Palanisamy; Donald Henshaw; Margaret O' Brien; Linda Kinkel; Kathrine McMahon; Renzo Kottmann; Linda Amaral-Zettler; John Hobbie; Philip Goldstein; Robert P. Guralnick; James Brunt; William K. Michener

2008-01-01

The Genomic Standards Consortium (GSC) invited a representative of the Long-Term Ecological Research (LTER) to its fifth workshop to present the Ecological Metadata Language (EML) metadata standard and its relationship to the Minimum Information about a Genome/Metagenome Sequence (MIGS/MIMS) and its implementation, the Genomic Contextual Data Markup Language (GCDML)....

The Congenital Heart Disease Genetic Network Study: rationale, design, and early results.

PubMed

Gelb, Bruce; Brueckner, Martina; Chung, Wendy; Goldmuntz, Elizabeth; Kaltman, Jonathan; Kaski, Juan Pablo; Kim, Richard; Kline, Jennie; Mercer-Rosa, Laura; Porter, George; Roberts, Amy; Rosenberg, Ellen; Seiden, Howard; Seidman, Christine; Sleeper, Lynn; Tennstedt, Sharon; Kaltman, Jonathan; Schramm, Charlene; Burns, Kristin; Pearson, Gail; Rosenberg, Ellen

2013-02-15

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome.

The Congenital Heart Disease Genetic Network Study

PubMed Central

2013-01-01

Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community’s use of Pediatric Cardiac Genomics Consortium resources is welcome. PMID:23410879

Proteogenomic Analysis of a Thermophilic Bacterial Consortium Adapted to Deconstruct Switchgrass

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'haeseleer, Patrik; Gladden, John M.; Allgaier, Martin

2013-07-19

Thermophilic bacteria are a potential source of enzymes for the deconstruction of lignocellulosic biomass. However, the complement of proteins used to deconstruct biomass and the specific roles of different microbial groups in thermophilic biomass deconstruction are not well-explored. Here we report on the metagenomic and proteogenomic analyses of a compost-derived bacterial consortium adapted to switchgrass at elevated temperature with high levels of glycoside hydrolase activities. Near-complete genomes were reconstructed for the most abundant populations, which included composite genomes for populations closely related to sequenced strains of Thermus thermophilus and Rhodothermus marinus, and for novel populations that are related to thermophilicmore » Paenibacilli and an uncultivated subdivision of the littlestudied Gemmatimonadetes phylum. Partial genomes were also reconstructed for a number of lower abundance thermophilic Chloroflexi populations. Identification of genes for lignocellulose processing and metabolic reconstructions suggested Rhodothermus, Paenibacillus and Gemmatimonadetes as key groups for deconstructing biomass, and Thermus as a group that may primarily metabolize low molecular weight compounds. Mass spectrometry-based proteomic analysis of the consortium was used to identify .3000 proteins in fractionated samples from the cultures, and confirmed the importance of Paenibacillus and Gemmatimonadetes to biomass deconstruction. These studies also indicate that there are unexplored proteins with important roles in bacterial lignocellulose deconstruction.« less

Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK

PubMed Central

Manunza, A.; Cardoso, T. F.; Noce, A.; Martínez, A.; Pons, A.; Bermejo, L. A.; Landi, V.; Sànchez, A.; Jordana, J.; Delgado, J. V.; Adán, S.; Capote, J.; Vidal, O.; Ugarte, E.; Arranz, J. J.; Calvo, J. H.; Casellas, J.; Amills, M.

2016-01-01

The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segureña) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150–154 Mb), Oar6 (4–49 Mb) and Oar13 (68–74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection. PMID:27272025

Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK.

PubMed

Manunza, A; Cardoso, T F; Noce, A; Martínez, A; Pons, A; Bermejo, L A; Landi, V; Sànchez, A; Jordana, J; Delgado, J V; Adán, S; Capote, J; Vidal, O; Ugarte, E; Arranz, J J; Calvo, J H; Casellas, J; Amills, M

2016-06-07

The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segureña) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150-154 Mb), Oar6 (4-49 Mb) and Oar13 (68-74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection.

On the Immortality of Television Sets: “Function” in the Human Genome According to the Evolution-Free Gospel of ENCODE

PubMed Central

Graur, Dan; Zheng, Yichen; Price, Nicholas; Azevedo, Ricardo B.R.; Zufall, Rebecca A.; Elhaik, Eran

2013-01-01

A recent slew of ENCyclopedia Of DNA Elements (ENCODE) Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 − 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these “functional” regions or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly by employing the seldom used “causal role” definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as “affirming the consequent,” by failing to appreciate the crucial difference between “junk DNA” and “garbage DNA,” by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and by emphasizing statistical significance rather than the magnitude of the effect. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten. PMID:23431001

Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study

PubMed Central

Preuss, Michael; König, Inke R.; Thompson, John R.; Erdmann, Jeanette; Absher, Devin; Assimes, Themistocles L.; Blankenberg, Stefan; Boerwinkle, Eric; Chen, Li; Cupples, L. Adrienne; Hall, Alistair S.; Halperin, Eran; Hengstenberg, Christian; Holm, Hilma; Laaksonen, Reijo; Li, Mingyao; März, Winfried; McPherson, Ruth; Musunuru, Kiran; Nelson, Christopher P.; Burnett, Mary Susan; Epstein, Stephen E.; O’Donnell, Christopher J.; Quertermous, Thomas; Rader, Daniel J.; Roberts, Robert; Schillert, Arne; Stefansson, Kari; Stewart, Alexandre F.R.; Thorleifsson, Gudmar; Voight, Benjamin F.; Wells, George A.; Ziegler, Andreas; Kathiresan, Sekar; Reilly, Muredach P.; Samani, Nilesh J.; Schunkert, Heribert

2011-01-01

Background Recent genome-wide association studies (GWAS) of myocardial infarction (MI) and other forms of coronary artery disease (CAD) have led to the discovery of at least 13 genetic loci. In addition to the effect size, power to detect associations is largely driven by sample size. Therefore, to maximize the chance of finding novel susceptibility loci for CAD and MI, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed. Methods and Results CARDIoGRAM combines data from all published and several unpublished GWAS in individuals with European ancestry; includes >22 000 cases with CAD, MI, or both and >60 000 controls; and unifies samples from the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology study, CADomics, Cohorts for Heart and Aging Research in Genomic Epidemiology, deCODE, the German Myocardial Infarction Family Studies I, II, and III, Ludwigshafen Risk and Cardiovascular Heath Study/AtheroRemo, MedStar, Myocardial Infarction Genetics Consortium, Ottawa Heart Genomics Study, PennCath, and the Wellcome Trust Case Control Consortium. Genotyping was carried out on Affymetrix or Illumina platforms followed by imputation of genotypes in most studies. On average, 2.2 million single nucleotide polymorphisms were generated per study. The results from each study are combined using meta-analysis. As proof of principle, we meta-analyzed risk variants at 9p21 and found that rs1333049 confers a 29% increase in risk for MI per copy (P=2×10−20). Conclusion CARDIoGRAM is poised to contribute to our understanding of the role of common genetic variation on risk for CAD and MI. PMID:20923989

Evaluating robustness of a diesel-degrading bacterial consortium isolated from contaminated soil.

PubMed

Sydow, Mateusz; Owsianiak, Mikołaj; Szczepaniak, Zuzanna; Framski, Grzegorz; Smets, Barth F; Ławniczak, Łukasz; Lisiecki, Piotr; Szulc, Alicja; Cyplik, Paweł; Chrzanowski, Łukasz

2016-12-25

It is not known whether diesel-degrading bacterial communities are structurally and functionally robust when exposed to different hydrocarbon types. Here, we exposed a diesel-degrading consortium to model either alkanes, cycloalkanes or aromatic hydrocarbons as carbon sources to study its structural resistance. The structural resistance was low, with changes in relative abundances of up to four orders of magnitude, depending on hydrocarbon type and bacterial taxon. This low resistance is explained by the presence of hydrocarbon-degrading specialists in the consortium and differences in growth kinetics on individual hydrocarbons. However, despite this low resistance, structural and functional resilience were high, as verified by re-exposing the hydrocarbon-perturbed consortium to diesel fuel. The high resilience is either due to the short exposure time, insufficient for permanent changes in consortium structure and function, or the ability of some consortium members to be maintained during exposure on degradation intermediates produced by other members. Thus, the consortium is expected to cope with short-term exposures to narrow carbon feeds, while maintaining its structural and functional integrity, which remains an advantage over biodegradation approaches using single species cultures. Copyright © 2016 Elsevier B.V. All rights reserved.

CPTAC Proteomics Data on UCSC Genome Browser | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium scientists are working together with the University of California, Santa Cruz (UCSC) Genomics Institute to provide public access to cancer proteomics data via the UCSC Genome Browser. This effort extends accessibility of the CPTAC data to more researchers and provides an additional level of analysis to assist the cancer biology community.

Draft Genome Sequence of Geobacillus sp. LEMMY01, a Thermophilic Bacterium Isolated from the Site of a Burning Grass Pile

PubMed Central

de Souza, Yuri Pinheiro Alves; da Mota, Fábio Faria

2017-01-01

ABSTRACT We report here the 3,586,065-bp draft genome of Geobacillus sp. LEMMY01, which was isolated (axenic culture) from a thermophilic chemolitoautotrophic consortium obtained from the site of a burning grass pile. The genome contains biosynthetic gene clusters coding for secondary metabolites, such as terpene and lantipeptide, confirming the biotechnological potential of this strain. PMID:28495764

A comparison of cataloged variation between International HapMap Consortium and 1000 Genomes Project data.

PubMed

Buchanan, Carrie C; Torstenson, Eric S; Bush, William S; Ritchie, Marylyn D

2012-01-01

Since publication of the human genome in 2003, geneticists have been interested in risk variant associations to resolve the etiology of traits and complex diseases. The International HapMap Consortium undertook an effort to catalog all common variation across the genome (variants with a minor allele frequency (MAF) of at least 5% in one or more ethnic groups). HapMap along with advances in genotyping technology led to genome-wide association studies which have identified common variants associated with many traits and diseases. In 2008 the 1000 Genomes Project aimed to sequence 2500 individuals and identify rare variants and 99% of variants with a MAF of <1%. To determine whether the 1000 Genomes Project includes all the variants in HapMap, we examined the overlap between single nucleotide polymorphisms (SNPs) genotyped in the two resources using merged phase II/III HapMap data and low coverage pilot data from 1000 Genomes. Comparison of the two data sets showed that approximately 72% of HapMap SNPs were also found in 1000 Genomes Project pilot data. After filtering out HapMap variants with a MAF of <5% (separately for each population), 99% of HapMap SNPs were found in 1000 Genomes data. Not all variants cataloged in HapMap are also cataloged in 1000 Genomes. This could affect decisions about which resource to use for SNP queries, rare variant validation, or imputation. Both the HapMap and 1000 Genomes Project databases are useful resources for human genetics, but it is important to understand the assumptions made and filtering strategies employed by these projects.

Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics.

PubMed

Agrawal, Arpana; Edenberg, Howard J; Gelernter, Joel

2016-09-01

Meta-analyses of genome-wide association study data have begun to lead to promising new discoveries for behavioral and psychiatrically relevant phenotypes (e.g., schizophrenia, educational attainment). We outline how this methodology can similarly lead to novel discoveries in genomic studies of substance use disorders, and discuss challenges that will need to be overcome to accomplish this goal. We illustrate our approach with the work of the newly established Substance Use Disorders workgroup of the Psychiatric Genomics Consortium.

Computational approaches to identify functional genetic variants in cancer genomes

PubMed Central

Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris; Ritchie, Graham R.S.; Creixell, Pau; Karchin, Rachel; Vazquez, Miguel; Fink, J. Lynn; Kassahn, Karin S.; Pearson, John V.; Bader, Gary; Boutros, Paul C.; Muthuswamy, Lakshmi; Ouellette, B.F. Francis; Reimand, Jüri; Linding, Rune; Shibata, Tatsuhiro; Valencia, Alfonso; Butler, Adam; Dronov, Serge; Flicek, Paul; Shannon, Nick B.; Carter, Hannah; Ding, Li; Sander, Chris; Stuart, Josh M.; Stein, Lincoln D.; Lopez-Bigas, Nuria

2014-01-01

The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor, but only a minority drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype. PMID:23900255

Memory management in genome-wide association studies

PubMed Central

2009-01-01

Genome-wide association is a powerful tool for the identification of genes that underlie common diseases. Genome-wide association studies generate billions of genotypes and pose significant computational challenges for most users including limited computer memory. We applied a recently developed memory management tool to two analyses of North American Rheumatoid Arthritis Consortium studies and measured the performance in terms of central processing unit and memory usage. We conclude that our memory management approach is simple, efficient, and effective for genome-wide association studies. PMID:20018047

MODBASE, a database of annotated comparative protein structure models

PubMed Central

Pieper, Ursula; Eswar, Narayanan; Stuart, Ashley C.; Ilyin, Valentin A.; Sali, Andrej

2002-01-01

MODBASE (http://guitar.rockefeller.edu/modbase) is a relational database of annotated comparative protein structure models for all available protein sequences matched to at least one known protein structure. The models are calculated by MODPIPE, an automated modeling pipeline that relies on PSI-BLAST, IMPALA and MODELLER. MODBASE uses the MySQL relational database management system for flexible and efficient querying, and the MODVIEW Netscape plugin for viewing and manipulating multiple sequences and structures. It is updated regularly to reflect the growth of the protein sequence and structure databases, as well as improvements in the software for calculating the models. For ease of access, MODBASE is organized into different datasets. The largest dataset contains models for domains in 304 517 out of 539 171 unique protein sequences in the complete TrEMBL database (23 March 2001); only models based on significant alignments (PSI-BLAST E-value < 10–4) and models assessed to have the correct fold are included. Other datasets include models for target selection and structure-based annotation by the New York Structural Genomics Research Consortium, models for prediction of genes in the Drosophila melanogaster genome, models for structure determination of several ribosomal particles and models calculated by the MODWEB comparative modeling web server. PMID:11752309

Genome-wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type.

PubMed

Green, Elaine K; Di Florio, Arianna; Forty, Liz; Gordon-Smith, Katherine; Grozeva, Detelina; Fraser, Christine; Richards, Alexander L; Moran, Jennifer L; Purcell, Shaun; Sklar, Pamela; Kirov, George; Owen, Michael J; O'Donovan, Michael C; Craddock, Nick; Jones, Lisa; Jones, Ian R

2017-12-01

Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated with RDC-SABP, we have performed a replication study using independent RDC-SABP cases (n = 144) and controls (n = 6,559), focusing on the 10 loci that reached a p-value <10 -5 for RDC-SABP in the Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder sample. Combining the WTCCC and replication datasets by meta-analysis (combined RDC-SABP, n = 423, controls, n = 9,494), we observed genome-wide significant association at one SNP, rs2352974, located within the intron of the gene TRAIP on chromosome 3p21.31 (p-value, 4.37 × 10 -8 ). This locus did not reach genome-wide significance in bipolar disorder or schizophrenia large Psychiatric Genomic Consortium datasets, suggesting that it may represent a relatively specific genetic risk for the bipolar subtype of schizoaffective disorder. © 2017 Wiley Periodicals, Inc.

Lignolytic-consortium omics analyses reveal novel genomes and pathways involved in lignin modification and valorization.

PubMed

Moraes, Eduardo C; Alvarez, Thabata M; Persinoti, Gabriela F; Tomazetto, Geizecler; Brenelli, Livia B; Paixão, Douglas A A; Ematsu, Gabriela C; Aricetti, Juliana A; Caldana, Camila; Dixon, Neil; Bugg, Timothy D H; Squina, Fabio M

2018-01-01

Lignin is a heterogeneous polymer representing a renewable source of aromatic and phenolic bio-derived products for the chemical industry. However, the inherent structural complexity and recalcitrance of lignin makes its conversion into valuable chemicals a challenge. Natural microbial communities produce biocatalysts derived from a large number of microorganisms, including those considered unculturable, which operate synergistically to perform a variety of bioconversion processes. Thus, metagenomic approaches are a powerful tool to reveal novel optimized metabolic pathways for lignin conversion and valorization. The lignin-degrading consortium (LigMet) was obtained from a sugarcane plantation soil sample. The LigMet taxonomical analyses (based on 16S rRNA) indicated prevalence of Proteobacteria , Actinobacteria and Firmicutes members, including the Alcaligenaceae and Micrococcaceae families, which were enriched in the LigMet compared to sugarcane soil. Analysis of global DNA sequencing revealed around 240,000 gene models, and 65 draft bacterial genomes were predicted. Along with depicting several peroxidases, dye-decolorizing peroxidases, laccases, carbohydrate esterases, and lignocellulosic auxiliary (redox) activities, the major pathways related to aromatic degradation were identified, including benzoate (or methylbenzoate) degradation to catechol (or methylcatechol), catechol ortho-cleavage, catechol meta-cleavage, and phthalate degradation. A novel Paenarthrobacter strain harboring eight gene clusters related to aromatic degradation was isolated from LigMet and was able to grow on lignin as major carbon source. Furthermore, a recombinant pathway for vanillin production was designed based on novel gene sequences coding for a feruloyl-CoA synthetase and an enoyl-CoA hydratase/aldolase retrieved from the metagenomic data set. The enrichment protocol described in the present study was successful for a microbial consortium establishment towards the lignin and aromatic metabolism, providing pathways and enzyme sets for synthetic biology engineering approaches. This work represents a pioneering study on lignin conversion and valorization strategies based on metagenomics, revealing several novel lignin conversion enzymes, aromatic-degrading bacterial genomes, and a novel bacterial strain of potential biotechnological interest. The validation of a biosynthetic route for vanillin synthesis confirmed the applicability of the targeted metagenome discovery approach for lignin valorization strategies.

The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup: Posttraumatic Stress Disorder Enters the Age of Large-Scale Genomic Collaboration

PubMed Central

Logue, Mark W; Amstadter, Ananda B; Baker, Dewleen G; Duncan, Laramie; Koenen, Karestan C; Liberzon, Israel; Miller, Mark W; Morey, Rajendra A; Nievergelt, Caroline M; Ressler, Kerry J; Smith, Alicia K; Smoller, Jordan W; Stein, Murray B; Sumner, Jennifer A; Uddin, Monica

2015-01-01

The development of posttraumatic stress disorder (PTSD) is influenced by genetic factors. Although there have been some replicated candidates, the identification of risk variants for PTSD has lagged behind genetic research of other psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Psychiatric genetics has moved beyond examination of specific candidate genes in favor of the genome-wide association study (GWAS) strategy of very large numbers of samples, which allows for the discovery of previously unsuspected genes and molecular pathways. The successes of genetic studies of schizophrenia and bipolar disorder have been aided by the formation of a large-scale GWAS consortium: the Psychiatric Genomics Consortium (PGC). In contrast, only a handful of GWAS of PTSD have appeared in the literature to date. Here we describe the formation of a group dedicated to large-scale study of PTSD genetics: the PGC-PTSD. The PGC-PTSD faces challenges related to the contingency on trauma exposure and the large degree of ancestral genetic diversity within and across participating studies. Using the PGC analysis pipeline supplemented by analyses tailored to address these challenges, we anticipate that our first large-scale GWAS of PTSD will comprise over 10 000 cases and 30 000 trauma-exposed controls. Following in the footsteps of our PGC forerunners, this collaboration—of a scope that is unprecedented in the field of traumatic stress—will lead the search for replicable genetic associations and new insights into the biological underpinnings of PTSD. PMID:25904361

Reference-based phasing using the Haplotype Reference Consortium panel.

PubMed

Loh, Po-Ru; Danecek, Petr; Palamara, Pier Francesco; Fuchsberger, Christian; A Reshef, Yakir; K Finucane, Hilary; Schoenherr, Sebastian; Forer, Lukas; McCarthy, Shane; Abecasis, Goncalo R; Durbin, Richard; L Price, Alkes

2016-11-01

Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing in a genotyped cohort, an approach that can yield high accuracy in very large cohorts but attains lower accuracy in smaller cohorts. Here we instead explore the paradigm of reference-based phasing. We introduce a new phasing algorithm, Eagle2, that attains high accuracy across a broad range of cohort sizes by efficiently leveraging information from large external reference panels (such as the Haplotype Reference Consortium; HRC) using a new data structure based on the positional Burrows-Wheeler transform. We demonstrate that Eagle2 attains a ∼20× speedup and ∼10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2× the accuracy of 1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC-based phasing via the Sanger Imputation Service and the Michigan Imputation Server.

CPTAC Releases Largest-Ever Colorectal Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

Cancer.gov

On September 4, 2013, NCI’s Clinical Proteomics Tumor Analysis Consortium (CPTAC) publicly released proteomic data produced from colorectal tumor samples previously analyzed by The Cancer Genome Atlas (TCGA).  This is the initial release of proteomic tumor data designed to complement genomic data on the same tumors. The data is publicly available at the CPTAC data portal.

Draft Genome Sequence of Geobacillus sp. LEMMY01, a Thermophilic Bacterium Isolated from the Site of a Burning Grass Pile.

PubMed

de Souza, Yuri Pinheiro Alves; da Mota, Fábio Faria; Rosado, Alexandre Soares

2017-05-11

We report here the 3,586,065-bp draft genome of Geobacillus sp. LEMMY01, which was isolated (axenic culture) from a thermophilic chemolitoautotrophic consortium obtained from the site of a burning grass pile. The genome contains biosynthetic gene clusters coding for secondary metabolites, such as terpene and lantipeptide, confirming the biotechnological potential of this strain. Copyright © 2017 de Souza et al.

Metagenomic Analysis of a Biphenyl-Degrading Soil Bacterial Consortium Reveals the Metabolic Roles of Specific Populations

PubMed Central

Garrido-Sanz, Daniel; Manzano, Javier; Martín, Marta; Redondo-Nieto, Miguel; Rivilla, Rafael

2018-01-01

Polychlorinated biphenyls (PCBs) are widespread persistent pollutants that cause several adverse health effects. Aerobic bioremediation of PCBs involves the activity of either one bacterial species or a microbial consortium. Using multiple species will enhance the range of PCB congeners co-metabolized since different PCB-degrading microorganisms exhibit different substrate specificity. We have isolated a bacterial consortium by successive enrichment culture using biphenyl (analog of PCBs) as the sole carbon and energy source. This consortium is able to grow on biphenyl, benzoate, and protocatechuate. Whole-community DNA extracted from the consortium was used to analyze biodiversity by Illumina sequencing of a 16S rRNA gene amplicon library and to determine the metagenome by whole-genome shotgun Illumina sequencing. Biodiversity analysis shows that the consortium consists of 24 operational taxonomic units (≥97% identity). The consortium is dominated by strains belonging to the genus Pseudomonas, but also contains betaproteobacteria and Rhodococcus strains. whole-genome shotgun (WGS) analysis resulted in contigs containing 78.3 Mbp of sequenced DNA, representing around 65% of the expected DNA in the consortium. Bioinformatic analysis of this metagenome has identified the genes encoding the enzymes implicated in three pathways for the conversion of biphenyl to benzoate and five pathways from benzoate to tricarboxylic acid (TCA) cycle intermediates, allowing us to model the whole biodegradation network. By genus assignment of coding sequences, we have also been able to determine that the three biphenyl to benzoate pathways are carried out by Rhodococcus strains. In turn, strains belonging to Pseudomonas and Bordetella are the main responsible of three of the benzoate to TCA pathways while the benzoate conversion into TCA cycle intermediates via benzoyl-CoA and the catechol meta-cleavage pathways are carried out by beta proteobacteria belonging to genera such as Achromobacter and Variovorax. We have isolated a Rhodococcus strain WAY2 from the consortium which contains the genes encoding the three biphenyl to benzoate pathways indicating that this strain is responsible for all the biphenyl to benzoate transformations. The presented results show that metagenomic analysis of consortia allows the identification of bacteria active in biodegradation processes and the assignment of specific reactions and pathways to specific bacterial groups. PMID:29497412

Proteome Characterization Centers - TCGA

Cancer.gov

The centers, a component of NCI’s Clinical Proteomic Tumor Analysis Consortium, will analyze a subset of TCGA samples to define proteins translated from cancer genomes and their related biological processes.

CuGene as a tool to view and explore genomic data

NASA Astrophysics Data System (ADS)

Haponiuk, Michał; Pawełkowicz, Magdalena; Przybecki, Zbigniew; Nowak, Robert M.

2017-08-01

Integrated CuGene is an easy-to-use, open-source, on-line tool that can be used to browse, analyze, and query genomic data and annotations. It places annotation tracks beneath genome coordinate positions, allowing rapid visual correlation of different types of information. It also allows users to upload and display their own experimental results or annotation sets. An important functionality of the application is a possibility to find similarity between sequences by applying four different algorithms of different accuracy. The presented tool was tested on real genomic data and is extensively used by Polish Consortium of Cucumber Genome Sequencing.

A comparison of cataloged variation between International HapMap Consortium and 1000 Genomes Project data

PubMed Central

Buchanan, Carrie C; Torstenson, Eric S; Bush, William S

2012-01-01

Background Since publication of the human genome in 2003, geneticists have been interested in risk variant associations to resolve the etiology of traits and complex diseases. The International HapMap Consortium undertook an effort to catalog all common variation across the genome (variants with a minor allele frequency (MAF) of at least 5% in one or more ethnic groups). HapMap along with advances in genotyping technology led to genome-wide association studies which have identified common variants associated with many traits and diseases. In 2008 the 1000 Genomes Project aimed to sequence 2500 individuals and identify rare variants and 99% of variants with a MAF of <1%. Methods To determine whether the 1000 Genomes Project includes all the variants in HapMap, we examined the overlap between single nucleotide polymorphisms (SNPs) genotyped in the two resources using merged phase II/III HapMap data and low coverage pilot data from 1000 Genomes. Results Comparison of the two data sets showed that approximately 72% of HapMap SNPs were also found in 1000 Genomes Project pilot data. After filtering out HapMap variants with a MAF of <5% (separately for each population), 99% of HapMap SNPs were found in 1000 Genomes data. Conclusions Not all variants cataloged in HapMap are also cataloged in 1000 Genomes. This could affect decisions about which resource to use for SNP queries, rare variant validation, or imputation. Both the HapMap and 1000 Genomes Project databases are useful resources for human genetics, but it is important to understand the assumptions made and filtering strategies employed by these projects. PMID:22319179

Newborn Sequencing in Genomic Medicine and Public Health

PubMed Central

Agrawal, Pankaj B.; Bailey, Donald B.; Beggs, Alan H.; Brenner, Steven E.; Brower, Amy M.; Cakici, Julie A.; Ceyhan-Birsoy, Ozge; Chan, Kee; Chen, Flavia; Currier, Robert J.; Dukhovny, Dmitry; Green, Robert C.; Harris-Wai, Julie; Holm, Ingrid A.; Iglesias, Brenda; Joseph, Galen; Kingsmore, Stephen F.; Koenig, Barbara A.; Kwok, Pui-Yan; Lantos, John; Leeder, Steven J.; Lewis, Megan A.; McGuire, Amy L.; Milko, Laura V.; Mooney, Sean D.; Parad, Richard B.; Pereira, Stacey; Petrikin, Joshua; Powell, Bradford C.; Powell, Cynthia M.; Puck, Jennifer M.; Rehm, Heidi L.; Risch, Neil; Roche, Myra; Shieh, Joseph T.; Veeraraghavan, Narayanan; Watson, Michael S.; Willig, Laurel; Yu, Timothy W.; Urv, Tiina; Wise, Anastasia L.

2017-01-01

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening. PMID:28096516

Skate Genome Project: Cyber-Enabled Bioinformatics Collaboration

PubMed Central

Vincent, J.

2011-01-01

The Skate Genome Project, a pilot project of the North East Cyber infrastructure Consortium, aims to produce a draft genome sequence of Leucoraja erinacea, the Little Skate. The pilot project was designed to also develop expertise in large scale collaborations across the NECC region. An overview of the bioinformatics and infrastructure challenges faced during the first year of the project will be presented. Results to date and lessons learned from the perspective of a bioinformatics core will be highlighted.

Pathway and network analysis of cancer genomes.

PubMed

Creixell, Pau; Reimand, Jüri; Haider, Syed; Wu, Guanming; Shibata, Tatsuhiro; Vazquez, Miguel; Mustonen, Ville; Gonzalez-Perez, Abel; Pearson, John; Sander, Chris; Raphael, Benjamin J; Marks, Debora S; Ouellette, B F Francis; Valencia, Alfonso; Bader, Gary D; Boutros, Paul C; Stuart, Joshua M; Linding, Rune; Lopez-Bigas, Nuria; Stein, Lincoln D

2015-07-01

Genomic information on tumors from 50 cancer types cataloged by the International Cancer Genome Consortium (ICGC) shows that only a few well-studied driver genes are frequently mutated, in contrast to many infrequently mutated genes that may also contribute to tumor biology. Hence there has been large interest in developing pathway and network analysis methods that group genes and illuminate the processes involved. We provide an overview of these analysis techniques and show where they guide mechanistic and translational investigations.

Northern New Jersey Nursing Education Consortium: a partnership for graduate nursing education.

PubMed

Quinless, F W; Levin, R F

1998-01-01

The purpose of this article is to describe the evolution and implementation of the Northern New Jersey Nursing Education consortium--a consortium of seven member institutions established in 1992. Details regarding the specific functions of the consortium relative to cross-registration of students in graduate courses, financial disbursement of revenue, faculty development activities, student services, library privileges, and institutional research review board mechanisms are described. The authors also review the administrative organizational structure through which the work conducted by the consortium occurs. Both the advantages and disadvantages of such a graduate consortium are explored, and specific examples of recent potential and real conflicts are fully discussed. The authors detail governance and structure of the consortium as a potential model for replication in other environments.

Bladder Cancer Advocacy Network

MedlinePlus

... Event No Repeat Daily Weekly Monthly Yearly Repeat gap Repeat by day SU MO TU WE TH ... is Bladder Cancer? Newly Diagnosed Treatments Clinical Trials Research Research Grants Think Tank Research Network Genomics Consortium ...

A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis

PubMed Central

Fogh, Isabella; Ratti, Antonia; Gellera, Cinzia; Lin, Kuang; Tiloca, Cinzia; Moskvina, Valentina; Corrado, Lucia; Sorarù, Gianni; Cereda, Cristina; Corti, Stefania; Gentilini, Davide; Calini, Daniela; Castellotti, Barbara; Mazzini, Letizia; Querin, Giorgia; Gagliardi, Stella; Del Bo, Roberto; Conforti, Francesca L.; Siciliano, Gabriele; Inghilleri, Maurizio; Saccà, Francesco; Bongioanni, Paolo; Penco, Silvana; Corbo, Massimo; Sorbi, Sandro; Filosto, Massimiliano; Ferlini, Alessandra; Di Blasio, Anna M.; Signorini, Stefano; Shatunov, Aleksey; Jones, Ashley; Shaw, Pamela J.; Morrison, Karen E.; Farmer, Anne E.; Van Damme, Philip; Robberecht, Wim; Chiò, Adriano; Traynor, Bryan J.; Sendtner, Michael; Melki, Judith; Meininger, Vincent; Hardiman, Orla; Andersen, Peter M.; Leigh, Nigel P.; Glass, Jonathan D.; Overste, Daniel; Diekstra, Frank P.; Veldink, Jan H.; van Es, Michael A.; Shaw, Christopher E.; Weale, Michael E.; Lewis, Cathryn M.; Williams, Julie; Brown, Robert H.; Landers, John E.; Ticozzi, Nicola; Ceroni, Mauro; Pegoraro, Elena; Comi, Giacomo P.; D'Alfonso, Sandra; van den Berg, Leonard H.; Taroni, Franco; Al-Chalabi, Ammar; Powell, John; Silani, Vincenzo; Brescia Morra, Vincenzo; Filla, Alessandro; Massimo, Filosto; Marsili, Angela; Viviana, Pensato; Puorro, Giorgia; La Bella, Vincenzo; Logroscino, Giancarlo; Monsurrò, Maria Rosaria; Quattrone, Aldo; Simone, Isabella Laura; Ahmeti, Kreshnik B.; Ajroud-Driss, Senda; Armstrong, Jennifer; Birve, Anne; Blauw, Hylke M.; Bruijn, Lucie; Chen, Wenjie; Comeau, Mary C.; Cronin, Simon; Soraya, Gkazi Athina; Grab, Josh D.; Groen, Ewout J.; Haines, Jonathan L.; Heller, Scott; Huang, Jie; Hung, Wu-Yen; Jaworski, James M.; Khan, Humaira; Langefeld, Carl D.; Marion, Miranda C.; McLaughlin, Russell L.; Miller, Jack W.; Mora, Gabriele; Pericak-Vance, Margaret A.; Rampersaud, Evadnie; Siddique, Nailah; Siddique, Teepu; Smith, Bradley N.; Sufit, Robert; Topp, Simon; Vance, Caroline; van Vught, Paul; Yang, Yi; Zheng, J.G.

2014-01-01

Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (∼90%) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P = 1.11 × 10−8; OR 0.82) that was validated when combined with genotype data from a replication cohort (P = 8.62 × 10−9; OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P = 7.69 × 10−9; OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as ∼12% using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci. PMID:24256812

Genome Sequence of Thalassospira profundimaris Type Strain WP0211

PubMed Central

Lai, Qiliang

2012-01-01

Thalassospira profundimaris WP0211T was isolated from a pyrene-degrading consortium, enriched from deep-sea sediment collected from the West Pacific Ocean. Here, we present the draft genome of strain WP0211T, which contains 4,380,232 bp with a G+C content of 55.19% and contains 4,040 protein-coding genes and 45 tRNAs. PMID:23209215

Genome sequence of Thalassospira profundimaris type strain WP0211.

PubMed

Lai, Qiliang; Shao, Zongze

2012-12-01

Thalassospira profundimaris WP0211(T) was isolated from a pyrene-degrading consortium, enriched from deep-sea sediment collected from the West Pacific Ocean. Here, we present the draft genome of strain WP0211(T), which contains 4,380,232 bp with a G+C content of 55.19% and contains 4,040 protein-coding genes and 45 tRNAs.

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma | Center for Cancer Research

Cancer.gov

About the Cover:  The Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC) Consortium (depicted as a tiger) emerges from foliage, representing molecular, clinical, and epidemiological studies from teams in the United States, Thailand, and Japan, to generate a multilayered genomic and genetic liver cancer data ecosystem (represented by the tiger’s

H3Africa: current perspectives

PubMed Central

Mulder, Nicola; Abimiku, Alash’le; Adebamowo, Sally N; de Vries, Jantina; Matimba, Alice; Olowoyo, Paul; Ramsay, Michele; Skelton, Michelle; Stein, Dan J

2018-01-01

Precision medicine is being enabled in high-income countries by the growing availability of health data, increasing knowledge of the genetic determinants of disease and variation in response to treatment (pharmacogenomics), and the decreasing costs of data generation, which promote routine application of genomic technologies in the health sector. However, there is uncertainty about the feasibility of applying precision medicine approaches in low- and middle-income countries, due to the lack of population-specific knowledge, skills, and resources. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive new research into the genetic and environmental basis for human diseases of relevance to Africans as well as to build capacity for genomic research on the continent. Precision medicine requires this capacity, in addition to reference data on local populations, and skills to analyze and interpret genomic data from the bedside. The H3Africa consortium is collectively processing samples and data for over 70,000 participants across the continent, accompanied in most cases by rich clinical information on a variety of non-communicable and infectious diseases. These projects are increasingly providing novel insights into the genetic basis of diseases in indigenous populations, insights that have the potential to drive the development of new diagnostics and treatments. The consortium has also invested significant resources into establishing high-quality biorepositories in Africa, a bioinformatic network, and a strong training program that has developed skills in genomic data analysis and interpretation among bioinformaticians, wet-lab researchers, and health-care professionals. Here, we describe the current perspectives of the H3Africa consortium and how it can contribute to making precision medicine in Africa a reality. PMID:29692621

LaGomiCs—Lagomorph Genomics Consortium: An International Collaborative Effort for Sequencing the Genomes of an Entire Mammalian Order

PubMed Central

Di Palma, Federica; Flicek, Paul; Smith, Andrew T.; Thulin, Carl-Gustaf

2016-01-01

The order Lagomorpha comprises about 90 living species, divided in 2 families: the pikas (Family Ochotonidae), and the rabbits, hares, and jackrabbits (Family Leporidae). Lagomorphs are important economically and scientifically as major human food resources, valued game species, pests of agricultural significance, model laboratory animals, and key elements in food webs. A quarter of the lagomorph species are listed as threatened. They are native to all continents except Antarctica, and occur up to 5000 m above sea level, from the equator to the Arctic, spanning a wide range of environmental conditions. The order has notable taxonomic problems presenting significant difficulties for defining a species due to broad phenotypic variation, overlap of morphological characteristics, and relatively recent speciation events. At present, only the genomes of 2 species, the European rabbit (Oryctolagus cuniculus) and American pika (Ochotona princeps) have been sequenced and assembled. Starting from a paucity of genome information, the main scientific aim of the Lagomorph Genomics Consortium (LaGomiCs), born from a cooperative initiative of the European COST Action “A Collaborative European Network on Rabbit Genome Biology—RGB-Net” and the World Lagomorph Society (WLS), is to provide an international framework for the sequencing of the genome of all extant and selected extinct lagomorphs. Sequencing the genomes of an entire order will provide a large amount of information to address biological problems not only related to lagomorphs but also to all mammals. We present current and planned sequencing programs and outline the final objective of LaGomiCs possible through broad international collaboration. PMID:26921276

Newborn Sequencing in Genomic Medicine and Public Health.

PubMed

Berg, Jonathan S; Agrawal, Pankaj B; Bailey, Donald B; Beggs, Alan H; Brenner, Steven E; Brower, Amy M; Cakici, Julie A; Ceyhan-Birsoy, Ozge; Chan, Kee; Chen, Flavia; Currier, Robert J; Dukhovny, Dmitry; Green, Robert C; Harris-Wai, Julie; Holm, Ingrid A; Iglesias, Brenda; Joseph, Galen; Kingsmore, Stephen F; Koenig, Barbara A; Kwok, Pui-Yan; Lantos, John; Leeder, Steven J; Lewis, Megan A; McGuire, Amy L; Milko, Laura V; Mooney, Sean D; Parad, Richard B; Pereira, Stacey; Petrikin, Joshua; Powell, Bradford C; Powell, Cynthia M; Puck, Jennifer M; Rehm, Heidi L; Risch, Neil; Roche, Myra; Shieh, Joseph T; Veeraraghavan, Narayanan; Watson, Michael S; Willig, Laurel; Yu, Timothy W; Urv, Tiina; Wise, Anastasia L

2017-02-01

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening. Copyright © 2017 by the American Academy of Pediatrics.

Novel tools for accelerated materials discovery in the AFLOWLIB.ORG repository: breakthroughs and challenges in the mapping of the materials genome

NASA Astrophysics Data System (ADS)

Buongiorno Nardelli, Marco

2015-03-01

High-Throughput Quantum-Mechanics computation of materials properties by ab initio methods has become the foundation of an effective approach to materials design, discovery and characterization. This data driven approach to materials science currently presents the most promising path to the development of advanced technological materials that could solve or mitigate important social and economic challenges of the 21st century. In particular, the rapid proliferation of computational data on materials properties presents the possibility to complement and extend materials property databases where the experimental data is lacking and difficult to obtain. Enhanced repositories such as AFLOWLIB, open novel opportunities for structure discovery and optimization, including uncovering of unsuspected compounds, metastable structures and correlations between various properties. The practical realization of these opportunities depends on the the design effcient algorithms for electronic structure simulations of realistic material systems, the systematic compilation and classification of the generated data, and its presentation in easily accessed form to the materials science community, the primary mission of the AFLOW consortium. This work was supported by ONR-MURI under Contract N00014-13-1-0635 and the Duke University Center for Materials Genomics.

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer and other research.

Human Cancer Models Initiative | Office of Cancer Genomics

Cancer.gov

The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

Draft genome sequence of a strictly anaerobic dichloromethane-degrading bacterium

DOE PAGES

Kleindienst, Sara; Higgins, Steven A.; Tsementzi, Despina; ...

2016-03-03

Here, an anaerobic, dichloromethane-degrading bacterium affiliated with novel Peptococcaceae was maintained in a microbial consortium. The organism originated from pristine freshwater sediment collected from Rio Mameyes in Luquillo, Puerto Rico, in October 2009 (latitude 18°21'43.9", longitude –65°46'8.4"). The draft genome sequence is 2.1 Mb and has a G+C content of 43.5%.

Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia.

PubMed

Logue, Mark W; van Rooij, Sanne J H; Dennis, Emily L; Davis, Sarah L; Hayes, Jasmeet P; Stevens, Jennifer S; Densmore, Maria; Haswell, Courtney C; Ipser, Jonathan; Koch, Saskia B J; Korgaonkar, Mayuresh; Lebois, Lauren A M; Peverill, Matthew; Baker, Justin T; Boedhoe, Premika S W; Frijling, Jessie L; Gruber, Staci A; Harpaz-Rotem, Ilan; Jahanshad, Neda; Koopowitz, Sheri; Levy, Ifat; Nawijn, Laura; O'Connor, Lauren; Olff, Miranda; Salat, David H; Sheridan, Margaret A; Spielberg, Jeffrey M; van Zuiden, Mirjam; Winternitz, Sherry R; Wolff, Jonathan D; Wolf, Erika J; Wang, Xin; Wrocklage, Kristen; Abdallah, Chadi G; Bryant, Richard A; Geuze, Elbert; Jovanovic, Tanja; Kaufman, Milissa L; King, Anthony P; Krystal, John H; Lagopoulos, Jim; Bennett, Maxwell; Lanius, Ruth; Liberzon, Israel; McGlinchey, Regina E; McLaughlin, Katie A; Milberg, William P; Miller, Mark W; Ressler, Kerry J; Veltman, Dick J; Stein, Dan J; Thomaes, Kathleen; Thompson, Paul M; Morey, Rajendra A

2018-02-01

Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma. Published by Elsevier Inc.

Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia

PubMed Central

Logue, Mark W.; van Rooij, Sanne J.H.; Dennis, Emily L.; Davis, Sarah L.; Hayes, Jasmeet P.; Stevens, Jennifer S.; Densmore, Maria; Haswell, Courtney C.; Ipser, Jonathan; Koch, Saskia B.J.; Korgaonkar, Mayuresh; Lebois, Lauren A.M.; Peverill, Matthew; Baker, Justin T.; Boedhoe, Premika S.W.; Frijling, Jessie L.; Gruber, Staci A.; Harpaz-Rotem, Ilan; Jahanshad, Neda; Koopowitz, Sheri; Levy, Ifat; Nawijn, Laura; O’Connor, Lauren; Olff, Miranda; Salat, David H.; Sheridan, Margaret A.; Spielberg, Jeffrey M.; van Zuiden, Mirjam; Winternitz, Sherry R.; Wolff, Jonathan D.; Wolf, Erika J.; Wang, Xin; Wrocklage, Kristen; Abdallah, Chadi G.; Bryant, Richard A.; Geuze, Elbert; Jovanovic, Tanja; Kaufman, Milissa L.; King, Anthony P.; Krystal, John H.; Lagopoulos, Jim; Bennett, Maxwell; Lanius, Ruth; Liberzon, Israel; McGlinchey, Regina E.; McLaughlin, Katie A.; Milberg, William P.; Miller, Mark W.; Ressler, Kerry J.; Veltman, Dick J.; Stein, Dan J.; Thomaes, Kathleen; Thompson, Paul M.; Morey, Rajendra A.

2018-01-01

BACKGROUND Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma. PMID:29217296

Genome databases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Courteau, J.

1991-10-11

Since the Genome Project began several years ago, a plethora of databases have been developed or are in the works. They range from the massive Genome Data Base at Johns Hopkins University, the central repository of all gene mapping information, to small databases focusing on single chromosomes or organisms. Some are publicly available, others are essentially private electronic lab notebooks. Still others limit access to a consortium of researchers working on, say, a single human chromosome. An increasing number incorporate sophisticated search and analytical software, while others operate as little more than data lists. In consultation with numerous experts inmore » the field, a list has been compiled of some key genome-related databases. The list was not limited to map and sequence databases but also included the tools investigators use to interpret and elucidate genetic data, such as protein sequence and protein structure databases. Because a major goal of the Genome Project is to map and sequence the genomes of several experimental animals, including E. coli, yeast, fruit fly, nematode, and mouse, the available databases for those organisms are listed as well. The author also includes several databases that are still under development - including some ambitious efforts that go beyond data compilation to create what are being called electronic research communities, enabling many users, rather than just one or a few curators, to add or edit the data and tag it as raw or confirmed.« less

Deep whole-genome sequencing of 90 Han Chinese genomes.

PubMed

Lan, Tianming; Lin, Haoxiang; Zhu, Wenjuan; Laurent, Tellier Christian Asker Melchior; Yang, Mengcheng; Liu, Xin; Wang, Jun; Wang, Jian; Yang, Huanming; Xu, Xun; Guo, Xiaosen

2017-09-01

Next-generation sequencing provides a high-resolution insight into human genetic information. However, the focus of previous studies has primarily been on low-coverage data due to the high cost of sequencing. Although the 1000 Genomes Project and the Haplotype Reference Consortium have both provided powerful reference panels for imputation, low-frequency and novel variants remain difficult to discover and call with accuracy on the basis of low-coverage data. Deep sequencing provides an optimal solution for the problem of these low-frequency and novel variants. Although whole-exome sequencing is also a viable choice for exome regions, it cannot account for noncoding regions, sometimes resulting in the absence of important, causal variants. For Han Chinese populations, the majority of variants have been discovered based upon low-coverage data from the 1000 Genomes Project. However, high-coverage, whole-genome sequencing data are limited for any population, and a large amount of low-frequency, population-specific variants remain uncharacterized. We have performed whole-genome sequencing at a high depth (∼×80) of 90 unrelated individuals of Chinese ancestry, collected from the 1000 Genomes Project samples, including 45 Northern Han Chinese and 45 Southern Han Chinese samples. Eighty-three of these 90 have been sequenced by the 1000 Genomes Project. We have identified 12 568 804 single nucleotide polymorphisms, 2 074 210 short InDels, and 26 142 structural variations from these 90 samples. Compared to the Han Chinese data from the 1000 Genomes Project, we have found 7 000 629 novel variants with low frequency (defined as minor allele frequency < 5%), including 5 813 503 single nucleotide polymorphisms, 1 169 199 InDels, and 17 927 structural variants. Using deep sequencing data, we have built a greatly expanded spectrum of genetic variation for the Han Chinese genome. Compared to the 1000 Genomes Project, these Han Chinese deep sequencing data enhance the characterization of a large number of low-frequency, novel variants. This will be a valuable resource for promoting Chinese genetics research and medical development. Additionally, it will provide a valuable supplement to the 1000 Genomes Project, as well as to other human genome projects. © The Authors 2017. Published by Oxford University Press.

Hymenoptera Genome Database: integrating genome annotations in HymenopteraMine

PubMed Central

Elsik, Christine G.; Tayal, Aditi; Diesh, Colin M.; Unni, Deepak R.; Emery, Marianne L.; Nguyen, Hung N.; Hagen, Darren E.

2016-01-01

We report an update of the Hymenoptera Genome Database (HGD) (http://HymenopteraGenome.org), a model organism database for insect species of the order Hymenoptera (ants, bees and wasps). HGD maintains genomic data for 9 bee species, 10 ant species and 1 wasp, including the versions of genome and annotation data sets published by the genome sequencing consortiums and those provided by NCBI. A new data-mining warehouse, HymenopteraMine, based on the InterMine data warehousing system, integrates the genome data with data from external sources and facilitates cross-species analyses based on orthology. New genome browsers and annotation tools based on JBrowse/WebApollo provide easy genome navigation, and viewing of high throughput sequence data sets and can be used for collaborative genome annotation. All of the genomes and annotation data sets are combined into a single BLAST server that allows users to select and combine sequence data sets to search. PMID:26578564

'Pop-Up' Governance: developing internal governance frameworks for consortia: the example of UK10K.

PubMed

Kaye, Jane; Muddyman, Dawn; Smee, Carol; Kennedy, Karen; Bell, Jessica

2015-01-01

Innovations in information technologies have facilitated the development of new styles of research networks and forms of governance. This is evident in genomics where increasingly, research is carried out by large, interdisciplinary consortia focussing on a specific research endeavour. The UK10K project is an example of a human genomics consortium funded to provide insights into the genomics of rare conditions, and establish a community resource from generated sequence data. To achieve its objectives according to the agreed timetable, the UK10K project established an internal governance system to expedite the research and to deal with the complex issues that arose. The project's governance structure exemplifies a new form of network governance called 'pop-up' governance. 'Pop-up' because: it was put together quickly, existed for a specific period, was designed for a specific purpose, and was dismantled easily on project completion. In this paper, we use UK10K to describe how 'pop-up' governance works on the ground and how relational, hierarchical and contractual governance mechanisms are used in this new form of network governance.

Machine learning derived risk prediction of anorexia nervosa.

PubMed

Guo, Yiran; Wei, Zhi; Keating, Brendan J; Hakonarson, Hakon

2016-01-20

Anorexia nervosa (AN) is a complex psychiatric disease with a moderate to strong genetic contribution. In addition to conventional genome wide association (GWA) studies, researchers have been using machine learning methods in conjunction with genomic data to predict risk of diseases in which genetics play an important role. In this study, we collected whole genome genotyping data on 3940 AN cases and 9266 controls from the Genetic Consortium for Anorexia Nervosa (GCAN), the Wellcome Trust Case Control Consortium 3 (WTCCC3), Price Foundation Collaborative Group and the Children's Hospital of Philadelphia (CHOP), and applied machine learning methods for predicting AN disease risk. The prediction performance is measured by area under the receiver operating characteristic curve (AUC), indicating how well the model distinguishes cases from unaffected control subjects. Logistic regression model with the lasso penalty technique generated an AUC of 0.693, while Support Vector Machines and Gradient Boosted Trees reached AUC's of 0.691 and 0.623, respectively. Using different sample sizes, our results suggest that larger datasets are required to optimize the machine learning models and achieve higher AUC values. To our knowledge, this is the first attempt to assess AN risk based on genome wide genotype level data. Future integration of genomic, environmental and family-based information is likely to improve the AN risk evaluation process, eventually benefitting AN patients and families in the clinical setting.

The FDA's Experience with Emerging Genomics Technologies-Past, Present, and Future.

PubMed

Xu, Joshua; Thakkar, Shraddha; Gong, Binsheng; Tong, Weida

2016-07-01

The rapid advancement of emerging genomics technologies and their application for assessing safety and efficacy of FDA-regulated products require a high standard of reliability and robustness supporting regulatory decision-making in the FDA. To facilitate the regulatory application, the FDA implemented a novel data submission program, Voluntary Genomics Data Submission (VGDS), and also to engage the stakeholders. As part of the endeavor, for the past 10 years, the FDA has led an international consortium of regulatory agencies, academia, pharmaceutical companies, and genomics platform providers, which was named MicroArray Quality Control Consortium (MAQC), to address issues such as reproducibility, precision, specificity/sensitivity, and data interpretation. Three projects have been completed so far assessing these genomics technologies: gene expression microarrays, whole genome genotyping arrays, and whole transcriptome sequencing (i.e., RNA-seq). The resultant studies provide the basic parameters for fit-for-purpose application of these new data streams in regulatory environments, and the solutions have been made available to the public through peer-reviewed publications. The latest MAQC project is also called the SEquencing Quality Control (SEQC) project focused on next-generation sequencing. Using reference samples with built-in controls, SEQC studies have demonstrated that relative gene expression can be measured accurately and reliably across laboratories and RNA-seq platforms. Besides prediction performance comparable to microarrays in clinical settings and safety assessments, RNA-seq is shown to have better sensitivity for low expression and reveal novel transcriptomic features. Future effort of MAQC will be focused on quality control of whole genome sequencing and targeted sequencing.

The FDA’s Experience with Emerging Genomics Technologies—Past, Present, and Future

PubMed Central

Xu, Joshua; Thakkar, Shraddha; Gong, Binsheng; Tong, Weida

2016-01-01

The rapid advancement of emerging genomics technologies and their application for assessing safety and efficacy of FDA-regulated products require a high standard of reliability and robustness supporting regulatory decision-making in the FDA. To facilitate the regulatory application, the FDA implemented a novel data submission program, Voluntary Genomics Data Submission (VGDS), and also to engage the stakeholders. As part of the endeavor, for the past 10 years, the FDA has led an international consortium of regulatory agencies, academia, pharmaceutical companies, and genomics platform providers, which was named MicroArray Quality Control Consortium (MAQC), to address issues such as reproducibility, precision, specificity/sensitivity, and data interpretation. Three projects have been completed so far assessing these genomics technologies: gene expression microarrays, whole genome genotyping arrays, and whole transcriptome sequencing (i.e., RNA-seq). The resultant studies provide the basic parameters for fit-for-purpose application of these new data streams in regulatory environments, and the solutions have been made available to the public through peer-reviewed publications. The latest MAQC project is also called the SEquencing Quality Control (SEQC) project focused on next-generation sequencing. Using reference samples with built-in controls, SEQC studies have demonstrated that relative gene expression can be measured accurately and reliably across laboratories and RNA-seq platforms. Besides prediction performance comparable to microarrays in clinical settings and safety assessments, RNA-seq is shown to have better sensitivity for low expression and reveal novel transcriptomic features. Future effort of MAQC will be focused on quality control of whole genome sequencing and targeted sequencing. PMID:27116022

LaGomiCs-Lagomorph Genomics Consortium: An International Collaborative Effort for Sequencing the Genomes of an Entire Mammalian Order.

PubMed

Fontanesi, Luca; Di Palma, Federica; Flicek, Paul; Smith, Andrew T; Thulin, Carl-Gustaf; Alves, Paulo C

2016-07-01

The order Lagomorpha comprises about 90 living species, divided in 2 families: the pikas (Family Ochotonidae), and the rabbits, hares, and jackrabbits (Family Leporidae). Lagomorphs are important economically and scientifically as major human food resources, valued game species, pests of agricultural significance, model laboratory animals, and key elements in food webs. A quarter of the lagomorph species are listed as threatened. They are native to all continents except Antarctica, and occur up to 5000 m above sea level, from the equator to the Arctic, spanning a wide range of environmental conditions. The order has notable taxonomic problems presenting significant difficulties for defining a species due to broad phenotypic variation, overlap of morphological characteristics, and relatively recent speciation events. At present, only the genomes of 2 species, the European rabbit (Oryctolagus cuniculus) and American pika (Ochotona princeps) have been sequenced and assembled. Starting from a paucity of genome information, the main scientific aim of the Lagomorph Genomics Consortium (LaGomiCs), born from a cooperative initiative of the European COST Action "A Collaborative European Network on Rabbit Genome Biology-RGB-Net" and the World Lagomorph Society (WLS), is to provide an international framework for the sequencing of the genome of all extant and selected extinct lagomorphs. Sequencing the genomes of an entire order will provide a large amount of information to address biological problems not only related to lagomorphs but also to all mammals. We present current and planned sequencing programs and outline the final objective of LaGomiCs possible through broad international collaboration. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas

We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequencemore » (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.« less

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

DOE PAGES

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas; ...

2017-08-08

Here, we present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a MetagenomeAssembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Genemore » Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.« less

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas

Here, we present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a MetagenomeAssembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Genemore » Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.« less

A novel member of the split betaalphabeta fold: Solution structure of the hypothetical protein YML108W from Saccharomyces cerevisiae.

PubMed

Pineda-Lucena, Antonio; Liao, Jack C C; Cort, John R; Yee, Adelinda; Kennedy, Michael A; Edwards, Aled M; Arrowsmith, Cheryl H

2003-05-01

As part of the Northeast Structural Genomics Consortium pilot project focused on small eukaryotic proteins and protein domains, we have determined the NMR structure of the protein encoded by ORF YML108W from Saccharomyces cerevisiae. YML108W belongs to one of the numerous structural proteomics targets whose biological function is unknown. Moreover, this protein does not have sequence similarity to any other protein. The NMR structure of YML108W consists of a four-stranded beta-sheet with strand order 2143 and two alpha-helices, with an overall topology of betabetaalphabetabetaalpha. Strand beta1 runs parallel to beta4, and beta2:beta1 and beta4:beta3 pairs are arranged in an antiparallel fashion. Although this fold belongs to the split betaalphabeta family, it appears to be unique among this family; it is a novel arrangement of secondary structure, thereby expanding the universe of protein folds.

The NIH Roadmap Epigenomics Program data resource

PubMed Central

Chadwick, Lisa Helbling

2012-01-01

The NIH Roadmap Reference Epigenome Mapping Consortium is developing a community resource of genome-wide epigenetic maps in a broad range of human primary cells and tissues. There are large amounts of data already available, and a number of different options for viewing and analyzing the data. This report will describe key features of the websites where users will find data, protocols and analysis tools developed by the consortium, and provide a perspective on how this unique resource will facilitate and inform human disease research, both immediately and in the future. PMID:22690667

The NIH Roadmap Epigenomics Program data resource.

PubMed

Chadwick, Lisa Helbling

2012-06-01

The NIH Roadmap Reference Epigenome Mapping Consortium is developing a community resource of genome-wide epigenetic maps in a broad range of human primary cells and tissues. There are large amounts of data already available, and a number of different options for viewing and analyzing the data. This report will describe key features of the websites where users will find data, protocols and analysis tools developed by the consortium, and provide a perspective on how this unique resource will facilitate and inform human disease research, both immediately and in the future.

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project.

PubMed

Blokland, Gabriëlla A M; Del Re, Elisabetta C; Mesholam-Gately, Raquelle I; Jovicich, Jorge; Trampush, Joey W; Keshavan, Matcheri S; DeLisi, Lynn E; Walters, James T R; Turner, Jessica A; Malhotra, Anil K; Lencz, Todd; Shenton, Martha E; Voineskos, Aristotle N; Rujescu, Dan; Giegling, Ina; Kahn, René S; Roffman, Joshua L; Holt, Daphne J; Ehrlich, Stefan; Kikinis, Zora; Dazzan, Paola; Murray, Robin M; Di Forti, Marta; Lee, Jimmy; Sim, Kang; Lam, Max; Wolthusen, Rick P F; de Zwarte, Sonja M C; Walton, Esther; Cosgrove, Donna; Kelly, Sinead; Maleki, Nasim; Osiecki, Lisa; Picchioni, Marco M; Bramon, Elvira; Russo, Manuela; David, Anthony S; Mondelli, Valeria; Reinders, Antje A T S; Falcone, M Aurora; Hartmann, Annette M; Konte, Bettina; Morris, Derek W; Gill, Michael; Corvin, Aiden P; Cahn, Wiepke; Ho, New Fei; Liu, Jian Jun; Keefe, Richard S E; Gollub, Randy L; Manoach, Dara S; Calhoun, Vince D; Schulz, S Charles; Sponheim, Scott R; Goff, Donald C; Buka, Stephen L; Cherkerzian, Sara; Thermenos, Heidi W; Kubicki, Marek; Nestor, Paul G; Dickie, Erin W; Vassos, Evangelos; Ciufolini, Simone; Reis Marques, Tiago; Crossley, Nicolas A; Purcell, Shaun M; Smoller, Jordan W; van Haren, Neeltje E M; Toulopoulou, Timothea; Donohoe, Gary; Goldstein, Jill M; Seidman, Larry J; McCarley, Robert W; Petryshen, Tracey L

2018-05-01

Schizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection. We identified existing samples collected for schizophrenia studies consisting of patients, controls, and/or individuals at familial high-risk (FHR) for schizophrenia. Samples had single nucleotide polymorphism (SNP) array data or genomic DNA, clinical and demographic data, and neuropsychological and/or brain magnetic resonance imaging (MRI) data. Data were subjected to quality control procedures at a central site. Sixteen research groups contributed data from 5199 psychosis patients, 4877 controls, and 725 FHR individuals. All participants have relevant demographic data and all patients have relevant clinical data. The sex ratio is 56.5% male and 43.5% female. Significant differences exist between diagnostic groups for premorbid and current IQ (both p<1×10 -10 ). Data from a diversity of neuropsychological tests are available for 92% of participants, and 30% have structural MRI scans (half also have diffusion-weighted MRI scans). SNP data are available for 76% of participants. The ancestry composition is 70% European, 20% East Asian, 7% African, and 3% other. The Consortium is investigating the genetic contribution to brain phenotypes in a schizophrenia sample collection of >10,000 participants. The breadth of data across clinical, genetic, neuropsychological, and MRI modalities provides an important opportunity for elucidating the genetic basis of neural processes underlying schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

The minimum information about a genome sequence (MIGS) specification

PubMed Central

Field, Dawn; Garrity, George; Gray, Tanya; Morrison, Norman; Selengut, Jeremy; Sterk, Peter; Tatusova, Tatiana; Thomson, Nicholas; Allen, Michael J; Angiuoli, Samuel V; Ashburner, Michael; Axelrod, Nelson; Baldauf, Sandra; Ballard, Stuart; Boore, Jeffrey; Cochrane, Guy; Cole, James; Dawyndt, Peter; De Vos, Paul; dePamphilis, Claude; Edwards, Robert; Faruque, Nadeem; Feldman, Robert; Gilbert, Jack; Gilna, Paul; Glöckner, Frank Oliver; Goldstein, Philip; Guralnick, Robert; Haft, Dan; Hancock, David; Hermjakob, Henning; Hertz-Fowler, Christiane; Hugenholtz, Phil; Joint, Ian; Kagan, Leonid; Kane, Matthew; Kennedy, Jessie; Kowalchuk, George; Kottmann, Renzo; Kolker, Eugene; Kravitz, Saul; Kyrpides, Nikos; Leebens-Mack, Jim; Lewis, Suzanna E; Li, Kelvin; Lister, Allyson L; Lord, Phillip; Maltsev, Natalia; Markowitz, Victor; Martiny, Jennifer; Methe, Barbara; Mizrachi, Ilene; Moxon, Richard; Nelson, Karen; Parkhill, Julian; Proctor, Lita; White, Owen; Sansone, Susanna-Assunta; Spiers, Andrew; Stevens, Robert; Swift, Paul; Taylor, Chris; Tateno, Yoshio; Tett, Adrian; Turner, Sarah; Ussery, David; Vaughan, Bob; Ward, Naomi; Whetzel, Trish; Gil, Ingio San; Wilson, Gareth; Wipat, Anil

2008-01-01

With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the ‘transparency’ of the information contained in existing genomic databases. PMID:18464787

CPTAC | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) is a national effort to accelerate the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis, or proteogenomics.

The RA-MAP Consortium: a working model for academia-industry collaboration.

PubMed

Cope, Andrew P; Barnes, Michael R; Belson, Alexandra; Binks, Michael; Brockbank, Sarah; Bonachela-Capdevila, Francisco; Carini, Claudio; Fisher, Benjamin A; Goodyear, Carl S; Emery, Paul; Ehrenstein, Michael R; Gozzard, Neil; Harris, Ray; Hollis, Sally; Keidel, Sarah; Levesque, Marc; Lindholm, Catharina; McDermott, Michael F; McInnes, Iain B; Mela, Christopher M; Parker, Gerry; Read, Simon; Pedersen, Ayako Wakatsuki; Ponchel, Frederique; Porter, Duncan; Rao, Ravi; Rowe, Anthony; Schulz-Knappe, Peter; Sleeman, Matthew A; Symmons, Deborah; Taylor, Peter C; Tom, Brian; Tsuji, Wayne; Verbeeck, Denny; Isaacs, John D

2018-01-01

Collaboration can be challenging; nevertheless, the emerging successes of large, multi-partner, multi-national cooperatives and research networks in the biomedical sector have sustained the appetite of academics and industry partners for developing and fostering new research consortia. This model has percolated down to national funding agencies across the globe, leading to funding for projects that aim to realise the true potential of genomic medicine in the 21st century and to reap the rewards of 'big data'. In this Perspectives article, the experiences of the RA-MAP consortium, a group of more than 140 individuals affiliated with 21 academic and industry organizations that are focused on making genomic medicine in rheumatoid arthritis a reality are described. The challenges of multi-partner collaboration in the UK are highlighted and wide-ranging solutions are offered that might benefit large research consortia around the world.

Multi-target parallel processing approach for gene-to-structure determination of the influenza polymerase PB2 subunit.

PubMed

Armour, Brianna L; Barnes, Steve R; Moen, Spencer O; Smith, Eric; Raymond, Amy C; Fairman, James W; Stewart, Lance J; Staker, Bart L; Begley, Darren W; Edwards, Thomas E; Lorimer, Donald D

2013-06-28

Pandemic outbreaks of highly virulent influenza strains can cause widespread morbidity and mortality in human populations worldwide. In the United States alone, an average of 41,400 deaths and 1.86 million hospitalizations are caused by influenza virus infection each year (1). Point mutations in the polymerase basic protein 2 subunit (PB2) have been linked to the adaptation of the viral infection in humans (2). Findings from such studies have revealed the biological significance of PB2 as a virulence factor, thus highlighting its potential as an antiviral drug target. The structural genomics program put forth by the National Institute of Allergy and Infectious Disease (NIAID) provides funding to Emerald Bio and three other Pacific Northwest institutions that together make up the Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is dedicated to providing the scientific community with three-dimensional protein structures of NIAID category A-C pathogens. Making such structural information available to the scientific community serves to accelerate structure-based drug design. Structure-based drug design plays an important role in drug development. Pursuing multiple targets in parallel greatly increases the chance of success for new lead discovery by targeting a pathway or an entire protein family. Emerald Bio has developed a high-throughput, multi-target parallel processing pipeline (MTPP) for gene-to-structure determination to support the consortium. Here we describe the protocols used to determine the structure of the PB2 subunit from four different influenza A strains.

AphidBase: A centralized bioinformatic resource for annotation of the pea aphid genome

PubMed Central

Legeai, Fabrice; Shigenobu, Shuji; Gauthier, Jean-Pierre; Colbourne, John; Rispe, Claude; Collin, Olivier; Richards, Stephen; Wilson, Alex C. C.; Tagu, Denis

2015-01-01

AphidBase is a centralized bioinformatic resource that was developed to facilitate community annotation of the pea aphid genome by the International Aphid Genomics Consortium (IAGC). The AphidBase Information System designed to organize and distribute genomic data and annotations for a large international community was constructed using open source software tools from the Generic Model Organism Database (GMOD). The system includes Apollo and GBrowse utilities as well as a wiki, blast search capabilities and a full text search engine. AphidBase strongly supported community cooperation and coordination in the curation of gene models during community annotation of the pea aphid genome. AphidBase can be accessed at http://www.aphidbase.com. PMID:20482635

Draft Genome Sequence of Thermoanaerobacter sp. Strain A7A, Reconstructed from a Metagenome Obtained from a High-Temperature Hydrocarbon Reservoir in the Bass Strait, Australia

PubMed Central

Li, Dongmei; Greenfield, Paul; Rosewarne, Carly P.

2013-01-01

The draft genome sequence of Thermoanaerobacter sp. strain A7A was reconstructed from a metagenome of a microbial consortium obtained from the Tuna oil field in the Gippsland Basin, Australia. The organism is a strict anaerobe that is predicted to ferment a range of simple sugars and undertake sulfur reduction. PMID:24029756

CPTAC researchers report first large-scale integrated proteomic and genomic analysis of a human cancer | Office of Cancer Clinical Proteomics Research

Cancer.gov

Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples are expressed at the protein level. The integration of proteomic and genomic data, or proteogenomics, provides a more comprehensive view of the biological features that drive cancer than genomic analysis alone and may help identify the most important targets for cancer detection and intervention.

Using optical mapping data for the improvement of vertebrate genome assemblies.

PubMed

Howe, Kerstin; Wood, Jonathan M D

2015-01-01

Optical mapping is a technology that gathers long-range information on genome sequences similar to ordered restriction digest maps. Because it is not subject to cloning, amplification, hybridisation or sequencing bias, it is ideally suited to the improvement of fragmented genome assemblies that can no longer be improved by classical methods. In addition, its low cost and rapid turnaround make it equally useful during the scaffolding process of de novo assembly from high throughput sequencing reads. We describe how optical mapping has been used in practice to produce high quality vertebrate genome assemblies. In particular, we detail the efforts undertaken by the Genome Reference Consortium (GRC), which maintains the reference genomes for human, mouse, zebrafish and chicken, and uses different optical mapping platforms for genome curation.

A 1000 Arab genome project to study the Emirati population.

PubMed

Al-Ali, Mariam; Osman, Wael; Tay, Guan K; AlSafar, Habiba S

2018-04-01

Discoveries from the human genome, HapMap, and 1000 genome projects have collectively contributed toward the creation of a catalog of human genetic variations that has improved our understanding of human diversity. Despite the collegial nature of many of these genome study consortiums, which has led to the cataloging of genetic variations of different ethnic groups from around the world, genome data on the Arab population remains overwhelmingly underrepresented. The National Arab Genome project in the United Arab Emirates (UAE) aims to address this deficiency by using Next Generation Sequencing (NGS) technology to provide data to improve our understanding of the Arab genome and catalog variants that are unique to the Arab population of the UAE. The project was conceived to shed light on the similarities and differences between the Arab genome and those of the other ethnic groups.

Effective electron-density map improvement and structure validation on a Linux multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web Service.

PubMed

Reddy, Vinod; Swanson, Stanley M; Segelke, Brent; Kantardjieff, Katherine A; Sacchettini, James C; Rupp, Bernhard

2003-12-01

Anticipating a continuing increase in the number of structures solved by molecular replacement in high-throughput crystallography and drug-discovery programs, a user-friendly web service for automated molecular replacement, map improvement, bias removal and real-space correlation structure validation has been implemented. The service is based on an efficient bias-removal protocol, Shake&wARP, and implemented using EPMR and the CCP4 suite of programs, combined with various shell scripts and Fortran90 routines. The service returns improved maps, converted data files and real-space correlation and B-factor plots. User data are uploaded through a web interface and the CPU-intensive iteration cycles are executed on a low-cost Linux multi-CPU cluster using the Condor job-queuing package. Examples of map improvement at various resolutions are provided and include model completion and reconstruction of absent parts, sequence correction, and ligand validation in drug-target structures.

Strategies and tools for whole genome alignments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Couronne, Olivier; Poliakov, Alexander; Bray, Nicolas

2002-11-25

The availability of the assembled mouse genome makespossible, for the first time, an alignment and comparison of two largevertebrate genomes. We have investigated different strategies ofalignment for the subsequent analysis of conservation of genomes that areeffective for different quality assemblies. These strategies were appliedto the comparison of the working draft of the human genome with the MouseGenome Sequencing Consortium assembly, as well as other intermediatemouse assemblies. Our methods are fast and the resulting alignmentsexhibit a high degree of sensitivity, covering more than 90 percent ofknown coding exons in the human genome. We have obtained such coveragewhile preserving specificity. With amore » view towards the end user, we havedeveloped a suite of tools and websites for automatically aligning, andsubsequently browsing and working with whole genome comparisons. Wedescribe the use of these tools to identify conserved non-coding regionsbetween the human and mouse genomes, some of which have not beenidentified by other methods.« less

Pharmacogenetics: Implications of Race and Ethnicity on Defining Genetic Profiles for Personalized Medicine

PubMed Central

Ortega, Victor E.; Meyers, Deborah A.

2014-01-01

Pharmacogenetics is being used to develop personalized therapies specific to individuals from different ethnic or racial groups. Pharmacogenetic studies to date have been primarily performed in trial cohorts consisting of non-Hispanic whites of European descent. A “bottleneck” or collapse of genetic diversity associated with the first human colonization of Europe during the Upper Paleolithic period, followed by the recent mixing of African, European, and Native American ancestries has resulted in different ethnic groups with varying degrees of genetic diversity. Differences in genetic ancestry may introduce genetic variation which has the potential to alter the therapeutic efficacy of commonly used asthma therapies, for example β2-adrenergic receptor agonists (beta agonists). Pharmacogenetic studies of admixed ethnic groups have been limited to small candidate gene association studies of which the best example is the gene coding for the receptor target of beta agonist therapy, ADRB2. Large consortium-based sequencing studies are using next-generation whole-genome sequencing to provide a diverse genome map of different admixed populations which can be used for future pharmacogenetic studies. These studies will include candidate gene studies, genome-wide association studies, and whole-genome admixture-based approaches which account for ancestral genetic structure, complex haplotypes, gene-gene interactions, and rare variants to detect and replicate novel pharmacogenetic loci. PMID:24369795

Hymenoptera Genome Database: integrating genome annotations in HymenopteraMine.

PubMed

Elsik, Christine G; Tayal, Aditi; Diesh, Colin M; Unni, Deepak R; Emery, Marianne L; Nguyen, Hung N; Hagen, Darren E

2016-01-04

We report an update of the Hymenoptera Genome Database (HGD) (http://HymenopteraGenome.org), a model organism database for insect species of the order Hymenoptera (ants, bees and wasps). HGD maintains genomic data for 9 bee species, 10 ant species and 1 wasp, including the versions of genome and annotation data sets published by the genome sequencing consortiums and those provided by NCBI. A new data-mining warehouse, HymenopteraMine, based on the InterMine data warehousing system, integrates the genome data with data from external sources and facilitates cross-species analyses based on orthology. New genome browsers and annotation tools based on JBrowse/WebApollo provide easy genome navigation, and viewing of high throughput sequence data sets and can be used for collaborative genome annotation. All of the genomes and annotation data sets are combined into a single BLAST server that allows users to select and combine sequence data sets to search. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Analysis pipelines and packages for Infinium HumanMethylation450 BeadChip (450k) data

PubMed Central

Morris, Tiffany J.; Beck, Stephan

2015-01-01

The Illumina HumanMethylation450 BeadChip has become a popular platform for interrogating DNA methylation in epigenome-wide association studies (EWAS) and related projects as well as resource efforts such as the International Cancer Genome Consortium (ICGC) and the International Human Epigenome Consortium (IHEC). This has resulted in an exponential increase of 450k data in recent years and triggered the development of numerous integrated analysis pipelines and stand-alone packages. This review will introduce and discuss the currently most popular pipelines and packages and is particularly aimed at new 450k users. PMID:25233806

Genome-Wide Association Study of Cardiac Structure and Systolic Function in African Americans: The Candidate Gene Association Resource (CARe) Study

PubMed Central

Fox, Ervin R.; Musani, Solomon K.; Barbalic, Maja; Lin, Honghuang; Yu, Bing; Ogunyankin, Kofo O.; Smith, Nicholas L.; Kutlar, Abdullah; Glazer, Nicole L.; Post, Wendy S.; Paltoo, Dina N.; Dries, Daniel L.; Farlow, Deborah N.; Duarte, Christine W.; Kardia, Sharon L.; Meyers, Kristin J.; Sun, Yan V.; Arnett, Donna K.; Patki, Amit A.; Sha, Jin; Cui, Xiangqui; Samdarshi, Tandaw E.; Penman, Alan D.; Bibbins-Domingo, Kirsten; Bůžková, Petra; Benjamin, Emelia J.; Bluemke, David A.; Morrison, Alanna C.; Heiss, Gerardo; Carr, J. Jeffrey; Tracy, Russell P.; Mosley, Thomas H.; Taylor, Herman A.; Psaty, Bruce M.; Heckbert, Susan R.; Cappola, Thomas P.; Vasan, Ramachandran S.

2013-01-01

Background Using data from four community-based cohorts of African Americans (AA), we tested the association between genome-wide markers (SNPs) and cardiac phenotypes in the Candidate-gene Association REsource (CARe) study. Methods and Results Among 6,765 AA, we related age, sex, height and weight-adjusted residuals for nine cardiac phenotypes (assessed by echocardiogram or MRI) to 2.5 million SNPs genotyped using Genome-Wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within cohort genome-wide association analysis was conducted followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0 ×10−07). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested look-ups in one consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (p=1.43 × 10−07) for left ventricular mass (LVM); rs7213314 in WIPI1 (p=1.68 × 10−07) for LV internal diastolic diameter (LVIDD); rs1571099 in PPAPDC1A (p= 2.57 × 10−08) for interventricular septal wall thickness (IVST); and rs9530176 in KLF5 (p=4.02 × 10−07) for ejection fraction (EF). Associated variants were enriched in three signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry were confirmed in look-ups in EchoGEN. Conclusions In the largest GWAS of cardiac structure and function to date in AA, we identified 4 genetic loci related to LVM, IVST, LVIDD and EF that reached genome-wide significance. Replication results suggest that these loci may represent unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes. PMID:23275298

Psychiatric Genomics: An Update and an Agenda.

PubMed

Sullivan, Patrick F; Agrawal, Arpana; Bulik, Cynthia M; Andreassen, Ole A; Børglum, Anders D; Breen, Gerome; Cichon, Sven; Edenberg, Howard J; Faraone, Stephen V; Gelernter, Joel; Mathews, Carol A; Nievergelt, Caroline M; Smoller, Jordan W; O'Donovan, Michael C

2018-01-01

The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver "actionable" findings-genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets. The central idea of the PGC is to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. The emerging findings suggest that we are entering a phase of accelerated genetic discovery for multiple psychiatric disorders. These findings are likely to elucidate the genetic portions of these truly complex traits, and this knowledge can then be mined for its relevance for improved therapeutics and its impact on psychiatric practice within a precision medicine framework. [AJP at 175: Remembering Our Past As We Envision Our Future November 1946: The Genetic Theory of Schizophrenia Franz Kallmann's influential twin study of schizophrenia in 691 twin pairs was the largest in the field for nearly four decades. (Am J Psychiatry 1946; 103:309-322 )].

Highlights from the WIN 2017 Symposium, 26-27 June 2017, Paris, France: 'Expediting Global Innovation in Precision Cancer Medicine'.

PubMed

Davies, Will

2017-01-01

The Worldwide Innovative Networking (WIN) symposium brings together representatives from academic institutions, pharmaceutical partners, technology companies and charitable organisations from across the globe for an annual summit, discussing ongoing research and the latest developments in precision medicine. Now, in its seventh year, the aims of the WIN consortium's annual meeting, to foster communication and collaboration between members and deliver clinical trial results that improve the care and outcomes of patients are presented in open dialogue to encourage debate and discussion. This year, the meeting was held in Paris, France from 26-27 June and consisted of six plenary sessions, two debates, and poster presentations from attendees. In keeping with the consortium's goals, presentations and posters focused on the development and integration of new therapies and updates in genome-based medicine. Among the presentations at this year's meeting, much of the focus fell on design and implementation of new designs of clinical trials, moving away from decades-long assessments of thousands of patients towards a nimble, adaptive design fitting the edicts of personalised medicine and delving into greater depths within genomic data, ranging beyond genome analysis to chart new targets in ligandomics, proteogenomics and more.

THE FEDERAL INTEGRATED BIOTREATMENT RESEARCH CONSORTIUM (FLASK TO FIELD)

EPA Science Inventory

The Federal Integrated Biotreatment Research Consortium (Flask to Field) represented a 7-year concerted effort by several research laboratories to develop bioremediation technologies for contaminated DoD sites. The consortium structure consisted of a director and four thrust are...

Enhanced guide-RNA design and targeting analysis for precise CRISPR genome editing of single and consortia of industrially relevant and non-model organisms.

PubMed

Mendoza, Brian J; Trinh, Cong T

2018-01-01

Genetic diversity of non-model organisms offers a repertoire of unique phenotypic features for exploration and cultivation for synthetic biology and metabolic engineering applications. To realize this enormous potential, it is critical to have an efficient genome editing tool for rapid strain engineering of these organisms to perform novel programmed functions. To accommodate the use of CRISPR/Cas systems for genome editing across organisms, we have developed a novel method, named CRISPR Associated Software for Pathway Engineering and Research (CASPER), for identifying on- and off-targets with enhanced predictability coupled with an analysis of non-unique (repeated) targets to assist in editing any organism with various endonucleases. Utilizing CASPER, we demonstrated a modest 2.4% and significant 30.2% improvement (F-test, P < 0.05) over the conventional methods for predicting on- and off-target activities, respectively. Further we used CASPER to develop novel applications in genome editing: multitargeting analysis (i.e. simultaneous multiple-site modification on a target genome with a sole guide-RNA requirement) and multispecies population analysis (i.e. guide-RNA design for genome editing across a consortium of organisms). Our analysis on a selection of industrially relevant organisms revealed a number of non-unique target sites associated with genes and transposable elements that can be used as potential sites for multitargeting. The analysis also identified shared and unshared targets that enable genome editing of single or multiple genomes in a consortium of interest. We envision CASPER as a useful platform to enhance the precise CRISPR genome editing for metabolic engineering and synthetic biology applications. https://github.com/TrinhLab/CASPER. ctrinh@utk.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

High-throughput annotation of full-length long noncoding RNAs with capture long-read sequencing.

PubMed

Lagarde, Julien; Uszczynska-Ratajczak, Barbara; Carbonell, Silvia; Pérez-Lluch, Sílvia; Abad, Amaya; Davis, Carrie; Gingeras, Thomas R; Frankish, Adam; Harrow, Jennifer; Guigo, Roderic; Johnson, Rory

2017-12-01

Accurate annotation of genes and their transcripts is a foundation of genomics, but currently no annotation technique combines throughput and accuracy. As a result, reference gene collections remain incomplete-many gene models are fragmentary, and thousands more remain uncataloged, particularly for long noncoding RNAs (lncRNAs). To accelerate lncRNA annotation, the GENCODE consortium has developed RNA Capture Long Seq (CLS), which combines targeted RNA capture with third-generation long-read sequencing. Here we present an experimental reannotation of the GENCODE intergenic lncRNA populations in matched human and mouse tissues that resulted in novel transcript models for 3,574 and 561 gene loci, respectively. CLS approximately doubled the annotated complexity of targeted loci, outperforming existing short-read techniques. Full-length transcript models produced by CLS enabled us to definitively characterize the genomic features of lncRNAs, including promoter and gene structure, and protein-coding potential. Thus, CLS removes a long-standing bottleneck in transcriptome annotation and generates manual-quality full-length transcript models at high-throughput scales.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide☆☆☆★

PubMed Central

Thompson, Paul M.; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Bearden, Carrie E.; Boedhoe, Premika S.; Brouwer, Rachel M.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cannon, Dara M.; Cohen, Ronald A.; Conrod, Patricia J.; Dale, Anders M.; Deary, Ian J.; Dennis, Emily L.; de Reus, Marcel A.; Desrivieres, Sylvane; Dima, Danai; Donohoe, Gary; Fisher, Simon E.; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Ganjgahi, Habib; Garavan, Hugh; Glahn, David C.; Grabe, Hans J.; Guadalupe, Tulio; Gutman, Boris A.; Hashimoto, Ryota; Hibar, Derrek P.; Holland, Dominic; Hoogman, Martine; Pol, Hilleke E. Hulshoff; Hosten, Norbert; Jahanshad, Neda; Kelly, Sinead; Kochunov, Peter; Kremen, William S.; Lee, Phil H.; Mackey, Scott; Martin, Nicholas G.; Mazoyer, Bernard; McDonald, Colm; Medland, Sarah E.; Morey, Rajendra A.; Nichols, Thomas E.; Paus, Tomas; Pausova, Zdenka; Schmaal, Lianne; Schumann, Gunter; Shen, Li; Sisodiya, Sanjay M.; Smit, Dirk J.A.; Smoller, Jordan W.; Stein, Dan J.; Stein, Jason L.; Toro, Roberto; Turner, Jessica A.; van den Heuvel, Martijn P.; van den Heuvel, Odile L.; van Erp, Theo G.M.; van Rooij, Daan; Veltman, Dick J.; Walter, Henrik; Wang, Yalin; Wardlaw, Joanna M.; Whelan, Christopher D.; Wright, Margaret J.; Ye, Jieping

2016-01-01

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) – a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date – of schizophrenia and major depression – ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens – now numbering over 30,000 MRI scans – have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants – and genetic variants in general – may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures – from tens of thousands of people – that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far. PMID:26658930

Single haplotype assembly of the human genome from a hydatidiform mole.

PubMed

Steinberg, Karyn Meltz; Schneider, Valerie A; Graves-Lindsay, Tina A; Fulton, Robert S; Agarwala, Richa; Huddleston, John; Shiryev, Sergey A; Morgulis, Aleksandr; Surti, Urvashi; Warren, Wesley C; Church, Deanna M; Eichler, Evan E; Wilson, Richard K

2014-12-01

A complete reference assembly is essential for accurately interpreting individual genomes and associating variation with phenotypes. While the current human reference genome sequence is of very high quality, gaps and misassemblies remain due to biological and technical complexities. Large repetitive sequences and complex allelic diversity are the two main drivers of assembly error. Although increasing the length of sequence reads and library fragments can improve assembly, even the longest available reads do not resolve all regions. In order to overcome the issue of allelic diversity, we used genomic DNA from an essentially haploid hydatidiform mole, CHM1. We utilized several resources from this DNA including a set of end-sequenced and indexed BAC clones and 100× Illumina whole-genome shotgun (WGS) sequence coverage. We used the WGS sequence and the GRCh37 reference assembly to create an assembly of the CHM1 genome. We subsequently incorporated 382 finished BAC clone sequences to generate a draft assembly, CHM1_1.1 (NCBI AssemblyDB GCA_000306695.2). Analysis of gene, repetitive element, and segmental duplication content show this assembly to be of excellent quality and contiguity. However, comparison to assembly-independent resources, such as BAC clone end sequences and PacBio long reads, indicate misassembled regions. Most of these regions are enriched for structural variation and segmental duplication, and can be resolved in the future. This publicly available assembly will be integrated into the Genome Reference Consortium curation framework for further improvement, with the ultimate goal being a completely finished gap-free assembly. © 2014 Steinberg et al.; Published by Cold Spring Harbor Laboratory Press.

Single haplotype assembly of the human genome from a hydatidiform mole

PubMed Central

Steinberg, Karyn Meltz; Schneider, Valerie A.; Graves-Lindsay, Tina A.; Fulton, Robert S.; Agarwala, Richa; Huddleston, John; Shiryev, Sergey A.; Morgulis, Aleksandr; Surti, Urvashi; Warren, Wesley C.; Church, Deanna M.; Eichler, Evan E.; Wilson, Richard K.

2014-01-01

A complete reference assembly is essential for accurately interpreting individual genomes and associating variation with phenotypes. While the current human reference genome sequence is of very high quality, gaps and misassemblies remain due to biological and technical complexities. Large repetitive sequences and complex allelic diversity are the two main drivers of assembly error. Although increasing the length of sequence reads and library fragments can improve assembly, even the longest available reads do not resolve all regions. In order to overcome the issue of allelic diversity, we used genomic DNA from an essentially haploid hydatidiform mole, CHM1. We utilized several resources from this DNA including a set of end-sequenced and indexed BAC clones and 100× Illumina whole-genome shotgun (WGS) sequence coverage. We used the WGS sequence and the GRCh37 reference assembly to create an assembly of the CHM1 genome. We subsequently incorporated 382 finished BAC clone sequences to generate a draft assembly, CHM1_1.1 (NCBI AssemblyDB GCA_000306695.2). Analysis of gene, repetitive element, and segmental duplication content show this assembly to be of excellent quality and contiguity. However, comparison to assembly-independent resources, such as BAC clone end sequences and PacBio long reads, indicate misassembled regions. Most of these regions are enriched for structural variation and segmental duplication, and can be resolved in the future. This publicly available assembly will be integrated into the Genome Reference Consortium curation framework for further improvement, with the ultimate goal being a completely finished gap-free assembly. PMID:25373144

Characterization of Pustular Mats and Related Rivularia-Rich Laminations in Oncoids From the Laguna Negra Lake (Argentina).

PubMed

Mlewski, Estela C; Pisapia, Céline; Gomez, Fernando; Lecourt, Lena; Soto Rueda, Eliana; Benzerara, Karim; Ménez, Bénédicte; Borensztajn, Stephan; Jamme, Frédéric; Réfrégiers, Matthieu; Gérard, Emmanuelle

2018-01-01

Stromatolites are organo-sedimentary structures that represent some of the oldest records of the early biosphere on Earth. Cyanobacteria are considered as a main component of the microbial mats that are supposed to produce stromatolite-like structures. Understanding the role of cyanobacteria and associated microorganisms on the mineralization processes is critical to better understand what can be preserved in the laminated structure of stromatolites. Laguna Negra (Catamarca, Argentina), a high-altitude hypersaline lake where stromatolites are currently formed, is considered as an analog environment of early Earth. This study aimed at characterizing carbonate precipitation within microbial mats and associated oncoids in Laguna Negra. In particular, we focused on carbonated black pustular mats. By combining Confocal Laser Scanning Microscopy, Scanning Electron Microscopy, Laser Microdissection and Whole Genome Amplification, Cloning and Sanger sequencing, and Focused Ion Beam milling for Transmission Electron Microscopy, we showed that carbonate precipitation did not directly initiate on the sheaths of cyanobacterial Rivularia , which dominate in the mat. It occurred via organo-mineralization processes within a large EPS matrix excreted by the diverse microbial consortium associated with Rivularia where diatoms and anoxygenic phototrophic bacteria were particularly abundant. By structuring a large microbial consortium, Rivularia should then favor the formation of organic-rich laminations of carbonates that can be preserved in stromatolites. By using Fourier Transform Infrared spectroscopy and Synchrotron-based deep UV fluorescence imaging, we compared laminations rich in structures resembling Rivularia to putatively chemically-precipitated laminations in oncoids associated with the mats. We showed that they presented a different mineralogy jointly with a higher content in organic remnants, hence providing some criteria of biogenicity to be searched for in the fossil record.

Characterization of Pustular Mats and Related Rivularia-Rich Laminations in Oncoids From the Laguna Negra Lake (Argentina)

PubMed Central

Mlewski, Estela C.; Pisapia, Céline; Gomez, Fernando; Lecourt, Lena; Soto Rueda, Eliana; Benzerara, Karim; Ménez, Bénédicte; Borensztajn, Stephan; Jamme, Frédéric; Réfrégiers, Matthieu; Gérard, Emmanuelle

2018-01-01

Stromatolites are organo-sedimentary structures that represent some of the oldest records of the early biosphere on Earth. Cyanobacteria are considered as a main component of the microbial mats that are supposed to produce stromatolite-like structures. Understanding the role of cyanobacteria and associated microorganisms on the mineralization processes is critical to better understand what can be preserved in the laminated structure of stromatolites. Laguna Negra (Catamarca, Argentina), a high-altitude hypersaline lake where stromatolites are currently formed, is considered as an analog environment of early Earth. This study aimed at characterizing carbonate precipitation within microbial mats and associated oncoids in Laguna Negra. In particular, we focused on carbonated black pustular mats. By combining Confocal Laser Scanning Microscopy, Scanning Electron Microscopy, Laser Microdissection and Whole Genome Amplification, Cloning and Sanger sequencing, and Focused Ion Beam milling for Transmission Electron Microscopy, we showed that carbonate precipitation did not directly initiate on the sheaths of cyanobacterial Rivularia, which dominate in the mat. It occurred via organo-mineralization processes within a large EPS matrix excreted by the diverse microbial consortium associated with Rivularia where diatoms and anoxygenic phototrophic bacteria were particularly abundant. By structuring a large microbial consortium, Rivularia should then favor the formation of organic-rich laminations of carbonates that can be preserved in stromatolites. By using Fourier Transform Infrared spectroscopy and Synchrotron-based deep UV fluorescence imaging, we compared laminations rich in structures resembling Rivularia to putatively chemically-precipitated laminations in oncoids associated with the mats. We showed that they presented a different mineralogy jointly with a higher content in organic remnants, hence providing some criteria of biogenicity to be searched for in the fossil record. PMID:29872427

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit

PubMed Central

Moen, Spencer O.; Smith, Eric; Raymond, Amy C.; Fairman, James W.; Stewart, Lance J.; Staker, Bart L.; Begley, Darren W.; Edwards, Thomas E.; Lorimer, Donald D.

2013-01-01

Pandemic outbreaks of highly virulent influenza strains can cause widespread morbidity and mortality in human populations worldwide. In the United States alone, an average of 41,400 deaths and 1.86 million hospitalizations are caused by influenza virus infection each year 1. Point mutations in the polymerase basic protein 2 subunit (PB2) have been linked to the adaptation of the viral infection in humans 2. Findings from such studies have revealed the biological significance of PB2 as a virulence factor, thus highlighting its potential as an antiviral drug target. The structural genomics program put forth by the National Institute of Allergy and Infectious Disease (NIAID) provides funding to Emerald Bio and three other Pacific Northwest institutions that together make up the Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is dedicated to providing the scientific community with three-dimensional protein structures of NIAID category A-C pathogens. Making such structural information available to the scientific community serves to accelerate structure-based drug design. Structure-based drug design plays an important role in drug development. Pursuing multiple targets in parallel greatly increases the chance of success for new lead discovery by targeting a pathway or an entire protein family. Emerald Bio has developed a high-throughput, multi-target parallel processing pipeline (MTPP) for gene-to-structure determination to support the consortium. Here we describe the protocols used to determine the structure of the PB2 subunit from four different influenza A strains. PMID:23851357

Identification of quantitative trait loci for fibrin clot phenotypes: The EuroCLOT study

PubMed Central

Williams, Frances MK; Carter, Angela M; Kato, Bernet; Falchi, Mario; Bathum, Lise; Surdulescu, Gabriela; Kyvik, Kirsten Ohm; Palotie, Aarno; Spector, Tim D; Grant, Peter J

2012-01-01

Objectives Fibrin makes up the structural basis of an occlusive arterial thrombus and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to 1) determine the heritability of fibrin phenotypes and 2) identify QTLs associated with fibrin phenotypes. Methods 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK Caucasian female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Results Estimates of heritability for d-dimer and turbidometric variables were in the range 17 - 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD>3 on 5 chromosomes (5, 6, 9, 16 and 17). Conclusions The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischaemic cardiovascular disorders and their therapy. PMID:19150881

Codon usage bias reveals genomic adaptations to environmental conditions in an acidophilic consortium.

PubMed

Hart, Andrew; Cortés, María Paz; Latorre, Mauricio; Martinez, Servet

2018-01-01

The analysis of codon usage bias has been widely used to characterize different communities of microorganisms. In this context, the aim of this work was to study the codon usage bias in a natural consortium of five acidophilic bacteria used for biomining. The codon usage bias of the consortium was contrasted with genes from an alternative collection of acidophilic reference strains and metagenome samples. Results indicate that acidophilic bacteria preferentially have low codon usage bias, consistent with both their capacity to live in a wide range of habitats and their slow growth rate, a characteristic probably acquired independently from their phylogenetic relationships. In addition, the analysis showed significant differences in the unique sets of genes from the autotrophic species of the consortium in relation to other acidophilic organisms, principally in genes which code for proteins involved in metal and oxidative stress resistance. The lower values of codon usage bias obtained in this unique set of genes suggest higher transcriptional adaptation to living in extreme conditions, which was probably acquired as a measure for resisting the elevated metal conditions present in the mine.

Disease Model Discovery from 3,328 Gene Knockouts by The International Mouse Phenotyping Consortium

PubMed Central

Meehan, Terrence F.; Conte, Nathalie; West, David B.; Jacobsen, Julius O.; Mason, Jeremy; Warren, Jonathan; Chen, Chao-Kung; Tudose, Ilinca; Relac, Mike; Matthews, Peter; Karp, Natasha; Santos, Luis; Fiegel, Tanja; Ring, Natalie; Westerberg, Henrik; Greenaway, Simon; Sneddon, Duncan; Morgan, Hugh; Codner, Gemma F; Stewart, Michelle E; Brown, James; Horner, Neil; Haendel, Melissa; Washington, Nicole; Mungall, Christopher J.; Reynolds, Corey L; Gallegos, Juan; Gailus-Durner, Valerie; Sorg, Tania; Pavlovic, Guillaume; Bower, Lynette R; Moore, Mark; Morse, Iva; Gao, Xiang; Tocchini-Valentini, Glauco P; Obata, Yuichi; Cho, Soo Young; Seong, Je Kyung; Seavitt, John; Beaudet, Arthur L.; Dickinson, Mary E.; Herault, Yann; Wurst, Wolfgang; de Angelis, Martin Hrabe; Lloyd, K.C. Kent; Flenniken, Ann M; Nutter, Lauryl MJ; Newbigging, Susan; McKerlie, Colin; Justice, Monica J.; Murray, Stephen A.; Svenson, Karen L.; Braun, Robert E.; White, Jacqueline K.; Bradley, Allan; Flicek, Paul; Wells, Sara; Skarnes, William C.; Adams, David J.; Parkinson, Helen; Mallon, Ann-Marie; Brown, Steve D.M.; Smedley, Damian

2017-01-01

Although next generation sequencing has revolutionised the ability to associate variants with human diseases, diagnostic rates and development of new therapies are still limited by our lack of knowledge of function and pathobiological mechanism for most genes. To address this challenge, the International Mouse Phenotyping Consortium (IMPC) is creating a genome- and phenome-wide catalogue of gene function by characterizing new knockout mouse strains across diverse biological systems through a broad set of standardised phenotyping tests, with all mice made readily available to the biomedical community. Analysing the first 3328 genes reveals models for 360 diseases including the first for type C Bernard-Soulier, Bardet-Biedl-5 and Gordon Holmes syndromes. 90% of our phenotype annotations are novel, providing the first functional evidence for 1092 genes and candidates in unsolved diseases such as Arrhythmogenic Right Ventricular Dysplasia 3. Finally, we describe our role in variant functional validation with the 100,000 Genomes and other projects. PMID:28650483

Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

PubMed Central

van Rooij, Frank J. A.; Ehret, Georg B.; Boerwinkle, Eric; Felix, Janine F.; Leak, Tennille S.; Harris, Tamara B.; Yang, Qiong; Dehghan, Abbas; Aspelund, Thor; Katz, Ronit; Homuth, Georg; Kocher, Thomas; Rettig, Rainer; Ried, Janina S.; Gieger, Christian; Prucha, Hanna; Pfeufer, Arne; Meitinger, Thomas; Coresh, Josef; Hofman, Albert; Sarnak, Mark J.; Chen, Yii-Der Ida; Uitterlinden, André G.; Chakravarti, Aravinda; Psaty, Bruce M.; van Duijn, Cornelia M.; Kao, W. H. Linda; Witteman, Jacqueline C. M.; Gudnason, Vilmundur; Siscovick, David S.; Fox, Caroline S.; Köttgen, Anna

2010-01-01

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ∼2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5×10−8) or suggestive associations (p<4×10−7) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4×10−7. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels. PMID:20700443

Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

PubMed Central

Debette, Stéphanie; Ibrahim Verbaas, Carla A.; Bressler, Jan; Schuur, Maaike; Smith, Albert; Bis, Joshua C.; Davies, Gail; Wolf, Christiane; Gudnason, Vilmundur; Chibnik, Lori B.; Yang, Qiong; deStefano, Anita L.; de Quervain, Dominique J.F.; Srikanth, Velandai; Lahti, Jari; Grabe, Hans J.; Smith, Jennifer A.; Priebe, Lutz; Yu, Lei; Karbalai, Nazanin; Hayward, Caroline; Wilson, James F.; Campbell, Harry; Petrovic, Katja; Fornage, Myriam; Chauhan, Ganesh; Yeo, Robin; Boxall, Ruth; Becker, James; Stegle, Oliver; Mather, Karen A.; Chouraki, Vincent; Sun, Qi; Rose, Lynda M.; Resnick, Susan; Oldmeadow, Christopher; Kirin, Mirna; Wright, Alan F.; Jonsdottir, Maria K.; Au, Rhoda; Becker, Albert; Amin, Najaf; Nalls, Mike A.; Turner, Stephen T.; Kardia, Sharon L.R.; Oostra, Ben; Windham, Gwen; Coker, Laura H.; Zhao, Wei; Knopman, David S.; Heiss, Gerardo; Griswold, Michael E.; Gottesman, Rebecca F.; Vitart, Veronique; Hastie, Nicholas D.; Zgaga, Lina; Rudan, Igor; Polasek, Ozren; Holliday, Elizabeth G.; Schofield, Peter; Choi, Seung Hoan; Tanaka, Toshiko; An, Yang; Perry, Rodney T.; Kennedy, Richard E.; Sale, Michèle M.; Wang, Jing; Wadley, Virginia G.; Liewald, David C.; Ridker, Paul M.; Gow, Alan J.; Pattie, Alison; Starr, John M.; Porteous, David; Liu, Xuan; Thomson, Russell; Armstrong, Nicola J.; Eiriksdottir, Gudny; Assareh, Arezoo A.; Kochan, Nicole A.; Widen, Elisabeth; Palotie, Aarno; Hsieh, Yi-Chen; Eriksson, Johan G.; Vogler, Christian; van Swieten, John C.; Shulman, Joshua M.; Beiser, Alexa; Rotter, Jerome; Schmidt, Carsten O.; Hoffmann, Wolfgang; Nöthen, Markus M.; Ferrucci, Luigi; Attia, John; Uitterlinden, Andre G.; Amouyel, Philippe; Dartigues, Jean-François; Amieva, Hélène; Räikkönen, Katri; Garcia, Melissa; Wolf, Philip A.; Hofman, Albert; Longstreth, W.T.; Psaty, Bruce M.; Boerwinkle, Eric; DeJager, Philip L.; Sachdev, Perminder S.; Schmidt, Reinhold; Breteler, Monique M.B.; Teumer, Alexander; Lopez, Oscar L.; Cichon, Sven; Chasman, Daniel I.; Grodstein, Francine; Müller-Myhsok, Bertram; Tzourio, Christophe; Papassotiropoulos, Andreas; Bennett, David A.; Ikram, Arfan M.; Deary, Ian J.; van Duijn, Cornelia M.; Launer, Lenore; Fitzpatrick, Annette L.; Seshadri, Sudha; Mosley, Thomas H.

2015-01-01

BACKGROUND Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. METHODS We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia-and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10−6) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. RESULTS rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10−10) and replication cohorts (p = 5.65 × 10−8). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10−8, and rs6813517 [SPOCK3], p = 2.58 × 10−8) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. CONCLUSIONS This largest study to date exploring the genetics of memory function in ~ 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways. PMID:25648963

Admixture Mapping of African-American Women in the AMBER Consortium Identifies New Loci for Breast Cancer and Estrogen-Receptor Subtypes.

PubMed

Ruiz-Narváez, Edward A; Sucheston-Campbell, Lara; Bensen, Jeannette T; Yao, Song; Haddad, Stephen; Haiman, Christopher A; Bandera, Elisa V; John, Esther M; Bernstein, Leslie; Hu, Jennifer J; Ziegler, Regina G; Deming, Sandra L; Olshan, Andrew F; Ambrosone, Christine B; Palmer, Julie R; Lunetta, Kathryn L

2016-01-01

Recent genetic admixture coupled with striking differences in incidence of estrogen receptor (ER) breast cancer subtypes, as well as severity, between women of African and European ancestry, provides an excellent rationale for performing admixture mapping in African American women with breast cancer risk. We performed the largest breast cancer admixture mapping study with in African American women to identify novel genomic regions associated with the disease. We conducted a genome-wide admixture scan using 2,624 autosomal ancestry informative markers (AIMs) in 3,629 breast cancer cases (including 1,968 ER-positive, 1093 ER-negative, and 601 triple-negative) and 4,658 controls from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a collaborative study of four large geographically different epidemiological studies of breast cancer in African American women. We used an independent case-control study to test for SNP association in regions with genome-wide significant admixture signals. We found two novel genome-wide significant regions of excess African ancestry, 4p16.1 and 17q25.1, associated with ER-positive breast cancer. Two regions known to harbor breast cancer variants, 10q26 and 11q13, were also identified with excess of African ancestry. Fine-mapping of the identified genome-wide significant regions suggests the presence of significant genetic associations with ER-positive breast cancer in 4p16.1 and 11q13. In summary, we identified three novel genomic regions associated with breast cancer risk by ER status, suggesting that additional previously unidentified variants may contribute to the racial differences in breast cancer risk in the African American population.

GWAS and admixture mapping identify different asthma-associated loci in Latinos: The GALA II Study

PubMed Central

Galanter, Joshua M; Gignoux, Christopher R; Torgerson, Dara G; Roth, Lindsey A; Eng, Celeste; Oh, Sam S; Nguyen, Elizabeth A; Drake, Katherine A; Huntsman, Scott; Hu, Donglei; Sen, Saunak; Davis, Adam; Farber, Harold J.; Avila, Pedro C.; Brigino-Buenaventura, Emerita; LeNoir, Michael A.; Meade, Kelley; Serebrisky, Denise; Borrell, Luisa N; Rodríguez-Cintrón, William; Estrada, Andres Moreno; Mendoza, Karla Sandoval; Winkler, Cheryl A.; Klitz, William; Romieu, Isabelle; London, Stephanie J.; Gilliland, Frank; Martinez, Fernando; Bustamante, Carlos; Williams, L Keoki; Kumar, Rajesh; Rodríguez-Santana, José R.; Burchard, and Esteban G.

2013-01-01

Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations and replication of positive associations has been inconsistent. Objective To identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1,893) and healthy controls (n = 1,881) were recruited from five sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest p-value: rs2523924, p < 5 × 10−6). This association replicates in a meta-analysis of the EVE Asthma Consortium (p = 0.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between the 17q21 asthma in Latinos (IKZF3, lowest p-value: rs90792, OR: 0.67, 95% CI 0.61 – 0.75, p = 6 × 10−13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, while genome-wide association confirms the previously identified locus on 17q21. PMID:24406073

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

PubMed

Klein, Alison P; Wolpin, Brian M; Risch, Harvey A; Stolzenberg-Solomon, Rachael Z; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J; Hoskins, Jason W; Jermusyk, Ashley; Zhong, Jun; Chen, Fei; Albanes, Demetrius; Andreotti, Gabriella; Arslan, Alan A; Babic, Ana; Bamlet, William R; Beane-Freeman, Laura; Berndt, Sonja I; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G; Chung, Charles C; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J Michael; Gazouli, Maria; Giles, Graham G; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Jacobs, Eric J; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H; Kupcinskas, Juozas; Kurtz, Robert J; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T; Lee, I-Min; LeMarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E; Neoptolemos, John P; Oberg, Ann L; Olson, Sara H; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D; Tobias, Geoffrey S; Van Den Eeden, Stephen K; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Obazee, Ofure; Petersen, Gloria M; Amundadottir, Laufey T

2018-02-08

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10 -8 ). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10 -14 ), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10 -10 ), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10 -8 ), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10 -8 ). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

32 CFR 37.515 - Must I do anything additional to determine the qualification of a consortium?

Code of Federal Regulations, 2010 CFR

2010-07-01

... SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business... relationship is essential to increase the research project's chances of success. (b) The collaboration... things, the consortium's: (1) Management structure. (2) Method of making payments to consortium members...

Development and Applications of a Bovine 50,000 SNP Chip

USDA-ARS?s Scientific Manuscript database

To develop an Illumina iSelect high density single nucleotide polymorphism (SNP) assay for cattle, the collaborative iBMC (Illumina, USDA ARS Beltsville, University of Missouri, USDA ARS Clay Center) Consortium first performed a de novo SNP discovery project in which genomic reduced representation l...

Data Release: DNA barcodes of plant species collected for the Global Genome Initiative for Gardens Program, National Museum of Natural History, Smithsonian Institution

PubMed Central

Zúñiga, Jose D.; Gostel, Morgan R.; Mulcahy, Daniel G.; Barker, Katharine; Asia Hill; Sedaghatpour, Maryam; Vo, Samantha Q.; Funk, Vicki A.; Coddington, Jonathan A.

2017-01-01

Abstract The Global Genome Initiative has sequenced and released 1961 DNA barcodes for genetic samples obtained as part of the Global Genome Initiative for Gardens Program. The dataset includes barcodes for 29 plant families and 309 genera that did not have sequences flagged as barcodes in GenBank and sequences from officially recognized barcoding genetic markers meet the data standard of the Consortium for the Barcode of Life. The genetic samples were deposited in the Smithsonian Institution’s National Museum of Natural History Biorepository and their records were made public through the Global Genome Biodiversity Network’s portal. The DNA barcodes are now available on GenBank. PMID:29118648

Retirement Plan Consortium Structures for K-12

ERIC Educational Resources Information Center

Kevin, John

2012-01-01

As school districts continue to seek administrative efficiencies and cost reductions in the wake of severe budget pressures, the resources they devote to creating or expanding retirement plan consortia is increasing. Understanding how to structure a retirement plan consortium is paramount to successfully achieving the many objectives of…

Accurate and reproducible functional maps in 127 human cell types via 2D genome segmentation

PubMed Central

Hardison, Ross C.

2017-01-01

Abstract The Roadmap Epigenomics Consortium has published whole-genome functional annotation maps in 127 human cell types by integrating data from studies of multiple epigenetic marks. These maps have been widely used for studying gene regulation in cell type-specific contexts and predicting the functional impact of DNA mutations on disease. Here, we present a new map of functional elements produced by applying a method called IDEAS on the same data. The method has several unique advantages and outperforms existing methods, including that used by the Roadmap Epigenomics Consortium. Using five categories of independent experimental datasets, we compared the IDEAS and Roadmap Epigenomics maps. While the overall concordance between the two maps is high, the maps differ substantially in the prediction details and in their consistency of annotation of a given genomic position across cell types. The annotation from IDEAS is uniformly more accurate than the Roadmap Epigenomics annotation and the improvement is substantial based on several criteria. We further introduce a pipeline that improves the reproducibility of functional annotation maps. Thus, we provide a high-quality map of candidate functional regions across 127 human cell types and compare the quality of different annotation methods in order to facilitate biomedical research in epigenomics. PMID:28973456

Using ancestry-informative markers to identify fine structure across 15 populations of European origin.

PubMed

Huckins, Laura M; Boraska, Vesna; Franklin, Christopher S; Floyd, James A B; Southam, Lorraine; Sullivan, Patrick F; Bulik, Cynthia M; Collier, David A; Tyler-Smith, Chris; Zeggini, Eleftheria; Tachmazidou, Ioanna

2014-10-01

The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia.

HCMI Organization | Office of Cancer Genomics

Cancer.gov

Consortium The Human Cancer Models Initiative (HCMI) was created and funded by the US National Cancer Institute, Cancer Research UK, the foundation Hubrecht Organoid Technology, and the Wellcome Sanger Institute. Together, these organizations develop policy and make programmatic decisions to contribute to the function of the HCMI. National Cancer Institute

NASA Systems Engineering Research Consortium: Defining the Path to Elegance in Systems

NASA Technical Reports Server (NTRS)

Watson, Michael D.; Farrington, Phillip A.

2016-01-01

The NASA Systems Engineering Research Consortium was formed at the end of 2010 to study the approaches to producing elegant systems on a consistent basis. This has been a transformative study looking at the engineering and organizational basis of systems engineering. The consortium has engaged in a variety of research topics to determine the path to elegant systems. In the second year of the consortium, a systems engineering framework emerged which structured the approach to systems engineering and guided our research. This led in the third year to set of systems engineering postulates that the consortium is continuing to refine. The consortium has conducted several research projects that have contributed significantly to the understanding of systems engineering. The consortium has surveyed the application of the NASA 17 systems engineering processes, explored the physics and statistics of systems integration, and considered organizational aspects of systems engineering discipline integration. The systems integration methods have included system exergy analysis, Akaike Information Criteria (AIC), State Variable Analysis, Multidisciplinary Coupling Analysis (MCA), Multidisciplinary Design Optimization (MDO), System Cost Modelling, System Robustness, and Value Modelling. Organizational studies have included the variability of processes in change evaluations, margin management within the organization, information theory of board structures, social categorization of unintended consequences, and initial looks at applying cognitive science to systems engineering. Consortium members have also studied the bidirectional influence of policy and law with systems engineering.

NASA Systems Engineering Research Consortium: Defining the Path to Elegance in Systems

NASA Technical Reports Server (NTRS)

Watson, Michael D.; Farrington, Phillip A.

2016-01-01

The NASA Systems Engineering Research Consortium was formed at the end of 2010 to study the approaches to producing elegant systems on a consistent basis. This has been a transformative study looking at the engineering and organizational basis of systems engineering. The consortium has engaged in a variety of research topics to determine the path to elegant systems. In the second year of the consortium, a systems engineering framework emerged which structured the approach to systems engineering and guided our research. This led in the third year to set of systems engineering postulates that the consortium is continuing to refine. The consortium has conducted several research projects that have contributed significantly to the understanding of systems engineering. The consortium has surveyed the application of the NASA 17 systems engineering processes, explored the physics and statistics of systems integration, and considered organizational aspects of systems engineering discipline integration. The systems integration methods have included system energy analysis, Akaike Information Criteria (AIC), State Variable Analysis, Multidisciplinary Coupling Analysis (MCA), Multidisciplinary Design Optimization (MDO), System Cost Modeling, System Robustness, and Value Modeling. Organizational studies have included the variability of processes in change evaluations, margin management within the organization, information theory of board structures, social categorization of unintended consequences, and initial looks at applying cognitive science to systems engineering. Consortium members have also studied the bidirectional influence of policy and law with systems engineering.

Recovery and characterization of a Citrus clementina Hort. ex Tan. 'Clemenules' haploid plant selected to establish the reference whole Citrus genome sequence.

PubMed

Aleza, Pablo; Juárez, José; Hernández, María; Pina, José A; Ollitrault, Patrick; Navarro, Luis

2009-08-22

In recent years, the development of structural genomics has generated a growing interest in obtaining haploid plants. The use of homozygous lines presents a significant advantage for the accomplishment of sequencing projects. Commercial citrus species are characterized by high heterozygosity, making it difficult to assemble large genome sequences. Thus, the International Citrus Genomic Consortium (ICGC) decided to establish a reference whole citrus genome sequence from a homozygous plant. Due to the existence of important molecular resources and previous success in obtaining haploid clementine plants, haploid clementine was selected as the target for the implementation of the reference whole genome citrus sequence. To obtain haploid clementine lines we used the technique of in situ gynogenesis induced by irradiated pollen. Flow cytometry, chromosome counts and SSR marker (Simple Sequence Repeats) analysis facilitated the identification of six different haploid lines (2n = x = 9), one aneuploid line (2n = 2x+4 = 22) and one doubled haploid plant (2n = 2x = 18) of 'Clemenules' clementine. One of the haploids, obtained directly from an original haploid embryo, grew vigorously and produced flowers after four years. This is the first haploid plant of clementine that has bloomed and we have, for the first time, characterized the histology of haploid and diploid flowers of clementine. Additionally a double haploid plant was obtained spontaneously from this haploid line. The first haploid plant of 'Clemenules' clementine produced directly by germination of a haploid embryo, which grew vigorously and produced flowers, has been obtained in this work. This haploid line has been selected and it is being used by the ICGC to establish the reference sequence of the nuclear genome of citrus.

Ayurgenomics for stratified medicine: TRISUTRA consortium initiative across ethnically and geographically diverse Indian populations.

PubMed

Prasher, Bhavana; Varma, Binuja; Kumar, Arvind; Khuntia, Bharat Krushna; Pandey, Rajesh; Narang, Ankita; Tiwari, Pradeep; Kutum, Rintu; Guin, Debleena; Kukreti, Ritushree; Dash, Debasis; Mukerji, Mitali

2017-02-02

Genetic differences in the target proteins, metabolizing enzymes and transporters that contribute to inter-individual differences in drug response are not integrated in contemporary drug development programs. Ayurveda, that has propelled many drug discovery programs albeit for the search of new chemical entities incorporates inter-individual variability "Prakriti" in development and administration of drug in an individualized manner. Prakriti of an individual largely determines responsiveness to external environment including drugs as well as susceptibility to diseases. Prakriti has also been shown to have molecular and genomic correlates. We highlight how integration of Prakriti concepts can augment the efficiency of drug discovery and development programs through a unique initiative of Ayurgenomics TRISUTRA consortium. Five aspects that have been carried out are (1) analysis of variability in FDA approved pharmacogenomics genes/SNPs in exomes of 72 healthy individuals including predominant Prakriti types and matched controls from a North Indian Indo-European cohort (2) establishment of a consortium network and development of five genetically homogeneous cohorts from diverse ethnic and geo-climatic background (3) identification of parameters and development of uniform standard protocols for objective assessment of Prakriti types (4) development of protocols for Prakriti evaluation and its application in more than 7500 individuals in the five cohorts (5) Development of data and sample repository and integrative omics pipelines for identification of genomic correlates. Highlight of the study are (1) Exome sequencing revealed significant differences between Prakriti types in 28 SNPs of 11 FDA approved genes of pharmacogenomics relevance viz. CYP2C19, CYP2B6, ESR1, F2, PGR, HLA-B, HLA-DQA1, HLA-DRB1, LDLR, CFTR, CPS1. These variations are polymorphic in diverse Indian and world populations included in 1000 genomes project. (2) Based on the phenotypic attributes of Prakriti we identified anthropometry for anatomical features, biophysical parameters for skin types, HRV for autonomic function tests, spirometry for vital capacity and gustometry for taste thresholds as objective parameters. (3) Comparison of Prakriti phenotypes across different ethnic, age and gender groups led to identification of invariant features as well as some that require weighted considerations across the cohorts. Considering the molecular and genomics differences underlying Prakriti and relevance in disease pharmacogenomics studies, this novel integrative platform would help in identification of differently susceptible and drug responsive population. Additionally, integrated analysis of phenomic and genomic variations would not only allow identification of clinical and genomic markers of Prakriti for application in personalized medicine but also its integration in drug discovery and development programs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Human genetics and genomics a decade after the release of the draft sequence of the human genome.

PubMed

Naidoo, Nasheen; Pawitan, Yudi; Soong, Richie; Cooper, David N; Ku, Chee-Seng

2011-10-01

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade.

Human genetics and genomics a decade after the release of the draft sequence of the human genome

PubMed Central

2011-01-01

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade. PMID:22155605

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

PubMed

Shah, Rupal L; Li, Qing; Zhao, Wanting; Tedja, Milly S; Tideman, J Willem L; Khawaja, Anthony P; Fan, Qiao; Yazar, Seyhan; Williams, Katie M; Verhoeven, Virginie J M; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W V; Hysi, Pirro G; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R; Jonas, Jost B; Mitchell, Paul; Hammond, Christopher J; Höhn, René; Baird, Paul N; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C W; Guggenheim, Jeremy A; Bailey-Wilson, Joan E

2018-01-01

To identify genes and genetic markers associated with corneal astigmatism. A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha ( PDGFRA ) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10 -9 . No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 ( CLDN7 ), acid phosphatase 2, lysosomal ( ACP2 ), and TNF alpha-induced protein 8 like 3 ( TNFAIP8L3 ). In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7 , ACP2 , and TNFAIP8L3 , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

PubMed

Trampush, J W; Yang, M L Z; Yu, J; Knowles, E; Davies, G; Liewald, D C; Starr, J M; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I; DeRosse, P; Lundervold, A J; Steen, V M; Espeseth, T; Räikkönen, K; Widen, E; Palotie, A; Eriksson, J G; Giegling, I; Konte, B; Roussos, P; Giakoumaki, S; Burdick, K E; Payton, A; Ollier, W; Horan, M; Chiba-Falek, O; Attix, D K; Need, A C; Cirulli, E T; Voineskos, A N; Stefanis, N C; Avramopoulos, D; Hatzimanolis, A; Arking, D E; Smyrnis, N; Bilder, R M; Freimer, N A; Cannon, T D; London, E; Poldrack, R A; Sabb, F W; Congdon, E; Conley, E D; Scult, M A; Dickinson, D; Straub, R E; Donohoe, G; Morris, D; Corvin, A; Gill, M; Hariri, A R; Weinberger, D R; Pendleton, N; Bitsios, P; Rujescu, D; Lahti, J; Le Hellard, S; Keller, M C; Andreassen, O A; Deary, I J; Glahn, D C; Malhotra, A K; Lencz, T

2017-03-01

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10 -8 ). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium

PubMed Central

Trampush, J W; Yang, M L Z; Yu, J; Knowles, E; Davies, G; Liewald, D C; Starr, J M; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I; DeRosse, P; Lundervold, A J; Steen, V M; Espeseth, T; Räikkönen, K; Widen, E; Palotie, A; Eriksson, J G; Giegling, I; Konte, B; Roussos, P; Giakoumaki, S; Burdick, K E; Payton, A; Ollier, W; Horan, M; Chiba-Falek, O; Attix, D K; Need, A C; Cirulli, E T; Voineskos, A N; Stefanis, N C; Avramopoulos, D; Hatzimanolis, A; Arking, D E; Smyrnis, N; Bilder, R M; Freimer, N A; Cannon, T D; London, E; Poldrack, R A; Sabb, F W; Congdon, E; Conley, E D; Scult, M A; Dickinson, D; Straub, R E; Donohoe, G; Morris, D; Corvin, A; Gill, M; Hariri, A R; Weinberger, D R; Pendleton, N; Bitsios, P; Rujescu, D; Lahti, J; Le Hellard, S; Keller, M C; Andreassen, O A; Deary, I J; Glahn, D C; Malhotra, A K; Lencz, T

2017-01-01

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10−8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness. PMID:28093568

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Paediatric Cohorts

PubMed Central

Groen-Blokhuis, Maria M.; Pourcain, Beate St.; Greven, Corina U.; Pappa, Irene; Tiesler, Carla M.T.; Ang, Wei; Nolte, Ilja M.; Vilor-Tejedor, Natalia; Bacelis, Jonas; Ebejer, Jane L.; Zhao, Huiying; Davies, Gareth E.; Ehli, Erik A.; Evans, David M.; Fedko, Iryna O.; Guxens, Mònica; Hottenga, Jouke-Jan; Hudziak, James J.; Jugessur, Astanand; Kemp, John P.; Krapohl, Eva; Martin, Nicholas G.; Murcia, Mario; Myhre, Ronny; Ormel, Johan; Ring, Susan M.; Standl, Marie; Stergiakouli, Evie; Stoltenberg, Camilla; Thiering, Elisabeth; Timpson, Nicholas J.; Trzaskowski, Maciej; van der Most, Peter J.; Wang, Carol; Nyholt, Dale R.; Medland, Sarah E.; Neale, Benjamin; Jacobsson, Bo; Sunyer, Jordi; Hartman, Catharina A.; Whitehouse, Andrew J.O.; Pennell, Craig E.; Heinrich, Joachim; Plomin, Robert; Smith, George Davey; Tiemeier, Henning; Posthuma, Danielle; Boomsma, Dorret I.

2016-01-01

Objective To elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (< 13 years) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46×10-6 and 2.66×10-6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and improve statistical power for identifying genetic variants. PMID:27663945

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.

PubMed

Horikoshi, Momoko; Mӓgi, Reedik; van de Bunt, Martijn; Surakka, Ida; Sarin, Antti-Pekka; Mahajan, Anubha; Marullo, Letizia; Thorleifsson, Gudmar; Hӓgg, Sara; Hottenga, Jouke-Jan; Ladenvall, Claes; Ried, Janina S; Winkler, Thomas W; Willems, Sara M; Pervjakova, Natalia; Esko, Tõnu; Beekman, Marian; Nelson, Christopher P; Willenborg, Christina; Wiltshire, Steven; Ferreira, Teresa; Fernandez, Juan; Gaulton, Kyle J; Steinthorsdottir, Valgerdur; Hamsten, Anders; Magnusson, Patrik K E; Willemsen, Gonneke; Milaneschi, Yuri; Robertson, Neil R; Groves, Christopher J; Bennett, Amanda J; Lehtimӓki, Terho; Viikari, Jorma S; Rung, Johan; Lyssenko, Valeriya; Perola, Markus; Heid, Iris M; Herder, Christian; Grallert, Harald; Müller-Nurasyid, Martina; Roden, Michael; Hypponen, Elina; Isaacs, Aaron; van Leeuwen, Elisabeth M; Karssen, Lennart C; Mihailov, Evelin; Houwing-Duistermaat, Jeanine J; de Craen, Anton J M; Deelen, Joris; Havulinna, Aki S; Blades, Matthew; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Kaprio, Jaakko; Tobin, Martin D; Samani, Nilesh J; Lind, Lars; Salomaa, Veikko; Lindgren, Cecilia M; Slagboom, P Eline; Metspalu, Andres; van Duijn, Cornelia M; Eriksson, Johan G; Peters, Annette; Gieger, Christian; Jula, Antti; Groop, Leif; Raitakari, Olli T; Power, Chris; Penninx, Brenda W J H; de Geus, Eco; Smit, Johannes H; Boomsma, Dorret I; Pedersen, Nancy L; Ingelsson, Erik; Thorsteinsdottir, Unnur; Stefansson, Kari; Ripatti, Samuli; Prokopenko, Inga; McCarthy, Mark I; Morris, Andrew P

2015-07-01

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.

Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation

PubMed Central

van de Bunt, Martijn; Surakka, Ida; Sarin, Antti-Pekka; Mahajan, Anubha; Marullo, Letizia; Thorleifsson, Gudmar; Hӓgg, Sara; Hottenga, Jouke-Jan; Ladenvall, Claes; Ried, Janina S.; Winkler, Thomas W.; Willems, Sara M.; Pervjakova, Natalia; Esko, Tõnu; Beekman, Marian; Nelson, Christopher P.; Willenborg, Christina; Ferreira, Teresa; Fernandez, Juan; Gaulton, Kyle J.; Steinthorsdottir, Valgerdur; Hamsten, Anders; Magnusson, Patrik K. E.; Willemsen, Gonneke; Milaneschi, Yuri; Robertson, Neil R.; Groves, Christopher J.; Bennett, Amanda J.; Lehtimӓki, Terho; Viikari, Jorma S.; Rung, Johan; Lyssenko, Valeriya; Perola, Markus; Heid, Iris M.; Herder, Christian; Grallert, Harald; Müller-Nurasyid, Martina; Roden, Michael; Hypponen, Elina; Isaacs, Aaron; van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Mihailov, Evelin; Houwing-Duistermaat, Jeanine J.; de Craen, Anton J. M.; Deelen, Joris; Havulinna, Aki S.; Blades, Matthew; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Kaprio, Jaakko; Tobin, Martin D.; Samani, Nilesh J.; Lind, Lars; Salomaa, Veikko; Lindgren, Cecilia M.; Slagboom, P. Eline; Metspalu, Andres; van Duijn, Cornelia M.; Eriksson, Johan G.; Peters, Annette; Gieger, Christian; Jula, Antti; Groop, Leif; Raitakari, Olli T.; Power, Chris; Penninx, Brenda W. J. H.; de Geus, Eco; Smit, Johannes H.; Boomsma, Dorret I.; Pedersen, Nancy L.; Ingelsson, Erik; Thorsteinsdottir, Unnur; Stefansson, Kari; Ripatti, Samuli; Prokopenko, Inga; McCarthy, Mark I.; Morris, Andrew P.

2015-01-01

Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated. PMID:26132169

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

PubMed Central

Bjelland, Douglas W.; Howrigan, Daniel P.; Abdellaoui, Abdel; Breen, Gerome; Borglum, Anders; Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Genovese, Giulio; Heilmann-Heimbach, Stefanie; Hoffman, Per; Maier, Wolfgang; Mattheisen, Manuel; Morris, Derek; Mowry, Bryan; Müller-Mhysok, Betram; Neale, Benjamin; Nenadic, Igor; Nöthen, Markus M.; O’Dushlaine, Colm; Rietschel, Marcella; Ruderfer, Douglas M.; Rujescu, Dan; Schulze, Thomas G.; Simonson, Matthew A.; Stahl, Eli; Strohmaier, Jana; Sullivan, Patrick F.; Keller, Matthew C.

2016-01-01

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest. PMID:27792727

Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic Consortium

PubMed Central

Ponce-de-Leon, Miguel; Tamarit, Daniel; Calle-Espinosa, Jorge; Mori, Matteo; Latorre, Amparo; Montero, Francisco; Pereto, Juli

2017-01-01

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism—which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca. Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid iBSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with iBSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions. PMID:29213256

Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic Consortium.

PubMed

Ponce-de-Leon, Miguel; Tamarit, Daniel; Calle-Espinosa, Jorge; Mori, Matteo; Latorre, Amparo; Montero, Francisco; Pereto, Juli

2017-01-01

Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism-which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca . Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid i BSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with i BSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions.

Stable carbon isotope fractionation of chlorinated ethenes by a microbial consortium containing multiple dechlorinating genes.

PubMed

Liu, Na; Ding, Longzhen; Li, Haijun; Zhang, Pengpeng; Zheng, Jixing; Weng, Chih-Huang

2018-08-01

The study aimed to determine the possible contribution of specific growth conditions and community structures to variable carbon enrichment factors (Ɛ- carbon ) values for the degradation of chlorinated ethenes (CEs) by a bacterial consortium with multiple dechlorinating genes. Ɛ- carbon values for trichloroethylene, cis-1,2-dichloroethylene, and vinyl chloride were -7.24% ± 0.59%, -14.6% ± 1.71%, and -21.1% ± 1.14%, respectively, during their degradation by a microbial consortium containing multiple dechlorinating genes including tceA and vcrA. The Ɛ- carbon values of all CEs were not greatly affected by changes in growth conditions and community structures, which directly or indirectly affected reductive dechlorination of CEs by this consortium. Stability analysis provided evidence that the presence of multiple dechlorinating genes within a microbial consortium had little effect on carbon isotope fractionation, as long as the genes have definite, non-overlapping functions. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Syst-OMICS Approach to Ensuring Food Safety and Reducing the Economic Burden of Salmonellosis.

PubMed

Emond-Rheault, Jean-Guillaume; Jeukens, Julie; Freschi, Luca; Kukavica-Ibrulj, Irena; Boyle, Brian; Dupont, Marie-Josée; Colavecchio, Anna; Barrere, Virginie; Cadieux, Brigitte; Arya, Gitanjali; Bekal, Sadjia; Berry, Chrystal; Burnett, Elton; Cavestri, Camille; Chapin, Travis K; Crouse, Alanna; Daigle, France; Danyluk, Michelle D; Delaquis, Pascal; Dewar, Ken; Doualla-Bell, Florence; Fliss, Ismail; Fong, Karen; Fournier, Eric; Franz, Eelco; Garduno, Rafael; Gill, Alexander; Gruenheid, Samantha; Harris, Linda; Huang, Carol B; Huang, Hongsheng; Johnson, Roger; Joly, Yann; Kerhoas, Maud; Kong, Nguyet; Lapointe, Gisèle; Larivière, Line; Loignon, Stéphanie; Malo, Danielle; Moineau, Sylvain; Mottawea, Walid; Mukhopadhyay, Kakali; Nadon, Céline; Nash, John; Ngueng Feze, Ida; Ogunremi, Dele; Perets, Ann; Pilar, Ana V; Reimer, Aleisha R; Robertson, James; Rohde, John; Sanderson, Kenneth E; Song, Lingqiao; Stephan, Roger; Tamber, Sandeep; Thomassin, Paul; Tremblay, Denise; Usongo, Valentine; Vincent, Caroline; Wang, Siyun; Weadge, Joel T; Wiedmann, Martin; Wijnands, Lucas; Wilson, Emily D; Wittum, Thomas; Yoshida, Catherine; Youfsi, Khadija; Zhu, Lei; Weimer, Bart C; Goodridge, Lawrence; Levesque, Roger C

2017-01-01

The Salmonella Syst-OMICS consortium is sequencing 4,500 Salmonella genomes and building an analysis pipeline for the study of Salmonella genome evolution, antibiotic resistance and virulence genes. Metadata, including phenotypic as well as genomic data, for isolates of the collection are provided through the Salmonella Foodborne Syst-OMICS database (SalFoS), at https://salfos.ibis.ulaval.ca/. Here, we present our strategy and the analysis of the first 3,377 genomes. Our data will be used to draw potential links between strains found in fresh produce, humans, animals and the environment. The ultimate goals are to understand how Salmonella evolves over time, improve the accuracy of diagnostic methods, develop control methods in the field, and identify prognostic markers for evidence-based decisions in epidemiology and surveillance.

Human genetics: international projects and personalized medicine.

PubMed

Apellaniz-Ruiz, Maria; Gallego, Cristina; Ruiz-Pinto, Sara; Carracedo, Angel; Rodríguez-Antona, Cristina

2016-03-01

In this article, we present the progress driven by the recent technological advances and new revolutionary massive sequencing technologies in the field of human genetics. We discuss this knowledge in relation with drug response prediction, from the germline genetic variation compiled in the 1000 Genomes Project or in the Genotype-Tissue Expression project, to the phenome-genome archives, the international cancer projects, such as The Cancer Genome Atlas or the International Cancer Genome Consortium, and the epigenetic variation and its influence in gene expression, including the regulation of drug metabolism. This review is based on the lectures presented by the speakers of the Symposium "Human Genetics: International Projects & New Technologies" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held on the 20th and 21st of April 2015.

The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas.

PubMed

Ecker, Joseph R; Geschwind, Daniel H; Kriegstein, Arnold R; Ngai, John; Osten, Pavel; Polioudakis, Damon; Regev, Aviv; Sestan, Nenad; Wickersham, Ian R; Zeng, Hongkui

2017-11-01

A comprehensive characterization of neuronal cell types, their distributions, and patterns of connectivity is critical for understanding the properties of neural circuits and how they generate behaviors. Here we review the experiences of the BRAIN Initiative Cell Census Consortium, ten pilot projects funded by the U.S. BRAIN Initiative, in developing, validating, and scaling up emerging genomic and anatomical mapping technologies for creating a complete inventory of neuronal cell types and their connections in multiple species and during development. These projects lay the foundation for a larger and longer-term effort to generate whole-brain cell atlases in species including mice and humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis pipelines and packages for Infinium HumanMethylation450 BeadChip (450k) data.

PubMed

Morris, Tiffany J; Beck, Stephan

2015-01-15

The Illumina HumanMethylation450 BeadChip has become a popular platform for interrogating DNA methylation in epigenome-wide association studies (EWAS) and related projects as well as resource efforts such as the International Cancer Genome Consortium (ICGC) and the International Human Epigenome Consortium (IHEC). This has resulted in an exponential increase of 450k data in recent years and triggered the development of numerous integrated analysis pipelines and stand-alone packages. This review will introduce and discuss the currently most popular pipelines and packages and is particularly aimed at new 450k users. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

PubMed Central

Reus, L. M.; Shen, X.; Gibson, J.; Wigmore, E.; Ligthart, L.; Adams, M. J.; Davies, G.; Cox, S. R.; Hagenaars, S. P.; Bastin, M. E.; Deary, I. J.; Whalley, H. C.; McIntosh, A. M.

2017-01-01

Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data comprised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). The calculation of polygenic risk scores was based on genome-wide association study results generated by the Psychiatric Genomics Consortium. Our findings indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders. PMID:28186152

Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank.

PubMed

Reus, L M; Shen, X; Gibson, J; Wigmore, E; Ligthart, L; Adams, M J; Davies, G; Cox, S R; Hagenaars, S P; Bastin, M E; Deary, I J; Whalley, H C; McIntosh, A M

2017-02-10

Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data comprised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). The calculation of polygenic risk scores was based on genome-wide association study results generated by the Psychiatric Genomics Consortium. Our findings indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

PubMed

Vasan, Ramachandran S; Glazer, Nicole L; Felix, Janine F; Lieb, Wolfgang; Wild, Philipp S; Felix, Stephan B; Watzinger, Norbert; Larson, Martin G; Smith, Nicholas L; Dehghan, Abbas; Grosshennig, Anika; Schillert, Arne; Teumer, Alexander; Schmidt, Reinhold; Kathiresan, Sekar; Lumley, Thomas; Aulchenko, Yurii S; König, Inke R; Zeller, Tanja; Homuth, Georg; Struchalin, Maksim; Aragam, Jayashri; Bis, Joshua C; Rivadeneira, Fernando; Erdmann, Jeanette; Schnabel, Renate B; Dörr, Marcus; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J; Greiser, Karin Halina; Levy, Daniel; Haritunians, Talin; Deckers, Jaap W; Stritzke, Jan; Lackner, Karl J; Völker, Uwe; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; O'Donnell, Christopher J; Heckbert, Susan R; Stricker, Bruno H; Ziegler, Andreas; Reffelmann, Thorsten; Redfield, Margaret M; Werdan, Karl; Mitchell, Gary F; Rice, Kenneth; Arnett, Donna K; Hofman, Albert; Gottdiener, John S; Uitterlinden, Andre G; Meitinger, Thomas; Blettner, Maria; Friedrich, Nele; Wang, Thomas J; Psaty, Bruce M; van Duijn, Cornelia M; Wichmann, H-Erich; Munzel, Thomas F; Kroemer, Heyo K; Benjamin, Emelia J; Rotter, Jerome I; Witteman, Jacqueline C; Schunkert, Heribert; Schmidt, Helena; Völzke, Henry; Blankenberg, Stefan

2009-07-08

Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation.

PubMed

Keates, Tracy; Cooper, Christopher D O; Savitsky, Pavel; Allerston, Charles K; Phillips, Claire; Hammarström, Martin; Daga, Neha; Berridge, Georgina; Mahajan, Pravin; Burgess-Brown, Nicola A; Müller, Susanne; Gräslund, Susanne; Gileadi, Opher

2012-06-15

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome. Copyright © 2011 Elsevier B.V. All rights reserved.

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation

PubMed Central

Keates, Tracy; Cooper, Christopher D.O.; Savitsky, Pavel; Allerston, Charles K.; Phillips, Claire; Hammarström, Martin; Daga, Neha; Berridge, Georgina; Mahajan, Pravin; Burgess-Brown, Nicola A.; Müller, Susanne; Gräslund, Susanne; Gileadi, Opher

2012-01-01

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome. PMID:22027370

Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cells from the Progenitor Cell Biology Consortium.

PubMed

Salomonis, Nathan; Dexheimer, Phillip J; Omberg, Larsson; Schroll, Robin; Bush, Stacy; Huo, Jeffrey; Schriml, Lynn; Ho Sui, Shannan; Keddache, Mehdi; Mayhew, Christopher; Shanmukhappa, Shiva Kumar; Wells, James; Daily, Kenneth; Hubler, Shane; Wang, Yuliang; Zambidis, Elias; Margolin, Adam; Hide, Winston; Hatzopoulos, Antonis K; Malik, Punam; Cancelas, Jose A; Aronow, Bruce J; Lutzko, Carolyn

2016-07-12

The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources of variability and downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed comprehensive experimental and genomic analyses of 58 iPSC from ten laboratories generated using a variety of reprogramming genes, vectors, and cells. Associated global molecular characterization studies identified functionally informative correlations in gene expression, DNA methylation, and/or copy-number variation among key developmental and oncogenic regulators as a result of donor, sex, line stability, reprogramming technology, and cell of origin. Furthermore, X-chromosome inactivation in PSC produced highly correlated differences in teratoma-lineage staining and regulator expression upon differentiation. All experimental results, and raw, processed, and metadata from these analyses, including powerful tools, are interactively accessible from a new online portal at https://www.synapse.org to serve as a reusable resource for the stem cell community. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Biotechnological potential of microbial consortia and future perspectives.

PubMed

Bhatia, Shashi Kant; Bhatia, Ravi Kant; Choi, Yong-Keun; Kan, Eunsung; Kim, Yun-Gon; Yang, Yung-Hun

2018-05-15

Design of a microbial consortium is a newly emerging field that enables researchers to extend the frontiers of biotechnology from a pure culture to mixed cultures. A microbial consortium enables microbes to use a broad range of carbon sources. It provides microbes with robustness in response to environmental stress factors. Microbes in a consortium can perform complex functions that are impossible for a single organism. With advancement of technology, it is now possible to understand microbial interaction mechanism and construct consortia. Microbial consortia can be classified in terms of their construction, modes of interaction, and functions. Here we discuss different trends in the study of microbial functions and interactions, including single-cell genomics (SCG), microfluidics, fluorescent imaging, and membrane separation. Community profile studies using polymerase chain-reaction denaturing gradient gel electrophoresis (PCR-DGGE), amplified ribosomal DNA restriction analysis (ARDRA), and terminal restriction fragment-length polymorphism (T-RFLP) are also reviewed. We also provide a few examples of their possible applications in areas of biopolymers, bioenergy, biochemicals, and bioremediation.

Construction of a map-based reference genome sequence for barley, Hordeum vulgare L.

PubMed Central

Beier, Sebastian; Himmelbach, Axel; Colmsee, Christian; Zhang, Xiao-Qi; Barrero, Roberto A.; Zhang, Qisen; Li, Lin; Bayer, Micha; Bolser, Daniel; Taudien, Stefan; Groth, Marco; Felder, Marius; Hastie, Alex; Šimková, Hana; Staňková, Helena; Vrána, Jan; Chan, Saki; Muñoz-Amatriaín, María; Ounit, Rachid; Wanamaker, Steve; Schmutzer, Thomas; Aliyeva-Schnorr, Lala; Grasso, Stefano; Tanskanen, Jaakko; Sampath, Dharanya; Heavens, Darren; Cao, Sujie; Chapman, Brett; Dai, Fei; Han, Yong; Li, Hua; Li, Xuan; Lin, Chongyun; McCooke, John K.; Tan, Cong; Wang, Songbo; Yin, Shuya; Zhou, Gaofeng; Poland, Jesse A.; Bellgard, Matthew I.; Houben, Andreas; Doležel, Jaroslav; Ayling, Sarah; Lonardi, Stefano; Langridge, Peter; Muehlbauer, Gary J.; Kersey, Paul; Clark, Matthew D.; Caccamo, Mario; Schulman, Alan H.; Platzer, Matthias; Close, Timothy J.; Hansson, Mats; Zhang, Guoping; Braumann, Ilka; Li, Chengdao; Waugh, Robbie; Scholz, Uwe; Stein, Nils; Mascher, Martin

2017-01-01

Barley (Hordeum vulgare L.) is a cereal grass mainly used as animal fodder and raw material for the malting industry. The map-based reference genome sequence of barley cv. ‘Morex’ was constructed by the International Barley Genome Sequencing Consortium (IBSC) using hierarchical shotgun sequencing. Here, we report the experimental and computational procedures to (i) sequence and assemble more than 80,000 bacterial artificial chromosome (BAC) clones along the minimum tiling path of a genome-wide physical map, (ii) find and validate overlaps between adjacent BACs, (iii) construct 4,265 non-redundant sequence scaffolds representing clusters of overlapping BACs, and (iv) order and orient these BAC clusters along the seven barley chromosomes using positional information provided by dense genetic maps, an optical map and chromosome conformation capture sequencing (Hi-C). Integrative access to these sequence and mapping resources is provided by the barley genome explorer (BARLEX). PMID:28448065

Epigenetics, chromatin and genome organization: recent advances from the ENCODE project.

PubMed

Siggens, L; Ekwall, K

2014-09-01

The organization of the genome into functional units, such as enhancers and active or repressed promoters, is associated with distinct patterns of DNA and histone modifications. The Encyclopedia of DNA Elements (ENCODE) project has advanced our understanding of the principles of genome, epigenome and chromatin organization, identifying hundreds of thousands of potential regulatory regions and transcription factor binding sites. Part of the ENCODE consortium, GENCODE, has annotated the human genome with novel transcripts including new noncoding RNAs and pseudogenes, highlighting transcriptional complexity. Many disease variants identified in genome-wide association studies are located within putative enhancer regions defined by the ENCODE project. Understanding the principles of chromatin and epigenome organization will help to identify new disease mechanisms, biomarkers and drug targets, particularly as ongoing epigenome mapping projects generate data for primary human cell types that play important roles in disease. © 2014 The Association for the Publication of the Journal of Internal Medicine.

The eMERGE Network: a consortium of biorepositories linked to electronic medical records data for conducting genomic studies.

PubMed

McCarty, Catherine A; Chisholm, Rex L; Chute, Christopher G; Kullo, Iftikhar J; Jarvik, Gail P; Larson, Eric B; Li, Rongling; Masys, Daniel R; Ritchie, Marylyn D; Roden, Dan M; Struewing, Jeffery P; Wolf, Wendy A

2011-01-26

The eMERGE (electronic MEdical Records and GEnomics) Network is an NHGRI-supported consortium of five institutions to explore the utility of DNA repositories coupled to Electronic Medical Record (EMR) systems for advancing discovery in genome science. eMERGE also includes a special emphasis on the ethical, legal and social issues related to these endeavors. The five sites are supported by an Administrative Coordinating Center. Setting of network goals is initiated by working groups: (1) Genomics, (2) Informatics, and (3) Consent & Community Consultation, which also includes active participation by investigators outside the eMERGE funded sites, and (4) Return of Results Oversight Committee. The Steering Committee, comprised of site PIs and representatives and NHGRI staff, meet three times per year, once per year with the External Scientific Panel. The primary site-specific phenotypes for which samples have undergone genome-wide association study (GWAS) genotyping are cataract and HDL, dementia, electrocardiographic QRS duration, peripheral arterial disease, and type 2 diabetes. A GWAS is also being undertaken for resistant hypertension in ≈ 2,000 additional samples identified across the network sites, to be added to data available for samples already genotyped. Funded by ARRA supplements, secondary phenotypes have been added at all sites to leverage the genotyping data, and hypothyroidism is being analyzed as a cross-network phenotype. Results are being posted in dbGaP. Other key eMERGE activities include evaluation of the issues associated with cross-site deployment of common algorithms to identify cases and controls in EMRs, data privacy of genomic and clinically-derived data, developing approaches for large-scale meta-analysis of GWAS data across five sites, and a community consultation and consent initiative at each site. Plans are underway to expand the network in diversity of populations and incorporation of GWAS findings into clinical care. By combining advanced clinical informatics, genome science, and community consultation, eMERGE represents a first step in the development of data-driven approaches to incorporate genomic information into routine healthcare delivery.

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

PubMed Central

Wild, Philipp S.; Felix, Janine F.; Schillert, Arne; Chen, Ming-Huei; Leening, Maarten J.G.; Völker, Uwe; Großmann, Vera; Brody, Jennifer A.; Irvin, Marguerite R.; Shah, Sanjiv J.; Pramana, Setia; Lieb, Wolfgang; Schmidt, Reinhold; Stanton, Alice V.; Malzahn, Dörthe; Lyytikäinen, Leo-Pekka; Tiller, Daniel; Smith, J. Gustav; Di Tullio, Marco R.; Musani, Solomon K.; Morrison, Alanna C.; Pers, Tune H.; Morley, Michael; Kleber, Marcus E.; Aragam, Jayashri; Bis, Joshua C.; Bisping, Egbert; Broeckel, Ulrich; Cheng, Susan; Deckers, Jaap W.; Del Greco M, Fabiola; Edelmann, Frank; Fornage, Myriam; Franke, Lude; Friedrich, Nele; Harris, Tamara B.; Hofer, Edith; Hofman, Albert; Huang, Jie; Hughes, Alun D.; Kähönen, Mika; investigators, KNHI; Kruppa, Jochen; Lackner, Karl J.; Lannfelt, Lars; Laskowski, Rafael; Launer, Lenore J.; Lindgren, Cecilia M.; Loley, Christina; Mayet, Jamil; Medenwald, Daniel; Morris, Andrew P.; Müller, Christian; Müller-Nurasyid, Martina; Nappo, Stefania; Nilsson, Peter M.; Nuding, Sebastian; Nutile, Teresa; Peters, Annette; Pfeufer, Arne; Pietzner, Diana; Pramstaller, Peter P.; Raitakari, Olli T.; Rice, Kenneth M.; Rotter, Jerome I.; Ruohonen, Saku T.; Sacco, Ralph L.; Samdarshi, Tandaw E.; Sharp, Andrew S.P.; Shields, Denis C.; Sorice, Rossella; Sotoodehnia, Nona; Stricker, Bruno H.; Surendran, Praveen; Töglhofer, Anna M.; Uitterlinden, André G.; Völzke, Henry; Ziegler, Andreas; Münzel, Thomas; März, Winfried; Cappola, Thomas P.; Hirschhorn, Joel N.; Mitchell, Gary F.; Smith, Nicholas L.; Fox, Ervin R.; Dueker, Nicole D.; Jaddoe, Vincent W.V.; Melander, Olle; Lehtimäki, Terho; Ciullo, Marina; Hicks, Andrew A.; Lind, Lars; Gudnason, Vilmundur; Pieske, Burkert; Barron, Anthony J.; Zweiker, Robert; Schunkert, Heribert; Ingelsson, Erik; Liu, Kiang; Arnett, Donna K.; Psaty, Bruce M.; Blankenberg, Stefan; Larson, Martin G.; Felix, Stephan B.; Franco, Oscar H.; Zeller, Tanja; Vasan, Ramachandran S.; Dörr, Marcus

2017-01-01

BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING. For detailed information per study, see Acknowledgments. PMID:28394258

Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowers, Robert M.; Kyrpides, Nikos C.; Stepanauskas, Ramunas

The number of genomes from uncultivated microbes will soon surpass the number of isolate genomes in public databases (Hugenholtz, Skarshewski, & Parks, 2016). Technological advancements in high-throughput sequencing and assembly, including single-cell genomics and the computational extraction of genomes from metagenomes (GFMs), are largely responsible. Here we propose community standards for reporting the Minimum Information about a Single-Cell Genome (MIxS-SCG) and Minimum Information about Genomes extracted From Metagenomes (MIxS-GFM) specific for Bacteria and Archaea. The standards have been developed in the context of the International Genomics Standards Consortium (GSC) community (Field et al., 2014) and can be viewed as amore » supplement to other GSC checklists including the Minimum Information about a Genome Sequence (MIGS), Minimum information about a Metagenomic Sequence(s) (MIMS) (Field et al., 2008) and Minimum Information about a Marker Gene Sequence (MIMARKS) (P. Yilmaz et al., 2011). Community-wide acceptance of MIxS-SCG and MIxS-GFM for Bacteria and Archaea will enable broad comparative analyses of genomes from the majority of taxa that remain uncultivated, improving our understanding of microbial function, ecology, and evolution.« less

Radiation biology and oncology in the genomic era.

PubMed

Kerns, Sarah L; Chuang, Kuang-Hsiang; Hall, William; Werner, Zachary; Chen, Yuhchyau; Ostrer, Harry; West, Catharine; Rosenstein, Barry

2018-06-14

Radiobiology research is building the foundation for applying genomics in precision radiation oncology. Advances in high-throughput approaches will underpin increased understanding of radiosensitivity and the development of future predictive assays for clinical application. There is an established contribution of genetics as a risk factor for radiotherapy side effects. An individual's radiosensitivity is an inherited polygenic trait with an architecture that includes rare mutations in a few genes that confer large effects and common variants in many genes with small effects. Current thinking is that some will be tissue specific, and future tests will be tailored to the normal tissues at risk. The relationship between normal and tumor cell radiosensitivity is poorly understood. Data are emerging suggesting interplay between germline genetic variation and epigenetic modification with growing evidence that changes in DNA methylation regulate the radiosensitivity of cancer cells and histone acetyltransferase inhibitors have radiosensitizing effects. Changes in histone methylation can also impair DNA damage response signaling and alter radiosensitivity. An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics. To address challenges in harmonizing data from multiple cohorts, the consortium established the REQUITE project to collect standardized data and genotyping for ~5,000 patients. The collection of detailed dosimetric data is important to produce validated multivariable models. Continued efforts will identify new genes that impact on radiosensitivity to generate new knowledge on toxicity pathogenesis and tests to incorporate into the clinical decision-making process.

Legacy System Engineering, VPERC Consortium

DTIC Science & Technology

2009-09-01

REPORT Legacy System Engineering, VPERC Consortium, Final Report, University of Utah for Work Ending Joly 15, 2009. 14. ABSTRACT 16. SECURITY...Engineering, VPERC Consortium, Final Report, University of Utah for Work Ending Joly 15, 2009. Report Title ABSTRACT This paper is one of three...Sons, 1995. [3] Turner MJ, Clough RW, Martin HC, Topp LJ. “Stiffness and deflection analysis of complex structures.” Journal of the Aeronautical

Landscape of Conditional eQTL in Dorsolateral Prefrontal Cortex and Co-localization with Schizophrenia GWAS.

PubMed

Dobbyn, Amanda; Huckins, Laura M; Boocock, James; Sloofman, Laura G; Glicksberg, Benjamin S; Giambartolomei, Claudia; Hoffman, Gabriel E; Perumal, Thanneer M; Girdhar, Kiran; Jiang, Yan; Raj, Towfique; Ruderfer, Douglas M; Kramer, Robin S; Pinto, Dalila; Akbarian, Schahram; Roussos, Panos; Domenici, Enrico; Devlin, Bernie; Sklar, Pamela; Stahl, Eli A; Sieberts, Solveig K

2018-06-07

Causal genes and variants within genome-wide association study (GWAS) loci can be identified by integrating GWAS statistics with expression quantitative trait loci (eQTL) and determining which variants underlie both GWAS and eQTL signals. Most analyses, however, consider only the marginal eQTL signal, rather than dissect this signal into multiple conditionally independent signals for each gene. Here we show that analyzing conditional eQTL signatures, which could be important under specific cellular or temporal contexts, leads to improved fine mapping of GWAS associations. Using genotypes and gene expression levels from post-mortem human brain samples (n = 467) reported by the CommonMind Consortium (CMC), we find that conditional eQTL are widespread; 63% of genes with primary eQTL also have conditional eQTL. In addition, genomic features associated with conditional eQTL are consistent with context-specific (e.g., tissue-, cell type-, or developmental time point-specific) regulation of gene expression. Integrating the 2014 Psychiatric Genomics Consortium schizophrenia (SCZ) GWAS and CMC primary and conditional eQTL data reveals 40 loci with strong evidence for co-localization (posterior probability > 0.8), including six loci with co-localization of conditional eQTL. Our co-localization analyses support previously reported genes, identify novel genes associated with schizophrenia risk, and provide specific hypotheses for their functional follow-up. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The Genomes OnLine Database (GOLD) v.5: a metadata management system based on a four level (meta)genome project classification

PubMed Central

Reddy, T.B.K.; Thomas, Alex D.; Stamatis, Dimitri; Bertsch, Jon; Isbandi, Michelle; Jansson, Jakob; Mallajosyula, Jyothi; Pagani, Ioanna; Lobos, Elizabeth A.; Kyrpides, Nikos C.

2015-01-01

The Genomes OnLine Database (GOLD; http://www.genomesonline.org) is a comprehensive online resource to catalog and monitor genetic studies worldwide. GOLD provides up-to-date status on complete and ongoing sequencing projects along with a broad array of curated metadata. Here we report version 5 (v.5) of the database. The newly designed database schema and web user interface supports several new features including the implementation of a four level (meta)genome project classification system and a simplified intuitive web interface to access reports and launch search tools. The database currently hosts information for about 19 200 studies, 56 000 Biosamples, 56 000 sequencing projects and 39 400 analysis projects. More than just a catalog of worldwide genome projects, GOLD is a manually curated, quality-controlled metadata warehouse. The problems encountered in integrating disparate and varying quality data into GOLD are briefly highlighted. GOLD fully supports and follows the Genomic Standards Consortium (GSC) Minimum Information standards. PMID:25348402

Significance of genome-wide association studies in molecular anthropology.

PubMed

Gupta, Vipin; Khadgawat, Rajesh; Sachdeva, Mohinder Pal

2009-12-01

The successful advent of a genome-wide approach in association studies raises the hopes of human geneticists for solving a genetic maze of complex traits especially the disorders. This approach, which is replete with the application of cutting-edge technology and supported by big science projects (like Human Genome Project; and even more importantly the International HapMap Project) and various important databases (SNP database, CNV database, etc.), has had unprecedented success in rapidly uncovering many of the genetic determinants of complex disorders. The magnitude of this approach in the genetics of classical anthropological variables like height, skin color, eye color, and other genome diversity projects has certainly expanded the horizons of molecular anthropology. Therefore, in this article we have proposed a genome-wide association approach in molecular anthropological studies by providing lessons from the exemplary study of the Wellcome Trust Case Control Consortium. We have also highlighted the importance and uniqueness of Indian population groups in facilitating the design and finding optimum solutions for other genome-wide association-related challenges.

Building Better Scientists through Cross-Disciplinary Collaboration in Synthetic Biology: A Report from the Genome Consortium for Active Teaching Workshop 2010

ERIC Educational Resources Information Center

Wolyniak, Michael J.; Alvarez, Consuelo J.; Chandrasekaran, Vidya; Grana, Theresa M.; Holgado, Andrea; Jones, Christopher J.; Morris, Robert W.; Pereira, Anil L.; Stamm, Joyce; Washington, Talitha M.; Yang, Yixin

2010-01-01

Synthetic biology is the application of engineering and mathematical principles to develop novel biological devices and circuits. What separates synthetic biology from traditional molecular biology is the development of standardized interchangeable DNA "parts," just as advances in engineering in the nineteenth century brought about standardized…

Core Clinical Data Elements for Cancer Genomic Repositories: A Multi-stakeholder Consensus.

PubMed

Conley, Robert B; Dickson, Dane; Zenklusen, Jean Claude; Al Naber, Jennifer; Messner, Donna A; Atasoy, Ajlan; Chaihorsky, Lena; Collyar, Deborah; Compton, Carolyn; Ferguson, Martin; Khozin, Sean; Klein, Roger D; Kotte, Sri; Kurzrock, Razelle; Lin, C Jimmy; Liu, Frank; Marino, Ingrid; McDonough, Robert; McNeal, Amy; Miller, Vincent; Schilsky, Richard L; Wang, Lisa I

2017-11-16

The Center for Medical Technology Policy and the Molecular Evidence Development Consortium gathered a diverse group of more than 50 stakeholders to develop consensus on a core set of data elements and values essential to understanding the clinical utility of molecularly targeted therapies in oncology. Copyright © 2017 Elsevier Inc. All rights reserved.

The"minimum information about an environmental sequence" (MIENS) specification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yilmaz, P.; Kottmann, R.; Field, D.

We present the Genomic Standards Consortium's (GSC) 'Minimum Information about an ENvironmental Sequence' (MIENS) standard for describing marker genes. Adoption of MIENS will enhance our ability to analyze natural genetic diversity across the Tree of Life as it is currently being documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere.

Proteomic analysis of Pigeonpea (cajanus cajan) seeds reveals the accumulation of numerous stress-related proteins

USDA-ARS?s Scientific Manuscript database

Pigeonpea is one of the major sources of dietary protein for more than a billion people living in South Asia. This hardy legume is often grown in low-input and risk-prone marginal environments. Considerable research effort has been devoted by a global research consortium to develop genomic resources...

Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia.

PubMed

Nakahara, Soichiro; Medland, Sarah; Turner, Jessica A; Calhoun, Vince D; Lim, Kelvin O; Mueller, Bryon A; Bustillo, Juan R; O'Leary, Daniel S; Vaidya, Jatin G; McEwen, Sarah; Voyvodic, James; Belger, Aysenil; Mathalon, Daniel H; Ford, Judith M; Guffanti, Guia; Macciardi, Fabio; Potkin, Steven G; van Erp, Theo G M

2018-06-12

This study assessed genetic contributions to six cognitive domains, identified by the MATRICS Cognitive Consensus Battery as relevant for schizophrenia, cognition-enhancing, clinical trials. Psychiatric Genomics Consortium Schizophrenia polygenic risk scores showed significant negative correlations with each cognitive domain. Genome-wide association analyses identified loci associated with attention/vigilance (rs830786 within HNF4G), verbal memory (rs67017972 near NDUFS4), and reasoning/problem solving (rs76872642 within HDAC9). Gene set analysis identified unique and shared genes across cognitive domains. These findings suggest involvement of common and unique mechanisms across cognitive domains and may contribute to the discovery of new therapeutic targets to treat cognitive deficits in schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Degradation of raw corn stover powder (RCSP) by an enriched microbial consortium and its community structure.

PubMed

Feng, Yujie; Yu, Yanling; Wang, Xin; Qu, Youpeng; Li, Dongmei; He, Weihua; Kim, Byung Hong

2011-01-01

A microbial consortium with a high cellulolytic activity was enriched to degrade raw corn stover powder (RCSP). This consortium degraded more than 51% of non-sterilized RCSP or 81% of non-sterilized filter paper within 8 days at 40°C under facultative anoxic conditions. Cellulosome-like structures were observed in scanning electron micrographs (SEM) of RCSP degradation residue. The high cellulolytic activity was maintained during 40 subcultures in a medium containing cellulosic substrate. Small ribosomal gene sequence analyses showed the consortium contains uncultured and cultured bacteria with or without cellulolytic activities. Among these bacteria, some are anaerobic others aerobic. Analyses of the culture filtrate showed a typical anoxic polysaccharide fermentation during the culturing process. Reducing sugar concentration increased at early stage followed by various fermentation products that were consumed at the late stage. Copyright © 2010 Elsevier Ltd. All rights reserved.

Genetic Influences on the Neural and Physiological Bases of Acute Threat: A Research Domain Criteria (RDoC) Perspective

PubMed Central

Sumner, Jennifer A.; Powers, Abigail; Jovanovic, Tanja; Koenen, Karestan C.

2015-01-01

The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis—from genes to observable behaviors—in order to better understand psychopathology. The acute threat (“fear”) construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: 1) neural circuits and 2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35-50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. PMID:26377804

VCGDB: a dynamic genome database of the Chinese population

PubMed Central

2014-01-01

Background The data released by the 1000 Genomes Project contain an increasing number of genome sequences from different nations and populations with a large number of genetic variations. As a result, the focus of human genome studies is changing from single and static to complex and dynamic. The currently available human reference genome (GRCh37) is based on sequencing data from 13 anonymous Caucasian volunteers, which might limit the scope of genomics, transcriptomics, epigenetics, and genome wide association studies. Description We used the massive amount of sequencing data published by the 1000 Genomes Project Consortium to construct the Virtual Chinese Genome Database (VCGDB), a dynamic genome database of the Chinese population based on the whole genome sequencing data of 194 individuals. VCGDB provides dynamic genomic information, which contains 35 million single nucleotide variations (SNVs), 0.5 million insertions/deletions (indels), and 29 million rare variations, together with genomic annotation information. VCGDB also provides a highly interactive user-friendly virtual Chinese genome browser (VCGBrowser) with functions like seamless zooming and real-time searching. In addition, we have established three population-specific consensus Chinese reference genomes that are compatible with mainstream alignment software. Conclusions VCGDB offers a feasible strategy for processing big data to keep pace with the biological data explosion by providing a robust resource for genomics studies; in particular, studies aimed at finding regions of the genome associated with diseases. PMID:24708222

Structuring intuition with theory: The high-throughput way

NASA Astrophysics Data System (ADS)

Fornari, Marco

2015-03-01

First principles methodologies have grown in accuracy and applicability to the point where large databases can be built, shared, and analyzed with the goal of predicting novel compositions, optimizing functional properties, and discovering unexpected relationships between the data. In order to be useful to a large community of users, data should be standardized, validated, and distributed. In addition, tools to easily manage large datasets should be made available to effectively lead to materials development. Within the AFLOW consortium we have developed a simple frame to expand, validate, and mine data repositories: the MTFrame. Our minimalistic approach complement AFLOW and other existing high-throughput infrastructures and aims to integrate data generation with data analysis. We present few examples from our work on materials for energy conversion. Our intent s to pinpoint the usefulness of high-throughput methodologies to guide the discovery process by quantitatively structuring the scientific intuition. This work was supported by ONR-MURI under Contract N00014-13-1-0635 and the Duke University Center for Materials Genomics.

Genomes OnLine Database (GOLD) v.6: data updates and feature enhancements

PubMed Central

Mukherjee, Supratim; Stamatis, Dimitri; Bertsch, Jon; Ovchinnikova, Galina; Verezemska, Olena; Isbandi, Michelle; Thomas, Alex D.; Ali, Rida; Sharma, Kaushal; Kyrpides, Nikos C.; Reddy, T. B. K.

2017-01-01

The Genomes Online Database (GOLD) (https://gold.jgi.doe.gov) is a manually curated data management system that catalogs sequencing projects with associated metadata from around the world. In the current version of GOLD (v.6), all projects are organized based on a four level classification system in the form of a Study, Organism (for isolates) or Biosample (for environmental samples), Sequencing Project and Analysis Project. Currently, GOLD provides information for 26 117 Studies, 239 100 Organisms, 15 887 Biosamples, 97 212 Sequencing Projects and 78 579 Analysis Projects. These are integrated with over 312 metadata fields from which 58 are controlled vocabularies with 2067 terms. The web interface facilitates submission of a diverse range of Sequencing Projects (such as isolate genome, single-cell genome, metagenome, metatranscriptome) and complex Analysis Projects (such as genome from metagenome, or combined assembly from multiple Sequencing Projects). GOLD provides a seamless interface with the Integrated Microbial Genomes (IMG) system and supports and promotes the Genomic Standards Consortium (GSC) Minimum Information standards. This paper describes the data updates and additional features added during the last two years. PMID:27794040

The Power and Potential of Genomics in Weed Biology and Management.

PubMed

Ravet, Karl; Patterson, Eric L; Krähmer, Hansjörg; Hamouzová, Kateřina; Fan, Longjiang; Jasieniuk, Marie; Lawton-Rauh, Amy; Malone, Jenna M; Scott McElroy, J; Merotto, Aldo; Westra, Philip; Preston, Christopher; Vila-Aiub, Martin M; Busi, Roberto; Tranel, Patrick J; Reinhardt, Carl; Saski, Christopher; Beffa, Roland; Neve, Paul; Gaines, Todd A

2018-04-24

There have been previous calls for, and efforts focused on, realizing the power and potential of weed genomics for better understanding of weeds. Sustained advances in genome sequencing and assembly technologies now make it possible for individual research groups to generate reference genomes for multiple weed species at reasonable costs. Here, we present the outcomes from several meetings, discussions, and workshops focused on establishing an International Weed Genomics Consortium (IWGC) for a coordinated international effort in weed genomics. We review the 'state of the art' in genomics and weed genomics, including technologies, applications, and on-going weed genome projects. We also report the outcomes from a workshop and a global survey of the weed science community to identify priority species, key biological questions, and weed management applications that can be addressed through greater availability of, and access to, genomic resources. Major focus areas include the evolution of herbicide resistance and weedy traits, the development of molecular diagnostics, and the identification of novel targets and approaches for weed management. There is increasing interest in, and need for, weed genomics, and the establishment of the IWGC will provide the necessary global platform for communication and coordination of weed genomics research. This article is protected by copyright. All rights reserved.

Oncogenomic portals for the visualization and analysis of genome-wide cancer data

PubMed Central

Klonowska, Katarzyna; Czubak, Karol; Wojciechowska, Marzena; Handschuh, Luiza; Zmienko, Agnieszka; Figlerowicz, Marek; Dams-Kozlowska, Hanna; Kozlowski, Piotr

2016-01-01

Somatically acquired genomic alterations that drive oncogenic cellular processes are of great scientific and clinical interest. Since the initiation of large-scale cancer genomic projects (e.g., the Cancer Genome Project, The Cancer Genome Atlas, and the International Cancer Genome Consortium cancer genome projects), a number of web-based portals have been created to facilitate access to multidimensional oncogenomic data and assist with the interpretation of the data. The portals provide the visualization of small-size mutations, copy number variations, methylation, and gene/protein expression data that can be correlated with the available clinical, epidemiological, and molecular features. Additionally, the portals enable to analyze the gathered data with the use of various user-friendly statistical tools. Herein, we present a highly illustrated review of seven portals, i.e., Tumorscape, UCSC Cancer Genomics Browser, ICGC Data Portal, COSMIC, cBioPortal, IntOGen, and BioProfiling.de. All of the selected portals are user-friendly and can be exploited by scientists from different cancer-associated fields, including those without bioinformatics background. It is expected that the use of the portals will contribute to a better understanding of cancer molecular etiology and will ultimately accelerate the translation of genomic knowledge into clinical practice. PMID:26484415

Oncogenomic portals for the visualization and analysis of genome-wide cancer data.

PubMed

Klonowska, Katarzyna; Czubak, Karol; Wojciechowska, Marzena; Handschuh, Luiza; Zmienko, Agnieszka; Figlerowicz, Marek; Dams-Kozlowska, Hanna; Kozlowski, Piotr

2016-01-05

Somatically acquired genomic alterations that drive oncogenic cellular processes are of great scientific and clinical interest. Since the initiation of large-scale cancer genomic projects (e.g., the Cancer Genome Project, The Cancer Genome Atlas, and the International Cancer Genome Consortium cancer genome projects), a number of web-based portals have been created to facilitate access to multidimensional oncogenomic data and assist with the interpretation of the data. The portals provide the visualization of small-size mutations, copy number variations, methylation, and gene/protein expression data that can be correlated with the available clinical, epidemiological, and molecular features. Additionally, the portals enable to analyze the gathered data with the use of various user-friendly statistical tools. Herein, we present a highly illustrated review of seven portals, i.e., Tumorscape, UCSC Cancer Genomics Browser, ICGC Data Portal, COSMIC, cBioPortal, IntOGen, and BioProfiling.de. All of the selected portals are user-friendly and can be exploited by scientists from different cancer-associated fields, including those without bioinformatics background. It is expected that the use of the portals will contribute to a better understanding of cancer molecular etiology and will ultimately accelerate the translation of genomic knowledge into clinical practice.

A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing

PubMed Central

Alioto, Tyler S.; Buchhalter, Ivo; Derdak, Sophia; Hutter, Barbara; Eldridge, Matthew D.; Hovig, Eivind; Heisler, Lawrence E.; Beck, Timothy A.; Simpson, Jared T.; Tonon, Laurie; Sertier, Anne-Sophie; Patch, Ann-Marie; Jäger, Natalie; Ginsbach, Philip; Drews, Ruben; Paramasivam, Nagarajan; Kabbe, Rolf; Chotewutmontri, Sasithorn; Diessl, Nicolle; Previti, Christopher; Schmidt, Sabine; Brors, Benedikt; Feuerbach, Lars; Heinold, Michael; Gröbner, Susanne; Korshunov, Andrey; Tarpey, Patrick S.; Butler, Adam P.; Hinton, Jonathan; Jones, David; Menzies, Andrew; Raine, Keiran; Shepherd, Rebecca; Stebbings, Lucy; Teague, Jon W.; Ribeca, Paolo; Giner, Francesc Castro; Beltran, Sergi; Raineri, Emanuele; Dabad, Marc; Heath, Simon C.; Gut, Marta; Denroche, Robert E.; Harding, Nicholas J.; Yamaguchi, Takafumi N.; Fujimoto, Akihiro; Nakagawa, Hidewaki; Quesada, Víctor; Valdés-Mas, Rafael; Nakken, Sigve; Vodák, Daniel; Bower, Lawrence; Lynch, Andrew G.; Anderson, Charlotte L.; Waddell, Nicola; Pearson, John V.; Grimmond, Sean M.; Peto, Myron; Spellman, Paul; He, Minghui; Kandoth, Cyriac; Lee, Semin; Zhang, John; Létourneau, Louis; Ma, Singer; Seth, Sahil; Torrents, David; Xi, Liu; Wheeler, David A.; López-Otín, Carlos; Campo, Elías; Campbell, Peter J.; Boutros, Paul C.; Puente, Xose S.; Gerhard, Daniela S.; Pfister, Stefan M.; McPherson, John D.; Hudson, Thomas J.; Schlesner, Matthias; Lichter, Peter; Eils, Roland; Jones, David T. W.; Gut, Ivo G.

2015-01-01

As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to ∼100 × shows benefits, as long as the tumour:control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy. PMID:26647970

A standard MIGS/MIMS compliant XML Schema: toward the development of the Genomic Contextual Data Markup Language (GCDML).

PubMed

Kottmann, Renzo; Gray, Tanya; Murphy, Sean; Kagan, Leonid; Kravitz, Saul; Lombardot, Thierry; Field, Dawn; Glöckner, Frank Oliver

2008-06-01

The Genomic Contextual Data Markup Language (GCDML) is a core project of the Genomic Standards Consortium (GSC) that implements the "Minimum Information about a Genome Sequence" (MIGS) specification and its extension, the "Minimum Information about a Metagenome Sequence" (MIMS). GCDML is an XML Schema for generating MIGS/MIMS compliant reports for data entry, exchange, and storage. When mature, this sample-centric, strongly-typed schema will provide a diverse set of descriptors for describing the exact origin and processing of a biological sample, from sampling to sequencing, and subsequent analysis. Here we describe the need for such a project, outline design principles required to support the project, and make an open call for participation in defining the future content of GCDML. GCDML is freely available, and can be downloaded, along with documentation, from the GSC Web site (http://gensc.org).

Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium

PubMed Central

Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Glazer, Nicole L.; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Smith, Albert V.; O’Connell, Jeffrey R.; Li, Man; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Johnson, Andrew D.; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Atkinson, Elizabeth J.; Zeller, Tanja; Lohman, Kurt; Cornelis, Marilyn C.; Probst-Hensch, Nicole M.; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Launer, Lenore; Harris, Tamara B.; Rapmersaud, Evadnie; Mitchell, Braxton D.; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffery; de Boer, Ian; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Psaty, Bruce M.; Zillikens, M. Carola; Oostra, Ben A.; Feitosa, Mary; Province, Michael; Levy, Daniel; de Andrade, Mariza; Turner, Stephen T.; Schillert, Arne; Ziegler, Andreas; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Muenzel, Thomas F.; Leak, Tennille S; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H.-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Hu, Frank B.; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Aulchenko, Yurii S; Rivadeneira, Fernando; Uitterlinden, Andre G; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Kroemer, Heyo K.; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Parker, Alexander N.; Ridker, Paul M.; Kardia, Sharon L. R.; Blankenberg, Stefan; Liu, Yongmei; Curhan, Gary C.; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Shlipak, Michael G.; van Duijn, Cornelia M.; Borecki, Ingrid; Krämer, Bernhard K.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Witteman, Jacqueline C.; Pramstaller, Peter P.; Rettig, Rainer; Hastie, Nick; Chasman, Daniel I.; Kao, W. H.; Heid, Iris M.; Fox, Caroline S.

2010-01-01

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney. PMID:20383146

Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

PubMed Central

Hamshere, Marian L; Segurado, Ricardo; Moskvina, Valentina; Nikolov, Ivan; Glaser, Beate; Holmans, Peter A

2007-01-01

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates. PMID:18466440

Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis.

PubMed

Aschard, Hugues; Kang, Jae H; Iglesias, Adriana I; Hysi, Pirro; Cooke Bailey, Jessica N; Khawaja, Anthony P; Allingham, R Rand; Ashley-Koch, Allison; Lee, Richard K; Moroi, Sayoko E; Brilliant, Murray H; Wollstein, Gadi; Schuman, Joel S; Fingert, John H; Budenz, Donald L; Realini, Tony; Gaasterland, Terry; Scott, William K; Singh, Kuldev; Sit, Arthur J; Igo, Robert P; Song, Yeunjoo E; Hark, Lisa; Ritch, Robert; Rhee, Douglas J; Gulati, Vikas; Haven, Shane; Vollrath, Douglas; Zack, Donald J; Medeiros, Felipe; Weinreb, Robert N; Cheng, Ching-Yu; Chasman, Daniel I; Christen, William G; Pericak-Vance, Margaret A; Liu, Yutao; Kraft, Peter; Richards, Julia E; Rosner, Bernard A; Hauser, Michael A; Klaver, Caroline C W; vanDuijn, Cornelia M; Haines, Jonathan; Wiggs, Janey L; Pasquale, Louis R

2017-11-01

Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10 -27 ) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 × 10 -5 ); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.

SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.

PubMed

Miyashita, Akinori; Koike, Asako; Jun, Gyungah; Wang, Li-San; Takahashi, Satoshi; Matsubara, Etsuro; Kawarabayashi, Takeshi; Shoji, Mikio; Tomita, Naoki; Arai, Hiroyuki; Asada, Takashi; Harigaya, Yasuo; Ikeda, Masaki; Amari, Masakuni; Hanyu, Haruo; Higuchi, Susumu; Ikeuchi, Takeshi; Nishizawa, Masatoyo; Suga, Masaichi; Kawase, Yasuhiro; Akatsu, Hiroyasu; Kosaka, Kenji; Yamamoto, Takayuki; Imagawa, Masaki; Hamaguchi, Tsuyoshi; Yamada, Masahito; Morihara, Takashi; Moriaha, Takashi; Takeda, Masatoshi; Takao, Takeo; Nakata, Kenji; Fujisawa, Yoshikatsu; Sasaki, Ken; Watanabe, Ken; Nakashima, Kenji; Urakami, Katsuya; Ooya, Terumi; Takahashi, Mitsuo; Yuzuriha, Takefumi; Serikawa, Kayoko; Yoshimoto, Seishi; Nakagawa, Ryuji; Kim, Jong-Won; Ki, Chang-Seok; Won, Hong-Hee; Na, Duk L; Seo, Sang Won; Mook-Jung, Inhee; St George-Hyslop, Peter; Mayeux, Richard; Haines, Jonathan L; Pericak-Vance, Margaret A; Yoshida, Makiko; Nishida, Nao; Tokunaga, Katsushi; Yamamoto, Ken; Tsuji, Shoji; Kanazawa, Ichiro; Ihara, Yasuo; Schellenberg, Gerard D; Farrer, Lindsay A; Kuwano, Ryozo

2013-01-01

To discover susceptibility genes of late-onset Alzheimer's disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values <2×10(-5) were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P = 7.33×10(-7) in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P = 1.77×10(-9)) and rs3781834 (P = 1.04×10(-8)). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P = 1.71×10(-5)) and rs744373 near BIN1 (P = 1.39×10(-4)). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations.

Comparative genomics of Roseobacter clade bacteria isolated from the accessory nidamental gland of Euprymna scolopes

PubMed Central

Collins, Andrew J.; Fullmer, Matthew S.; Gogarten, Johann P.; Nyholm, Spencer V.

2015-01-01

The accessory nidamental gland (ANG) of the female Hawaiian bobtail squid, Euprymna scolopes, houses a consortium of bacteria including members of the Flavobacteriales, Rhizobiales, and Verrucomicrobia but is dominated by members of the Roseobacter clade (Rhodobacterales) within the Alphaproteobacteria. These bacteria are deposited into the jelly coat of the squid’s eggs, however, the function of the ANG and its bacterial symbionts has yet to be elucidated. In order to gain insight into this consortium and its potential role in host reproduction, we cultured 12 Rhodobacterales isolates from ANGs of sexually mature female squid and sequenced their genomes with Illumina sequencing technology. For taxonomic analyses, the ribosomal proteins of 79 genomes representing both roseobacters and non-roseobacters along with a separate MLSA analysis of 33 housekeeping genes from Roseobacter organisms placed all 12 isolates from the ANG within two groups of a single Roseobacter clade. Average nucelotide identity analysis suggests the ANG isolates represent three genera (Leisingera, Ruegeria, and Tateyamaria) comprised of seven putative species groups. All but one of the isolates contains a predicted Type VI secretion system, which has been shown to be important in secreting signaling and/or effector molecules in host–microbe associations and in bacteria–bacteria interactions. All sequenced genomes also show potential for secondary metabolite production, and are predicted to be involved with the production of acyl homoserine lactones (AHLs) and/or siderophores. An AHL bioassay confirmed AHL production in three tested isolates and from whole ANG homogenates. The dominant symbiont, Leisingera sp. ANG1, showed greater viability in iron-limiting conditions compared to other roseobacters, possibly due to higher levels of siderophore production. Future comparisons will try to elucidate novel metabolic pathways of the ANG symbionts to understand their putative role in host development. PMID:25755651

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

PubMed Central

Wang, Li-San; Matsubara, Etsuro; Kawarabayashi, Takeshi; Shoji, Mikio; Tomita, Naoki; Arai, Hiroyuki; Asada, Takashi; Harigaya, Yasuo; Ikeda, Masaki; Amari, Masakuni; Hanyu, Haruo; Higuchi, Susumu; Ikeuchi, Takeshi; Nishizawa, Masatoyo; Suga, Masaichi; Kawase, Yasuhiro; Akatsu, Hiroyasu; Kosaka, Kenji; Yamamoto, Takayuki; Imagawa, Masaki; Hamaguchi, Tsuyoshi; Yamada, Masahito; Moriaha, Takashi; Takeda, Masatoshi; Takao, Takeo; Nakata, Kenji; Sasaki, Ken; Watanabe, Ken; Nakashima, Kenji; Urakami, Katsuya; Ooya, Terumi; Takahashi, Mitsuo; Yuzuriha, Takefumi; Serikawa, Kayoko; Yoshimoto, Seishi; Nakagawa, Ryuji; Kim, Jong-Won; Ki, Chang-Seok; Won, Hong-Hee; Na, Duk L.; Seo, Sang Won; Mook-Jung, Inhee; St. George-Hyslop, Peter; Mayeux, Richard; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Yoshida, Makiko; Nishida, Nao; Tokunaga, Katsushi; Yamamoto, Ken; Tsuji, Shoji; Kanazawa, Ichiro; Ihara, Yasuo; Schellenberg, Gerard D.; Farrer, Lindsay A.; Kuwano, Ryozo

2013-01-01

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values <2×10−5 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P = 7.33×10−7 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P = 1.77×10−9) and rs3781834 (P = 1.04×10−8). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P = 1.71×10−5) and rs744373 near BIN1 (P = 1.39×10−4). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations. PMID:23565137

The FaceBase Consortium: A comprehensive program to facilitate craniofacial research

PubMed Central

Hochheiser, Harry; Aronow, Bruce J.; Artinger, Kristin; Beaty, Terri H.; Brinkley, James F.; Chai, Yang; Clouthier, David; Cunningham, Michael L.; Dixon, Michael; Donahue, Leah Rae; Fraser, Scott E.; Hallgrimsson, Benedikt; Iwata, Junichi; Klein, Ophir; Marazita, Mary L.; Murray, Jeffrey C.; Murray, Stephen; de Villena, Fernando Pardo-Manuel; Postlethwait, John; Potter, Steven; Shapiro, Linda; Spritz, Richard; Visel, Axel; Weinberg, Seth M.; Trainor, Paul A.

2012-01-01

The FaceBase Consortium consists of ten interlinked research and technology projects whose goal is to generate craniofacial research data and technology for use by the research community through a central data management and integrated bioinformatics hub. Funded by the National Institute of Dental and Craniofacial Research (NIDCR) and currently focused on studying the development of the middle region of the face, the Consortium will produce comprehensive datasets of global gene expression patterns, regulatory elements and sequencing; will generate anatomical and molecular atlases; will provide human normative facial data and other phenotypes; conduct follow up studies of a completed genome-wide association study; generate independent data on the genetics of craniofacial development, build repositories of animal models and of human samples and data for community access and analysis; and will develop software tools and animal models for analyzing and functionally testing and integrating these data. The FaceBase website (http://www.facebase.org) will serve as a web home for these efforts, providing interactive tools for exploring these datasets, together with discussion forums and other services to support and foster collaboration within the craniofacial research community. PMID:21458441

[ENCODE apophenia or a panglossian analysis of the human genome].

PubMed

Casane, Didier; Fumey, Julien; Laurenti, Patrick

2015-01-01

In September 2012, a batch of more than 30 articles presenting the results of the ENCODE (Encyclopaedia of DNA Elements) project was released. Many of these articles appeared in Nature and Science, the two most prestigious interdisciplinary scientific journals. Since that time, hundreds of other articles dedicated to the further analyses of the Encode data have been published. The time of hundreds of scientists and hundreds of millions of dollars were not invested in vain since this project had led to an apparent paradigm shift: contrary to the classical view, 80% of the human genome is not junk DNA, but is functional. This hypothesis has been criticized by evolutionary biologists, sometimes eagerly, and detailed refutations have been published in specialized journals with impact factors far below those that published the main contribution of the Encode project to our understanding of genome architecture. In 2014, the Encode consortium released a new batch of articles that neither suggested that 80% of the genome is functional nor commented on the disappearance of their 2012 scientific breakthrough. Unfortunately, by that time many biologists had accepted the idea that 80% of the genome is functional, or at least, that this idea is a valid alternative to the long held evolutionary genetic view that it is not. In order to understand the dynamics of the genome, it is necessary to re-examine the basics of evolutionary genetics because, not only are they well established, they also will allow us to avoid the pitfall of a panglossian interpretation of Encode. Actually, the architecture of the genome and its dynamics are the product of trade-offs between various evolutionary forces, and many structural features are not related to functional properties. In other words, evolution does not produce the best of all worlds, not even the best of all possible worlds, but only one possible world. © 2015 médecine/sciences – Inserm.

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

PubMed Central

Gibson, J; Russ, T C; Adams, M J; Clarke, T-K; Howard, D M; Hall, L S; Fernandez-Pujals, A M; Wigmore, E M; Hayward, C; Davies, G; Murray, A D; Smith, B H; Porteous, D J; Deary, I J; McIntosh, A M

2017-01-01

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (rG=−0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants. PMID:28418403

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data.

PubMed

Gibson, J; Russ, T C; Adams, M J; Clarke, T-K; Howard, D M; Hall, L S; Fernandez-Pujals, A M; Wigmore, E M; Hayward, C; Davies, G; Murray, A D; Smith, B H; Porteous, D J; Deary, I J; McIntosh, A M

2017-04-18

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (r G =-0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants.

Verification and Validation Process for Progressive Damage and Failure Analysis Methods in the NASA Advanced Composites Consortium

NASA Technical Reports Server (NTRS)

Wanthal, Steven; Schaefer, Joseph; Justusson, Brian; Hyder, Imran; Engelstad, Stephen; Rose, Cheryl

2017-01-01

The Advanced Composites Consortium is a US Government/Industry partnership supporting technologies to enable timeline and cost reduction in the development of certified composite aerospace structures. A key component of the consortium's approach is the development and validation of improved progressive damage and failure analysis methods for composite structures. These methods will enable increased use of simulations in design trade studies and detailed design development, and thereby enable more targeted physical test programs to validate designs. To accomplish this goal with confidence, a rigorous verification and validation process was developed. The process was used to evaluate analysis methods and associated implementation requirements to ensure calculation accuracy and to gage predictability for composite failure modes of interest. This paper introduces the verification and validation process developed by the consortium during the Phase I effort of the Advanced Composites Project. Specific structural failure modes of interest are first identified, and a subset of standard composite test articles are proposed to interrogate a progressive damage analysis method's ability to predict each failure mode of interest. Test articles are designed to capture the underlying composite material constitutive response as well as the interaction of failure modes representing typical failure patterns observed in aerospace structures.

The 'PUCE CAFE' Project: the First 15K Coffee Microarray, a New Tool for Discovering Candidate Genes correlated to Agronomic and Quality Traits

PubMed Central

2011-01-01

Background Understanding the genetic elements that contribute to key aspects of coffee biology will have an impact on future agronomical improvements for this economically important tree. During the past years, EST collections were generated in Coffee, opening the possibility to create new tools for functional genomics. Results The "PUCE CAFE" Project, organized by the scientific consortium NESTLE/IRD/CIRAD, has developed an oligo-based microarray using 15,721 unigenes derived from published coffee EST sequences mostly obtained from different stages of fruit development and leaves in Coffea Canephora (Robusta). Hybridizations for two independent experiments served to compare global gene expression profiles in three types of tissue matter (mature beans, leaves and flowers) in C. canephora as well as in the leaves of three different coffee species (C. canephora, C. eugenoides and C. arabica). Microarray construction, statistical analyses and validation by Q-PCR analysis are presented in this study. Conclusion We have generated the first 15 K coffee array during this PUCE CAFE project, granted by Génoplante (the French consortium for plant genomics). This new tool will help study functional genomics in a wide range of experiments on various plant tissues, such as analyzing bean maturation or resistance to pathogens or drought. Furthermore, the use of this array has proven to be valid in different coffee species (diploid or tetraploid), drastically enlarging its impact for high-throughput gene expression in the community of coffee research. PMID:21208403

Enrichment analysis in high-throughput genomics - accounting for dependency in the NULL.

PubMed

Gold, David L; Coombes, Kevin R; Wang, Jing; Mallick, Bani

2007-03-01

Translating the overwhelming amount of data generated in high-throughput genomics experiments into biologically meaningful evidence, which may for example point to a series of biomarkers or hint at a relevant pathway, is a matter of great interest in bioinformatics these days. Genes showing similar experimental profiles, it is hypothesized, share biological mechanisms that if understood could provide clues to the molecular processes leading to pathological events. It is the topic of further study to learn if or how a priori information about the known genes may serve to explain coexpression. One popular method of knowledge discovery in high-throughput genomics experiments, enrichment analysis (EA), seeks to infer if an interesting collection of genes is 'enriched' for a Consortium particular set of a priori Gene Ontology Consortium (GO) classes. For the purposes of statistical testing, the conventional methods offered in EA software implicitly assume independence between the GO classes. Genes may be annotated for more than one biological classification, and therefore the resulting test statistics of enrichment between GO classes can be highly dependent if the overlapping gene sets are relatively large. There is a need to formally determine if conventional EA results are robust to the independence assumption. We derive the exact null distribution for testing enrichment of GO classes by relaxing the independence assumption using well-known statistical theory. In applications with publicly available data sets, our test results are similar to the conventional approach which assumes independence. We argue that the independence assumption is not detrimental.

The 'PUCE CAFE' Project: the first 15K coffee microarray, a new tool for discovering candidate genes correlated to agronomic and quality traits.

PubMed

Privat, Isabelle; Bardil, Amélie; Gomez, Aureliano Bombarely; Severac, Dany; Dantec, Christelle; Fuentes, Ivanna; Mueller, Lukas; Joët, Thierry; Pot, David; Foucrier, Séverine; Dussert, Stéphane; Leroy, Thierry; Journot, Laurent; de Kochko, Alexandre; Campa, Claudine; Combes, Marie-Christine; Lashermes, Philippe; Bertrand, Benoit

2011-01-05

Understanding the genetic elements that contribute to key aspects of coffee biology will have an impact on future agronomical improvements for this economically important tree. During the past years, EST collections were generated in Coffee, opening the possibility to create new tools for functional genomics. The "PUCE CAFE" Project, organized by the scientific consortium NESTLE/IRD/CIRAD, has developed an oligo-based microarray using 15,721 unigenes derived from published coffee EST sequences mostly obtained from different stages of fruit development and leaves in Coffea Canephora (Robusta). Hybridizations for two independent experiments served to compare global gene expression profiles in three types of tissue matter (mature beans, leaves and flowers) in C. canephora as well as in the leaves of three different coffee species (C. canephora, C. eugenoides and C. arabica). Microarray construction, statistical analyses and validation by Q-PCR analysis are presented in this study. We have generated the first 15 K coffee array during this PUCE CAFE project, granted by Génoplante (the French consortium for plant genomics). This new tool will help study functional genomics in a wide range of experiments on various plant tissues, such as analyzing bean maturation or resistance to pathogens or drought. Furthermore, the use of this array has proven to be valid in different coffee species (diploid or tetraploid), drastically enlarging its impact for high-throughput gene expression in the community of coffee research.

A genome-wide association study of corneal astigmatism: The CREAM Consortium

PubMed Central

Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W.V.; Hysi, Pirro G.; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R.; Jonas, Jost B.; Mitchell, Paul; Hammond, Christopher J.; Höhn, René; Baird, Paul N.; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A.; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C.W.; Bailey-Wilson, Joan E.

2018-01-01

Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism. PMID:29422769

Development and Evaluation of a 9K SNP Array for Peach by Internationally Coordinated SNP Detection and Validation in Breeding Germplasm

PubMed Central

Scalabrin, Simone; Gilmore, Barbara; Lawley, Cynthia T.; Gasic, Ksenija; Micheletti, Diego; Rosyara, Umesh R.; Cattonaro, Federica; Vendramin, Elisa; Main, Dorrie; Aramini, Valeria; Blas, Andrea L.; Mockler, Todd C.; Bryant, Douglas W.; Wilhelm, Larry; Troggio, Michela; Sosinski, Bryon; Aranzana, Maria José; Arús, Pere; Iezzoni, Amy; Morgante, Michele; Peace, Cameron

2012-01-01

Although a large number of single nucleotide polymorphism (SNP) markers covering the entire genome are needed to enable molecular breeding efforts such as genome wide association studies, fine mapping, genomic selection and marker-assisted selection in peach [Prunus persica (L.) Batsch] and related Prunus species, only a limited number of genetic markers, including simple sequence repeats (SSRs), have been available to date. To address this need, an international consortium (The International Peach SNP Consortium; IPSC) has pursued a coordinated effort to perform genome-scale SNP discovery in peach using next generation sequencing platforms to develop and characterize a high-throughput Illumina Infinium® SNP genotyping array platform. We performed whole genome re-sequencing of 56 peach breeding accessions using the Illumina and Roche/454 sequencing technologies. Polymorphism detection algorithms identified a total of 1,022,354 SNPs. Validation with the Illumina GoldenGate® assay was performed on a subset of the predicted SNPs, verifying ∼75% of genic (exonic and intronic) SNPs, whereas only about a third of intergenic SNPs were verified. Conservative filtering was applied to arrive at a set of 8,144 SNPs that were included on the IPSC peach SNP array v1, distributed over all eight peach chromosomes with an average spacing of 26.7 kb between SNPs. Use of this platform to screen a total of 709 accessions of peach in two separate evaluation panels identified a total of 6,869 (84.3%) polymorphic SNPs. The almost 7,000 SNPs verified as polymorphic through extensive empirical evaluation represent an excellent source of markers for future studies in genetic relatedness, genetic mapping, and dissecting the genetic architecture of complex agricultural traits. The IPSC peach SNP array v1 is commercially available and we expect that it will be used worldwide for genetic studies in peach and related stone fruit and nut species. PMID:22536421

The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome

PubMed Central

Sela, D. A.; Chapman, J.; Adeuya, A.; Kim, J. H.; Chen, F.; Whitehead, T. R.; Lapidus, A.; Rokhsar, D. S.; Lebrilla, C. B.; German, J. B.; Price, N. P.; Richardson, P. M.; Mills, D. A.

2008-01-01

Following birth, the breast-fed infant gastrointestinal tract is rapidly colonized by a microbial consortium often dominated by bifidobacteria. Accordingly, the complete genome sequence of Bifidobacterium longum subsp. infantis ATCC15697 reflects a competitive nutrient-utilization strategy targeting milk-borne molecules which lack a nutritive value to the neonate. Several chromosomal loci reflect potential adaptation to the infant host including a 43 kbp cluster encoding catabolic genes, extracellular solute binding proteins and permeases predicted to be active on milk oligosaccharides. An examination of in vivo metabolism has detected the hallmarks of milk oligosaccharide utilization via the central fermentative pathway using metabolomic and proteomic approaches. Finally, conservation of gene clusters in multiple isolates corroborates the genomic mechanism underlying milk utilization for this infant-associated phylotype. PMID:19033196

Construction of the third-generation Zea mays haplotype map.

PubMed

Bukowski, Robert; Guo, Xiaosen; Lu, Yanli; Zou, Cheng; He, Bing; Rong, Zhengqin; Wang, Bo; Xu, Dawen; Yang, Bicheng; Xie, Chuanxiao; Fan, Longjiang; Gao, Shibin; Xu, Xun; Zhang, Gengyun; Li, Yingrui; Jiao, Yinping; Doebley, John F; Ross-Ibarra, Jeffrey; Lorant, Anne; Buffalo, Vince; Romay, M Cinta; Buckler, Edward S; Ware, Doreen; Lai, Jinsheng; Sun, Qi; Xu, Yunbi

2018-04-01

Characterization of genetic variations in maize has been challenging, mainly due to deterioration of collinearity between individual genomes in the species. An international consortium of maize research groups combined resources to develop the maize haplotype version 3 (HapMap 3), built from whole-genome sequencing data from 1218 maize lines, covering predomestication and domesticated Zea mays varieties across the world. A new computational pipeline was set up to process more than 12 trillion bp of sequencing data, and a set of population genetics filters was applied to identify more than 83 million variant sites. We identified polymorphisms in regions where collinearity is largely preserved in the maize species. However, the fact that the B73 genome used as the reference only represents a fraction of all haplotypes is still an important limiting factor.

The Genomes OnLine Database (GOLD) v.5: a metadata management system based on a four level (meta)genome project classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, Tatiparthi B. K.; Thomas, Alex D.; Stamatis, Dimitri

The Genomes OnLine Database (GOLD; http://www.genomesonline.org) is a comprehensive online resource to catalog and monitor genetic studies worldwide. GOLD provides up-to-date status on complete and ongoing sequencing projects along with a broad array of curated metadata. Within this paper, we report version 5 (v.5) of the database. The newly designed database schema and web user interface supports several new features including the implementation of a four level (meta)genome project classification system and a simplified intuitive web interface to access reports and launch search tools. The database currently hosts information for about 19 200 studies, 56 000 Biosamples, 56 000 sequencingmore » projects and 39 400 analysis projects. More than just a catalog of worldwide genome projects, GOLD is a manually curated, quality-controlled metadata warehouse. The problems encountered in integrating disparate and varying quality data into GOLD are briefly highlighted. Lastly, GOLD fully supports and follows the Genomic Standards Consortium (GSC) Minimum Information standards.« less

Reuse at the Software Productivity Consortium

NASA Technical Reports Server (NTRS)

Weiss, David M.

1989-01-01

The Software Productivity Consortium is sponsored by 14 aerospace companies as a developer of software engineering methods and tools. Software reuse and prototyping are currently the major emphasis areas. The Methodology and Measurement Project in the Software Technology Exploration Division has developed some concepts for reuse which they intend to develop into a synthesis process. They have identified two approaches to software reuse: opportunistic and systematic. The assumptions underlying the systematic approach, phrased as hypotheses, are the following: the redevelopment hypothesis, i.e., software developers solve the same problems repeatedly; the oracle hypothesis, i.e., developers are able to predict variations from one redevelopment to others; and the organizational hypothesis, i.e., software must be organized according to behavior and structure to take advantage of the predictions that the developers make. The conceptual basis for reuse includes: program families, information hiding, abstract interfaces, uses and information hiding hierarchies, and process structure. The primary reusable software characteristics are black-box descriptions, structural descriptions, and composition and decomposition based on program families. Automated support can be provided for systematic reuse, and the Consortium is developing a prototype reuse library and guidebook. The software synthesis process that the Consortium is aiming toward includes modeling, refinement, prototyping, reuse, assessment, and new construction.

The ENCODE project: implications for psychiatric genetics.

PubMed

Kavanagh, D H; Dwyer, S; O'Donovan, M C; Owen, M J

2013-05-01

The ENCyclopedia Of DNA Elements (ENCODE) project is a public research consortium that aims to identify all functional elements of the human genome sequence. The project comprised 1640 data sets, from 147 different cell type and the findings were released in a coordinated set of 34 publications across several journals. The ENCODE publications report that 80.4% of the human genome displays some functionality. These data have important implications for interpreting results from large-scale genetics studies. We reviewed some of the key findings from the ENCODE publications and discuss how they can influence or inform further investigations into the genetic factors contributing to neuropsychiatric disorders.

Consortium genome-wide meta-analysis for childhood dental caries traits.

PubMed

Haworth, Simon; Shungin, Dmitry; van der Tas, Justin T; Vucic, Strahinja; Medina-Gomez, Carolina; Yakimov, Victor; Feenstra, Bjarke; Shaffer, John R; Lee, Myoung Keun; Standl, Marie; Thiering, Elisabeth; Wang, Carol; Bønnelykke, Klaus; Waage, Johannes; Eyrich Jessen, Leon; Nørrisgaard, Pia Elisabeth; Joro, Raimo; Seppälä, Ilkka; Raitakari, Olli; Dudding, Tom; Grgic, Olja; Ongkosuwito, Edwin; Vierola, Anu; Eloranta, Aino-Maija; West, Nicola X; Thomas, Steven J; McNeil, Daniel W; Levy, Steven M; Slayton, Rebecca; Nohr, Ellen A; Lehtimäki, Terho; Lakka, Timo; Bisgaard, Hans; Pennell, Craig; Kühnisch, Jan; Marazita, Mary L; Melbye, Mads; Geller, Frank; Rivadeneira, Fernando; Wolvius, Eppo B; Franks, Paul W; Johansson, Ingegerd; Timpson, Nicholas J

2018-06-20

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from 9 contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and results were combined using fixed-effects meta-analysis. Analysis included up to 19,003 individuals (7,530 affected) for primary teeth and 13,353 individuals (5,875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth (intronic within ALLC, Odds Ratio (OR) 0.85, Effect Allele Frequency (EAF) 0.60, p 4.13e-8) and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, p 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low (h2 of 1% [95% CI: 0%:7%] and 6% [95% CI 0%:13%] for primary and permanent dentitions, respectively) compared to corresponding within-study estimates (h2 of 28%, [95% CI: 9%:48%] and 17% [95% CI:2%:31%]) or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

INFOBIOMED: European Network of Excellence on Biomedical Informatics to support individualised healthcare.

PubMed

Maojo, Victor; de la Calle, Guillermo; Martín-Sánchez, Fernando; Díaz, Carlos; Sanz, Ferran

2005-01-01

INFOBIOMED is an European Network of Excellence (NoE) funded by the Information Society Directorate-General of the European Commission (EC). A consortium of European organizations from ten different countries is involved within the network. Four pilots, all related to linking clinical and genomic information, are being carried out. From an informatics perspective, various challenges, related to data integration and mining, are included.

Resequencing of the common marmoset genome improves genome assemblies and gene-coding sequence analysis.

PubMed

Sato, Kengo; Kuroki, Yoko; Kumita, Wakako; Fujiyama, Asao; Toyoda, Atsushi; Kawai, Jun; Iriki, Atsushi; Sasaki, Erika; Okano, Hideyuki; Sakakibara, Yasubumi

2015-11-20

The first draft of the common marmoset (Callithrix jacchus) genome was published by the Marmoset Genome Sequencing and Analysis Consortium. The draft was based on whole-genome shotgun sequencing, and the current assembly version is Callithrix_jacches-3.2.1, but there still exist 187,214 undetermined gap regions and supercontigs and relatively short contigs that are unmapped to chromosomes in the draft genome. We performed resequencing and assembly of the genome of common marmoset by deep sequencing with high-throughput sequencing technology. Several different sequence runs using Illumina sequencing platforms were executed, and 181 Gbp of high-quality bases including mate-pairs with long insert lengths of 3, 8, 20, and 40 Kbp were obtained, that is, approximately 60× coverage. The resequencing significantly improved the MGSAC draft genome sequence. The N50 of the contigs, which is a statistical measure used to evaluate assembly quality, doubled. As a result, 51% of the contigs (total length: 299 Mbp) that were unmapped to chromosomes in the MGSAC draft were merged with chromosomal contigs, and the improved genome sequence helped to detect 5,288 new genes that are homologous to human cDNAs and the gaps in 5,187 transcripts of the Ensembl gene annotations were completely filled.

Systematic comparison of variant calling pipelines using gold standard personal exome variants

PubMed Central

Hwang, Sohyun; Kim, Eiru; Lee, Insuk; Marcotte, Edward M.

2015-01-01

The success of clinical genomics using next generation sequencing (NGS) requires the accurate and consistent identification of personal genome variants. Assorted variant calling methods have been developed, which show low concordance between their calls. Hence, a systematic comparison of the variant callers could give important guidance to NGS-based clinical genomics. Recently, a set of high-confident variant calls for one individual (NA12878) has been published by the Genome in a Bottle (GIAB) consortium, enabling performance benchmarking of different variant calling pipelines. Based on the gold standard reference variant calls from GIAB, we compared the performance of thirteen variant calling pipelines, testing combinations of three read aligners—BWA-MEM, Bowtie2, and Novoalign—and four variant callers—Genome Analysis Tool Kit HaplotypeCaller (GATK-HC), Samtools mpileup, Freebayes and Ion Proton Variant Caller (TVC), for twelve data sets for the NA12878 genome sequenced by different platforms including Illumina2000, Illumina2500, and Ion Proton, with various exome capture systems and exome coverage. We observed different biases toward specific types of SNP genotyping errors by the different variant callers. The results of our study provide useful guidelines for reliable variant identification from deep sequencing of personal genomes. PMID:26639839

Assigning ecological roles to the populations belonging to a phenanthrene-degrading bacterial consortium using omic approaches

PubMed Central

Coppotelli, Bibiana Marina; Madueño, Laura; Loviso, Claudia Lorena; Macchi, Marianela; Neme Tauil, Ricardo Martin; Valacco, María Pía; Morelli, Irma Susana

2017-01-01

The present study describes the behavior of a natural phenanthrene-degrading consortium (CON), a synthetic consortium (constructed with isolated strains from CON) and an isolated strain form CON (Sphingobium sp. AM) in phenanthrene cultures to understand the interactions among the microorganisms present in the natural consortium during phenanthrene degradation as a sole carbon and energy source in liquid cultures. In the contaminant degradation assay, the defined consortium not only achieved a major phenanthrene degradation percentage (> 95%) but also showed a more efficient elimination of the intermediate metabolite. The opposite behavior occurred in the CON culture where the lowest phenanthrene degradation and the highest HNA accumulation were observed, which suggests the presence of positive and also negative interaction in CON. To consider the uncultured bacteria present in CON, a metagenomic library was constructed with total CON DNA. One of the resulting scaffolds (S1P3) was affiliated with the Betaproteobacteria class and resulted in a significant similarity with a genome fragment from Burkholderia sp. HB1 chromosome 1. A complete gene cluster, which is related to one of the lower pathways (meta-cleavage of catechol) involved in PAH degradation (ORF 31–43), mobile genetic elements and associated proteins, was found. These results suggest the presence of at least one other microorganism in CON besides Sphingobium sp. AM, which is capable of degrading PAH through the meta-cleavage pathway. Burkholderiales order was further found, along with Sphingomonadales order, by a metaproteomic approach, which indicated that both orders were metabolically active in CON. Our results show the presence of negative interactions between bacterial populations found in a natural consortium selected by enrichment techniques; moreover, the synthetic syntrophic processing chain with only one microorganism with the capability of degrading phenanthrene was more efficient in contaminant and intermediate metabolite degradation than a generalist strain (Sphingobium sp. AM). PMID:28886166

Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities.

PubMed

Falk, Marni J; Shen, Lishuang; Gonzalez, Michael; Leipzig, Jeremy; Lott, Marie T; Stassen, Alphons P M; Diroma, Maria Angela; Navarro-Gomez, Daniel; Yeske, Philip; Bai, Renkui; Boles, Richard G; Brilhante, Virginia; Ralph, David; DaRe, Jeana T; Shelton, Robert; Terry, Sharon F; Zhang, Zhe; Copeland, William C; van Oven, Mannis; Prokisch, Holger; Wallace, Douglas C; Attimonelli, Marcella; Krotoski, Danuta; Zuchner, Stephan; Gai, Xiaowu

2015-03-01

Success rates for genomic analyses of highly heterogeneous disorders can be greatly improved if a large cohort of patient data is assembled to enhance collective capabilities for accurate sequence variant annotation, analysis, and interpretation. Indeed, molecular diagnostics requires the establishment of robust data resources to enable data sharing that informs accurate understanding of genes, variants, and phenotypes. The "Mitochondrial Disease Sequence Data Resource (MSeqDR) Consortium" is a grass-roots effort facilitated by the United Mitochondrial Disease Foundation to identify and prioritize specific genomic data analysis needs of the global mitochondrial disease clinical and research community. A central Web portal (https://mseqdr.org) facilitates the coherent compilation, organization, annotation, and analysis of sequence data from both nuclear and mitochondrial genomes of individuals and families with suspected mitochondrial disease. This Web portal provides users with a flexible and expandable suite of resources to enable variant-, gene-, and exome-level sequence analysis in a secure, Web-based, and user-friendly fashion. Users can also elect to share data with other MSeqDR Consortium members, or even the general public, either by custom annotation tracks or through the use of a convenient distributed annotation system (DAS) mechanism. A range of data visualization and analysis tools are provided to facilitate user interrogation and understanding of genomic, and ultimately phenotypic, data of relevance to mitochondrial biology and disease. Currently available tools for nuclear and mitochondrial gene analyses include an MSeqDR GBrowse instance that hosts optimized mitochondrial disease and mitochondrial DNA (mtDNA) specific annotation tracks, as well as an MSeqDR locus-specific database (LSDB) that curates variant data on more than 1300 genes that have been implicated in mitochondrial disease and/or encode mitochondria-localized proteins. MSeqDR is integrated with a diverse array of mtDNA data analysis tools that are both freestanding and incorporated into an online exome-level dataset curation and analysis resource (GEM.app) that is being optimized to support needs of the MSeqDR community. In addition, MSeqDR supports mitochondrial disease phenotyping and ontology tools, and provides variant pathogenicity assessment features that enable community review, feedback, and integration with the public ClinVar variant annotation resource. A centralized Web-based informed consent process is being developed, with implementation of a Global Unique Identifier (GUID) system to integrate data deposited on a given individual from different sources. Community-based data deposition into MSeqDR has already begun. Future efforts will enhance capabilities to incorporate phenotypic data that enhance genomic data analyses. MSeqDR will fill the existing void in bioinformatics tools and centralized knowledge that are necessary to enable efficient nuclear and mtDNA genomic data interpretation by a range of shareholders across both clinical diagnostic and research settings. Ultimately, MSeqDR is focused on empowering the global mitochondrial disease community to better define and explore mitochondrial diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Perspectives from the Avian Phylogenomics Project: Questions that Can Be Answered with Sequencing All Genomes of a Vertebrate Class.

PubMed

Jarvis, Erich D

2016-01-01

The rapid pace of advances in genome technology, with concomitant reductions in cost, makes it feasible that one day in our lifetime we will have available extant genomes of entire classes of species, including vertebrates. I recently helped cocoordinate the large-scale Avian Phylogenomics Project, which collected and sequenced genomes of 48 bird species representing most currently classified orders to address a range of questions in phylogenomics and comparative genomics. The consortium was able to answer questions not previously possible with just a few genomes. This success spurred on the creation of a project to sequence the genomes of at least one individual of all extant ∼10,500 bird species. The initiation of this project has led us to consider what questions now impossible to answer could be answered with all genomes, and could drive new questions now unimaginable. These include the generation of a highly resolved family tree of extant species, genome-wide association studies across species to identify genetic substrates of many complex traits, redefinition of species and the species concept, reconstruction of the genomes of common ancestors, and generation of new computational tools to address these questions. Here I present visions for the future by posing and answering questions regarding what scientists could potentially do with available genomes of an entire vertebrate class.

Towards a standards-compliant genomic and metagenomic publication record

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fenner, Marsha W; Garrity, George M.; Field, Dawn

2008-04-01

Increasingly we are aware as a community of the growing need to manage the avalanche of genomic and metagenomic data, in addition to related data types like ribosomal RNA and barcode sequences, in a way that tightly integrates contextual data with traditional literature in a machine-readable way. It is for this reason that the Genomic Standards Consortium (GSC) formed in 2005. Here we suggest that we move beyond the development of standards and tackle standards-compliance and improved data capture at the level of the scientific publication. We are supported in this goal by the fact that the scientific community ismore » in the midst of a publishing revolution. This revolution is marked by a growing shift away from a traditional dichotomy between 'journal articles' and 'database entries' and an increasing adoption of hybrid models of collecting and disseminating scientific information. With respect to genomes and metagenomes and related data types, we feel the scientific community would be best served by the immediate launch of a central repository of short, highly structured 'Genome Notes' that must be standards-compliant. This could be done in the context of an existing journal, but we also suggest the more radical solution of launching a new journal. Such a journal could be designed to cater to a wide range of standards-related content types that are not currently centralized in the published literature. It could also support the demand for centralizing aspects of the 'gray literature' (documents developed by institutions or communities) such as the call by the GSCl for a central repository of Standard Operating Procedures describing the genomic annotation pipelines of the major sequencing centers. We argue that such an 'eJournal', published under the Open Access paradigm by the GSC, could be an attractive publishing forum for a broader range of standardization initiatives within, and beyond, the GSC and thereby fill an unoccupied yet increasingly important niche within the current research landscape.« less

Construction of the third-generation Zea mays haplotype map

PubMed Central

Bukowski, Robert; Guo, Xiaosen; Lu, Yanli; Zou, Cheng; He, Bing; Rong, Zhengqin; Wang, Bo; Xu, Dawen; Yang, Bicheng; Xie, Chuanxiao; Fan, Longjiang; Gao, Shibin; Xu, Xun; Zhang, Gengyun; Li, Yingrui; Jiao, Yinping; Doebley, John F; Ross-Ibarra, Jeffrey; Lorant, Anne; Buffalo, Vince; Romay, M Cinta; Buckler, Edward S; Ware, Doreen; Lai, Jinsheng; Sun, Qi

2017-01-01

Abstract Background Characterization of genetic variations in maize has been challenging, mainly due to deterioration of collinearity between individual genomes in the species. An international consortium of maize research groups combined resources to develop the maize haplotype version 3 (HapMap 3), built from whole-genome sequencing data from 1218 maize lines, covering predomestication and domesticated Zea mays varieties across the world. Results A new computational pipeline was set up to process more than 12 trillion bp of sequencing data, and a set of population genetics filters was applied to identify more than 83 million variant sites. Conclusions We identified polymorphisms in regions where collinearity is largely preserved in the maize species. However, the fact that the B73 genome used as the reference only represents a fraction of all haplotypes is still an important limiting factor. PMID:29300887

A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

PubMed Central

2011-01-01

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome. PMID:21526222

Chemical probes targeting epigenetic proteins: Applications beyond oncology

PubMed Central

Ackloo, Suzanne; Brown, Peter J.; Müller, Susanne

2017-01-01

ABSTRACT Epigenetic chemical probes are potent, cell-active, small molecule inhibitors or antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about 4 thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro. Epigenetic chemical probes have been critical tools in oncology research and have uncovered mechanistic insights into well-established targets, as well as identify new therapeutic starting points. Indeed, the literature primarily links epigenetic proteins to oncology, but applications in inflammation, viral, metabolic and neurodegenerative diseases are now being reported. We summarize the literature of these emerging applications and provide examples where existing probes might be used. PMID:28080202

Roll-to-Roll Advanced Materials Manufacturing DOE Lab Consortium - FY16 Annual Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniel, Claus; Wood, III, David L.; Krumdick, Gregory

2016-12-01

A DOE laboratory consortium comprised of ORNL, ANL, NREL and LBNL, coordinating with Kodak’s Eastman Business Park (Kodak) and other selected industry partners, was formed to address enhancing battery electrode performance and R2R manufacturing challenges. The objective of the FY 2016 seed project was to develop a materials genome synthesis process amenable to R2R manufacturing and to provide modeling, simulation, processing, and manufacturing techniques that demonstrate the feasibility of process controls and scale-up potential for improved battery electrodes. The research efforts were to predict and measure changes and results in electrode morphology and performance based on process condition changes; tomore » evaluate mixed, active, particle size deposition and drying for novel electrode materials; and to model various process condition changes and the resulting morphology and electrode performance.« less

ICONE: An International Consortium of Neuro Endovascular Centres.

PubMed

Raymond, J; White, P; Kallmes, D F; Spears, J; Marotta, T; Roy, D; Guilbert, F; Weill, A; Nguyen, T; Molyneux, A J; Cloft, H; Cekirge, S; Saatci, I; Bracard, S; Meder, J F; Moret, J; Cognard, C; Qureshi, A I; Turk, A S; Berenstein, A

2008-06-30

The proliferation of new endovascular devices and therapeutic strategies calls for a prudentand rational evaluation of their clinical benefit. This evaluation must be done in an effective manner and in collaboration with industry. Such research initiative requires organisation a land methodological support to survive and thrive in a competitive environment. We propose the formation of an international consortium, an academic alliance committed to the pursuit of effective neurovascular therapies. Such a consortium would be dedicated to the designand execution of basic science, device developmentand clinical trials. The Consortium is owned and operated by its members. Members are international leaders in neurointerventional research and clinical practice. The Consortium brings competency, knowledge, and expertise to industry as well as to its membership across aspectrum of research initiatives such as: expedited review of clinical trials, protocol development, surveys and systematic reviews; laboratory expertise and support for research design and grant applications to public agencies. Once objectives and protocols are approved, the Consortium provides a stable network of centers capable of timely realization of clinical trials or pre clinical investigations in an optimal environment. The Consortium is a non-profit organization. The potential revenue generated from clientsponsored financial agreements will be redirected to the academic and research objectives of the organization. The Consortium wishes to work inconcert with industry, to support emerging trends in neurovascular therapeutic development. The Consortium is a realistic endeavour optimally structured to promote excellence through scientific appraisal of our treatments, and to accelerate technical progress while maximizing patients' safety and welfare.

Trans-ethnic follow-up of breast cancer GWAS hits using the preferential linkage disequilibrium approach

PubMed Central

Zhu, Qianqian; Shepherd, Lori; Lunetta, Kathryn L.; Yao, Song; Liu, Qian; Hu, Qiang; Haddad, Stephen A.; Sucheston-Campbell, Lara; Bensen, Jeannette T.; Bandera, Elisa V.; Rosenberg, Lynn; Liu, Song; Haiman, Christopher A.; Olshan, Andrew F.; Palmer, Julie R.; Ambrosone, Christine B.

2016-01-01

Leveraging population-distinct linkage equilibrium (LD) patterns, trans-ethnic follow-up of variants discovered from genome-wide association studies (GWAS) has proved to be useful in facilitating the identification of bona fide causal variants. We previously developed the preferential LD approach, a novel method that successfully identified causal variants driving the GWAS signals within European-descent populations even when the causal variants were only weakly linked with the GWAS-discovered variants. To evaluate the performance of our approach in a trans-ethnic setting, we applied it to follow up breast cancer GWAS hits identified mostly from populations of European ancestry in African Americans (AA). We evaluated 74 breast cancer GWAS variants in 8,315 AA women from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Only 27% of them were associated with breast cancer risk at significance level α=0.05, suggesting race-specificity of the identified breast cancer risk loci. We followed up on those replicated GWAS hits in the AMBER consortium utilizing the preferential LD approach, to search for causal variants or better breast cancer markers from the 1000 Genomes variant catalog. Our approach identified stronger breast cancer markers for 80% of the GWAS hits with at least nominal breast cancer association, and in 81% of these cases, the marker identified was among the top 10 of all 1000 Genomes variants in the corresponding locus. The results support trans-ethnic application of the preferential LD approach in search for candidate causal variants, and may have implications for future genetic research of breast cancer in AA women. PMID:27825120

A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis.

PubMed

Mechelli, Rosella; Umeton, Renato; Policano, Claudia; Annibali, Viviana; Coarelli, Giulia; Ricigliano, Vito A G; Vittori, Danila; Fornasiero, Arianna; Buscarinu, Maria Chiara; Romano, Silvia; Salvetti, Marco; Ristori, Giovanni

2013-01-01

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

PubMed Central

Policano, Claudia; Annibali, Viviana; Coarelli, Giulia; Ricigliano, Vito A. G.; Vittori, Danila; Fornasiero, Arianna; Buscarinu, Maria Chiara; Romano, Silvia; Salvetti, Marco; Ristori, Giovanni

2013-01-01

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms. PMID:23696811

Athlome Project Consortium: a concerted effort to discover genomic and other “omic” markers of athletic performance

PubMed Central

Tanaka, Masashi; Eynon, Nir; Bouchard, Claude; North, Kathryn N.; Williams, Alun G.; Collins, Malcolm; Britton, Steven L.; Fuku, Noriyuki; Ashley, Euan A.; Klissouras, Vassilis; Lucia, Alejandro; Ahmetov, Ildus I.; de Geus, Eco; Alsayrafi, Mohammed

2015-01-01

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14–17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium. PMID:26715623

Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance.

PubMed

Pitsiladis, Yannis P; Tanaka, Masashi; Eynon, Nir; Bouchard, Claude; North, Kathryn N; Williams, Alun G; Collins, Malcolm; Moran, Colin N; Britton, Steven L; Fuku, Noriyuki; Ashley, Euan A; Klissouras, Vassilis; Lucia, Alejandro; Ahmetov, Ildus I; de Geus, Eco; Alsayrafi, Mohammed

2016-03-01

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14-17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium. Copyright © 2016 the American Physiological Society.

Genome-wide association study of coronary and aortic calcification in lung cancer screening CT

NASA Astrophysics Data System (ADS)

de Vos, Bob D.; van Setten, Jessica; de Jong, Pim A.; Mali, Willem P.; Oudkerk, Matthijs; Viergever, Max A.; Išgum, Ivana

2016-03-01

Arterial calcification has been related to cardiovascular disease (CVD) and osteoporosis. However, little is known about the role of genetics and exact pathways leading to arterial calcification and its relation to bone density changes indicating osteoporosis. In this study, we conducted a genome-wide association study of arterial calcification burden, followed by a look-up of known single nucleotide polymorphisms (SNPs) for coronary artery disease (CAD) and myocardial infarction (MI), and bone mineral density (BMD) to test for a shared genetic basis between the traits. The study included a subcohort of the Dutch-Belgian lung cancer screening trial comprised of 2,561 participants. Participants underwent baseline CT screening in one of two hospitals participating in the trial. Low-dose chest CT images were acquired without contrast enhancement and without ECG-synchronization. In these images coronary and aortic calcifications were identified automatically. Subsequently, the detected calcifications were quantified using coronary artery calcium Agatston and volume scores. Genotype data was available for these participants. A genome-wide association study was conducted on 10,220,814 SNPs using a linear regression model. To reduce multiple testing burden, known CAD/MI and BMD SNPs were specifically tested (45 SNPs from the CARDIoGRAMplusC4D consortium and 60 SNPS from the GEFOS consortium). No novel significant SNPs were found. Significant enrichment for CAD/MI SNPs was observed in testing Agatston and coronary artery calcium volume scores. Moreover, a significant enrichment of BMD SNPs was shown in aortic calcium volume scores. This may indicate genetic relation of BMD SNPs and arterial calcification burden.

Design and Methods of the Mood Disorder Cohort Research Consortium (MDCRC) Study

PubMed Central

Cho, Chul-Hyun; Ahn, Yong-Min; Kim, Se Joo; Ha, Tae Hyun; Jeon, Hong Jin; Cha, Boseok; Moon, Eunsoo; Park, Dong Yeon; Baek, Ji Hyun; Kang, Hee-Ju; Ryu, Vin; An, Hyonggin

2017-01-01

The Mood Disorder Cohort Research Consortium (MDCRC) study is designed as a naturalistic observational prospective cohort study for early-onset mood disorders (major depressive disorders, bipolar disorders type 1 and 2) in South Korea. The study subjects consist of two populations: 1) patients with mood disorders under 25 years old and 2) patients with mood disorders within 2 years of treatment under 35 years old. After successful screening, the subjects are evaluated using baseline assessments and serial follow-up assessments at 3-month intervals. Between the follow-up assessments, subjects are dictated to check their own daily mood status before bedtime using the eMood chart application or a paper mood diary. At the regular visits every 3 months, inter-visit assessments are evaluated based on daily mood charts and interviews with patients. In addition to the daily mood chart, sleep quality, inter-visit major and minor mood episodes, stressful life events, and medical usage pattern with medical expenses are also assessed. Genomic DNA from blood is obtained for genomic analyses. From the MDCRC study, the clinical course, prognosis, and related factors of early-onset mood disorders can be clarified. The MDCRC is also able to facilitate translational research for mood disorders and provide a resource for the convergence study of mood disorders. PMID:28096882

Highlights from the 2016 WIN Symposium, 27-29 June 2016, Paris: personalised therapy beyond next-generation sequencing.

PubMed

Schilsky, Richard; Davies, Will

2016-01-01

The Worldwide Innovative Networking (WIN) consortium is an alliance of academic institutions, pharmaceutical partners, representatives from technology companies and charitable/health payer organisations from across the globe. For the last six years, the consortium's aims have been to foster communication and collaboration between members, encourage dialogue in an open forum, and deliver clinical trial results that improve the care and outcomes of patients with cancer using the latest advances in genomic-based medicine. The annual WIN Symposium, held over two days, is a chance for its members to come together and discuss ongoing research, recent announcements, and introduce new developments in personalised medicine. This year's conference, held in Paris, France 27-29 June, consisted of six dedicated sessions, including two debates, and posters from members and participating organisations, all focusing on the latest therapeutic advances and updates in genomic analysis. Special highlights from this year included discussion of the MINDACT clinical trial, which uses a gene expression test to identify patients with breast cancer who can safely forego adjuvant chemotherapy, and the reflections on the SHIVA trial. Of particular interest to many speakers was the utilisation of liquid biopsy samples to produce near real time snapshots of tumour mutational profiles and vulnerability.

Stakeholder engagement: a key component of integrating genomic information into electronic health records

PubMed Central

Hartzler, Andrea; McCarty, Catherine A.; Rasmussen, Luke V.; Williams, Marc S.; Brilliant, Murray; Bowton, Erica A.; Clayton, Ellen Wright; Faucett, William A.; Ferryman, Kadija; Field, Julie R.; Fullerton, Stephanie M.; Horowitz, Carol R.; Koenig, Barbara A.; McCormick, Jennifer B.; Ralston, James D.; Sanderson, Saskia C.; Smith, Maureen E.; Trinidad, Susan Brown

2014-01-01

Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine. PMID:24030437

Future potential of the Human Epigenome Project.

PubMed

Eckhardt, Florian; Beck, Stephan; Gut, Ivo G; Berlin, Kurt

2004-09-01

Deciphering the information encoded in the human genome is key for the further understanding of human biology, physiology and evolution. With the draft sequence of the human genome completed, elucidation of the epigenetic information layer of the human genome becomes accessible. Epigenetic mechanisms are mediated by either chemical modifications of the DNA itself or by modifications of proteins that are closely associated with DNA. Defects of the epigenetic regulation involved in processes such as imprinting, X chromosome inactivation, transcriptional control of genes, as well as mutations affecting DNA methylation enzymes, contribute fundamentally to the etiology of many human diseases. Headed by the Human Epigenome Consortium, the Human Epigenome Project is a joint effort by an international collaboration that aims to identify, catalog and interpret genome-wide DNA methylation patterns of all human genes in all major tissues. Methylation variable positions are thought to reflect gene activity, tissue type and disease state, and are useful epigenetic markers revealing the dynamic state of the genome. Like single nucleotide polymorphisms, methylation variable positions will greatly advance our ability to elucidate and diagnose the molecular basis of human diseases.

An eMERGE Clinical Center at Partners Personalized Medicine

PubMed Central

Smoller, Jordan W.; Karlson, Elizabeth W.; Green, Robert C.; Kathiresan, Sekar; MacArthur, Daniel G.; Talkowski, Michael E.; Murphy, Shawn N.; Weiss, Scott T.

2016-01-01

The integration of electronic medical records (EMRs) and genomic research has become a major component of efforts to advance personalized and precision medicine. The Electronic Medical Records and Genomics (eMERGE) network, initiated in 2007, is an NIH-funded consortium devoted to genomic discovery and implementation research by leveraging biorepositories linked to EMRs. In its most recent phase, eMERGE III, the network is focused on facilitating implementation of genomic medicine by detecting and disclosing rare pathogenic variants in clinically relevant genes. Partners Personalized Medicine (PPM) is a center dedicated to translating personalized medicine into clinical practice within Partners HealthCare. One component of the PPM is the Partners Healthcare Biobank, a biorepository comprising broadly consented DNA samples linked to the Partners longitudinal EMR. In 2015, PPM joined the eMERGE Phase III network. Here we describe the elements of the eMERGE clinical center at PPM, including plans for genomic discovery using EMR phenotypes, evaluation of rare variant penetrance and pleiotropy, and a novel randomized trial of the impact of returning genetic results to patients and clinicians. PMID:26805891

An eMERGE Clinical Center at Partners Personalized Medicine.

PubMed

Smoller, Jordan W; Karlson, Elizabeth W; Green, Robert C; Kathiresan, Sekar; MacArthur, Daniel G; Talkowski, Michael E; Murphy, Shawn N; Weiss, Scott T

2016-01-20

The integration of electronic medical records (EMRs) and genomic research has become a major component of efforts to advance personalized and precision medicine. The Electronic Medical Records and Genomics (eMERGE) network, initiated in 2007, is an NIH-funded consortium devoted to genomic discovery and implementation research by leveraging biorepositories linked to EMRs. In its most recent phase, eMERGE III, the network is focused on facilitating implementation of genomic medicine by detecting and disclosing rare pathogenic variants in clinically relevant genes. Partners Personalized Medicine (PPM) is a center dedicated to translating personalized medicine into clinical practice within Partners HealthCare. One component of the PPM is the Partners Healthcare Biobank, a biorepository comprising broadly consented DNA samples linked to the Partners longitudinal EMR. In 2015, PPM joined the eMERGE Phase III network. Here we describe the elements of the eMERGE clinical center at PPM, including plans for genomic discovery using EMR phenotypes, evaluation of rare variant penetrance and pleiotropy, and a novel randomized trial of the impact of returning genetic results to patients and clinicians.

Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.

PubMed

Li, Zhiqiang; Chen, Jianhua; Yu, Hao; He, Lin; Xu, Yifeng; Zhang, Dai; Yi, Qizhong; Li, Changgui; Li, Xingwang; Shen, Jiawei; Song, Zhijian; Ji, Weidong; Wang, Meng; Zhou, Juan; Chen, Boyu; Liu, Yahui; Wang, Jiqiang; Wang, Peng; Yang, Ping; Wang, Qingzhong; Feng, Guoyin; Liu, Benxiu; Sun, Wensheng; Li, Baojie; He, Guang; Li, Weidong; Wan, Chunling; Xu, Qi; Li, Wenjin; Wen, Zujia; Liu, Ke; Huang, Fang; Ji, Jue; Ripke, Stephan; Yue, Weihua; Sullivan, Patrick F; O'Donovan, Michael C; Shi, Yongyong

2017-11-01

We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.

[Current Status and Future Perspectives of SCRUM-Japan].

PubMed

Ohtsu, Atsushi; Goto, Koichi; Yoshino, Takayuki; Okamoto, Wataru; Tsuchihara, Katsuya

2017-08-01

SCRUM-Japan was launched as a nation-wide genome screening consortium for recruiting patients to 35 sponsor-/investigator- initiated registration trials in collaboration with 15 pharmaceutical companies and 240 hospitals. During the first period between February 2015 and March 2017, a total of 4,805 patients have been enrolled. Genomic profiling of each cancer were analyzed and newdrug applications of label expansion are in preparation based on the results of several registration studies including investigator-initiated trial of vandetanib for RET fusion gene positive non-small cell lung cancer. In addition, on-time clinical-genome data sharing with industries and academic institutions and prospective cohort registry for new drug evaluation as a historical control data have already initiated, which will facilitate new agent development in Japan. In the second period started from April 2017, new studies using cutting-edge liquid biopsy and immune-genome panel for precision medi- cine will start soon. These efforts are attempted towards a leading group for innovative clinical/translations researches in the world.

LIFEdb: a database for functional genomics experiments integrating information from external sources, and serving as a sample tracking system

PubMed Central

Bannasch, Detlev; Mehrle, Alexander; Glatting, Karl-Heinz; Pepperkok, Rainer; Poustka, Annemarie; Wiemann, Stefan

2004-01-01

We have implemented LIFEdb (http://www.dkfz.de/LIFEdb) to link information regarding novel human full-length cDNAs generated and sequenced by the German cDNA Consortium with functional information on the encoded proteins produced in functional genomics and proteomics approaches. The database also serves as a sample-tracking system to manage the process from cDNA to experimental read-out and data interpretation. A web interface enables the scientific community to explore and visualize features of the annotated cDNAs and ORFs combined with experimental results, and thus helps to unravel new features of proteins with as yet unknown functions. PMID:14681468

Statistical methods to detect novel genetic variants using publicly available GWAS summary data.

PubMed

Guo, Bin; Wu, Baolin

2018-03-01

We propose statistical methods to detect novel genetic variants using only genome-wide association studies (GWAS) summary data without access to raw genotype and phenotype data. With more and more summary data being posted for public access in the post GWAS era, the proposed methods are practically very useful to identify additional interesting genetic variants and shed lights on the underlying disease mechanism. We illustrate the utility of our proposed methods with application to GWAS meta-analysis results of fasting glucose from the international MAGIC consortium. We found several novel genome-wide significant loci that are worth further study. Copyright © 2018 Elsevier Ltd. All rights reserved.

Practical Considerations for Implementing Genomic Information Resources

PubMed Central

Overby, Casey L.; Connolly, John; Chute, Christopher G.; Denny, Joshua C.; Freimuth, Robert R.; Hartzler, Andrea L.; Holm, Ingrid A.; Manzi, Shannon; Pathak, Jyotishman; Peissig, Peggy L.; Smith, Maureen; Williams, Marc S.; Shirts, Brian H.; Stoffel, Elena M.; Tarczy-Hornoch, Peter; Vitek, Carolyn R. Rohrer; Wolf, Wendy A.; Starren, Justin

2016-01-01

Summary Objectives To understand opinions and perceptions on the state of information resources specifically targeted to genomics, and approaches to delivery in clinical practice. Methods We conducted a survey of genomic content use and its clinical delivery from representatives across eight institutions in the electronic Medical Records and Genomics (eMERGE) network and two institutions in the Clinical Sequencing Exploratory Research (CSER) consortium in 2014. Results Eleven responses representing distinct projects across ten sites showed heterogeneity in how content is being delivered, with provider-facing content primarily delivered via the electronic health record (EHR) (n=10), and paper/pamphlets as the leading mode for patient-facing content (n=9). There was general agreement (91%) that new content is needed for patients and providers specific to genomics, and that while aspects of this content could be shared across institutions there remain site-specific needs (73% in agreement). Conclusion This work identifies a need for the improved access to and expansion of information resources to support genomic medicine, and opportunities for content developers and EHR vendors to partner with institutions to develop needed resources, and streamline their use – such as a central content site in multiple modalities while implementing approaches to allow for site-specific customization. PMID:27652374

Comprehensive analysis of the N-glycan biosynthetic pathway using bioinformatics to generate UniCorn: A theoretical N-glycan structure database.

PubMed

Akune, Yukie; Lin, Chi-Hung; Abrahams, Jodie L; Zhang, Jingyu; Packer, Nicolle H; Aoki-Kinoshita, Kiyoko F; Campbell, Matthew P

2016-08-05

Glycan structures attached to proteins are comprised of diverse monosaccharide sequences and linkages that are produced from precursor nucleotide-sugars by a series of glycosyltransferases. Databases of these structures are an essential resource for the interpretation of analytical data and the development of bioinformatics tools. However, with no template to predict what structures are possible the human glycan structure databases are incomplete and rely heavily on the curation of published, experimentally determined, glycan structure data. In this work, a library of 45 human glycosyltransferases was used to generate a theoretical database of N-glycan structures comprised of 15 or less monosaccharide residues. Enzyme specificities were sourced from major online databases including Kyoto Encyclopedia of Genes and Genomes (KEGG) Glycan, Consortium for Functional Glycomics (CFG), Carbohydrate-Active enZymes (CAZy), GlycoGene DataBase (GGDB) and BRENDA. Based on the known activities, more than 1.1 million theoretical structures and 4.7 million synthetic reactions were generated and stored in our database called UniCorn. Furthermore, we analyzed the differences between the predicted glycan structures in UniCorn and those contained in UniCarbKB (www.unicarbkb.org), a database which stores experimentally described glycan structures reported in the literature, and demonstrate that UniCorn can be used to aid in the assignment of ambiguous structures whilst also serving as a discovery database. Copyright © 2016 Elsevier Ltd. All rights reserved.

A reference genetic map of C. clementina hort. ex Tan.; citrus evolution inferences from comparative mapping

PubMed Central

2012-01-01

Background Most modern citrus cultivars have an interspecific origin. As a foundational step towards deciphering the interspecific genome structures, a reference whole genome sequence was produced by the International Citrus Genome Consortium from a haploid derived from Clementine mandarin. The availability of a saturated genetic map of Clementine was identified as an essential prerequisite to assist the whole genome sequence assembly. Clementine is believed to be a ‘Mediterranean’ mandarin × sweet orange hybrid, and sweet orange likely arose from interspecific hybridizations between mandarin and pummelo gene pools. The primary goals of the present study were to establish a Clementine reference map using codominant markers, and to perform comparative mapping of pummelo, sweet orange, and Clementine. Results Five parental genetic maps were established from three segregating populations, which were genotyped with Single Nucleotide Polymorphism (SNP), Simple Sequence Repeats (SSR) and Insertion-Deletion (Indel) markers. An initial medium density reference map (961 markers for 1084.1 cM) of the Clementine was established by combining male and female Clementine segregation data. This Clementine map was compared with two pummelo maps and a sweet orange map. The linear order of markers was highly conserved in the different species. However, significant differences in map size were observed, which suggests a variation in the recombination rates. Skewed segregations were much higher in the male than female Clementine mapping data. The mapping data confirmed that Clementine arose from hybridization between ‘Mediterranean’ mandarin and sweet orange. The results identified nine recombination break points for the sweet orange gamete that contributed to the Clementine genome. Conclusions A reference genetic map of citrus, used to facilitate the chromosome assembly of the first citrus reference genome sequence, was established. The high conservation of marker order observed at the interspecific level should allow reasonable inferences of most citrus genome sequences by mapping next-generation sequencing (NGS) data in the reference genome sequence. The genome of the haploid Clementine used to establish the citrus reference genome sequence appears to have been inherited primarily from the ‘Mediterranean’ mandarin. The high frequency of skewed allelic segregations in the male Clementine data underline the probable extent of deviation from Mendelian segregation for characters controlled by heterozygous loci in male parents. PMID:23126659

The Human Proteome Organization Chromosome 6 Consortium: integrating chromosome-centric and biology/disease driven strategies.

PubMed

Borchers, C H; Kast, J; Foster, L J; Siu, K W M; Overall, C M; Binkowski, T A; Hildebrand, W H; Scherer, A; Mansoor, M; Keown, P A

2014-04-04

The Human Proteome Project (HPP) is designed to generate a comprehensive map of the protein-based molecular architecture of the human body, to provide a resource to help elucidate biological and molecular function, and to advance diagnosis and treatment of diseases. Within this framework, the chromosome-based HPP (C-HPP) has allocated responsibility for mapping individual chromosomes by country or region, while the biology/disease HPP (B/D-HPP) coordinates these teams in cross-functional disease-based groups. Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins. Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences. The unique combination of genomic, proteomic, metabolomic, phenomic and health services data being drawn together within the Ch6 program has enormous potential to advance personalized medicine by promoting robust biomarkers, subunit vaccines and new drug targets. The strong liaison between the clinical and laboratory teams, and the structured framework for technology transfer and health policy decisions within Canada will increase the speed and efficacy of this transition, and the value of this translational research. Canada has been selected to play a leading role in the international Human Proteome Project, the global counterpart of the Human Genome Project designed to understand the structure and function of the human proteome in health and disease. Canada will lead an international team focusing on chromosome 6, which is functionally associated with more than 120 major human diseases, including immune and inflammatory disorders affecting the brain, skeletal system, heart and blood vessels, lungs, kidney, liver, gastrointestinal tract and endocrine system. Many of these chronic and persistent diseases have a high population prevalence, devastating clinical impact and profound societal consequences. As a result, they impose a multi-billion dollar economic burden on Canada and on all advanced societies through direct costs of patient care, the loss of health and productivity, and extensive caregiver burden. There is no definitive treatment at the present time for any of these disorders. The manuscript outlines the research which will involve a systematic assessment of all chromosome 6 genes, development of a knowledge base, and development of assays and reagents for all chromosome 6 proteins. We feel that the informatic infrastructure and MRM assays developed will place the chromosome 6 consortium in an excellent position to be a leading player in this major international research initiative. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes? © 2013.

Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

PubMed

de Moor, Marleen H M; van den Berg, Stéphanie M; Verweij, Karin J H; Krueger, Robert F; Luciano, Michelle; Arias Vasquez, Alejandro; Matteson, Lindsay K; Derringer, Jaime; Esko, Tõnu; Amin, Najaf; Gordon, Scott D; Hansell, Narelle K; Hart, Amy B; Seppälä, Ilkka; Huffman, Jennifer E; Konte, Bettina; Lahti, Jari; Lee, Minyoung; Miller, Mike; Nutile, Teresa; Tanaka, Toshiko; Teumer, Alexander; Viktorin, Alexander; Wedenoja, Juho; Abecasis, Goncalo R; Adkins, Daniel E; Agrawal, Arpana; Allik, Jüri; Appel, Katja; Bigdeli, Timothy B; Busonero, Fabio; Campbell, Harry; Costa, Paul T; Davey Smith, George; Davies, Gail; de Wit, Harriet; Ding, Jun; Engelhardt, Barbara E; Eriksson, Johan G; Fedko, Iryna O; Ferrucci, Luigi; Franke, Barbara; Giegling, Ina; Grucza, Richard; Hartmann, Annette M; Heath, Andrew C; Heinonen, Kati; Henders, Anjali K; Homuth, Georg; Hottenga, Jouke-Jan; Iacono, William G; Janzing, Joost; Jokela, Markus; Karlsson, Robert; Kemp, John P; Kirkpatrick, Matthew G; Latvala, Antti; Lehtimäki, Terho; Liewald, David C; Madden, Pamela A F; Magri, Chiara; Magnusson, Patrik K E; Marten, Jonathan; Maschio, Andrea; Medland, Sarah E; Mihailov, Evelin; Milaneschi, Yuri; Montgomery, Grant W; Nauck, Matthias; Ouwens, Klaasjan G; Palotie, Aarno; Pettersson, Erik; Polasek, Ozren; Qian, Yong; Pulkki-Råback, Laura; Raitakari, Olli T; Realo, Anu; Rose, Richard J; Ruggiero, Daniela; Schmidt, Carsten O; Slutske, Wendy S; Sorice, Rossella; Starr, John M; St Pourcain, Beate; Sutin, Angelina R; Timpson, Nicholas J; Trochet, Holly; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Wouda, Jasper; Wright, Margaret J; Zgaga, Lina; Porteous, David; Minelli, Alessandra; Palmer, Abraham A; Rujescu, Dan; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Metspalu, Andres; Kaprio, Jaakko; Deary, Ian J; Räikkönen, Katri; Wilson, James F; Keltikangas-Järvinen, Liisa; Bierut, Laura J; Hettema, John M; Grabe, Hans J; van Duijn, Cornelia M; Evans, David M; Schlessinger, David; Pedersen, Nancy L; Terracciano, Antonio; McGue, Matt; Penninx, Brenda W J H; Martin, Nicholas G; Boomsma, Dorret I

2015-07-01

Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

The ISPRS Student Consortium: From launch to tenth anniversary

NASA Astrophysics Data System (ADS)

Kanjir, U.; Detchev, I.; Reyes, S. R.; Akkartal Aktas, A.; Lo, C. Y.; Miyazaki, H.

2014-04-01

The ISPRS Student Consortium is an international organization for students and young professionals in the fields of photogrammetry, remote sensing, and the geospatial information sciences. Since its start ten years ago, the number of members of the Student Consortium has been steadily growing, now reaching close to 1000. Its increased popularity, especially in recent years, is mainly due to the organization's worldwide involvement in student matters. The Student Consortium has helped organize numerous summer schools, youth forums, and student technical sessions at ISPRS sponsored conferences. In addition, the organization publishes a newsletter, and hosts several social media outlets in order to keep its global membership up-to-date on a regular basis. This paper will describe the structure of the organization, and it will give some example of its past student related activities.

Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms

PubMed Central

Fusco, Diana; Barnum, Timothy J.; Bruno, Andrew E.; Luft, Joseph R.; Snell, Edward H.; Mukherjee, Sayan; Charbonneau, Patrick

2014-01-01

X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis. PMID:24988076

Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms.

PubMed

Fusco, Diana; Barnum, Timothy J; Bruno, Andrew E; Luft, Joseph R; Snell, Edward H; Mukherjee, Sayan; Charbonneau, Patrick

2014-01-01

X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis.

A Comparative Encyclopedia of DNA Elements in the Mouse Genome

PubMed Central

Yue, Feng; Cheng, Yong; Breschi, Alessandra; Vierstra, Jeff; Wu, Weisheng; Ryba, Tyrone; Sandstrom, Richard; Ma, Zhihai; Davis, Carrie; Pope, Benjamin D.; Shen, Yin; Pervouchine, Dmitri D.; Djebali, Sarah; Thurman, Bob; Kaul, Rajinder; Rynes, Eric; Kirilusha, Anthony; Marinov, Georgi K.; Williams, Brian A.; Trout, Diane; Amrhein, Henry; Fisher-Aylor, Katherine; Antoshechkin, Igor; DeSalvo, Gilberto; See, Lei-Hoon; Fastuca, Meagan; Drenkow, Jorg; Zaleski, Chris; Dobin, Alex; Prieto, Pablo; Lagarde, Julien; Bussotti, Giovanni; Tanzer, Andrea; Denas, Olgert; Li, Kanwei; Bender, M. A.; Zhang, Miaohua; Byron, Rachel; Groudine, Mark T.; McCleary, David; Pham, Long; Ye, Zhen; Kuan, Samantha; Edsall, Lee; Wu, Yi-Chieh; Rasmussen, Matthew D.; Bansal, Mukul S.; Keller, Cheryl A.; Morrissey, Christapher S.; Mishra, Tejaswini; Jain, Deepti; Dogan, Nergiz; Harris, Robert S.; Cayting, Philip; Kawli, Trupti; Boyle, Alan P.; Euskirchen, Ghia; Kundaje, Anshul; Lin, Shin; Lin, Yiing; Jansen, Camden; Malladi, Venkat S.; Cline, Melissa S.; Erickson, Drew T.; Kirkup, Vanessa M; Learned, Katrina; Sloan, Cricket A.; Rosenbloom, Kate R.; de Sousa, Beatriz Lacerda; Beal, Kathryn; Pignatelli, Miguel; Flicek, Paul; Lian, Jin; Kahveci, Tamer; Lee, Dongwon; Kent, W. James; Santos, Miguel Ramalho; Herrero, Javier; Notredame, Cedric; Johnson, Audra; Vong, Shinny; Lee, Kristen; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Canfield, Theresa; Sabo, Peter J.; Wilken, Matthew S.; Reh, Thomas A.; Giste, Erika; Shafer, Anthony; Kutyavin, Tanya; Haugen, Eric; Dunn, Douglas; Reynolds, Alex P.; Neph, Shane; Humbert, Richard; Hansen, R. Scott; De Bruijn, Marella; Selleri, Licia; Rudensky, Alexander; Josefowicz, Steven; Samstein, Robert; Eichler, Evan E.; Orkin, Stuart H.; Levasseur, Dana; Papayannopoulou, Thalia; Chang, Kai-Hsin; Skoultchi, Arthur; Gosh, Srikanta; Disteche, Christine; Treuting, Piper; Wang, Yanli; Weiss, Mitchell J.; Blobel, Gerd A.; Good, Peter J.; Lowdon, Rebecca F.; Adams, Leslie B.; Zhou, Xiao-Qiao; Pazin, Michael J.; Feingold, Elise A.; Wold, Barbara; Taylor, James; Kellis, Manolis; Mortazavi, Ali; Weissman, Sherman M.; Stamatoyannopoulos, John; Snyder, Michael P.; Guigo, Roderic; Gingeras, Thomas R.; Gilbert, David M.; Hardison, Ross C.; Beer, Michael A.; Ren, Bing

2014-01-01

Summary As the premier model organism in biomedical research, the laboratory mouse shares the majority of protein-coding genes with humans, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications, and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases. PMID:25409824

A comparative encyclopedia of DNA elements in the mouse genome.

PubMed

Yue, Feng; Cheng, Yong; Breschi, Alessandra; Vierstra, Jeff; Wu, Weisheng; Ryba, Tyrone; Sandstrom, Richard; Ma, Zhihai; Davis, Carrie; Pope, Benjamin D; Shen, Yin; Pervouchine, Dmitri D; Djebali, Sarah; Thurman, Robert E; Kaul, Rajinder; Rynes, Eric; Kirilusha, Anthony; Marinov, Georgi K; Williams, Brian A; Trout, Diane; Amrhein, Henry; Fisher-Aylor, Katherine; Antoshechkin, Igor; DeSalvo, Gilberto; See, Lei-Hoon; Fastuca, Meagan; Drenkow, Jorg; Zaleski, Chris; Dobin, Alex; Prieto, Pablo; Lagarde, Julien; Bussotti, Giovanni; Tanzer, Andrea; Denas, Olgert; Li, Kanwei; Bender, M A; Zhang, Miaohua; Byron, Rachel; Groudine, Mark T; McCleary, David; Pham, Long; Ye, Zhen; Kuan, Samantha; Edsall, Lee; Wu, Yi-Chieh; Rasmussen, Matthew D; Bansal, Mukul S; Kellis, Manolis; Keller, Cheryl A; Morrissey, Christapher S; Mishra, Tejaswini; Jain, Deepti; Dogan, Nergiz; Harris, Robert S; Cayting, Philip; Kawli, Trupti; Boyle, Alan P; Euskirchen, Ghia; Kundaje, Anshul; Lin, Shin; Lin, Yiing; Jansen, Camden; Malladi, Venkat S; Cline, Melissa S; Erickson, Drew T; Kirkup, Vanessa M; Learned, Katrina; Sloan, Cricket A; Rosenbloom, Kate R; Lacerda de Sousa, Beatriz; Beal, Kathryn; Pignatelli, Miguel; Flicek, Paul; Lian, Jin; Kahveci, Tamer; Lee, Dongwon; Kent, W James; Ramalho Santos, Miguel; Herrero, Javier; Notredame, Cedric; Johnson, Audra; Vong, Shinny; Lee, Kristen; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Canfield, Theresa; Sabo, Peter J; Wilken, Matthew S; Reh, Thomas A; Giste, Erika; Shafer, Anthony; Kutyavin, Tanya; Haugen, Eric; Dunn, Douglas; Reynolds, Alex P; Neph, Shane; Humbert, Richard; Hansen, R Scott; De Bruijn, Marella; Selleri, Licia; Rudensky, Alexander; Josefowicz, Steven; Samstein, Robert; Eichler, Evan E; Orkin, Stuart H; Levasseur, Dana; Papayannopoulou, Thalia; Chang, Kai-Hsin; Skoultchi, Arthur; Gosh, Srikanta; Disteche, Christine; Treuting, Piper; Wang, Yanli; Weiss, Mitchell J; Blobel, Gerd A; Cao, Xiaoyi; Zhong, Sheng; Wang, Ting; Good, Peter J; Lowdon, Rebecca F; Adams, Leslie B; Zhou, Xiao-Qiao; Pazin, Michael J; Feingold, Elise A; Wold, Barbara; Taylor, James; Mortazavi, Ali; Weissman, Sherman M; Stamatoyannopoulos, John A; Snyder, Michael P; Guigo, Roderic; Gingeras, Thomas R; Gilbert, David M; Hardison, Ross C; Beer, Michael A; Ren, Bing

2014-11-20

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases.

Creating reference gene annotation for the mouse C57BL6/J genome assembly.

PubMed

Mudge, Jonathan M; Harrow, Jennifer

2015-10-01

Annotation on the reference genome of the C57BL6/J mouse has been an ongoing project ever since the draft genome was first published. Initially, the principle focus was on the identification of all protein-coding genes, although today the importance of describing long non-coding RNAs, small RNAs, and pseudogenes is recognized. Here, we describe the progress of the GENCODE mouse annotation project, which combines manual annotation from the HAVANA group with Ensembl computational annotation, alongside experimental and in silico validation pipelines from other members of the consortium. We discuss the more recent incorporation of next-generation sequencing datasets into this workflow, including the usage of mass-spectrometry data to potentially identify novel protein-coding genes. Finally, we will outline how the C57BL6/J genebuild can be used to gain insights into the variant sites that distinguish different mouse strains and species.

Maternal alcohol consumption and offspring DNA methylation: findings from six general population-based birth cohorts

PubMed Central

Sharp, Gemma C; Arathimos, Ryan; Reese, Sarah E; Page, Christian M; Felix, Janine; Küpers, Leanne K; Rifas-Shiman, Sheryl L; Liu, Chunyu; Burrows, Kimberley; Zhao, Shanshan; Magnus, Maria C; Duijts, Liesbeth; Corpeleijn, Eva; DeMeo, Dawn L; Litonjua, Augusto; Baccarelli, Andrea; Hivert, Marie-France; Oken, Emily; Snieder, Harold; Jaddoe, Vincent; Nystad, Wenche; London, Stephanie J; Relton, Caroline L; Zuccolo, Luisa

2018-01-01

Aim: Alcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero. Materials & methods: We meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium. Results: We found no strong evidence of association at either individual CpGs or across larger regions of the genome. Conclusion: Our findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association. PMID:29172695

Data sharing and intellectual property in a genomic epidemiology network: policies for large-scale research collaboration.

PubMed Central

Chokshi, Dave A.; Parker, Michael; Kwiatkowski, Dominic P.

2006-01-01

Genomic epidemiology is a field of research that seeks to improve the prevention and management of common diseases through an understanding of their molecular origins. It involves studying thousands of individuals, often from different populations, with exacting techniques. The scale and complexity of such research has required the formation of research consortia. Members of these consortia need to agree on policies for managing shared resources and handling genetic data. Here we consider data-sharing and intellectual property policies for an international research consortium working on the genomic epidemiology of malaria. We outline specific guidelines governing how samples and data are transferred among its members; how results are released into the public domain; when to seek protection for intellectual property; and how intellectual property should be managed. We outline some pragmatic solutions founded on the basic principles of promoting innovation and access. PMID:16710548

Draft genome sequence of Paraburkholderia tropica Ppe8 strain, a sugarcane endophytic diazotrophic bacterium.

PubMed

Silva, Paula Renata Alves da; Simões-Araújo, Jean Luiz; Vidal, Márcia Soares; Cruz, Leonardo Magalhães; Souza, Emanuel Maltempi de; Baldani, José Ivo

Paraburkholderia tropica (syn Burkholderia tropica) are nitrogen-fixing bacteria commonly found in sugarcane. The Paraburkholderia tropica strain Ppe8 is part of the sugarcane inoculant consortium that has a beneficial effect on yield. Here, we report a draft genome sequence of this strain elucidating the mechanisms involved in its interaction mainly with Poaceae. A genome size of approximately 8.75Mb containing 7844 protein coding genes distributed in 526 subsystems was de novo assembled with ABySS and annotated by RAST. Genes related to the nitrogen fixation process, the secretion systems (I, II, III, IV, and VI), and related to a variety of metabolic traits, such as metabolism of carbohydrates, amino acids, vitamins, and proteins, were detected, suggesting a broad metabolic capacity and possible adaptation to plant association. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

The MRI-Linear Accelerator Consortium: Evidence-Based Clinical Introduction of an Innovation in Radiation Oncology Connecting Researchers, Methodology, Data Collection, Quality Assurance, and Technical Development.

PubMed

Kerkmeijer, Linda G W; Fuller, Clifton D; Verkooijen, Helena M; Verheij, Marcel; Choudhury, Ananya; Harrington, Kevin J; Schultz, Chris; Sahgal, Arjun; Frank, Steven J; Goldwein, Joel; Brown, Kevin J; Minsky, Bruce D; van Vulpen, Marco

2016-01-01

An international research consortium has been formed to facilitate evidence-based introduction of MR-guided radiotherapy (MR-linac) and to address how the MR-linac could be used to achieve an optimized radiation treatment approach to improve patients' survival, local, and regional tumor control and quality of life. The present paper describes the organizational structure of the clinical part of the MR-linac consortium. Furthermore, it elucidates why collaboration on this large project is necessary, and how a central data registry program will be implemented.

The Generation Challenge Programme Platform: Semantic Standards and Workbench for Crop Science

PubMed Central

Bruskiewich, Richard; Senger, Martin; Davenport, Guy; Ruiz, Manuel; Rouard, Mathieu; Hazekamp, Tom; Takeya, Masaru; Doi, Koji; Satoh, Kouji; Costa, Marcos; Simon, Reinhard; Balaji, Jayashree; Akintunde, Akinnola; Mauleon, Ramil; Wanchana, Samart; Shah, Trushar; Anacleto, Mylah; Portugal, Arllet; Ulat, Victor Jun; Thongjuea, Supat; Braak, Kyle; Ritter, Sebastian; Dereeper, Alexis; Skofic, Milko; Rojas, Edwin; Martins, Natalia; Pappas, Georgios; Alamban, Ryan; Almodiel, Roque; Barboza, Lord Hendrix; Detras, Jeffrey; Manansala, Kevin; Mendoza, Michael Jonathan; Morales, Jeffrey; Peralta, Barry; Valerio, Rowena; Zhang, Yi; Gregorio, Sergio; Hermocilla, Joseph; Echavez, Michael; Yap, Jan Michael; Farmer, Andrew; Schiltz, Gary; Lee, Jennifer; Casstevens, Terry; Jaiswal, Pankaj; Meintjes, Ayton; Wilkinson, Mark; Good, Benjamin; Wagner, James; Morris, Jane; Marshall, David; Collins, Anthony; Kikuchi, Shoshi; Metz, Thomas; McLaren, Graham; van Hintum, Theo

2008-01-01

The Generation Challenge programme (GCP) is a global crop research consortium directed toward crop improvement through the application of comparative biology and genetic resources characterization to plant breeding. A key consortium research activity is the development of a GCP crop bioinformatics platform to support GCP research. This platform includes the following: (i) shared, public platform-independent domain models, ontology, and data formats to enable interoperability of data and analysis flows within the platform; (ii) web service and registry technologies to identify, share, and integrate information across diverse, globally dispersed data sources, as well as to access high-performance computational (HPC) facilities for computationally intensive, high-throughput analyses of project data; (iii) platform-specific middleware reference implementations of the domain model integrating a suite of public (largely open-access/-source) databases and software tools into a workbench to facilitate biodiversity analysis, comparative analysis of crop genomic data, and plant breeding decision making. PMID:18483570

Analysis of mammalian gene function through broad based phenotypic screens across a consortium of mouse clinics

PubMed Central

Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl MJ; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie

2015-01-01

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse ES cell knockout resource provides a basis for characterisation of relationships between gene and phenotype. The EUMODIC consortium developed and validated robust methodologies for broad-based phenotyping of knockouts through a pipeline comprising 20 disease-orientated platforms. We developed novel statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no prior functional annotation. We captured data from over 27,000 mice finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. Novel phenotypes were uncovered for many genes with unknown function providing a powerful basis for hypothesis generation and further investigation in diverse systems. PMID:26214591

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

PubMed Central

Stringer, S; Minică, C C; Verweij, K J H; Mbarek, H; Bernard, M; Derringer, J; van Eijk, K R; Isen, J D; Loukola, A; Maciejewski, D F; Mihailov, E; van der Most, P J; Sánchez-Mora, C; Roos, L; Sherva, R; Walters, R; Ware, J J; Abdellaoui, A; Bigdeli, T B; Branje, S J T; Brown, S A; Bruinenberg, M; Casas, M; Esko, T; Garcia-Martinez, I; Gordon, S D; Harris, J M; Hartman, C A; Henders, A K; Heath, A C; Hickie, I B; Hickman, M; Hopfer, C J; Hottenga, J J; Huizink, A C; Irons, D E; Kahn, R S; Korhonen, T; Kranzler, H R; Krauter, K; van Lier, P A C; Lubke, G H; Madden, P A F; Mägi, R; McGue, M K; Medland, S E; Meeus, W H J; Miller, M B; Montgomery, G W; Nivard, M G; Nolte, I M; Oldehinkel, A J; Pausova, Z; Qaiser, B; Quaye, L; Ramos-Quiroga, J A; Richarte, V; Rose, R J; Shin, J; Stallings, M C; Stiby, A I; Wall, T L; Wright, M J; Koot, H M; Paus, T; Hewitt, J K; Ribasés, M; Kaprio, J; Boks, M P; Snieder, H; Spector, T; Munafò, M R; Metspalu, A; Gelernter, J; Boomsma, D I; Iacono, W G; Martin, N G; Gillespie, N A; Derks, E M; Vink, J M

2016-01-01

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40–48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13–20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10−8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use. PMID:27023175

Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.

PubMed

Ahmeti, Kreshnik B; Ajroud-Driss, Senda; Al-Chalabi, Ammar; Andersen, Peter M; Armstrong, Jennifer; Birve, Anne; Blauw, Hylke M; Brown, Robert H; Bruijn, Lucie; Chen, Wenjie; Chio, Adriano; Comeau, Mary C; Cronin, Simon; Diekstra, Frank P; Soraya Gkazi, Athina; Glass, Jonathan D; Grab, Josh D; Groen, Ewout J; Haines, Jonathan L; Hardiman, Orla; Heller, Scott; Huang, Jie; Hung, Wu-Yen; Jaworski, James M; Jones, Ashley; Khan, Humaira; Landers, John E; Langefeld, Carl D; Leigh, P Nigel; Marion, Miranda C; McLaughlin, Russell L; Meininger, Vincent; Melki, Judith; Miller, Jack W; Mora, Gabriele; Pericak-Vance, Margaret A; Rampersaud, Evadnie; Robberecht, Wim; Russell, Laurie P; Salachas, Francois; Saris, Christiaan G; Shatunov, Aleksey; Shaw, Christopher E; Siddique, Nailah; Siddique, Teepu; Smith, Bradley N; Sufit, Robert; Topp, Simon; Traynor, Bryan J; Vance, Caroline; van Damme, Philip; van den Berg, Leonard H; van Es, Michael A; van Vught, Paul W; Veldink, Jan H; Yang, Yi; Zheng, J G

2013-01-01

Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. Individuals with ALS rapidly progress to paralysis and die from respiratory failure within 3 to 5 years after symptom onset. Epidemiological factors explain only a modest amount of the risk for ALS. However, there is growing evidence of a strong genetic component to both familial and sporadic ALS risk. The International Consortium on Amyotrophic Lateral Sclerosis Genetics was established to bring together existing genome-wide association cohorts and identify sporadic ALS susceptibility and age at symptom onset loci. Here, we report the results of a meta-analysis of the International Consortium on Amyotrophic Lateral Sclerosis Genetics genome-wide association samples, consisting of 4243 ALS cases and 5112 controls from 13 European ancestry cohorts from across the United States and Europe. Eight genomic regions provided evidence of association with ALS, including 9p21.2 (rs3849942, odds ratio [OR] = 1.21; p = 4.41 × 10(-7)), 17p11.2 (rs7477, OR = 1.30; p = 2.89 × 10(-7)), and 19p13 (rs12608932, OR = 1.37, p = 1.29 × 10(-7)). Six genomic regions were associated with age at onset of ALS. The strongest evidence for an age of onset locus was observed at 1p34.1, with comparable evidence at rs3011225 (R(2)(partial) = 0.0061; p = 6.59 × 10(-8)) and rs803675 (R(2)(partial) = 0.0060; p = 6.96 × 10(-8)). These associations were consistent across all 13 cohorts. For rs3011225, individuals with at least 1 copy of the minor allele had an earlier average age of onset of over 2 years. Identifying the underlying pathways influencing susceptibility to and age at onset of ALS may provide insight into the pathogenic mechanisms and motivate new pharmacologic targets for this fatal neurodegenerative disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical providers' experiences with returning results from genomic sequencing: an interview study.

PubMed

Wynn, Julia; Lewis, Katie; Amendola, Laura M; Bernhardt, Barbara A; Biswas, Sawona; Joshi, Manasi; McMullen, Carmit; Scollon, Sarah

2018-05-08

Current medical practice includes the application of genomic sequencing (GS) in clinical and research settings. Despite expanded use of this technology, the process of disclosure of genomic results to patients and research participants has not been thoroughly examined and there are no established best practices. We conducted semi-structured interviews with 21 genetic and non-genetic clinicians returning results of GS as part of the NIH funded Clinical Sequencing Exploratory Research (CSER) Consortium projects. Interviews focused on the logistics of sessions, participant/patient reactions and factors influencing them, how the sessions changed with experience, and resources and training recommended to return genomic results. The length of preparation and disclosure sessions varied depending on the type and number of results and their implications. Internal and external databases, online resources and result review meetings were used to prepare. Respondents reported that participants' reactions were variable and ranged from enthusiasm and relief to confusion and disappointment. Factors influencing reactions were types of results, expectations and health status. A recurrent challenge was managing inflated expectations about GS. Other challenges included returning multiple, unanticipated and/or uncertain results and navigating a rare diagnosis. Methods to address these challenges included traditional genetic counseling techniques and modifying practice over time in order to provide anticipatory guidance and modulate expectations. Respondents made recommendations to improve access to genomic resources and genetic referrals to prepare future providers as the uptake of GS increases in both genetic and non-genetic settings. These findings indicate that returning genomic results is similar to return of results in traditional genetic testing but is magnified by the additional complexity and potential uncertainty of the results. Managing patient expectations, initially identified in studies of informed consent, remains an ongoing challenge and highlights the need to address this issue throughout the testing process. The results of this study will help to guide future providers in the disclosure of genomic results and highlight educational needs and resources necessary to prepare providers. Future research on the patient experience, understanding and follow-up of recommendations is needed to more fully understand the disclosure process.

A novel cross-disciplinary multi-institute approach to translational cancer research: lessons learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC).

PubMed

Patel, Ashokkumar A; Gilbertson, John R; Showe, Louise C; London, Jack W; Ross, Eric; Ochs, Michael F; Carver, Joseph; Lazarus, Andrea; Parwani, Anil V; Dhir, Rajiv; Beck, J Robert; Liebman, Michael; Garcia, Fernando U; Prichard, Jeff; Wilkerson, Myra; Herberman, Ronald B; Becich, Michael J

2007-06-08

The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium's intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer-specific biomarkers and encourage collaborative research efforts among the participating centers. The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions' IRB/HIPAA standards. Currently, this "virtual biorepository" has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semi-automated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium's web site. The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.

PubMed

Ng, Maggie C Y; Graff, Mariaelisa; Lu, Yingchang; Justice, Anne E; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Yanek, Lisa R; Feitosa, Mary F; Wojczynski, Mary K; Rand, Kristin; Brody, Jennifer A; Cade, Brian E; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A; Nalls, Michael A; Okut, Hayrettin; Tajuddin, Salman M; Tayo, Bamidele O; Vedantam, Sailaja; Bradfield, Jonathan P; Chen, Guanjie; Chen, Wei-Min; Chesi, Alessandra; Irvin, Marguerite R; Padhukasahasram, Badri; Smith, Jennifer A; Zheng, Wei; Allison, Matthew A; Ambrosone, Christine B; Bandera, Elisa V; Bartz, Traci M; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Bottinger, Erwin P; Carpten, John; Chanock, Stephen J; Chen, Yii-Der Ida; Conti, David V; Cooper, Richard S; Fornage, Myriam; Freedman, Barry I; Garcia, Melissa; Goodman, Phyllis J; Hsu, Yu-Han H; Hu, Jennifer; Huff, Chad D; Ingles, Sue A; John, Esther M; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Ogunniyi, Adesola; Olshan, Andrew; Press, Michael F; Rohde, Rebecca; Rybicki, Benjamin A; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S; Stanford, Janet L; Stevens, Victoria L; Stram, Alex; Strom, Sara S; Vaidya, Dhananjay; Witte, John S; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G; Zonderman, Alan B; Adeyemo, Adebowale; Ambs, Stefan; Cushman, Mary; Faul, Jessica D; Hakonarson, Hakon; Levin, Albert M; Nathanson, Katherine L; Ware, Erin B; Weir, David R; Zhao, Wei; Zhi, Degui; Arnett, Donna K; Grant, Struan F A; Kardia, Sharon L R; Oloapde, Olufunmilayo I; Rao, D C; Rotimi, Charles N; Sale, Michele M; Williams, L Keoki; Zemel, Babette S; Becker, Diane M; Borecki, Ingrid B; Evans, Michele K; Harris, Tamara B; Hirschhorn, Joel N; Li, Yun; Patel, Sanjay R; Psaty, Bruce M; Rotter, Jerome I; Wilson, James G; Bowden, Donald W; Cupples, L Adrienne; Haiman, Christopher A; Loos, Ruth J F; North, Kari E

2017-04-01

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

Implementation of genomics research in Africa: challenges and recommendations

PubMed Central

Adebamowo, Sally N.; Francis, Veronica; Tambo, Ernest; Diallo, Seybou H.; Landouré, Guida; Nembaware, Victoria; Dareng, Eileen; Muhamed, Babu; Odutola, Michael; Akeredolu, Teniola; Nerima, Barbara; Ozumba, Petronilla J.; Mbhele, Slee; Ghanash, Anita; Wachinou, Ablo P.; Ngomi, Nicholas

2018-01-01

ABSTRACT Background: There is exponential growth in the interest and implementation of genomics research in Africa. This growth has been facilitated by the Human Hereditary and Health in Africa (H3Africa) initiative, which aims to promote a contemporary research approach to the study of genomics and environmental determinants of common diseases in African populations. Objective: The purpose of this article is to describe important challenges affecting genomics research implementation in Africa. Methods: The observations, challenges and recommendations presented in this article were obtained through discussions by African scientists at teleconferences and face-to-face meetings, seminars at consortium conferences and in-depth individual discussions. Results: Challenges affecting genomics research implementation in Africa, which are related to limited resources include ill-equipped facilities, poor accessibility to research centers, lack of expertise and an enabling environment for research activities in local hospitals. Challenges related to the research study include delayed funding, extensive procedures and interventions requiring multiple visits, delays setting up research teams and insufficient staff training, language barriers and an underappreciation of cultural norms. While many African countries are struggling to initiate genomics projects, others have set up genomics research facilities that meet international standards. Conclusions: The lessons learned in implementing successful genomics projects in Africa are recommended as strategies to overcome these challenges. These recommendations may guide the development and application of new research programs in low-resource settings. PMID:29336236

Implementation of genomics research in Africa: challenges and recommendations.

PubMed

Adebamowo, Sally N; Francis, Veronica; Tambo, Ernest; Diallo, Seybou H; Landouré, Guida; Nembaware, Victoria; Dareng, Eileen; Muhamed, Babu; Odutola, Michael; Akeredolu, Teniola; Nerima, Barbara; Ozumba, Petronilla J; Mbhele, Slee; Ghanash, Anita; Wachinou, Ablo P; Ngomi, Nicholas

2018-01-01

There is exponential growth in the interest and implementation of genomics research in Africa. This growth has been facilitated by the Human Hereditary and Health in Africa (H3Africa) initiative, which aims to promote a contemporary research approach to the study of genomics and environmental determinants of common diseases in African populations. The purpose of this article is to describe important challenges affecting genomics research implementation in Africa. The observations, challenges and recommendations presented in this article were obtained through discussions by African scientists at teleconferences and face-to-face meetings, seminars at consortium conferences and in-depth individual discussions. Challenges affecting genomics research implementation in Africa, which are related to limited resources include ill-equipped facilities, poor accessibility to research centers, lack of expertise and an enabling environment for research activities in local hospitals. Challenges related to the research study include delayed funding, extensive procedures and interventions requiring multiple visits, delays setting up research teams and insufficient staff training, language barriers and an underappreciation of cultural norms. While many African countries are struggling to initiate genomics projects, others have set up genomics research facilities that meet international standards. The lessons learned in implementing successful genomics projects in Africa are recommended as strategies to overcome these challenges. These recommendations may guide the development and application of new research programs in low-resource settings.

Childhood adiposity and risk of type 1 diabetes: A Mendelian randomization study

PubMed Central

Todd, John A.

2017-01-01

Background The incidence of type 1 diabetes (T1D) is increasing globally. One hypothesis is that increasing childhood obesity rates may explain part of this increase, but, as T1D is rare, intervention studies are challenging to perform. The aim of this study was to assess this hypothesis with a Mendelian randomization approach that uses genetic variants as instrumental variables to test for causal associations. Methods and findings We created a genetic instrument of 23 single nucleotide polymorphisms (SNPs) associated with childhood adiposity in children aged 2–10 years. Summary-level association results for these 23 SNPs with childhood-onset (<17 years) T1D were extracted from a meta-analysis of genome-wide association study with 5,913 T1D cases and 8,828 reference samples. Using inverse-variance weighted Mendelian randomization analysis, we found support for an effect of childhood adiposity on T1D risk (odds ratio 1.32, 95% CI 1.06–1.64 per standard deviation score in body mass index [SDS-BMI]). A sensitivity analysis provided evidence of horizontal pleiotropy bias (p = 0.04) diluting the estimates towards the null. We therefore applied Egger regression and multivariable Mendelian randomization methods to control for this type of bias and found evidence in support of a role of childhood adiposity in T1D (odds ratio in Egger regression, 2.76, 95% CI 1.40–5.44). Limitations of our study include that underlying genes and their mechanisms for most of the genetic variants included in the score are not known. Mendelian randomization requires large sample sizes, and power was limited to provide precise estimates. This research has been conducted using data from the Early Growth Genetics (EGG) Consortium, the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, the Tobacco and Genetics (TAG) Consortium, and the Social Science Genetic Association Consortium (SSGAC), as well as meta-analysis results from a T1D genome-wide association study. Conclusions This study provides genetic support for a link between childhood adiposity and T1D risk. Together with evidence from observational studies, our findings further emphasize the importance of measures to reduce the global epidemic of childhood obesity and encourage mechanistic studies. PMID:28763444

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.

PubMed

Elliott, Katherine S; Chapman, Kay; Day-Williams, Aaron; Panoutsopoulou, Kalliope; Southam, Lorraine; Lindgren, Cecilia M; Arden, Nigel; Aslam, Nadim; Birrell, Fraser; Carluke, Ian; Carr, Andrew; Deloukas, Panos; Doherty, Michael; Loughlin, John; McCaskie, Andrew; Ollier, William E R; Rai, Ashok; Ralston, Stuart; Reed, Mike R; Spector, Timothy D; Valdes, Ana M; Wallis, Gillian A; Wilkinson, Mark; Zeggini, Eleftheria

2013-06-01

Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI. We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium

PubMed Central

Shete, Sanjay; Lau, Ching C; Houlston, Richard S; Claus, Elizabeth B; Barnholtz-Sloan, Jill; Lai, Rose; Il’yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Johansen, Christoffer; Bernstein, Jonine L; Olson, Sara H; Jenkins, Robert B; Yang, Ping; Vick, Nicholas A; Wrensch, Margaret; Davis, Faith G; McCarthy, Bridget J; Leung, Eastwood Hon-chiu; Davis, Caleb; Cheng, Rita; Hosking, Fay J; Armstrong, Georgina N; Liu, Yanhong; Yu, Robert K; Henriksson, Roger; Consortium, The Gliogene; Melin, Beatrice S; Bondy, Melissa L

2011-01-01

Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have demonstrated that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P=0.0005) at 17q12–21.32 and the Z-score of 4.20 (P=0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P=0.008) and the Z-score of 1.47 (P=0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P=0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. PMID:22037877

A genome-wide association study of anorexia nervosa.

PubMed

Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

2014-10-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

PubMed Central

Elliott, Katherine S; Chapman, Kay; Day-Williams, Aaron; Panoutsopoulou, Kalliope; Southam, Lorraine; Lindgren, Cecilia M; Arden, Nigel; Aslam, Nadim; Birrell, Fraser; Carluke, Ian; Carr, Andrew; Deloukas, Panos; Doherty, Michael; Loughlin, John; McCaskie, Andrew; Ollier, William E R; Rai, Ashok; Ralston, Stuart; Reed, Mike R; Spector, Timothy D; Valdes, Ana M; Wallis, Gillian A; Wilkinson, Mark; Zeggini, Eleftheria

2013-01-01

Objectives Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale. Methods We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls. Results We found significant overlap between osteoarthritis and height (p=3.3×10−5 for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10−5). As expected, this signal was attenuated when we adjusted for BMI. Conclusions We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset. PMID:22956599

A genome-wide association study of anorexia nervosa

PubMed Central

Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

2015-01-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation.

PubMed

Bramon, Elvira; Pirinen, Matti; Strange, Amy; Lin, Kuang; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J; Arranz, Maria J; Bakker, Steven; Bender, Stephan; Bruggeman, Richard; Cahn, Wiepke; Chandler, David; Collier, David A; Crespo-Facorro, Benedicto; Dazzan, Paola; de Haan, Lieuwe; Di Forti, Marta; Dragović, Milan; Giegling, Ina; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, René S; Kalaydjieva, Luba; Kravariti, Eugenia; Lawrie, Stephen; Linszen, Don H; Mata, Ignacio; McDonald, Colm; McIntosh, Andrew; Myin-Germeys, Inez; Ophoff, Roel A; Pariante, Carmine M; Paunio, Tiina; Picchioni, Marco; Ripke, Stephan; Rujescu, Dan; Sauer, Heinrich; Shaikh, Madiha; Sussmann, Jessika; Suvisaari, Jaana; Tosato, Sarah; Toulopoulou, Timothea; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Whalley, Heather; Wiersma, Durk; Blackwell, Jenefer M; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A Z; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Wood, Nicholas W; Barroso, Ines; Peltonen, Leena; Lewis, Cathryn M; Murray, Robin M; Donnelly, Peter; Powell, John; Spencer, Chris C A

2014-03-01

Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. 1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls). No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p = .003). A polygenic score analysis found that the Psychiatric GWAS Consortium's panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 × 10(-14)) and explained approximately 2% of the phenotypic variance. Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through meta-analysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Military and Veterans Rehabilitation and Recovery from Injury Network (MAVERICK): Chronic Effects of Neurotrauma Consortium (CENC)

DTIC Science & Technology

2014-10-01

veterans with combat- related mTBI and non-TBI combat-exposed controls on comprehensive neuropsychological, neuroimaging, genomics , biomarkers, and...existing VA healthcare data to study the chronic effects of mild traumatic brain injury (mTBI) on neurodegenerative disease and other comorbidities... mice at different time points pre- and post- single mTBI and repetitive mTBI, and g. Began analysis of tissues samples obtained via the protocol. IX

Japan PGx Data Science Consortium Database: SNPs and HLA genotype data from 2994 Japanese healthy individuals for pharmacogenomics studies.

PubMed

Kamitsuji, Shigeo; Matsuda, Takashi; Nishimura, Koichi; Endo, Seiko; Wada, Chisa; Watanabe, Kenji; Hasegawa, Koichi; Hishigaki, Haretsugu; Masuda, Masatoshi; Kuwahara, Yusuke; Tsuritani, Katsuki; Sugiura, Kenkichi; Kubota, Tomoko; Miyoshi, Shinji; Okada, Kinya; Nakazono, Kazuyuki; Sugaya, Yuki; Yang, Woosung; Sawamoto, Taiji; Uchida, Wataru; Shinagawa, Akira; Fujiwara, Tsutomu; Yamada, Hisaharu; Suematsu, Koji; Tsutsui, Naohisa; Kamatani, Naoyuki; Liou, Shyh-Yuh

2015-06-01

Japan Pharmacogenomics Data Science Consortium (JPDSC) has assembled a database for conducting pharmacogenomics (PGx) studies in Japanese subjects. The database contains the genotypes of 2.5 million single-nucleotide polymorphisms (SNPs) and 5 human leukocyte antigen loci from 2994 Japanese healthy volunteers, as well as 121 kinds of clinical information, including self-reports, physiological data, hematological data and biochemical data. In this article, the reliability of our data was evaluated by principal component analysis (PCA) and association analysis for hematological and biochemical traits by using genome-wide SNP data. PCA of the SNPs showed that all the samples were collected from the Japanese population and that the samples were separated into two major clusters by birthplace, Okinawa and other than Okinawa, as had been previously reported. Among 87 SNPs that have been reported to be associated with 18 hematological and biochemical traits in genome-wide association studies (GWAS), the associations of 56 SNPs were replicated using our data base. Statistical power simulations showed that the sample size of the JPDSC control database is large enough to detect genetic markers having a relatively strong association even when the case sample size is small. The JPDSC database will be useful as control data for conducting PGx studies to explore genetic markers to improve the safety and efficacy of drugs either during clinical development or in post-marketing.

The metabolic pathway of metamifop degradation by consortium ME-1 and its bacterial community structure.

PubMed

Dong, Weiliang; Liu, Kuan; Wang, Fei; Xin, Fengxue; Zhang, Wenming; Zhang, Min; Wu, Hao; Ma, Jiangfeng; Jiang, Min

2017-06-01

Metamifop is universally used in agriculture as a post-emergence aryloxyphenoxy propionate herbicide (AOPP), however its microbial degradation mechanism remains unclear. Consortium ME-1 isolated from AOPP-contaminated soil can degrade metamifop completely after 6 days and utilize it as the carbon source for bacterial growth. Meanwhile, consortium ME-1 possessed the ability to degrade metamifop stably under a wide range of pH (6.0-10.0) or temperature (20-42 °C). HPLC-MS analysis shows that N-(2-fluorophenyl)-2-(4-hydroxyphenoxy)-N-methyl propionamide, 2-(4-hydroxyphenoxy)-propionic acid, 6-chloro-2-benzoxazolinone and N-methyl-2-fluoroaniline, were detected and identified as four intermediate metabolites. Based on the metabolites identified, a putative metabolic pathway of metamifop was proposed for the first time. In addition, the consortium ME-1 was also able to transform or degrade other AOPP such as fenoxaprop-p-ethyl, clodinafop-propargyl, quizalofop-p-ethyl and cyhalofop-butyl. Moreover, the community structure of ME-1 with lower microbial diversity compared with the initial soil sample was investigated by high throughput sequencing. β-Proteobacteria and Sphingobacteria were the largest class with sequence percentages of 46.6% and 27.55% at the class level. In addition, 50 genera were classified in consortium ME-1, of which Methylobacillus, Sphingobacterium, Bordetella and Flavobacterium were the dominant genera with sequence percentages of 25.79, 25.61, 14.68 and 9.55%, respectively.

CUBN Is a Gene Locus for Albuminuria

PubMed Central

Böger, Carsten A.; Chen, Ming-Huei; Tin, Adrienne; Olden, Matthias; Köttgen, Anna; de Boer, Ian H.; Fuchsberger, Christian; O'Seaghdha, Conall M.; Pattaro, Cristian; Teumer, Alexander; Liu, Ching-Ti; Glazer, Nicole L.; Li, Man; O'Connell, Jeffrey R.; Tanaka, Toshiko; Peralta, Carmen A.; Kutalik, Zoltán; Luan, Jian'an; Zhao, Jing Hua; Hwang, Shih-Jen; Akylbekova, Ermeg; Kramer, Holly; van der Harst, Pim; Smith, Albert V.; Lohman, Kurt; de Andrade, Mariza; Hayward, Caroline; Kollerits, Barbara; Tönjes, Anke; Aspelund, Thor; Ingelsson, Erik; Eiriksdottir, Gudny; Launer, Lenore J.; Harris, Tamara B.; Shuldiner, Alan R.; Mitchell, Braxton D.; Arking, Dan E.; Franceschini, Nora; Boerwinkle, Eric; Egan, Josephine; Hernandez, Dena; Reilly, Muredach; Townsend, Raymond R.; Lumley, Thomas; Siscovick, David S.; Psaty, Bruce M.; Kestenbaum, Bryan; Haritunians, Talin; Bergmann, Sven; Vollenweider, Peter; Waeber, Gerard; Mooser, Vincent; Waterworth, Dawn; Johnson, Andrew D.; Florez, Jose C.; Meigs, James B.; Lu, Xiaoning; Turner, Stephen T.; Atkinson, Elizabeth J.; Leak, Tennille S.; Aasarød, Knut; Skorpen, Frank; Syvänen, Ann-Christine; Illig, Thomas; Baumert, Jens; Koenig, Wolfgang; Krämer, Bernhard K.; Devuyst, Olivier; Mychaleckyj, Josyf C.; Minelli, Cosetta; Bakker, Stephan J.L.; Kedenko, Lyudmyla; Paulweber, Bernhard; Coassin, Stefan; Endlich, Karlhans; Kroemer, Heyo K.; Biffar, Reiner; Stracke, Sylvia; Völzke, Henry; Stumvoll, Michael; Mägi, Reedik; Campbell, Harry; Vitart, Veronique; Hastie, Nicholas D.; Gudnason, Vilmundur; Kardia, Sharon L.R.; Liu, Yongmei; Polasek, Ozren; Curhan, Gary; Kronenberg, Florian; Prokopenko, Inga; Rudan, Igor; Ärnlöv, Johan; Hallan, Stein; Navis, Gerjan; Parsa, Afshin; Ferrucci, Luigi; Coresh, Josef; Shlipak, Michael G.; Bull, Shelley B.; Paterson, Andrew D.; Wichmann, H.-Erich; Wareham, Nicholas J.; Loos, Ruth J.F.; Rotter, Jerome I.; Pramstaller, Peter P.; Cupples, L. Adrienne; Beckmann, Jacques S.; Yang, Qiong; Heid, Iris M.; Rettig, Rainer; Dreisbach, Albert W.; Bochud, Murielle

2011-01-01

Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 × 10−11) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes. PMID:21355061

A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype

PubMed Central

Hass, Johanna; Walton, Esther; Kirsten, Holger; Liu, Jingyu; Priebe, Lutz; Wolf, Christiane; Karbalai, Nazanin; Gollub, Randy; White, Tonya; Roessner, Veit; Müller, Kathrin U.; Paus, Tomas; Smolka, Michael N.; Schumann, Gunter; Scholz, Markus; Cichon, Sven; Calhoun, Vince; Ehrlich, Stefan

2013-01-01

Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP) related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328). A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170) on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10) had p-values between 6.75×10−6 and 8.3×10−7. Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings. Identification of causal variants and their functional effects may unveil yet unknown players in the neurodevelopment and the pathogenesis of neuropsychiatric disorders. PMID:23805179

Use of low-coverage, large-insert, short-read data for rapid and accurate generation of enhanced-quality draft Pseudomonas genome sequences.

PubMed

O'Brien, Heath E; Gong, Yunchen; Fung, Pauline; Wang, Pauline W; Guttman, David S

2011-01-01

Next-generation genomic technology has both greatly accelerated the pace of genome research as well as increased our reliance on draft genome sequences. While groups such as the Genomics Standards Consortium have made strong efforts to promote genome standards there is a still a general lack of uniformity among published draft genomes, leading to challenges for downstream comparative analyses. This lack of uniformity is a particular problem when using standard draft genomes that frequently have large numbers of low-quality sequencing tracts. Here we present a proposal for an "enhanced-quality draft" genome that identifies at least 95% of the coding sequences, thereby effectively providing a full accounting of the genic component of the genome. Enhanced-quality draft genomes are easily attainable through a combination of small- and large-insert next-generation, paired-end sequencing. We illustrate the generation of an enhanced-quality draft genome by re-sequencing the plant pathogenic bacterium Pseudomonas syringae pv. phaseolicola 1448A (Pph 1448A), which has a published, closed genome sequence of 5.93 Mbp. We use a combination of Illumina paired-end and mate-pair sequencing, and surprisingly find that de novo assemblies with 100x paired-end coverage and mate-pair sequencing with as low as low as 2-5x coverage are substantially better than assemblies based on higher coverage. The rapid and low-cost generation of large numbers of enhanced-quality draft genome sequences will be of particular value for microbial diagnostics and biosecurity, which rely on precise discrimination of potentially dangerous clones from closely related benign strains.

Genome-wide association studies in preterm birth: implications for the practicing obstetrician-gynaecologist

PubMed Central

2013-01-01

Preterm birth has the highest mortality and morbidity of all pregnancy complications. The burden of preterm birth on public health worldwide is enormous, yet there are few effective means to prevent a preterm delivery. To date, much of its etiology is unexplained, but genetic predisposition is thought to play a major role. In the upcoming year, the international Preterm Birth Genome Project (PGP) consortium plans to publish a large genome wide association study in early preterm birth. Genome-wide association studies (GWAS) are designed to identify common genetic variants that influence health and disease. Despite the many challenges that are involved, GWAS can be an important discovery tool, revealing genetic variations that are associated with preterm birth. It is highly unlikely that findings of a GWAS can be directly translated into clinical practice in the short run. Nonetheless, it will help us to better understand the etiology of preterm birth and the GWAS results will generate new hypotheses for further research, thus enhancing our understanding of preterm birth and informing prevention efforts in the long run. PMID:23445776

Genome-wide association studies in preterm birth: implications for the practicing obstetrician-gynaecologist.

PubMed

Dolan, Siobhan M; Christiaens, Inge

2013-01-01

Preterm birth has the highest mortality and morbidity of all pregnancy complications. The burden of preterm birth on public health worldwide is enormous, yet there are few effective means to prevent a preterm delivery. To date, much of its etiology is unexplained, but genetic predisposition is thought to play a major role. In the upcoming year, the international Preterm Birth Genome Project (PGP) consortium plans to publish a large genome wide association study in early preterm birth. Genome-wide association studies (GWAS) are designed to identify common genetic variants that influence health and disease. Despite the many challenges that are involved, GWAS can be an important discovery tool, revealing genetic variations that are associated with preterm birth. It is highly unlikely that findings of a GWAS can be directly translated into clinical practice in the short run. Nonetheless, it will help us to better understand the etiology of preterm birth and the GWAS results will generate new hypotheses for further research, thus enhancing our understanding of preterm birth and informing prevention efforts in the long run.

Functional Genomics Using the Saccharomyces cerevisiae Yeast Deletion Collections.

PubMed

Nislow, Corey; Wong, Lai Hong; Lee, Amy Huei-Yi; Giaever, Guri

2016-09-01

Constructed by a consortium of 16 laboratories, the Saccharomyces genome-wide deletion collections have, for the past decade, provided a powerful, rapid, and inexpensive approach for functional profiling of the yeast genome. Loss-of-function deletion mutants were systematically created using a polymerase chain reaction (PCR)-based gene deletion strategy to generate a start-to-stop codon replacement of each open reading frame by homologous recombination. Each strain carries two molecular barcodes that serve as unique strain identifiers, enabling their growth to be analyzed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays or through the use of next-generation sequencing technologies. Functional profiling of the deletion collections, using either strain-by-strain or parallel assays, provides an unbiased approach to systematically survey the yeast genome. The Saccharomyces yeast deletion collections have proved immensely powerful in contributing to the understanding of gene function, including functional relationships between genes and genetic pathways in response to diverse genetic and environmental perturbations. © 2016 Cold Spring Harbor Laboratory Press.

Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers

PubMed Central

Im, Kate M.; Kirchhoff, Tomas; Wang, Xianshu; Green, Todd; Chow, Clement Y.; Vijai, Joseph; Korn, Joshua; Gaudet, Mia M.; Fredericksen, Zachary; Pankratz, V. Shane; Guiducci, Candace; Crenshaw, Andrew; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Mai, Phuong L.; Greene, Mark H.; Piedmonte, Marion; Rubinstein, Wendy S.; Hogervorst, Frans B.; Rookus, Matti A.; Collée, J. Margriet; Hoogerbrugge, Nicoline; van Asperen, Christi J.; Meijers-Heijboer, Hanne E. J.; Van Roozendaal, Cees E.; Caldes, Trinidad; Perez-Segura, Pedro; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Blecharz, Paweł; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Barkardottir, Rosa B.; Montagna, Marco; D'Andrea, Emma; Devilee, Peter; Olopade, Olufunmilayo I.; Neuhausen, Susan L.; Peissel, Bernard; Bonanni, Bernardo; Peterlongo, Paolo; Singer, Christian F.; Rennert, Gad; Lejbkowicz, Flavio; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda Ewart; Caligo, Maria Adelaide; Beattie, Mary S.; Chan, Salina; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Phelan, Catherine; Narod, Steven; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary-Beth; Tung, Nadine; Hansen, Thomas v. O.; Osorio, Ana; Benitez, Javier; Durán, Mercedes; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare T.; Frost, Debra; Platte, Radka; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Paterson, Joan; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary; Walker, Lisa; Rogers, Mark T.; Side, Lucy E.; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Laitman, Yael; Meindl, Alfons; Deissler, Helmut; Varon-Mateeva, Raymonda; Preisler-Adams, Sabine; Kast, Karin; Venat-Bouvet, Laurence; Stoppa-Lyonnet, Dominique; Chenevix-Trench, Georgia; Easton, Douglas F.; Klein, Robert J.; Daly, Mark J.; Friedman, Eitan; Dean, Michael; Clark, Andrew G.; Altshuler, David M.; Antoniou, Antonis C.; Couch, Fergus J.; Offit, Kenneth; Gold, Bert

2011-01-01

Abstract Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals predict long-range linkage dis-equilibrium (LD) resulting from a selective sweep, although genetic drift in a founder population may also act to create long-distance LD. To date, few studies have used the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of hundreds of women from a large international consortium of BRCA1 and BRCA2 mutation carriers and found that AJ women exhibited long-range haplotypes compared to CNJ women. More than 50% of the AJ chromosomes with the BRCA1 185delAG mutation share an identical 2.1 Mb haplotype and nearly 16% of AJ chromosomes carrying the BRCA2 6174delT mutation share a 1.4 Mb haplotype. Simulations based on the best inference of Ashkenazi population demography indicate that long-range haplotypes are expected in the context of a genome-wide survey. Our results are consistent with the hypothesis that a local bottleneck effect from population size constriction events could by chance have resulted in the large haplotype blocks observed at high frequency in the BRCA1 and BRCA2 regions of Ashkenazi Jews. PMID:21597964

Surmounting the unique challenges in health disparities education: a multi-institution qualitative study.

PubMed

Carter-Pokras, Olivia; Bereknyei, Sylvia; Lie, Desiree; Braddock, Clarence H

2010-05-01

The National Consortium for Multicultural Education for Health Professionals (Consortium) comprises educators representing 18 US medical schools, funded by the National Institutes of Health. Collective lessons learned from curriculum implementation by principal investigators (PIs) have the potential to guide similar educational endeavors. Describe Consortium PI's self-reported challenges with curricular development, solutions and their new curricular products. Information was collected from PIs over 2 months using a 53-question structured three-part questionnaire. The questionnaire addressed PI demographics, curriculum implementation challenges and solutions, and newly created curricular products. Study participants were 18 Consortium PIs. Descriptive analysis was used for quantitative data. Narrative responses were analyzed and interpreted using qualitative thematic coding. Response rate was 100%. Common barriers and challenges identified by PIs were: finding administrative and leadership support, sustaining the momentum, continued funding, finding curricular space, accessing and engaging communities, and lack of education research methodology skills. Solutions identified included engaging stakeholders, project-sharing across schools, advocacy and active participation in committees and community, and seeking sustainable funding. All Consortium PIs reported new curricular products and extensive dissemination efforts outside their own institutions. The Consortium model has added benefits for curricular innovation and dissemination for cultural competence education to address health disparities. Lessons learned may be applicable to other educational innovation efforts.

BioNano genome mapping of individual chromosomes supports physical mapping and sequence assembly in complex plant genomes.

PubMed

Staňková, Helena; Hastie, Alex R; Chan, Saki; Vrána, Jan; Tulpová, Zuzana; Kubaláková, Marie; Visendi, Paul; Hayashi, Satomi; Luo, Mingcheng; Batley, Jacqueline; Edwards, David; Doležel, Jaroslav; Šimková, Hana

2016-07-01

The assembly of a reference genome sequence of bread wheat is challenging due to its specific features such as the genome size of 17 Gbp, polyploid nature and prevalence of repetitive sequences. BAC-by-BAC sequencing based on chromosomal physical maps, adopted by the International Wheat Genome Sequencing Consortium as the key strategy, reduces problems caused by the genome complexity and polyploidy, but the repeat content still hampers the sequence assembly. Availability of a high-resolution genomic map to guide sequence scaffolding and validate physical map and sequence assemblies would be highly beneficial to obtaining an accurate and complete genome sequence. Here, we chose the short arm of chromosome 7D (7DS) as a model to demonstrate for the first time that it is possible to couple chromosome flow sorting with genome mapping in nanochannel arrays and create a de novo genome map of a wheat chromosome. We constructed a high-resolution chromosome map composed of 371 contigs with an N50 of 1.3 Mb. Long DNA molecules achieved by our approach facilitated chromosome-scale analysis of repetitive sequences and revealed a ~800-kb array of tandem repeats intractable to current DNA sequencing technologies. Anchoring 7DS sequence assemblies obtained by clone-by-clone sequencing to the 7DS genome map provided a valuable tool to improve the BAC-contig physical map and validate sequence assembly on a chromosome-arm scale. Our results indicate that creating genome maps for the whole wheat genome in a chromosome-by-chromosome manner is feasible and that they will be an affordable tool to support the production of improved pseudomolecules. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Congruence as a measurement of extended haplotype structure across the genome

PubMed Central

2012-01-01

Background Historically, extended haplotypes have been defined using only a few data points, such as alleles for several HLA genes in the MHC. High-density SNP data, and the increasing affordability of whole genome SNP typing, creates the opportunity to define higher resolution extended haplotypes. This drives the need for new tools that support quantification and visualization of extended haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP data across the major histocompatibility complex (MHC) for 2,300 complete families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC), we developed software for studying extended haplotypes. Methods The software, called ExHap (Extended Haplotype), uses a similarity measurement we term congruence to identify and quantify long-range allele identity. Using ExHap, we analyzed congruence in both the T1DGC data and family-phased data from the International HapMap Project. Results Congruent chromosomes from the T1DGC data have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64 megabases of the MHC (HLA-DRB1 to HLA-A). Thirty-three of 132 DQ-DR-B-A defined haplotype groups have > 50% congruent chromosomes in this region. For example, 92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to HLA-A (99.8% allele identity). We also applied ExHap to all 22 autosomes for both CEU and YRI cohorts from the International HapMap Project, identifying multiple candidate extended haplotypes. Conclusions Long-range congruence is not unique to the MHC region. Patterns of allele identity on phased chromosomes provide a simple, straightforward approach to visually and quantitatively inspect complex long-range structural patterns in the genome. Such patterns aid the biologist in appreciating genetic similarities and differences across cohorts, and can lead to hypothesis generation for subsequent studies. PMID:22369243

Beyond the genomics blueprint: the 4th Human Variome Project Meeting, UNESCO, Paris, 2012.

PubMed

Kohonen-Corish, Maija R J; Smith, Timothy D; Robinson, Helen M

2013-07-01

The 4th Biennial Meeting of the Human Variome Project Consortium was held at the headquarters of the United Nations Educational, Scientific and Cultural Organization (UNESCO) in Paris, 11-15 June 2012. The Human Variome Project, a nongovernmental organization and an official partner of UNESCO, enables the routine collection, curation, interpretation, and sharing of information on all human genetic variation. This meeting was attended by more than 180 delegates from 39 countries and continued the theme of addressing issues of implementation in this unique project. The meeting was structured around the four main themes of the Human Variome Project strategic plan, "Project Roadmap 2012-2016": setting normative function, behaving ethically, sharing knowledge, and building capacity. During the meeting, the members held extensive discussions to formulate an action plan in the key areas of the Human Variome Project. The actions agreed on were promulgated at the Project's two Advisory Council and Scientific Advisory Committee postconference meetings.

Highlights from SelectBio 2015: Academic Drug Discovery Conference, Cambridge, UK, 19-20 May 2015.

PubMed

Spencer, John; Coaker, Hannah

2015-01-01

The SelectBio 2015: Academic Drug Discovery Conference was held in Cambridge, UK, on 19-20 May 2015. Building on the success of academic drug discovery events in the USA, this conference aimed to showcase the exciting new research emerging from academic drug discovery and to help bridge the gap between basic research and commercial application. At the event the authors heard from a number of speakers on a broad array of topics, from partnering models for academia and industry to novel drug discovery approaches across various therapeutic areas, with a few talks, such as those by Susanne Muller-Knapp (Structure Genomics Consortium, Oxford University, Oxford, UK) and Julian Blagg (Institute of Cancer Research, UK), covering both remits, by highlighting a number of such partnerships and then delving into some case studies. The conference concluded with a heated debate on whether phenotypic discovery should be favored over targeted discovery in academia and pharma, in a panel discussion chaired by Roland Wolkowicz (San Diego State University, USA).

Metabolic resource allocation in individual microbes determines ecosystem interactions and spatial dynamics

PubMed Central

Harcombe, William R.; Riehl, William J.; Dukovski, Ilija; Granger, Brian R.; Betts, Alex; Lang, Alex H.; Bonilla, Gracia; Kar, Amrita; Leiby, Nicholas; Mehta, Pankaj; Marx, Christopher J.; Segrè, Daniel

2014-01-01

Summary The inter-species exchange of metabolites plays a key role in the spatio-temporal dynamics of microbial communities. This raises the question whether ecosystem-level behavior of structured communities can be predicted using genome-scale models of metabolism for multiple organisms. We developed a modeling framework that integrates dynamic flux balance analysis with diffusion on a lattice, and applied it to engineered consortia. First, we predicted, and experimentally confirmed, the species-ratio to which a 2-species mutualistic consortium converges, and the equilibrium composition of a newly engineered 3-member community. We next identified a specific spatial arrangement of colonies, which gives rise to what we term the “eclipse dilemma”: does a competitor placed between a colony and its cross-feeding partner benefit or hurt growth of the original colony? Our experimentally validated finding, that the net outcome is beneficial, highlights the complex nature of metabolic interactions in microbial communities, while at the same time demonstrating their predictability. PMID:24794435

Announcing the Launch of CPTAC’s Proteogenomics DREAM Challenge | Office of Cancer Clinical Proteomics Research

Cancer.gov

This week, we are excited to announce the launch of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) Proteogenomics Computational DREAM Challenge.  The aim of this Challenge is to encourage the generation of computational methods for extracting information from the cancer proteome and for linking those data to genomic and transcriptomic information.  The specific goals are to predict proteomic and phosphoproteomic data from other multiple data types including transcriptomics and genetics.

Schizophrenia: Hope on the Horizon.

PubMed

Sullivan, Patrick F

2015-01-01

In July 2014, an international consortium of schizophrenia researchers co-founded by the author mounted the largest biological experiment in the history of psychiatry and found eighty new regions in the genome associated with the illness. With many more avenues for exploring the biological underpinnings of schizophrenia now available to neuroscientists, hope may be on the way for the estimated 2.4 million Americans and 1 in 100 people worldwide affected by the illness, one in which drugs have limited impact and there is no known cure.

Rheumatoid arthritis association at 6q23

PubMed Central

Thomson, Wendy; Barton, Anne; Ke, Xiayi; Eyre, Steve; Hinks, Anne; Bowes, John; Donn, Rachelle; Symmons, Deborah; Hider, Samantha; Bruce, Ian N; Wilson, Anthony G; Marinou, Ioanna; Morgan, Ann; Emery, Paul; Carter, Angela; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Strachan, David; Worthington, Jane

2009-01-01

The Wellcome Trust Case Control Consortium (WTCCC) identified nine single SNPs putatively associated with rheumatoid arthritis at P = 1 × 10 -5 - 5 × 10-7 in a genome-wide association screen. One, rs6920220, was unequivocally replicated (trend P = 1.1 × 10-8) in a validation study, as described here. This SNP maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-α-induced protein 3 (TNFAIP3). PMID:17982455

Knowledge Mobilization across Boundaries with the Use of Novel Organizational Structures, Conferencing Strategies, and Technological Tools: The Ontario Consortium of Undergraduate Biology Educators (oCUBE) Model

ERIC Educational Resources Information Center

Kajiura, Lovaye; Smit, Julie; Montpetit, Colin; Kelly, Tamara; Waugh, Jennifer; Rawle, Fiona; Clark, Julie; Neumann, Melody; French, Michelle

2014-01-01

The Ontario Consortium of Undergraduate Biology Educators (oCUBE) brings together over 50 biology educators from 18 Ontario universities with the common goal to improve the biology undergraduate experience for both students and educators. This goal is achieved through an innovative mix of highly interactive face-to-face meetings, online…

The pediatric diabetes consortium: improving care of children with type 1 diabetes through collaborative research.

PubMed

2010-09-01

Although there are some interactions between the major pediatric diabetes programs in the United States, there has been no formal, independent structure for collaboration, the sharing of information, and the development of joint research projects that utilize common outcome measures. To fill this unmet clinical and research need, a consortium of seven pediatric diabetes centers in the United States has formed the Pediatric Diabetes Consortium (PDC) through an unrestricted grant from Novo Nordisk, Inc. (Princeton, NJ). This article describes the organizational structure of the PDC and the design of a study of important clinical outcomes in children and adolescents with new-onset, type 1 diabetes mellitus (T1DM). The outcomes study will describe the changes in A1c levels, the frequency of adverse events (diabetic ketoacidosis/severe hypoglycemia), and the frequency and timing of the "honeymoon" phase in newly diagnosed patients with T1DM over the first 12-24 months of the disease and examine the relationship between these clinical outcomes and demographic, socioeconomic, and treatment factors. This project will also allow the Consortium to develop a cohort of youth with T1DM whose clinical course has been well characterized and who wish to participate in future clinical trials and/or contribute to a repository of biological samples.

Successive changes in community structure of an ethylbenzene-degrading sulfate-reducing consortium.

PubMed

Nakagawa, Tatsunori; Sato, Shinya; Yamamoto, Yoko; Fukui, Manabu

2002-06-01

The microbial community structure and successive changes in a mesophilic ethylbenzene-degrading sulfate-reducing consortium were for the first time clarified by the denaturing gradient gel electrophoresis (DGGE) analysis of the PCR amplified 16S rRNA gene fragments. At least ten bands on the DGGE gel were detected in the stationary phase. Phylogenetic analysis of the DGGE bands revealed that the consortium consisted of different eubacterial phyla including the delta subgroup of Proteobacteria, the order Sphingobacteriales, the order Spirochaetales, and the unknown bacterium. The most abundant band C was closely related to strain mXyS1, an m-xylene-degrading sulfate-reducing bacterium (SRB), and occurred as a sole band on DGGE gels in the logarithmic growth phase that 40% ethylbenzene was consumed accompanied by sulfide production. During further prolonged incubation, the dominancy of band C did not change. These results suggest that SRB corresponds to the most abundant band C and contributes mainly to the degradation of ethylbenzene coupled with sulfate reduction.

Planning the Human Variome Project: The Spain Report†

PubMed Central

Kaput, Jim; Cotton, Richard G. H.; Hardman, Lauren; Al Aqeel, Aida I.; Al-Aama, Jumana Y.; Al-Mulla, Fahd; Aretz, Stefan; Auerbach, Arleen D.; Axton, Myles; Bapat, Bharati; Bernstein, Inge T.; Bhak, Jong; Bleoo, Stacey L.; Blöcker, Helmut; Brenner, Steven E.; Burn, John; Bustamante, Mariona; Calzone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T.; Díaz, Carlos; Dobrowolski, Steven; dos Santos, M. Rosário N.; Ekong, Rosemary; Flanagan, Simon B.; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V.; Greenblatt, Marc S.; Hamosh, Ada; Hancock, John M.; Hardison, Ross; Harrison, Terence M.; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J.; Barash, Carol Isaacson; Izagirre, Neskuts; Jung, Jongsun; Kojima, Toshio; Laradi, Sandrine; Lee, Yeon-Su; Lee, Jong-Young; Gil-da-Silva-Lopes, Vera L.; Macrae, Finlay A.; Maglott, Donna; Marafie, Makia J.; Marsh, Steven G.E.; Matsubara, Yoichi; Messiaen, Ludwine M.; Möslein, Gabriela; Netea, Mihai G.; Norton, Melissa L.; Oefner, Peter J.; Oetting, William S.; O’Leary, James C.; de Ramirez, Ana Maria Oller; Paalman, Mark H.; Parboosingh, Jillian; Patrinos, George P.; Perozzi, Giuditta; Phillips, Ian R.; Povey, Sue; Prasad, Suyash; Qi, Ming; Quin, David J.; Ramesar, Rajkumar S.; Richards, C. Sue; Savige, Judith; Scheible, Dagmar G.; Scott, Rodney J.; Seminara, Daniela; Shephard, Elizabeth A.; Sijmons, Rolf H.; Smith, Timothy D.; Sobrido, María-Jesús; Tanaka, Toshihiro; Tavtigian, Sean V.; Taylor, Graham R.; Teague, Jon; Töpel, Thoralf; Ullman-Cullere, Mollie; Utsunomiya, Joji; van Kranen, Henk J.; Vihinen, Mauno; Watson, Michael; Webb, Elizabeth; Weber, Thomas K.; Yeager, Meredith; Yeom, Young I.; Yim, Seon-Hee; Yoo, Hyang-Sook

2018-01-01

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Since variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008. PMID:19306394

Planning the human variome project: the Spain report.

PubMed

Kaput, Jim; Cotton, Richard G H; Hardman, Lauren; Watson, Michael; Al Aqeel, Aida I; Al-Aama, Jumana Y; Al-Mulla, Fahd; Alonso, Santos; Aretz, Stefan; Auerbach, Arleen D; Bapat, Bharati; Bernstein, Inge T; Bhak, Jong; Bleoo, Stacey L; Blöcker, Helmut; Brenner, Steven E; Burn, John; Bustamante, Mariona; Calzone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T; Díaz, Carlos; Dobrowolski, Steven; dos Santos, M Rosário N; Ekong, Rosemary; Flanagan, Simon B; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V; Greenblatt, Marc S; Hamosh, Ada; Hancock, John M; Hardison, Ross; Harrison, Terence M; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J; Barash, Carol Isaacson; Izagirre, Neskuts; Jung, Jongsun; Kojima, Toshio; Laradi, Sandrine; Lee, Yeon-Su; Lee, Jong-Young; Gil-da-Silva-Lopes, Vera L; Macrae, Finlay A; Maglott, Donna; Marafie, Makia J; Marsh, Steven G E; Matsubara, Yoichi; Messiaen, Ludwine M; Möslein, Gabriela; Netea, Mihai G; Norton, Melissa L; Oefner, Peter J; Oetting, William S; O'Leary, James C; de Ramirez, Ana Maria Oller; Paalman, Mark H; Parboosingh, Jillian; Patrinos, George P; Perozzi, Giuditta; Phillips, Ian R; Povey, Sue; Prasad, Suyash; Qi, Ming; Quin, David J; Ramesar, Rajkumar S; Richards, C Sue; Savige, Judith; Scheible, Dagmar G; Scott, Rodney J; Seminara, Daniela; Shephard, Elizabeth A; Sijmons, Rolf H; Smith, Timothy D; Sobrido, María-Jesús; Tanaka, Toshihiro; Tavtigian, Sean V; Taylor, Graham R; Teague, Jon; Töpel, Thoralf; Ullman-Cullere, Mollie; Utsunomiya, Joji; van Kranen, Henk J; Vihinen, Mauno; Webb, Elizabeth; Weber, Thomas K; Yeager, Meredith; Yeom, Young I; Yim, Seon-Hee; Yoo, Hyang-Sook

2009-04-01

The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008. (c) 2009 Wiley-Liss, Inc.

The modest beginnings of one genome project.

PubMed

Kaback, David B

2013-06-01

One of the top things on a geneticist's wish list has to be a set of mutants for every gene in their particular organism. Such a set was produced for the yeast, Saccharomyces cerevisiae near the end of the 20th century by a consortium of yeast geneticists. However, the functional genomic analysis of one chromosome, its smallest, had already begun more than 25 years earlier as a project that was designed to define most or all of that chromosome's essential genes by temperature-sensitive lethal mutations. When far fewer than expected genes were uncovered, the relatively new field of molecular cloning enabled us and indeed, the entire community of yeast researchers to approach this problem more definitively. These studies ultimately led to cloning, genomic sequencing, and the production and phenotypic analysis of the entire set of knockout mutations for this model organism as well as a better concept of what defines an essential function, a wish fulfilled that enables this model eukaryote to continue at the forefront of research in modern biology.

The clinical implications of immunogenomics in colorectal cancer: A path for precision medicine.

PubMed

Riley, Jenny M; Cross, Ashley W; Paulos, Chrystal M; Rubinstein, Mark P; Wrangle, John; Camp, E Ramsay

2018-04-15

Colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths in the United States. Large multi-omic databases, such as The Cancer Genome Atlas and the International Colorectal Cancer Subtyping Consortium, have identified distinct molecular subtypes related to anatomy. The identification of genomic alterations in CRC is now critical because of the recent success and US Food and Drug Administration approval of pembrolizumab and nivolumab for microsatellite-instable tumors. In parallel, landmark studies have established the prognostic significance of the CRC tumor-infiltrating lymphocyte and the clinical impact of the tumor immune microenvironment. As a result, there is a growing appreciation for immunogenomics, the interconnected relation between tumor genomics and the immune microenvironment. The clinical implications of CRC immunogenomics continue to expand, and it will likely serve as a guide for next-generation immunotherapy strategies for improving outcomes for this disease. Cancer 2018;124:1650-9. © 2018 American Cancer Society. © 2018 American Cancer Society.

Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization

PubMed Central

Zhang, Ben; Shu, Xiao-Ou; Delahanty, Ryan J.; Zeng, Chenjie; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Wen, Wanqing; Long, Jirong; Li, Chun; Dunning, Alison M.; Chang-Claude, Jenny; Shah, Mitul; Perkins, Barbara J.; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; Floris, Giuseppe; Schmidt, Marjanka K.; Rookus, Matti A.; van den Hurk, Katja; de Kort, Wim L. A. M.; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Li, Jingmei; Humphreys, Keith; Brand, Judith; Guénel, Pascal; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Benitez, Javier; Zamora, M. Pilar; Perez, Jose I. A.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Chenevix-Trench, Georgia; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Marchand, Loic Le; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J.; Martens, John W. M.; Tilanus-Linthorst, Madeleine M. A.; Collée, J. Margriet; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony J.; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Garcia-Closas, Montserrat; Brinton, Louise; Lissowska, Jolanta; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Radice, Paolo; Bogdanova, Natalia; Antonenkova, Natalia; Dörk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Devilee, Peter; Seynaeve, Caroline; Van Asperen, Christi J.; Jakubowska, Anna; Lubiński, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Hamann, Ute; Torres, Diana; Schmutzler, Rita K.; Neuhausen, Susan L.; Anton-Culver, Hoda; Kristensen, Vessela N.; Grenaker Alnæs, Grethe I.; Pierce, Brandon L.; Kraft, Peter; Peters, Ulrike; Lindstrom, Sara; Seminara, Daniela; Burgess, Stephen; Ahsan, Habibul; Whittemore, Alice S.; John, Esther M.; Gammon, Marilie D.; Malone, Kathleen E.; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Pharoah, Paul D. P.; Simard, Jacques; Hall, Per; Hunter, David J.; Easton, Douglas F.

2015-01-01

Background: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. Methods: We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control subjects, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control subjects. Results: The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor–positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5×10–8. Conclusions: Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer. PMID:26296642

Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

PubMed

de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed; White, Jacqui; Morgan, Hugh; Ramirez-Solis, Ramiro; Sorg, Tania; Wells, Sara; Fuchs, Helmut; Fray, Martin; Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl Mj; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie; Holmes, Chris; Steel, Karen P; Herault, Yann; Gailus-Durner, Valérie; Mallon, Ann-Marie; Brown, Steve Dm

2015-09-01

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.

ENT COBRA (Consortium for Brachytherapy Data Analysis): interdisciplinary standardized data collection system for head and neck patients treated with interventional radiotherapy (brachytherapy).

PubMed

Tagliaferri, Luca; Kovács, György; Autorino, Rosa; Budrukkar, Ashwini; Guinot, Jose Luis; Hildebrand, Guido; Johansson, Bengt; Monge, Rafael Martìnez; Meyer, Jens E; Niehoff, Peter; Rovirosa, Angeles; Takàcsi-Nagy, Zoltàn; Dinapoli, Nicola; Lanzotti, Vito; Damiani, Andrea; Soror, Tamer; Valentini, Vincenzo

2016-08-01

Aim of the COBRA (Consortium for Brachytherapy Data Analysis) project is to create a multicenter group (consortium) and a web-based system for standardized data collection. GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Radiotherapy & Oncology) Head and Neck (H&N) Working Group participated in the project and in the implementation of the consortium agreement, the ontology (data-set) and the necessary COBRA software services as well as the peer reviewing of the general anatomic site-specific COBRA protocol. The ontology was defined by a multicenter task-group. Eleven centers from 6 countries signed an agreement and the consortium approved the ontology. We identified 3 tiers for the data set: Registry (epidemiology analysis), Procedures (prediction models and DSS), and Research (radiomics). The COBRA-Storage System (C-SS) is not time-consuming as, thanks to the use of "brokers", data can be extracted directly from the single center's storage systems through a connection with "structured query language database" (SQL-DB), Microsoft Access(®), FileMaker Pro(®), or Microsoft Excel(®). The system is also structured to perform automatic archiving directly from the treatment planning system or afterloading machine. The architecture is based on the concept of "on-purpose data projection". The C-SS architecture is privacy protecting because it will never make visible data that could identify an individual patient. This C-SS can also benefit from the so called "distributed learning" approaches, in which data never leave the collecting institution, while learning algorithms and proposed predictive models are commonly shared. Setting up a consortium is a feasible and practicable tool in the creation of an international and multi-system data sharing system. COBRA C-SS seems to be well accepted by all involved parties, primarily because it does not influence the center's own data storing technologies, procedures, and habits. Furthermore, the method preserves the privacy of all patients.

Return of Genomic Results to Research Participants: The Floor, the Ceiling, and the Choices In Between

PubMed Central

Jarvik, Gail P.; Amendola, Laura M.; Berg, Jonathan S.; Brothers, Kyle; Clayton, Ellen W.; Chung, Wendy; Evans, Barbara J.; Evans, James P.; Fullerton, Stephanie M.; Gallego, Carlos J.; Garrison, Nanibaa’ A.; Gray, Stacy W.; Holm, Ingrid A.; Kullo, Iftikhar J.; Lehmann, Lisa Soleymani; McCarty, Cathy; Prows, Cynthia A.; Rehm, Heidi L.; Sharp, Richard R.; Salama, Joseph; Sanderson, Saskia; Van Driest, Sara L.; Williams, Marc S.; Wolf, Susan M.; Wolf, Wendy A.; Harley, John; Myers, Melanie; Namjou, Bahram; Vinks, Sander; Connolly, John; Keating, Brendan; Gerhard, Glenn; Sundaresan, Agnes; Tromp, Gerard; Crosslin, David; Leppig, Kathy; Wicklund, Cathy; Chute, Christopher; Lynch, John; De Andrade, Mariza; Heit, John; McCormick, Jen; Brilliant, Murray; Kitchner, Terrie; Ritchie, Marylyn; Böttinger, Erwin; Peter, Inga; Persell, Stephen; Rasmussen-Torvik, Laura; McGregor, Tracy; Roden, Dan; Antommaria, Armand; Chiavacci, Rosetta; Faucett, Andy; Ledbetter, David; Williams, Janet; Hartzler, Andrea; Vitek, Carolyn R. Rohrer; Frost, Norm; Ferryman, Kadija; Horowitz, Carol; Rhodes, Rosamond; Zinberg, Randi; Aufox, Sharon; Pan, Vivian; Long, Rochelle; Ramos, Erin; Odgis, Jackie; Wise, Anastasia; Hull, Sara; Gitlin, Jonathan; Green, Robert; Metterville, Danielle; McGuire, Amy; Kong, Sek Won; Trinidad, Sue; Veenstra, David; Roche, Myra; Skinner, Debra; Raspberry, Kelly; O’Daniel, Julianne; Parsons, Will; Eng, Christine; Hilsenbeck, Susan; Karavite, Dean; Conlin, Laura; Spinner, Nancy; Krantz, Ian; Falk, Marni; Santani, Avni; Dechene, Elizabeth; Dulik, Matthew; Bernhardt, Barbara; Schuetze, Scott; Everett, Jessica; Gornick, Michele Caroline; Wilfond, Ben; Tabor, Holly; Lemke, Amy A.; Richards, Sue; Goddard, Katrina; Cooper, Greg; East, Kelly; Barsh, Greg; Koenig, Barbara; Van Allen, Eliezer; Garber, Judy; Garrett, Jeremy; Zawati, Ma’n; Lewis, Michelle; Savage, Sarah; Smith, Maureen; Roychowdhury, Sameek; Bailey, Alice; Berkman, Benjamin; Anan, Charlisse Caga; Hindorff, Lucia; Hutter, Carolyn; King, Rosalind; Li, Rongling; Lockhart, Nicole; McEwen, Jean; Scholes, Derek; Schully, Sheri; Sun, Kathie; Burke, Wylie

2014-01-01

As more research studies incorporate next-generation sequencing (including whole-genome or whole-exome sequencing), investigators and institutional review boards face difficult questions regarding which genomic results to return to research participants and how. An American College of Medical Genetics and Genomics 2013 policy paper suggesting that pathogenic mutations in 56 specified genes should be returned in the clinical setting has raised the question of whether comparable recommendations should be considered in research settings. The Clinical Sequencing Exploratory Research (CSER) Consortium and the Electronic Medical Records and Genomics (eMERGE) Network are multisite research programs that aim to develop practical strategies for addressing questions concerning the return of results in genomic research. CSER and eMERGE committees have identified areas of consensus regarding the return of genomic results to research participants. In most circumstances, if results meet an actionability threshold for return and the research participant has consented to return, genomic results, along with referral for appropriate clinical follow-up, should be offered to participants. However, participants have a right to decline the receipt of genomic results, even when doing so might be viewed as a threat to the participants’ health. Research investigators should be prepared to return research results and incidental findings discovered in the course of their research and meeting an actionability threshold, but they have no ethical obligation to actively search for such results. These positions are consistent with the recognition that clinical research is distinct from medical care in both its aims and its guiding moral principles. PMID:24814192

ESHRE PGD Consortium data collection XIV-XV: cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013.

PubMed

De Rycke, M; Goossens, V; Kokkali, G; Meijer-Hoogeveen, M; Coonen, E; Moutou, C

2017-10-01

How does the data collection XIV-XV of the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium compare with the cumulative data for data collections I-XIII? The 14th and 15th retrospective collection represents valuable data on PGD/PGS cycles, pregnancies and children: the main trend observed is the increased application of array technology at the cost of FISH testing in PGS cycles and in PGD cycles for chromosomal abnormalities. Since 1999, the PGD Consortium has collected, analysed and published 13 previous data sets and an overview of the first 10 years of data collections. Data were collected from each participating centre using a FileMaker Pro database (versions 5-12). Separate predesigned FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar years 2011 and 2012 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2013). Data were submitted by 71 centres (full PGD Consortium members). Records with incomplete or inconsistent data were excluded from the calculations. Corrections, calculations and tables were made by expert co-authors. For data collection XIV-XV, 71 centres reported data for 11 637 cycles with oocyte retrieval (OR), along with details of the follow-up on 2147 pregnancies and 1755 babies born. A total of 1953 cycles to OR were reported for chromosomal abnormalities, 144 cycles to OR for sexing for X-linked diseases, 3445 cycles to OR for monogenic diseases, 6095 cycles to OR for PGS and 38 cycles to OR for social sexing. From 2010 until 2012, the use of arrays for genetic testing increased from 4% to 20% in PGS and from 6% to 13% in PGD cycles for chromosomal abnormalities; the uptake of biopsy at the blastocyst stage (from <1% up to 7%) was only observed in cycles for structural chromosomal abnormalities, alongside the application of array comparative genomic hybridization. The findings apply to the 71 participating centres and may not represent worldwide trends in PGD. The annual data collections provide an important resource for data mining and for following trends in PGD/PGS practice. None. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Surmounting the Unique Challenges in Health Disparities Education: A Multi-Institution Qualitative Study

PubMed Central

Bereknyei, Sylvia; Lie, Desiree; Braddock, Clarence H.

2010-01-01

Background The National Consortium for Multicultural Education for Health Professionals (Consortium) comprises educators representing 18 US medical schools, funded by the National Institutes of Health. Collective lessons learned from curriculum implementation by principal investigators (PIs) have the potential to guide similar educational endeavors. Objective Describe Consortium PI’s self-reported challenges with curricular development, solutions and their new curricular products. Methods Information was collected from PIs over 2 months using a 53-question structured three-part questionnaire. The questionnaire addressed PI demographics, curriculum implementation challenges and solutions, and newly created curricular products. Study participants were 18 Consortium PIs. Descriptive analysis was used for quantitative data. Narrative responses were analyzed and interpreted using qualitative thematic coding. Results Response rate was 100%. Common barriers and challenges identified by PIs were: finding administrative and leadership support, sustaining the momentum, continued funding, finding curricular space, accessing and engaging communities, and lack of education research methodology skills. Solutions identified included engaging stakeholders, project-sharing across schools, advocacy and active participation in committees and community, and seeking sustainable funding. All Consortium PIs reported new curricular products and extensive dissemination efforts outside their own institutions. Conclusion The Consortium model has added benefits for curricular innovation and dissemination for cultural competence education to address health disparities. Lessons learned may be applicable to other educational innovation efforts. PMID:20352503

Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins

PubMed Central

Hill, W D; Davies, G; van de Lagemaat, L N; Christoforou, A; Marioni, R E; Fernandes, C P D; Liewald, D C; Croning, M D R; Payton, A; Craig, L C A; Whalley, L J; Horan, M; Ollier, W; Hansell, N K; Wright, M J; Martin, N G; Montgomery, G W; Steen, V M; Le Hellard, S; Espeseth, T; Lundervold, A J; Reinvang, I; Starr, J M; Pendleton, N; Grant, S G N; Bates, T C; Deary, I J

2014-01-01

Differences in general cognitive ability (intelligence) account for approximately half of the variation in any large battery of cognitive tests and are predictive of important life events including health. Genome-wide analyses of common single-nucleotide polymorphisms indicate that they jointly tag between a quarter and a half of the variance in intelligence. However, no single polymorphism has been reliably associated with variation in intelligence. It remains possible that these many small effects might be aggregated in networks of functionally linked genes. Here, we tested a network of 1461 genes in the postsynaptic density and associated complexes for an enriched association with intelligence. These were ascertained in 3511 individuals (the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium) phenotyped for general cognitive ability, fluid cognitive ability, crystallised cognitive ability, memory and speed of processing. By analysing the results of a genome wide association study (GWAS) using Gene Set Enrichment Analysis, a significant enrichment was found for fluid cognitive ability for the proteins found in the complexes of N-methyl-D-aspartate receptor complex; P=0.002. Replication was sought in two additional cohorts (N=670 and 2062). A meta-analytic P-value of 0.003 was found when these were combined with the CAGES consortium. The results suggest that genetic variation in the macromolecular machines formed by membrane-associated guanylate kinase (MAGUK) scaffold proteins and their interaction partners contributes to variation in intelligence. PMID:24399044

The Tennessee Mouse Genome Consortium: Identification of ocular mutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jablonski, Monica M.; Wang, Xiaofei; Lu, Lu

2005-06-01

The Tennessee Mouse Genome Consortium (TMGC) is in its fifth year of a ethylnitrosourea (ENU)-based mutagenesis screen to detect recessive mutations that affect the eye and brain. Each pedigree is tested by various phenotyping domains including the eye, neurohistology, behavior, aging, ethanol, drug, social behavior, auditory, and epilepsy domains. The utilization of a highly efficient breeding protocol and coordination of various universities across Tennessee makes it possible for mice with ENU-induced mutations to be evaluated by nine distinct phenotyping domains within this large-scale project known as the TMGC. Our goal is to create mutant lines that model human diseases andmore » disease syndromes and to make the mutant mice available to the scientific research community. Within the eye domain, mice are screened for anterior and posterior segment abnormalities using slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, eye weight, histology, and immunohistochemistry. As of January 2005, we have screened 958 pedigrees and 4800 mice, excluding those used in mapping studies. We have thus far identified seven pedigrees with primary ocular abnormalities. Six of the mutant pedigrees have retinal or subretinal aberrations, while the remaining pedigree presents with an abnormal eye size. Continued characterization of these mutant mice should in most cases lead to the identification of the mutated gene, as well as provide insight into the function of each gene. Mice from each of these pedigrees of mutant mice are available for distribution to researchers for independent study.« less

An overview of the genetic dissection of complex traits.

PubMed

Rao, D C

2008-01-01

Thanks to the recent revolutionary genomic advances such as the International HapMap consortium, resolution of the genetic architecture of common complex traits is beginning to look hopeful. While demonstrating the feasibility of genome-wide association (GWA) studies, the pathbreaking Wellcome Trust Case Control Consortium (WTCCC) study also serves to underscore the critical importance of very large sample sizes and draws attention to potential problems, which need to be addressed as part of the study design. Even the large WTCCC study had vastly inadequate power for several of the associations reported (and confirmed) and, therefore, most of the regions harboring relevant associations may not be identified anytime soon. This chapter provides an overview of some of the key developments in the methodological approaches to genetic dissection of common complex traits. Constrained Bayesian networks are suggested as especially useful for analysis of pathway-based SNPs. Likewise, composite likelihood is suggested as a promising method for modeling complex systems. It discusses the key steps in a study design, with an emphasis on GWA studies. Potential limitations highlighted by the WTCCC GWA study are discussed, including problems associated with massive genotype imputation, analysis of pooled national samples, shared controls, and the critical role of interactions. GWA studies clearly need massive sample sizes that are only possible through genuine collaborations. After all, for common complex traits, the question is not whether we can find some pieces of the puzzle, but how large and what kind of a sample we need to (nearly) solve the genetic puzzle.

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

PubMed Central

Lu, Yingchang; Justice, Anne E.; Mudgal, Poorva; Liu, Ching-Ti; Young, Kristin; Feitosa, Mary F.; Rand, Kristin; Dimitrov, Latchezar; Duan, Qing; Guo, Xiuqing; Lange, Leslie A.; Nalls, Michael A.; Okut, Hayrettin; Tayo, Bamidele O.; Vedantam, Sailaja; Bradfield, Jonathan P.; Chen, Guanjie; Chesi, Alessandra; Irvin, Marguerite R.; Padhukasahasram, Badri; Zheng, Wei; Allison, Matthew A.; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Blot, William J.; Bottinger, Erwin P.; Carpten, John; Chanock, Stephen J.; Chen, Yii-Der Ida; Conti, David V.; Cooper, Richard S.; Fornage, Myriam; Freedman, Barry I.; Garcia, Melissa; Goodman, Phyllis J.; Hsu, Yu-Han H.; Hu, Jennifer; Huff, Chad D.; Ingles, Sue A.; John, Esther M.; Kittles, Rick; Klein, Eric; Li, Jin; McKnight, Barbara; Nayak, Uma; Nemesure, Barbara; Olshan, Andrew; Salako, Babatunde; Sanderson, Maureen; Shao, Yaming; Siscovick, David S.; Stanford, Janet L.; Strom, Sara S.; Witte, John S.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Regina G.; Zonderman, Alan B.; Ambs, Stefan; Cushman, Mary; Faul, Jessica D.; Hakonarson, Hakon; Levin, Albert M.; Nathanson, Katherine L.; Weir, David R.; Zhi, Degui; Arnett, Donna K.; Kardia, Sharon L. R.; Oloapde, Olufunmilayo I.; Rao, D. C.; Williams, L. Keoki; Becker, Diane M.; Borecki, Ingrid B.; Evans, Michele K.; Harris, Tamara B.; Hirschhorn, Joel N.; Psaty, Bruce M.; Wilson, James G.; Bowden, Donald W.; Cupples, L. Adrienne; Haiman, Christopher A.; Loos, Ruth J. F.; North, Kari E.

2017-01-01

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations. PMID:28430825

Development of Bioinformatics Infrastructure for Genomics Research.

PubMed

Mulder, Nicola J; Adebiyi, Ezekiel; Adebiyi, Marion; Adeyemi, Seun; Ahmed, Azza; Ahmed, Rehab; Akanle, Bola; Alibi, Mohamed; Armstrong, Don L; Aron, Shaun; Ashano, Efejiro; Baichoo, Shakuntala; Benkahla, Alia; Brown, David K; Chimusa, Emile R; Fadlelmola, Faisal M; Falola, Dare; Fatumo, Segun; Ghedira, Kais; Ghouila, Amel; Hazelhurst, Scott; Isewon, Itunuoluwa; Jung, Segun; Kassim, Samar Kamal; Kayondo, Jonathan K; Mbiyavanga, Mamana; Meintjes, Ayton; Mohammed, Somia; Mosaku, Abayomi; Moussa, Ahmed; Muhammd, Mustafa; Mungloo-Dilmohamud, Zahra; Nashiru, Oyekanmi; Odia, Trust; Okafor, Adaobi; Oladipo, Olaleye; Osamor, Victor; Oyelade, Jellili; Sadki, Khalid; Salifu, Samson Pandam; Soyemi, Jumoke; Panji, Sumir; Radouani, Fouzia; Souiai, Oussama; Tastan Bishop, Özlem

2017-06-01

Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community. H3ABioNet set out to develop core bioinformatics infrastructure and capacity for genomics research in various aspects of data collection, transfer, storage, and analysis. Various resources have been developed to address genomic data management and analysis needs of H3Africa researchers and other scientific communities on the continent. NetMap was developed and used to build an accurate picture of network performance within Africa and between Africa and the rest of the world, and Globus Online has been rolled out to facilitate data transfer. A participant recruitment database was developed to monitor participant enrollment, and data is being harmonized through the use of ontologies and controlled vocabularies. The standardized metadata will be integrated to provide a search facility for H3Africa data and biospecimens. Because H3Africa projects are generating large-scale genomic data, facilities for analysis and interpretation are critical. H3ABioNet is implementing several data analysis platforms that provide a large range of bioinformatics tools or workflows, such as Galaxy, the Job Management System, and eBiokits. A set of reproducible, portable, and cloud-scalable pipelines to support the multiple H3Africa data types are also being developed and dockerized to enable execution on multiple computing infrastructures. In addition, new tools have been developed for analysis of the uniquely divergent African data and for downstream interpretation of prioritized variants. To provide support for these and other bioinformatics queries, an online bioinformatics helpdesk backed by broad consortium expertise has been established. Further support is provided by means of various modes of bioinformatics training. For the past 4 years, the development of infrastructure support and human capacity through H3ABioNet, have significantly contributed to the establishment of African scientific networks, data analysis facilities, and training programs. Here, we describe the infrastructure and how it has affected genomics and bioinformatics research in Africa. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

Genome-wide Analysis of Genetic Loci Associated with Alzheimer’s Disease

PubMed Central

Seshadri, Sudha; Fitzpatrick, Annette L.; Arfan Ikram, M; DeStefano, Anita L.; Gudnason, Vilmundur; Boada, Merce; Bis, Joshua C.; Smith, Albert V.; Carassquillo, Minerva M.; Charles Lambert, Jean; Harold, Denise; Schrijvers, Elisabeth M. C.; Ramirez-Lorca, Reposo; Debette, Stephanie; Longstreth, W.T.; Janssens, A. Cecile J.W.; Shane Pankratz, V.; Dartigues, Jean François; Hollingworth, Paul; Aspelund, Thor; Hernandez, Isabel; Beiser, Alexa; Kuller, Lewis H.; Koudstaal, Peter J.; Dickson, Dennis W.; Tzourio, Christophe; Abraham, Richard; Antunez, Carmen; Du, Yangchun; Rotter, Jerome I.; Aulchenko, Yurii S.; Harris, Tamara B.; Petersen, Ronald C.; Berr, Claudine; Owen, Michael J.; Lopez-Arrieta, Jesus; Varadarajan, Badri N.; Becker, James T.; Rivadeneira, Fernando; Nalls, Michael A.; Graff-Radford, Neill R.; Campion, Dominique; Auerbach, Sanford; Rice, Kenneth; Hofman, Albert; Jonsson, Palmi V.; Schmidt, Helena; Lathrop, Mark; Mosley, Thomas H.; Au, Rhoda; Psaty, Bruce M.; Uitterlinden, Andre G.; Farrer, Lindsay A.; Lumley, Thomas; Ruiz, Agustin; Williams, Julie; Amouyel, Philippe; Younkin, Steve G.; Wolf, Philip A.; Launer, Lenore J.; Lopez, Oscar L.; van Duijn, Cornelia M.; Breteler, Monique M. B.

2010-01-01

Context Genome wide association studies (GWAS) have recently identified CLU, PICALM and CR1 as novel genes for late-onset Alzheimer’s disease (AD). Objective In a three-stage analysis of new and previously published GWAS on over 35000 persons (8371 AD cases), we sought to identify and strengthen additional loci associated with AD and confirm these in an independent sample. We also examined the contribution of recently identified genes to AD risk prediction. Design, Setting, and Participants We identified strong genetic associations (p<10−3) in a Stage 1 sample of 3006 AD cases and 14642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (1367 AD cases (973 incident)) with previously reported results from the Translational Genomics Research Institute (TGEN) and Mayo AD GWAS. We identified 2708 single nucleotide polymorphisms (SNPs) with p-values<10−3, and in Stage 2 pooled results for these SNPs with the European AD Initiative (2032 cases, 5328 controls) to identify ten loci with p-values<10−5. In Stage 3, we combined data for these ten loci with data from the Genetic and Environmental Risk in AD consortium (3333 cases, 6995 controls) to identify four SNPs with a p-value<1.7×10−8. These four SNPs were replicated in an independent Spanish sample (1140 AD cases and 1209 controls). Main outcome measure Alzheimer’s Disease. Results We showed genome-wide significance for two new loci: rs744373 near BIN1 (OR:1.13; 95%CI:1.06–1.21 per copy of the minor allele; p=1.6×10−11) and rs597668 near EXOC3L2/BLOC1S3/MARK4 (OR:1.18; 95%CI1.07–1.29; p=6.5×10−9). Associations of CLU, PICALM, BIN1 and EXOC3L2 with AD were confirmed in the Spanish sample (p<0.05). However, CLU and PICALM did not improve incident AD prediction beyond age, sex, and APOE (improvement in area under receiver-operating-characteristic curve <0.003). Conclusions Two novel genetic loci for AD are reported that for the first time reach genome-wide statistical significance; these findings were replicated in an independent population. Two recently reported associations were also confirmed, but these loci did not improve AD risk prediction, although they implicate biological pathways that may be useful targets for potential interventions. PMID:20460622

Characterization of full-length sequenced cDNA inserts (FLIcs) from Atlantic salmon (Salmo salar)

PubMed Central

Andreassen, Rune; Lunner, Sigbjørn; Høyheim, Bjørn

2009-01-01

Background Sequencing of the Atlantic salmon genome is now being planned by an international research consortium. Full-length sequenced inserts from cDNAs (FLIcs) are an important tool for correct annotation and clustering of the genomic sequence in any species. The large amount of highly similar duplicate sequences caused by the relatively recent genome duplication in the salmonid ancestor represents a particular challenge for the genome project. FLIcs will therefore be an extremely useful resource for the Atlantic salmon sequencing project. In addition to be helpful in order to distinguish between duplicate genome regions and in determining correct gene structures, FLIcs are an important resource for functional genomic studies and for investigation of regulatory elements controlling gene expression. In contrast to the large number of ESTs available, including the ESTs from 23 developmental and tissue specific cDNA libraries contributed by the Salmon Genome Project (SGP), the number of sequences where the full-length of the cDNA insert has been determined has been small. Results High quality full-length insert sequences from 560 pre-smolt white muscle tissue specific cDNAs were generated, accession numbers [GenBank: BT043497 - BT044056]. Five hundred and ten (91%) of the transcripts were annotated using Gene Ontology (GO) terms and 440 of the FLIcs are likely to contain a complete coding sequence (cCDS). The sequence information was used to identify putative paralogs, characterize salmon Kozak motifs, polyadenylation signal variation and to identify motifs likely to be involved in the regulation of particular genes. Finally, conserved 7-mers in the 3'UTRs were identified, of which some were identical to miRNA target sequences. Conclusion This paper describes the first Atlantic salmon FLIcs from a tissue and developmental stage specific cDNA library. We have demonstrated that many FLIcs contained a complete coding sequence (cCDS). This suggests that the remaining cDNA libraries generated by SGP represent a valuable cCDS FLIc source. The conservation of 7-mers in 3'UTRs indicates that these motifs are functionally important. Identity between some of these 7-mers and miRNA target sequences suggests that they are miRNA targets in Salmo salar transcripts as well. PMID:19878547

Molecular and Genomic Alterations in Glioblastoma Multiforme.

PubMed

Crespo, Ines; Vital, Ana Louisa; Gonzalez-Tablas, María; Patino, María del Carmen; Otero, Alvaro; Lopes, María Celeste; de Oliveira, Catarina; Domingues, Patricia; Orfao, Alberto; Tabernero, Maria Dolores

2015-07-01

In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Smoking Gun or Circumstantial Evidence? Comparison of Statistical Learning Methods using Functional Annotations for Prioritizing Risk Variants.

PubMed

Gagliano, Sarah A; Ravji, Reena; Barnes, Michael R; Weale, Michael E; Knight, Jo

2015-08-24

Although technology has triumphed in facilitating routine genome sequencing, new challenges have been created for the data-analyst. Genome-scale surveys of human variation generate volumes of data that far exceed capabilities for laboratory characterization. By incorporating functional annotations as predictors, statistical learning has been widely investigated for prioritizing genetic variants likely to be associated with complex disease. We compared three published prioritization procedures, which use different statistical learning algorithms and different predictors with regard to the quantity, type and coding. We also explored different combinations of algorithm and annotation set. As an application, we tested which methodology performed best for prioritizing variants using data from a large schizophrenia meta-analysis by the Psychiatric Genomics Consortium. Results suggest that all methods have considerable (and similar) predictive accuracies (AUCs 0.64-0.71) in test set data, but there is more variability in the application to the schizophrenia GWAS. In conclusion, a variety of algorithms and annotations seem to have a similar potential to effectively enrich true risk variants in genome-scale datasets, however none offer more than incremental improvement in prediction. We discuss how methods might be evolved for risk variant prediction to address the impending bottleneck of the new generation of genome re-sequencing studies.

Disproportionate Contributions of Select Genomic Compartments and Cell Types to Genetic Risk for Coronary Artery Disease

PubMed Central

Won, Hong-Hee; Natarajan, Pradeep; Dobbyn, Amanda; Jordan, Daniel M.; Roussos, Panos; Lage, Kasper; Raychaudhuri, Soumya

2015-01-01

Large genome-wide association studies (GWAS) have identified many genetic loci associated with risk for myocardial infarction (MI) and coronary artery disease (CAD). Concurrently, efforts such as the National Institutes of Health (NIH) Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE) Consortium have provided unprecedented data on functional elements of the human genome. In the present study, we systematically investigate the biological link between genetic variants associated with this complex disease and their impacts on gene function. First, we examined the heritability of MI/CAD according to genomic compartments. We observed that single nucleotide polymorphisms (SNPs) residing within nearby regulatory regions show significant polygenicity and contribute between 59–71% of the heritability for MI/CAD. Second, we showed that the polygenicity and heritability explained by these SNPs are enriched in histone modification marks in specific cell types. Third, we found that a statistically higher number of 45 MI/CAD-associated SNPs that have been identified from large-scale GWAS studies reside within certain functional elements of the genome, particularly in active enhancer and promoter regions. Finally, we observed significant heterogeneity of this signal across cell types, with strong signals observed within adipose nuclei, as well as brain and spleen cell types. These results suggest that the genetic etiology of MI/CAD is largely explained by tissue-specific regulatory perturbation within the human genome. PMID:26509271

Bridging graduate education in public health and the liberal arts.

PubMed

Aelion, C Marjorie; Gubrium, Aline C; Aulino, Felicity; Krause, Elizabeth L; Leatherman, Thomas L

2015-03-01

The University of Massachusetts Amherst is part of Five-Colleges Inc, a consortium that includes the university and four liberal arts colleges. Consortium faculty from the School of Public Health and Health Sciences at the university and from the colleges are working to bridge liberal arts with public health graduate education. We outline four key themes guiding this effort and exemplary curricular tools for innovative community-based and multidisciplinary academic and research programs. The structure of the consortium has created a novel trajectory for student learning and engagement, with important ramifications for pedagogy and professional practice in public health. We show how graduate public health education and liberal arts can, and must, work in tandem to transform public health practice in the 21st century.

Bat Biology, Genomes, and the Bat1K Project: To Generate Chromosome-Level Genomes for All Living Bat Species.

PubMed

Teeling, Emma C; Vernes, Sonja C; Dávalos, Liliana M; Ray, David A; Gilbert, M Thomas P; Myers, Eugene

2018-02-15

Bats are unique among mammals, possessing some of the rarest mammalian adaptations, including true self-powered flight, laryngeal echolocation, exceptional longevity, unique immunity, contracted genomes, and vocal learning. They provide key ecosystem services, pollinating tropical plants, dispersing seeds, and controlling insect pest populations, thus driving healthy ecosystems. They account for more than 20% of all living mammalian diversity, and their crown-group evolutionary history dates back to the Eocene. Despite their great numbers and diversity, many species are threatened and endangered. Here we announce Bat1K, an initiative to sequence the genomes of all living bat species (n∼1,300) to chromosome-level assembly. The Bat1K genome consortium unites bat biologists (>148 members as of writing), computational scientists, conservation organizations, genome technologists, and any interested individuals committed to a better understanding of the genetic and evolutionary mechanisms that underlie the unique adaptations of bats. Our aim is to catalog the unique genetic diversity present in all living bats to better understand the molecular basis of their unique adaptations; uncover their evolutionary history; link genotype with phenotype; and ultimately better understand, promote, and conserve bats. Here we review the unique adaptations of bats and highlight how chromosome-level genome assemblies can uncover the molecular basis of these traits. We present a novel sequencing and assembly strategy and review the striking societal and scientific benefits that will result from the Bat1K initiative.

Bovine Genome Database: supporting community annotation and analysis of the Bos taurus genome

PubMed Central

2010-01-01

Background A goal of the Bovine Genome Database (BGD; http://BovineGenome.org) has been to support the Bovine Genome Sequencing and Analysis Consortium (BGSAC) in the annotation and analysis of the bovine genome. We were faced with several challenges, including the need to maintain consistent quality despite diversity in annotation expertise in the research community, the need to maintain consistent data formats, and the need to minimize the potential duplication of annotation effort. With new sequencing technologies allowing many more eukaryotic genomes to be sequenced, the demand for collaborative annotation is likely to increase. Here we present our approach, challenges and solutions facilitating a large distributed annotation project. Results and Discussion BGD has provided annotation tools that supported 147 members of the BGSAC in contributing 3,871 gene models over a fifteen-week period, and these annotations have been integrated into the bovine Official Gene Set. Our approach has been to provide an annotation system, which includes a BLAST site, multiple genome browsers, an annotation portal, and the Apollo Annotation Editor configured to connect directly to our Chado database. In addition to implementing and integrating components of the annotation system, we have performed computational analyses to create gene evidence tracks and a consensus gene set, which can be viewed on individual gene pages at BGD. Conclusions We have provided annotation tools that alleviate challenges associated with distributed annotation. Our system provides a consistent set of data to all annotators and eliminates the need for annotators to format data. Involving the bovine research community in genome annotation has allowed us to leverage expertise in various areas of bovine biology to provide biological insight into the genome sequence. PMID:21092105

Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.

PubMed

Smeland, Olav B; Frei, Oleksandr; Kauppi, Karolina; Hill, W David; Li, Wen; Wang, Yunpeng; Krull, Florian; Bettella, Francesco; Eriksen, Jon A; Witoelar, Aree; Davies, Gail; Fan, Chun C; Thompson, Wesley K; Lam, Max; Lencz, Todd; Chen, Chi-Hua; Ueland, Torill; Jönsson, Erik G; Djurovic, Srdjan; Deary, Ian J; Dale, Anders M; Andreassen, Ole A

2017-10-01

Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10-7), general cognitive function (z score, -4.43; P = 9.42 × 10-6), and verbal-numerical reasoning (z score, -5.43; P = 5.64 × 10-8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

G-Protein Genomic Association With Normal Variation in Gray Matter Density

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Arias-Vasquez, Alejandro; Zwiers, Marcel P.; van Hulzen, Kimm; Fernández, Guillén; Fisher, Simon E.; Franke, Barbara; Turner, Jessica A.; Liu, Jingyu

2017-01-01

While detecting genetic variations underlying brain structures helps reveal mechanisms of neural disorders, high data dimensionality poses a major challenge for imaging genomic association studies. In this work, we present the application of a recently proposed approach, parallel independent component analysis with reference (pICA-R), to investigate genomic factors potentially regulating gray matter variation in a healthy population. This approach simultaneously assesses many variables for an aggregate effect and helps to elicit particular features in the data. We applied pICA-R to analyze gray matter density (GMD) images (274,131 voxels) in conjunction with single nucleotide polymorphism (SNP) data (666,019 markers) collected from 1,256 healthy individuals of the Brain Imaging Genetics (BIG) study. Guided by a genetic reference derived from the gene GNA14, pICA-R identified a significant SNP-GMD association (r = −0.16, P = 2.34 × 10−8), implying that subjects with specific genotypes have lower localized GMD. The identified components were then projected to an independent dataset from the Mind Clinical Imaging Consortium (MCIC) including 89 healthy individuals, and the obtained loadings again yielded a significant SNP-GMD association (r = −0.25, P = 0.02). The imaging component reflected GMD variations in frontal, precuneus, and cingulate regions. The SNP component was enriched in genes with neuronal functions, including synaptic plasticity, axon guidance, molecular signal transduction via PKA and CREB, highlighting the GRM1, PRKCH, GNA12, and CAMK2B genes. Collectively, our findings suggest that GNA12 and GNA14 play a key role in the genetic architecture underlying normal GMD variation in frontal and parietal regions. PMID:26248772

Federation in genomics pipelines: techniques and challenges.

PubMed

Chaterji, Somali; Koo, Jinkyu; Li, Ninghui; Meyer, Folker; Grama, Ananth; Bagchi, Saurabh

2017-08-29

Federation is a popular concept in building distributed cyberinfrastructures, whereby computational resources are provided by multiple organizations through a unified portal, decreasing the complexity of moving data back and forth among multiple organizations. Federation has been used in bioinformatics only to a limited extent, namely, federation of datastores, e.g. SBGrid Consortium for structural biology and Gene Expression Omnibus (GEO) for functional genomics. Here, we posit that it is important to federate both computational resources (CPU, GPU, FPGA, etc.) and datastores to support popular bioinformatics portals, with fast-increasing data volumes and increasing processing requirements. A prime example, and one that we discuss here, is in genomics and metagenomics. It is critical that the processing of the data be done without having to transport the data across large network distances. We exemplify our design and development through our experience with metagenomics-RAST (MG-RAST), the most popular metagenomics analysis pipeline. Currently, it is hosted completely at Argonne National Laboratory. However, through a recently started collaborative National Institutes of Health project, we are taking steps toward federating this infrastructure. Being a widely used resource, we have to move toward federation without disrupting 50 K annual users. In this article, we describe the computational tools that will be useful for federating a bioinformatics infrastructure and the open research challenges that we see in federating such infrastructures. It is hoped that our manuscript can serve to spur greater federation of bioinformatics infrastructures by showing the steps involved, and thus, allow them to scale to support larger user bases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identification of mutated driver pathways in cancer using a multi-objective optimization model.

PubMed

Zheng, Chun-Hou; Yang, Wu; Chong, Yan-Wen; Xia, Jun-Feng

2016-05-01

New-generation high-throughput technologies, including next-generation sequencing technology, have been extensively applied to solve biological problems. As a result, large cancer genomics projects such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium are producing large amount of rich and diverse data in multiple cancer types. The identification of mutated driver genes and driver pathways from these data is a significant challenge. Genome aberrations in cancer cells can be divided into two types: random 'passenger mutation' and functional 'driver mutation'. In this paper, we introduced a Multi-objective Optimization model based on a Genetic Algorithm (MOGA) to solve the maximum weight submatrix problem, which can be employed to identify driver genes and driver pathways promoting cancer proliferation. The maximum weight submatrix problem defined to find mutated driver pathways is based on two specific properties, i.e., high coverage and high exclusivity. The multi-objective optimization model can adjust the trade-off between high coverage and high exclusivity. We proposed an integrative model by combining gene expression data and mutation data to improve the performance of the MOGA algorithm in a biological context. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serratia symbiotica from the aphid Cinara cedri: a missing link from facultative to obligate insect endosymbiont.

PubMed

Lamelas, Araceli; Gosalbes, María José; Manzano-Marín, Alejandro; Peretó, Juli; Moya, Andrés; Latorre, Amparo

2011-11-01

The genome sequencing of Buchnera aphidicola BCc from the aphid Cinara cedri, which is the smallest known Buchnera genome, revealed that this bacterium had lost its symbiotic role, as it was not able to synthesize tryptophan and riboflavin. Moreover, the biosynthesis of tryptophan is shared with the endosymbiont Serratia symbiotica SCc, which coexists with B. aphidicola in this aphid. The whole-genome sequencing of S. symbiotica SCc reveals an endosymbiont in a stage of genome reduction that is closer to an obligate endosymbiont, such as B. aphidicola from Acyrthosiphon pisum, than to another S. symbiotica, which is a facultative endosymbiont in this aphid, and presents much less gene decay. The comparison between both S. symbiotica enables us to propose an evolutionary scenario of the transition from facultative to obligate endosymbiont. Metabolic inferences of B. aphidicola BCc and S. symbiotica SCc reveal that most of the functions carried out by B. aphidicola in A. pisum are now either conserved in B. aphidicola BCc or taken over by S. symbiotica. In addition, there are several cases of metabolic complementation giving functional stability to the whole consortium and evolutionary preservation of the actors involved.

High-resolution linkage map and chromosome-scale genome assembly for cassava (Manihot esculenta Crantz) from 10 populations.

PubMed

2014-12-11

Cassava (Manihot esculenta Crantz) is a major staple crop in Africa, Asia, and South America, and its starchy roots provide nourishment for 800 million people worldwide. Although native to South America, cassava was brought to Africa 400-500 years ago and is now widely cultivated across sub-Saharan Africa, but it is subject to biotic and abiotic stresses. To assist in the rapid identification of markers for pathogen resistance and crop traits, and to accelerate breeding programs, we generated a framework map for M. esculenta Crantz from reduced representation sequencing [genotyping-by-sequencing (GBS)]. The composite 2412-cM map integrates 10 biparental maps (comprising 3480 meioses) and organizes 22,403 genetic markers on 18 chromosomes, in agreement with the observed karyotype. We used the map to anchor 71.9% of the draft genome assembly and 90.7% of the predicted protein-coding genes. The chromosome-anchored genome sequence will be useful for breeding improvement by assisting in the rapid identification of markers linked to important traits, and in providing a framework for genomic selection-enhanced breeding of this important crop. Copyright © 2015 International Cassava Genetic Map Consortium (ICGMC).

Transethnic genome-wide scan identifies novel Alzheimer's disease loci.

PubMed

Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse; Barber, Robert; Beecham, Gary W; Bennett, David A; Buxbaum, Joseph D; Byrd, Goldie S; Carrasquillo, Minerva M; Crane, Paul K; Cruchaga, Carlos; De Jager, Philip; Ertekin-Taner, Nilufer; Evans, Denis; Fallin, M Danielle; Foroud, Tatiana M; Friedland, Robert P; Goate, Alison M; Graff-Radford, Neill R; Hendrie, Hugh; Hall, Kathleen S; Hamilton-Nelson, Kara L; Inzelberg, Rivka; Kamboh, M Ilyas; Kauwe, John S K; Kukull, Walter A; Kunkle, Brian W; Kuwano, Ryozo; Larson, Eric B; Logue, Mark W; Manly, Jennifer J; Martin, Eden R; Montine, Thomas J; Mukherjee, Shubhabrata; Naj, Adam; Reiman, Eric M; Reitz, Christiane; Sherva, Richard; St George-Hyslop, Peter H; Thornton, Timothy; Younkin, Steven G; Vardarajan, Badri N; Wang, Li-San; Wendlund, Jens R; Winslow, Ashley R; Haines, Jonathan; Mayeux, Richard; Pericak-Vance, Margaret A; Schellenberg, Gerard; Lunetta, Kathryn L; Farrer, Lindsay A

2017-07-01

Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10 -8 ) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10 -6 ) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10 -6 ). Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions.

PubMed

Hill, W D; Davies, G; Harris, S E; Hagenaars, S P; Liewald, D C; Penke, L; Gale, C R; Deary, I J

2016-12-13

Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n=53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissue-specific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ~2.6% of the SNPs from each GWAS but accounted for ~40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions.

Molecular genetic aetiology of general cognitive function is enriched in evolutionarily conserved regions

PubMed Central

Hill, W D; Davies, G; Harris, S E; Hagenaars, S P; Davies, Gail; Deary, Ian J; Debette, Stephanie; Verbaas, Carla I; Bressler, Jan; Schuur, Maaike; Smith, Albert V; Bis, Joshua C; Bennett, David A; Ikram, M Arfan; Launer, Lenore J; Fitzpatrick, Annette L; Seshadri, Sudha; van Duijn, Cornelia M; Mosley Jr, Thomas H; Liewald, D C; Penke, L; Gale, C R; Deary, I J

2016-01-01

Differences in general cognitive function have been shown to be partly heritable and to show genetic correlations with several psychiatric and physical disease states. However, to date, few single-nucleotide polymorphisms (SNPs) have demonstrated genome-wide significance, hampering efforts aimed at determining which genetic variants are most important for cognitive function and which regions drive the genetic associations between cognitive function and disease states. Here, we combine multiple large genome-wide association study (GWAS) data sets, from the CHARGE cognitive consortium (n=53 949) and UK Biobank (n=36 035), to partition the genome into 52 functional annotations and an additional 10 annotations describing tissue-specific histone marks. Using stratified linkage disequilibrium score regression we show that, in two measures of cognitive function, SNPs associated with cognitive function cluster in regions of the genome that are under evolutionary negative selective pressure. These conserved regions contained ~2.6% of the SNPs from each GWAS but accounted for ~40% of the SNP-based heritability. The results suggest that the search for causal variants associated with cognitive function, and those variants that exert a pleiotropic effect between cognitive function and health, will be facilitated by examining these enriched regions. PMID:27959336

Equine Clinical Genomics: A Clinician’s Primer

PubMed Central

Brosnahan, Margaret Mary; Brooks, Samantha A.; Antczak, Douglas F.

2012-01-01

Summary The objective of this review is to introduce equine clinicians to the rapidly evolving field of clinical genomics with a vision of improving the health and welfare of the domestic horse. For fifteen years a consortium of veterinary geneticists and clinicians has worked together under the umbrella of The Horse Genome Project. This group, encompassing 22 laboratories in 12 countries, has made rapid progress, developing several iterations of linkage, physical and comparative gene maps of the horse with increasing levels of detail. In early 2006, the research was greatly facilitated when the U.S. National Human Genome Research Institute of the National Institutes of Health added the horse to the list of mammalian species scheduled for whole genome sequencing. The genome of the domestic horse has now been sequenced and is available to researchers worldwide in publicly accessible databases. This achievement creates the potential for transformative change within the horse industry, particularly in the fields of internal medicine, sports medicine and reproduction. The genome sequence has enabled the development of new genome-wide tools and resources for studying inherited diseases of the horse. To date, researchers have identified eleven mutations causing ten clinical syndromes in the horse. Testing is commercially available for all but one of these diseases. Future research will probably identify the genetic bases for other equine diseases, produce new diagnostic tests and generate novel therapeutics for some of these conditions. This will enable equine clinicians to play a critical role in ensuring the thoughtful and appropriate application of this knowledge as they assist clients with breeding and clinical decision-making. PMID:20840582

CPTAC Evaluates Long-Term Reproducibility of Quantitative Proteomics Using Breast Cancer Xenografts | Office of Cancer Clinical Proteomics Research

Cancer.gov

Liquid chromatography tandem-mass spectrometry (LC-MS/MS)- based methods such as isobaric tags for relative and absolute quantification (iTRAQ) and tandem mass tags (TMT) have been shown to provide overall better quantification accuracy and reproducibility over other LC-MS/MS techniques. However, large scale projects like the Clinical Proteomic Tumor Analysis Consortium (CPTAC) require comparisons across many genomically characterized clinical specimens in a single study and often exceed the capability of traditional iTRAQ-based quantification.

RNAcentral: an international database of ncRNA sequences

DOE PAGES

Williams, Kelly Porter

2014-10-28

The field of non-coding RNA biology has been hampered by the lack of availability of a comprehensive, up-to-date collection of accessioned RNA sequences. Here we present the first release of RNAcentral, a database that collates and integrates information from an international consortium of established RNA sequence databases. The initial release contains over 8.1 million sequences, including representatives of all major functional classes. A web portal (http://rnacentral.org) provides free access to data, search functionality, cross-references, source code and an integrated genome browser for selected species.

Genomewide Clonal Analysis of Lethal Mutations in the Drosophila melanogaster Eye: Comparison of the X Chromosome and Autosomes

PubMed Central

Call, Gerald B.; Olson, John M.; Chen, Jiong; Villarasa, Nikki; Ngo, Kathy T.; Yabroff, Allison M.; Cokus, Shawn; Pellegrini, Matteo; Bibikova, Elena; Bui, Chris; Cespedes, Albert; Chan, Cheryl; Chan, Stacy; Cheema, Amrita K.; Chhabra, Akanksha; Chitsazzadeh, Vida; Do, Minh-Tu; Fang, Q. Angela; Folick, Andrew; Goodstein, Gelsey L.; Huang, Cheng R.; Hung, Tony; Kim, Eunha; Kim, William; Kim, Yulee; Kohan, Emil; Kuoy, Edward; Kwak, Robert; Lee, Eric; Lee, JiEun; Lin, Henry; Liu, H-C. Angela; Moroz, Tatiana; Prasad, Tharani; Prashad, Sacha L.; Patananan, Alexander N.; Rangel, Alma; Rosselli, Desiree; Sidhu, Sohrab; Sitz, Daniel; Taber, Chelsea E.; Tan, Jingwen; Topp, Kasey; Tran, PhuongThao; Tran, Quynh-Minh; Unkovic, Mary; Wells, Maggie; Wickland, Jessica; Yackle, Kevin; Yavari, Amir; Zaretsky, Jesse M.; Allen, Christopher M.; Alli, Latifat; An, Ju; Anwar, Abbas; Arevalo, Sonia; Ayoub, Danny; Badal, Shawn S.; Baghdanian, Armonde; Baghdanian, Arthur H.; Baumann, Sara A.; Becerra, Vivian N.; Chan, Hei J.; Chang, Aileen E.; Cheng, Xibin A.; Chin, Mabel; Chong, Fleurette; Crisostomo, Carlyn; Datta, Sanjit; Delosreyes, Angela; Diep, Francie; Ekanayake, Preethika; Engeln, Mark; Evers, Elizabeth; Farshidi, Farzin; Fischer, Katrina; Formanes, Arlene J.; Gong, Jun; Gupta, Riju; Haas, Blake E.; Hahm, Vicky; Hsieh, Michael; Hui, James Z.; Iao, Mei L.; Jin, Sophia D.; Kim, Angela Y.; Kim, Lydia S-H.; King, Megan; Knudsen-Robbins, Chloe; Kohanchi, David; Kovshilovskaya, Bogdana; Ku, Amy; Kung, Raymond W.; Landig, Mark E. L.; Latterman, Stephanie S.; Lauw, Stephanie S.; Lee, Daniel S.; Lee, Joann S.; Lei, Kai C.; Leung, Lesley L.; Lerner, Renata; Lin, Jian-ya; Lin, Kathleen; Lim, Bryon C.; Lui, Crystal P. Y.; Liu, Tiffany Q.; Luong, Vincent; Makshanoff, Jacob; Mei, An-Chi; Meza, Miguel; Mikhaeil, Yara A.; Moarefi, Majid; Nguyen, Long H.; Pai, Shekhar S.; Pandya, Manish; Patel, Aadit R.; Picard, Paul D.; Safaee, Michael M.; Salame, Carol; Sanchez, Christian; Sanchez, Nina; Seifert, Christina C.; Shah, Abhishek; Shilgevorkyan, Oganes H.; Singh, Inderroop; Soma, Vanessa; Song, Junia J.; Srivastava, Neetika; Sta.Ana, Jennifer L.; Sun, Christie; Tan, Diane; Teruya, Alison S.; Tikia, Robyn; Tran, Trinh; Travis, Emily G.; Trinh, Jennifer D.; Vo, Diane; Walsh, Thomas; Wong, Regan S.; Wu, Katherine; Wu, Ya-Whey; Yang, Nkau X. V.; Yeranosian, Michael; Yu, James S.; Zhou, Jennifer J.; Zhu, Ran X.; Abrams, Anna; Abramson, Amanda; Amado, Latiffe; Anderson, Jenny; Bashour, Keenan; Beyer, Elsa; Bookatz, Allen; Brewer, Sarah; Buu, Natalie; Calvillo, Stephanie; Cao, Joseph; Chan, Amy; Chan, Jenny; Chang, Aileen; Chang, Daniel; Chang, Yuli; Chen, YiBing; Choi, Joo; Chou, Jeyling; Dang, Peter; Datta, Sumit; Davarifar, Ardy; Deravanesian, Artemis; Desai, Poonam; Fabrikant, Jordan; Farnad, Shahbaz; Fu, Katherine; Garcia, Eddie; Garrone, Nick; Gasparyan, Srpouhi; Gayda, Phyllis; Go, Sherrylene; Goffstein, Chad; Gonzalez, Courtney; Guirguis, Mariam; Hassid, Ryan; Hermogeno, Brenda; Hong, Julie; Hong, Aria; Hovestreydt, Lindsay; Hu, Charles; Huff, Devon; Jamshidian, Farid; Jen, James; Kahen, Katrin; Kao, Linda; Kelley, Melissa; Kho, Thomas; Kim, Yein; Kim, Sarah; Kirkpatrick, Brian; Langenbacher, Adam; Laxamana, Santino; Lee, Janet; Lee, Chris; Lee, So-Youn; Lee, ToHang S.; Lee, Toni; Lewis, Gemma; Lezcano, Sheila; Lin, Peter; Luu, Thanh; Luu, Julie; Marrs, Will; Marsh, Erin; Marshall, Jamie; Min, Sarah; Minasian, Tanya; Minye, Helena; Misra, Amit; Morimoto, Miles; Moshfegh, Yasaman; Murray, Jessica; Nguyen, Kha; Nguyen, Cynthia; Nodado, Ernesto; O'Donahue, Amanda; Onugha, Ndidi; Orjiakor, Nneka; Padhiar, Bhavin; Paul, Eric; Pavel-Dinu, Mara; Pavlenko, Alex; Paz, Edwin; Phaklides, Sarah; Pham, Lephong; Poulose, Preethi; Powell, Russell; Pusic, Aya; Ramola, Divi; Regalia, Kirsten; Ribbens, Meghann; Rifai, Bassel; Saakyan, Manyak; Saarikoski, Pamela; Segura, Miriam; Shadpour, Farnaz; Shemmassian, Aram; Singh, Ramnik; Singh, Vivek; Skinner, Emily; Solomin, Daniel; Soneji, Kosha; Spivey, Kristin; Stageberg, Erika; Stavchanskiy, Marina; Tekchandani, Leena; Thai, Leo; Thiyanaratnam, Jayantha; Tong, Maurine; Toor, Aneet; Tovar, Steve; Trangsrud, Kelly; Tsang, Wah-Yung; Uemura, Marc; Vollmer, Emily; Weiss, Emily; Wood, Damien; Wu, Joy; Wu, Sophia; Wu, Winston; Xu, Qing; Yamauchi, Yuki; Yarosh, Will; Yee, Laura; Yen, George; Banerjee, Utpal

2007-01-01

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes. PMID:17720911

Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African-Americans

PubMed Central

Carty, Cara L.; Keene, Keith L.; Cheng, Yu-Ching; Meschia, James F.; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C.; Kittner, Steven J.; Rich, Stephen S.; Tajuddin, Salman; Zonderman, Alan B.; Evans, Michele K.; Langefeld, Carl D.; Gottesman, Rebecca; Mosley, Thomas H.; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, YongMei; Sale, Michèle M.; Dichgans, Martin; Malik, Rainer; Longstreth, WT; Mitchell, Braxton D.; Psaty, Bruce M.; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B.; Fornage, Myriam

2015-01-01

Background and Purpose The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African-Americans despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population genome-wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods Using METAL, we conducted meta-analyses of GWAS in 14,746 African-Americans (1,365 ischemic and 1,592 total stroke cases) from COMPASS, and tested SNPs with P<10−6 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613, P=3.9×10−8) in African-Americans. Nominal associations (P<10−6) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/ mRNA pre-splicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B and ZFHX3) were nominally associated (P<0.05) with stroke in COMPASS. Conclusions We identified a novel SNP associated with total stroke in African-Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African-Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. PMID:26089329

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

PubMed

Fabbri, C; Tansey, K E; Perlis, R H; Hauser, J; Henigsberg, N; Maier, W; Mors, O; Placentino, A; Rietschel, M; Souery, D; Breen, G; Curtis, C; Sang-Hyuk, L; Newhouse, S; Patel, H; Guipponi, M; Perroud, N; Bondolfi, G; O'Donovan, M; Lewis, G; Biernacka, J M; Weinshilboum, R M; Farmer, A; Aitchison, K J; Craig, I; McGuffin, P; Uher, R; Lewis, C M

2017-11-21

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.The Pharmacogenomics Journal advance online publication, 21 November 2017; doi:10.1038/tpj.2017.44.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

PubMed

Siddiq, Afshan; Couch, Fergus J; Chen, Gary K; Lindström, Sara; Eccles, Diana; Millikan, Robert C; Michailidou, Kyriaki; Stram, Daniel O; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M; Buring, Julie E; Buys, Saundra S; Campa, Daniele; Carpenter, Jane E; Chasman, Daniel I; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S; Czene, Kamila; Deming, Sandra L; Diasio, Robert B; Diver, W Ryan; Dunning, Alison M; Durcan, Lorraine; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M; Gerty, Susan M; Rodriguez-Gil, Jorge L; Giles, Graham G; van Gils, Carla H; Godwin, Andrew K; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N; Hopper, John L; Hu, Jennifer J; Huntsman, Scott; Ingles, Sue A; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B; John, Esther M; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N; Coetzee, Gerhard A; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G; McLean, Catriona A; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R; Montgomery, Grant W; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J; Palmer, Julie R; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F; Schmutzler, Rita K; Slager, Susan; Southey, Melissa C; Stevens, Kristen N; Sinn, Hans-Peter; Press, Michael F; Ross, Eric; Riboli, Elio; Ridker, Paul M; Schumacher, Fredrick R; Severi, Gianluca; Dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J; Thun, Michael J; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, Joellen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F; Hunter, David J; Henderson, Brian E; Chanock, Stephen J; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A; Vachon, Celine M

2012-12-15

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

PubMed Central

Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindström, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, JoEllen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R.; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

2012-01-01

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10-5 in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10−8) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10–6) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10−9), and with both ER-positive (OR = 1.09; P = 1.5 × 10−5) and ER-negative (OR = 1.16, P = 2.5 × 10−7) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci. PMID:22976474

Northeast Artificial Intelligence Consortium Annual Report 1987. Volume 2, Part B. Discussing, Using, and Recognizing Plans

DTIC Science & Technology

1989-03-01

1978. Williams. B.C. Qualitative Analysis of MOS Circuits. Artificial Inteligence . 1984. 24.. Wilson. K. From Association to Structure. Amsterdam:North...D-A208 378 RADC-TR-88-324, Vol II (of nine), Part B Interim Report March 1969 4. NORTHEAST ARTIFICIAL INTELLIGENCE CONSORTIUM ANNUAL REPORT 1987...II (of nine), Part B 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Northeast Artificial (ff ’aolicbl

Bridging Graduate Education in Public Health and the Liberal Arts

PubMed Central

Gubrium, Aline C.; Aulino, Felicity; Krause, Elizabeth L.; Leatherman, Thomas L.

2015-01-01

The University of Massachusetts Amherst is part of Five-Colleges Inc, a consortium that includes the university and four liberal arts colleges. Consortium faculty from the School of Public Health and Health Sciences at the university and from the colleges are working to bridge liberal arts with public health graduate education. We outline four key themes guiding this effort and exemplary curricular tools for innovative community-based and multidisciplinary academic and research programs. The structure of the consortium has created a novel trajectory for student learning and engagement, with important ramifications for pedagogy and professional practice in public health. We show how graduate public health education and liberal arts can, and must, work in tandem to transform public health practice in the 21st century. PMID:25706025

Return of genomic results to research participants: the floor, the ceiling, and the choices in between.

PubMed

Jarvik, Gail P; Amendola, Laura M; Berg, Jonathan S; Brothers, Kyle; Clayton, Ellen W; Chung, Wendy; Evans, Barbara J; Evans, James P; Fullerton, Stephanie M; Gallego, Carlos J; Garrison, Nanibaa' A; Gray, Stacy W; Holm, Ingrid A; Kullo, Iftikhar J; Lehmann, Lisa Soleymani; McCarty, Cathy; Prows, Cynthia A; Rehm, Heidi L; Sharp, Richard R; Salama, Joseph; Sanderson, Saskia; Van Driest, Sara L; Williams, Marc S; Wolf, Susan M; Wolf, Wendy A; Burke, Wylie

2014-06-05

As more research studies incorporate next-generation sequencing (including whole-genome or whole-exome sequencing), investigators and institutional review boards face difficult questions regarding which genomic results to return to research participants and how. An American College of Medical Genetics and Genomics 2013 policy paper suggesting that pathogenic mutations in 56 specified genes should be returned in the clinical setting has raised the question of whether comparable recommendations should be considered in research settings. The Clinical Sequencing Exploratory Research (CSER) Consortium and the Electronic Medical Records and Genomics (eMERGE) Network are multisite research programs that aim to develop practical strategies for addressing questions concerning the return of results in genomic research. CSER and eMERGE committees have identified areas of consensus regarding the return of genomic results to research participants. In most circumstances, if results meet an actionability threshold for return and the research participant has consented to return, genomic results, along with referral for appropriate clinical follow-up, should be offered to participants. However, participants have a right to decline the receipt of genomic results, even when doing so might be viewed as a threat to the participants' health. Research investigators should be prepared to return research results and incidental findings discovered in the course of their research and meeting an actionability threshold, but they have no ethical obligation to actively search for such results. These positions are consistent with the recognition that clinical research is distinct from medical care in both its aims and its guiding moral principles. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Discovery of the "RNA continent" through a contrarian's research strategy.

PubMed

Hayashizaki, Yoshihide

2011-01-01

The International Human Genome Sequencing Consortium completed the decoding of the human genome sequence in 2003. Readers will be aware of the paradigm shift which has occurred since then in the field of life science research. At last, mankind has been able to focus on a complete picture of the full extent of the genome, on which is recorded the basic information that controls all life. Meanwhile, another genome project, centered on Japan and known as the mouse genome encyclopedia project, was progressing with participation from around the world. Led by our research group at RIKEN, it was a full-length cDNA project which aimed to decode the whole RNA (transcriptome) using the mouse as a model. The basic information that controls all life is recorded on the genome, but in order to obtain a complete picture of this extensive information, the decoding of the genome alone is far from sufficient. These two genome projects established that the number of letters in the genome, which is the blueprint of life, is finite, that the number of RNA molecules derived from it is also finite, and that the number of protein molecules derived from the RNA is probably finite too. A massive number of combinations is still involved, but we are now able to understand one section of the network formed by these data. Once an object of study has been understood to be finite, establishing an image of the whole is certain to lead us to an understanding of the whole. Omics is an approach that views the information controlling life as finite and seeks to assemble and analyze it as a whole. Here, I would like to present our transcriptome research while making reference to our unique research strategy.

TIMES-SS--recent refinements resulting from an industrial skin sensitisation consortium.

PubMed

Patlewicz, G; Kuseva, C; Mehmed, A; Popova, Y; Dimitrova, G; Ellis, G; Hunziker, R; Kern, P; Low, L; Ringeissen, S; Roberts, D W; Mekenyan, O

2014-01-01

The TImes MEtabolism Simulator platform for predicting Skin Sensitisation (TIMES-SS) is a hybrid expert system, first developed at Bourgas University using funding and data from a consortium of industry and regulators. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic 3D QSARs. The model estimates semi-quantitative skin sensitisation potency classes and has been developed with the aim of minimising animal testing, and also to be scientifically valid in accordance with the OECD principles for (Q)SAR validation. In 2007 an external validation exercise was undertaken to fully address these principles. In 2010, a new industry consortium was established to coordinate research efforts in three specific areas: refinement of abiotic reactions in the skin (namely autoxidation) in the skin, refinement of the manner in which chemical reactivity was captured in terms of structure-toxicity rules (inclusion of alert reliability parameters) and defining the domain based on the underlying experimental data (study of discrepancies between local lymph node assay Local Lymph Node Assay (LLNA) and Guinea Pig Maximisation Test (GPMT)). The present paper summarises the progress of these activities and explains how the insights derived have been translated into refinements, resulting in increased confidence and transparency in the robustness of the TIMES-SS predictions.

GlycomeDB – integration of open-access carbohydrate structure databases

PubMed Central

Ranzinger, René; Herget, Stephan; Wetter, Thomas; von der Lieth, Claus-Wilhelm

2008-01-01

Background Although carbohydrates are the third major class of biological macromolecules, after proteins and DNA, there is neither a comprehensive database for carbohydrate structures nor an established universal structure encoding scheme for computational purposes. Funding for further development of the Complex Carbohydrate Structure Database (CCSD or CarbBank) ceased in 1997, and since then several initiatives have developed independent databases with partially overlapping foci. For each database, different encoding schemes for residues and sequence topology were designed. Therefore, it is virtually impossible to obtain an overview of all deposited structures or to compare the contents of the various databases. Results We have implemented procedures which download the structures contained in the seven major databases, e.g. GLYCOSCIENCES.de, the Consortium for Functional Glycomics (CFG), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Bacterial Carbohydrate Structure Database (BCSDB). We have created a new database called GlycomeDB, containing all structures, their taxonomic annotations and references (IDs) for the original databases. More than 100000 datasets were imported, resulting in more than 33000 unique sequences now encoded in GlycomeDB using the universal format GlycoCT. Inconsistencies were found in all public databases, which were discussed and corrected in multiple feedback rounds with the responsible curators. Conclusion GlycomeDB is a new, publicly available database for carbohydrate sequences with a unified, all-encompassing structure encoding format and NCBI taxonomic referencing. The database is updated weekly and can be downloaded free of charge. The JAVA application GlycoUpdateDB is also available for establishing and updating a local installation of GlycomeDB. With the advent of GlycomeDB, the distributed islands of knowledge in glycomics are now bridged to form a single resource. PMID:18803830

Comparative Proteomics Reveals a Significant Bias Toward Alternative Protein Isoforms with Conserved Structure and Function

PubMed Central

Ezkurdia, Iakes; del Pozo, Angela; Frankish, Adam; Rodriguez, Jose Manuel; Harrow, Jennifer; Ashman, Keith; Valencia, Alfonso; Tress, Michael L.

2012-01-01

Advances in high-throughput mass spectrometry are making proteomics an increasingly important tool in genome annotation projects. Peptides detected in mass spectrometry experiments can be used to validate gene models and verify the translation of putative coding sequences (CDSs). Here, we have identified peptides that cover 35% of the genes annotated by the GENCODE consortium for the human genome as part of a comprehensive analysis of experimental spectra from two large publicly available mass spectrometry databases. We detected the translation to protein of “novel” and “putative” protein-coding transcripts as well as transcripts annotated as pseudogenes and nonsense-mediated decay targets. We provide a detailed overview of the population of alternatively spliced protein isoforms that are detectable by peptide identification methods. We found that 150 genes expressed multiple alternative protein isoforms. This constitutes the largest set of reliably confirmed alternatively spliced proteins yet discovered. Three groups of genes were highly overrepresented. We detected alternative isoforms for 10 of the 25 possible heterogeneous nuclear ribonucleoproteins, proteins with a key role in the splicing process. Alternative isoforms generated from interchangeable homologous exons and from short indels were also significantly enriched, both in human experiments and in parallel analyses of mouse and Drosophila proteomics experiments. Our results show that a surprisingly high proportion (almost 25%) of the detected alternative isoforms are only subtly different from their constitutive counterparts. Many of the alternative splicing events that give rise to these alternative isoforms are conserved in mouse. It was striking that very few of these conserved splicing events broke Pfam functional domains or would damage globular protein structures. This evidence of a strong bias toward subtle differences in CDS and likely conserved cellular function and structure is remarkable and strongly suggests that the translation of alternative transcripts may be subject to selective constraints. PMID:22446687

Design and characterization of a 52K SNP chip for goats.

PubMed

Tosser-Klopp, Gwenola; Bardou, Philippe; Bouchez, Olivier; Cabau, Cédric; Crooijmans, Richard; Dong, Yang; Donnadieu-Tonon, Cécile; Eggen, André; Heuven, Henri C M; Jamli, Saadiah; Jiken, Abdullah Johari; Klopp, Christophe; Lawley, Cynthia T; McEwan, John; Martin, Patrice; Moreno, Carole R; Mulsant, Philippe; Nabihoudine, Ibouniyamine; Pailhoux, Eric; Palhière, Isabelle; Rupp, Rachel; Sarry, Julien; Sayre, Brian L; Tircazes, Aurélie; Jun Wang; Wang, Wen; Zhang, Wenguang

2014-01-01

The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50-60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF) suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed): Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on >10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc) and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes), sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years.

Design and Characterization of a 52K SNP Chip for Goats

PubMed Central

Tosser-Klopp, Gwenola; Bardou, Philippe; Bouchez, Olivier; Cabau, Cédric; Crooijmans, Richard; Dong, Yang; Donnadieu-Tonon, Cécile; Eggen, André; Heuven, Henri C. M.; Jamli, Saadiah; Jiken, Abdullah Johari; Klopp, Christophe; Lawley, Cynthia T.; McEwan, John; Martin, Patrice; Moreno, Carole R.; Mulsant, Philippe; Nabihoudine, Ibouniyamine; Pailhoux, Eric; Palhière, Isabelle; Rupp, Rachel; Sarry, Julien; Sayre, Brian L.; Tircazes, Aurélie; Jun Wang; Wang, Wen; Zhang, Wenguang

2014-01-01

The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50–60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF) suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed): Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on >10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc) and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes), sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years. PMID:24465974

GBOOST: a GPU-based tool for detecting gene-gene interactions in genome-wide case control studies.

PubMed

Yung, Ling Sing; Yang, Can; Wan, Xiang; Yu, Weichuan

2011-05-01

Collecting millions of genetic variations is feasible with the advanced genotyping technology. With a huge amount of genetic variations data in hand, developing efficient algorithms to carry out the gene-gene interaction analysis in a timely manner has become one of the key problems in genome-wide association studies (GWAS). Boolean operation-based screening and testing (BOOST), a recent work in GWAS, completes gene-gene interaction analysis in 2.5 days on a desktop computer. Compared with central processing units (CPUs), graphic processing units (GPUs) are highly parallel hardware and provide massive computing resources. We are, therefore, motivated to use GPUs to further speed up the analysis of gene-gene interactions. We implement the BOOST method based on a GPU framework and name it GBOOST. GBOOST achieves a 40-fold speedup compared with BOOST. It completes the analysis of Wellcome Trust Case Control Consortium Type 2 Diabetes (WTCCC T2D) genome data within 1.34 h on a desktop computer equipped with Nvidia GeForce GTX 285 display card. GBOOST code is available at http://bioinformatics.ust.hk/BOOST.html#GBOOST.

Cellulose biosynthesis by the beta-proteobacterium, Chromobacterium violaceum.

PubMed

Recouvreux, Derce O S; Carminatti, Claudimir A; Pitlovanciv, Ana K; Rambo, Carlos R; Porto, Luismar M; Antônio, Regina V

2008-11-01

The Chromobacterium violaceum ATCC 12472 genome was sequenced by The Brazilian National Genome Project Consortium. Previous annotation reported the presence of cellulose biosynthesis genes in that genome. Analysis of these genes showed that, as observed in other bacteria, they are organized in two operons. In the present work, experimental evidences of the presence of cellulose in the extracellular matrix of the biofilm produced by C. violaceum in static cultures are shown. Biofilm samples were enzymatically digested by cellulase, releasing glucose units, suggesting the presence of cellulose as an extracellular matrix component. Fluorescence microscopy observations showed that C. violaceum produces a cellulase-sensitive extracellular matrix composed of fibers able to bind calcofluor. C. violaceum grows on medium containing Congo red, forming brown-red colonies. Together, these results suggest that cellulase-susceptible matrix material is cellulose. Scanning electronic microscopy analysis showed that the extracellular matrix exhibited a network of microfibrils, typical of bacterial cellulose. Although cellulose production is widely distributed between several bacterial species, including at least the groups of Gram-negative proteobacteria alpha and gamma, we give for the first time experimental evidence for cellulose production in beta-proteobacteria.

A Comparison of Variant Calling Pipelines Using Genome in a Bottle as a Reference

PubMed Central

2015-01-01

High-throughput sequencing, especially of exomes, is a popular diagnostic tool, but it is difficult to determine which tools are the best at analyzing this data. In this study, we use the NIST Genome in a Bottle results as a novel resource for validation of our exome analysis pipeline. We use six different aligners and five different variant callers to determine which pipeline, of the 30 total, performs the best on a human exome that was used to help generate the list of variants detected by the Genome in a Bottle Consortium. Of these 30 pipelines, we found that Novoalign in conjunction with GATK UnifiedGenotyper exhibited the highest sensitivity while maintaining a low number of false positives for SNVs. However, it is apparent that indels are still difficult for any pipeline to handle with none of the tools achieving an average sensitivity higher than 33% or a Positive Predictive Value (PPV) higher than 53%. Lastly, as expected, it was found that aligners can play as vital a role in variant detection as variant callers themselves. PMID:26539496

A genome-wide scan for common alleles affecting risk for autism

PubMed Central

Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R.; Correia, Catarina; Abrahams, Brett S.; Sykes, Nuala; Pagnamenta, Alistair T.; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J.; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F.; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R.; Casallo, Guillermo; Casey, Jillian; Chu, Su H.; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L.; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A.; Folstein, Susan E.; Fombonne, Eric; Freitag, Christine M.; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T.; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J.; Hakonarson, Hakon; Heron, Elizabeth A.; Hill, Matthew; Holt, Richard; Howe, Jennifer L.; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M.; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M.; Lamb, Janine A.; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L.; Lionel, Anath C.; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C.; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R.; McConachie, Helen; McDougle, Christopher J.; McGrath, Jane; McMahon, William M.; Melhem, Nadine M.; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J.; Mirza, Ghazala K.; Munson, Jeff; Nelson, Stanley F.; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R.; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L.; Bierut, Laura J.; Rice, John P.; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C.; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P.; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B.; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H.; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L.; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D.; Cantor, Rita M.; Cook, Edwin H.; Coon, Hilary; Cuccaro, Michael L.; Gallagher, Louise; Geschwind, Daniel H.; Gill, Michael; Haines, Jonathan L.; Miller, Judith; Monaco, Anthony P.; Nurnberger, John I.; Paterson, Andrew D.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Sutcliffe, James S.; Szatmari, Peter; Vicente, Astrid M.; Vieland, Veronica J.; Wijsman, Ellen M.; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

2010-01-01

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C. PMID:20663923

The AraGWAS Catalog: a curated and standardized Arabidopsis thaliana GWAS catalog

PubMed Central

Togninalli, Matteo; Seren, Ümit; Meng, Dazhe; Fitz, Joffrey; Nordborg, Magnus; Weigel, Detlef

2018-01-01

Abstract The abundance of high-quality genotype and phenotype data for the model organism Arabidopsis thaliana enables scientists to study the genetic architecture of many complex traits at an unprecedented level of detail using genome-wide association studies (GWAS). GWAS have been a great success in A. thaliana and many SNP-trait associations have been published. With the AraGWAS Catalog (https://aragwas.1001genomes.org) we provide a publicly available, manually curated and standardized GWAS catalog for all publicly available phenotypes from the central A. thaliana phenotype repository, AraPheno. All GWAS have been recomputed on the latest imputed genotype release of the 1001 Genomes Consortium using a standardized GWAS pipeline to ensure comparability between results. The catalog includes currently 167 phenotypes and more than 222 000 SNP-trait associations with P < 10−4, of which 3887 are significantly associated using permutation-based thresholds. The AraGWAS Catalog can be accessed via a modern web-interface and provides various features to easily access, download and visualize the results and summary statistics across GWAS. PMID:29059333

Common variant at 16p11.2 conferring risk of psychosis.

PubMed

Steinberg, S; de Jong, S; Mattheisen, M; Costas, J; Demontis, D; Jamain, S; Pietiläinen, O P H; Lin, K; Papiol, S; Huttenlocher, J; Sigurdsson, E; Vassos, E; Giegling, I; Breuer, R; Fraser, G; Walker, N; Melle, I; Djurovic, S; Agartz, I; Tuulio-Henriksson, A; Suvisaari, J; Lönnqvist, J; Paunio, T; Olsen, L; Hansen, T; Ingason, A; Pirinen, M; Strengman, E; Hougaard, D M; Orntoft, T; Didriksen, M; Hollegaard, M V; Nordentoft, M; Abramova, L; Kaleda, V; Arrojo, M; Sanjuán, J; Arango, C; Etain, B; Bellivier, F; Méary, A; Schürhoff, F; Szoke, A; Ribolsi, M; Magni, V; Siracusano, A; Sperling, S; Rossner, M; Christiansen, C; Kiemeney, L A; Franke, B; van den Berg, L H; Veldink, J; Curran, S; Bolton, P; Poot, M; Staal, W; Rehnstrom, K; Kilpinen, H; Freitag, C M; Meyer, J; Magnusson, P; Saemundsen, E; Martsenkovsky, I; Bikshaieva, I; Martsenkovska, I; Vashchenko, O; Raleva, M; Paketchieva, K; Stefanovski, B; Durmishi, N; Pejovic Milovancevic, M; Lecic Tosevski, D; Silagadze, T; Naneishvili, N; Mikeladze, N; Surguladze, S; Vincent, J B; Farmer, A; Mitchell, P B; Wright, A; Schofield, P R; Fullerton, J M; Montgomery, G W; Martin, N G; Rubino, I A; van Winkel, R; Kenis, G; De Hert, M; Réthelyi, J M; Bitter, I; Terenius, L; Jönsson, E G; Bakker, S; van Os, J; Jablensky, A; Leboyer, M; Bramon, E; Powell, J; Murray, R; Corvin, A; Gill, M; Morris, D; O'Neill, F A; Kendler, K; Riley, B; Craddock, N; Owen, M J; O'Donovan, M C; Thorsteinsdottir, U; Kong, A; Ehrenreich, H; Carracedo, A; Golimbet, V; Andreassen, O A; Børglum, A D; Mors, O; Mortensen, P B; Werge, T; Ophoff, R A; Nöthen, M M; Rietschel, M; Cichon, S; Ruggeri, M; Tosato, S; Palotie, A; St Clair, D; Rujescu, D; Collier, D A; Stefansson, H; Stefansson, K

2014-01-01

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

Genetic findings in anorexia and bulimia nervosa.

PubMed

Hinney, Anke; Scherag, Susann; Hebebrand, Johannes

2010-01-01

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders associated with disordered eating behavior. Heritability estimates derived from twin and family studies are high, so that substantial genetic influences on the etiology can be assumed for both. As the monoaminergic neurotransmitter systems are involved in eating disorders (EDs), candidate gene studies have centered on related genes; additionally, genes relevant for body weight regulation have been considered as candidates. Unfortunately, this approach has yielded very few positive results; confirmed associations or findings substantiated in meta-analyses are scant. None of these associations can be considered unequivocally validated. Systematic genome-wide approaches have been performed to identify genes with no a priori evidence for their relevance in EDs. Family-based scans revealed linkage peaks in single chromosomal regions for AN and BN. Analyses of candidate genes in one of these regions led to the identification of genetic variants associated with AN. Currently, an international consortium is conducting a genome-wide association study for AN, which will hopefully lead to the identification of the first genome-wide significant markers. Copyright © 2010 Elsevier Inc. All rights reserved.

A genome-wide scan for common alleles affecting risk for autism.

PubMed

Anney, Richard; Klei, Lambertus; Pinto, Dalila; Regan, Regina; Conroy, Judith; Magalhaes, Tiago R; Correia, Catarina; Abrahams, Brett S; Sykes, Nuala; Pagnamenta, Alistair T; Almeida, Joana; Bacchelli, Elena; Bailey, Anthony J; Baird, Gillian; Battaglia, Agatino; Berney, Tom; Bolshakova, Nadia; Bölte, Sven; Bolton, Patrick F; Bourgeron, Thomas; Brennan, Sean; Brian, Jessica; Carson, Andrew R; Casallo, Guillermo; Casey, Jillian; Chu, Su H; Cochrane, Lynne; Corsello, Christina; Crawford, Emily L; Crossett, Andrew; Dawson, Geraldine; de Jonge, Maretha; Delorme, Richard; Drmic, Irene; Duketis, Eftichia; Duque, Frederico; Estes, Annette; Farrar, Penny; Fernandez, Bridget A; Folstein, Susan E; Fombonne, Eric; Freitag, Christine M; Gilbert, John; Gillberg, Christopher; Glessner, Joseph T; Goldberg, Jeremy; Green, Jonathan; Guter, Stephen J; Hakonarson, Hakon; Heron, Elizabeth A; Hill, Matthew; Holt, Richard; Howe, Jennifer L; Hughes, Gillian; Hus, Vanessa; Igliozzi, Roberta; Kim, Cecilia; Klauck, Sabine M; Kolevzon, Alexander; Korvatska, Olena; Kustanovich, Vlad; Lajonchere, Clara M; Lamb, Janine A; Laskawiec, Magdalena; Leboyer, Marion; Le Couteur, Ann; Leventhal, Bennett L; Lionel, Anath C; Liu, Xiao-Qing; Lord, Catherine; Lotspeich, Linda; Lund, Sabata C; Maestrini, Elena; Mahoney, William; Mantoulan, Carine; Marshall, Christian R; McConachie, Helen; McDougle, Christopher J; McGrath, Jane; McMahon, William M; Melhem, Nadine M; Merikangas, Alison; Migita, Ohsuke; Minshew, Nancy J; Mirza, Ghazala K; Munson, Jeff; Nelson, Stanley F; Noakes, Carolyn; Noor, Abdul; Nygren, Gudrun; Oliveira, Guiomar; Papanikolaou, Katerina; Parr, Jeremy R; Parrini, Barbara; Paton, Tara; Pickles, Andrew; Piven, Joseph; Posey, David J; Poustka, Annemarie; Poustka, Fritz; Prasad, Aparna; Ragoussis, Jiannis; Renshaw, Katy; Rickaby, Jessica; Roberts, Wendy; Roeder, Kathryn; Roge, Bernadette; Rutter, Michael L; Bierut, Laura J; Rice, John P; Salt, Jeff; Sansom, Katherine; Sato, Daisuke; Segurado, Ricardo; Senman, Lili; Shah, Naisha; Sheffield, Val C; Soorya, Latha; Sousa, Inês; Stoppioni, Vera; Strawbridge, Christina; Tancredi, Raffaella; Tansey, Katherine; Thiruvahindrapduram, Bhooma; Thompson, Ann P; Thomson, Susanne; Tryfon, Ana; Tsiantis, John; Van Engeland, Herman; Vincent, John B; Volkmar, Fred; Wallace, Simon; Wang, Kai; Wang, Zhouzhi; Wassink, Thomas H; Wing, Kirsty; Wittemeyer, Kerstin; Wood, Shawn; Yaspan, Brian L; Zurawiecki, Danielle; Zwaigenbaum, Lonnie; Betancur, Catalina; Buxbaum, Joseph D; Cantor, Rita M; Cook, Edwin H; Coon, Hilary; Cuccaro, Michael L; Gallagher, Louise; Geschwind, Daniel H; Gill, Michael; Haines, Jonathan L; Miller, Judith; Monaco, Anthony P; Nurnberger, John I; Paterson, Andrew D; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Scherer, Stephen W; Sutcliffe, James S; Szatmari, Peter; Vicente, Astrid M; Vieland, Veronica J; Wijsman, Ellen M; Devlin, Bernie; Ennis, Sean; Hallmayer, Joachim

2010-10-15

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

PubMed Central

Kessler, Michael D.; Yerges-Armstrong, Laura; Taub, Margaret A.; Shetty, Amol C.; Maloney, Kristin; Jeng, Linda Jo Bone; Ruczinski, Ingo; Levin, Albert M.; Williams, L. Keoki; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Boorgula, Meher Preethi; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Scott, Alan F.; Vergara, Candelaria; Gao, Jingjing; Hu, Yijuan; Johnston, Henry Richard; Qin, Zhaohui S.; Padhukasahasram, Badri; Dunston, Georgia M.; Faruque, Mezbah U.; Kenny, Eimear E.; Gietzen, Kimberly; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-YounA; Kumar, Rajesh; Schleimer, Robert; Bustamante, Carlos; De La Vega, Francisco M.; Gignoux, Chris R.; Shringarpure, Suyash S.; Musharoff, Shaila; Wojcik, Genevieve; Burchard, Esteban G.; Eng, Celeste; Gourraud, Pierre-Antoine; Hernandez, Ryan D.; Lizee, Antoine; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O.; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Abecasis, Goncalo; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Pissamai, Maul R. N.; Trevor, Maul R. N.; Watson, Harold; Araujo, Maria Ilma; Oliveira, Ricardo Riccio; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Herrera-Paz, Edwin Francisco; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Vasquez, Olga Marina; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria; O'Connor, Timothy D.

2016-01-01

To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=−0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations. PMID:27725664

TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages

PubMed Central

Bontempi, Gianluca; Ceccarelli, Michele; Noushmehr, Houtan

2016-01-01

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox,  TCGAbiolinks. PMID:28232861

TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages.

PubMed

Silva, Tiago C; Colaprico, Antonio; Olsen, Catharina; D'Angelo, Fulvio; Bontempi, Gianluca; Ceccarelli, Michele; Noushmehr, Houtan

2016-01-01

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox,  TCGAbiolinks.

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

A Metagenomic Approach to Cyanobacterial Genomics

PubMed Central

Alvarenga, Danillo O.; Fiore, Marli F.; Varani, Alessandro M.

2017-01-01

Cyanobacteria, or oxyphotobacteria, are primary producers that establish ecological interactions with a wide variety of organisms. Although their associations with eukaryotes have received most attention, interactions with bacterial and archaeal symbionts have also been occurring for billions of years. Due to these associations, obtaining axenic cultures of cyanobacteria is usually difficult, and most isolation efforts result in unicyanobacterial cultures containing a number of associated microbes, hence composing a microbial consortium. With rising numbers of cyanobacterial blooms due to climate change, demand for genomic evaluations of these microorganisms is increasing. However, standard genomic techniques call for the sequencing of axenic cultures, an approach that not only adds months or even years for culture purification, but also appears to be impossible for some cyanobacteria, which is reflected in the relatively low number of publicly available genomic sequences of this phylum. Under the framework of metagenomics, on the other hand, cumbersome techniques for achieving axenic growth can be circumvented and individual genomes can be successfully obtained from microbial consortia. This review focuses on approaches for the genomic and metagenomic assessment of non-axenic cyanobacterial cultures that bypass requirements for axenity. These methods enable researchers to achieve faster and less costly genomic characterizations of cyanobacterial strains and raise additional information about their associated microorganisms. While non-axenic cultures may have been previously frowned upon in cyanobacteriology, latest advancements in metagenomics have provided new possibilities for in vitro studies of oxyphotobacteria, renewing the value of microbial consortia as a reliable and functional resource for the rapid assessment of bloom-forming cyanobacteria. PMID:28536564

Use of microsatellite markers for the assessment of bambara groundnut breeding system and varietal purity before genome sequencing.

PubMed

Ho, Wai Kuan; Muchugi, Alice; Muthemba, Samuel; Kariba, Robert; Mavenkeni, Busiso Olga; Hendre, Prasad; Song, Bo; Van Deynze, Allen; Massawe, Festo; Mayes, Sean

2016-06-01

Maximizing the research output from a limited investment is often the major challenge for minor and underutilized crops. However, such crops may be tolerant to biotic and abiotic stresses and are adapted to local, marginal, and low-input environments. Their development through breeding will provide an important resource for future agricultural system resilience and diversification in the context of changing climates and the need to achieve food security. The African Orphan Crops Consortium recognizes the values of genomic resources in facilitating the improvement of such crops. Prior to beginning genome sequencing there is a need for an assessment of line varietal purity and to estimate any residual heterozygosity. Here we present an example from bambara groundnut (Vigna subterranea (L.) Verdc.), an underutilized drought tolerant African legume. Two released varieties from Zimbabwe, identified as potential genotypes for whole genome sequencing (WGS), were genotyped with 20 species-specific SSR markers. The results indicate that the cultivars are actually a mix of related inbred genotypes, and the analysis allowed a strategy of single plant selection to be used to generate non-heterogeneous DNA for WGS. The markers also confirmed very low levels of heterozygosity within individual plants. The application of a pre-screen using co-dominant microsatellite markers is expected to substantially improve the genome assembly, compared to a cultivar bulking approach that could have been adopted.

Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource.

PubMed

Shim, Hongseok; Kim, Ji Hyun; Kim, Chan Yeong; Hwang, Sohyun; Kim, Hyojin; Yang, Sunmo; Lee, Ji Eun; Lee, Insuk

2016-11-16

Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish (Danio rerio), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet (www.inetbio.org/danionet), which was constructed by Bayesian integration of genomics big data. Rigorous statistical assessment confirmed the high prediction capacity of DanioNet for a wide variety of human diseases. To demonstrate the feasibility of the function-driven disease gene discovery using DanioNet, we predicted genes for ciliopathies and performed experimental validation for eight candidate genes. We also validated the existence of heterozygous rare variants in the candidate genes of individuals with ciliopathies yet not in controls derived from the UK10K consortium, suggesting that these variants are potentially involved in enhancing the risk of ciliopathies. These results showed that an integrated genomics big data for a model animal of diseases can expand our opportunity for harnessing WES data in disease gene discovery. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Developing knowledge resources to support precision medicine: principles from the Clinical Pharmacogenetics Implementation Consortium (CPIC).

PubMed

Hoffman, James M; Dunnenberger, Henry M; Kevin Hicks, J; Caudle, Kelly E; Whirl Carrillo, Michelle; Freimuth, Robert R; Williams, Marc S; Klein, Teri E; Peterson, Josh F

2016-07-01

To move beyond a select few genes/drugs, the successful adoption of pharmacogenomics into routine clinical care requires a curated and machine-readable database of pharmacogenomic knowledge suitable for use in an electronic health record (EHR) with clinical decision support (CDS). Recognizing that EHR vendors do not yet provide a standard set of CDS functions for pharmacogenetics, the Clinical Pharmacogenetics Implementation Consortium (CPIC) Informatics Working Group is developing and systematically incorporating a set of EHR-agnostic implementation resources into all CPIC guidelines. These resources illustrate how to integrate pharmacogenomic test results in clinical information systems with CDS to facilitate the use of patient genomic data at the point of care. Based on our collective experience creating existing CPIC resources and implementing pharmacogenomics at our practice sites, we outline principles to define the key features of future knowledge bases and discuss the importance of these knowledge resources for pharmacogenomics and ultimately precision medicine. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A distinct group of CpG islands shows differential DNA methylation between replicas of the same cell line in vitro

PubMed Central

2013-01-01

Background CpG dinucleotide-rich genomic DNA regions, known as CpG islands (CGIs), can be methylated at their cytosine residues as an epigenetic mark that is stably inherited during cell mitosis. Differentially methylated regions (DMRs) are genomic regions showing different degrees of DNA methylation in multiple samples. In this study, we focused our attention on CGIs showing different DNA methylation between two culture replicas of the same cell line. Results We used methylation data of 35 cell lines from the Encyclopedia of DNA Elements (ENCODE) consortium to identify CpG islands that were differentially methylated between replicas of the same cell line and denoted them Inter Replicas Differentially Methylated CpG islands (IRDM-CGIs). We identified a group of IRDM-CGIs that was consistently shared by different cell lines, and denoted it common IRDM-CGIs. X chromosome CGIs were overrepresented among common IRDM-CGIs. Autosomal IRDM-CGIs were preferentially located in gene bodies and intergenic regions had a lower G + C content, a smaller mean length, and a reduced CpG percentage. Functional analysis of the genes associated with autosomal IRDM-CGIs showed that many of them are involved in DNA binding and development. Conclusions Our results show that several specific functional and structural features characterize common IRDM-CGIs. They may represent a specific subset of CGIs that are more prone to being differentially methylated for their intrinsic characteristics. PMID:24106769

Identification of common variants associated with human hippocampal and intracranial volumes.

PubMed

Stein, Jason L; Medland, Sarah E; Vasquez, Alejandro Arias; Hibar, Derrek P; Senstad, Rudy E; Winkler, Anderson M; Toro, Roberto; Appel, Katja; Bartecek, Richard; Bergmann, Ørjan; Bernard, Manon; Brown, Andrew A; Cannon, Dara M; Chakravarty, M Mallar; Christoforou, Andrea; Domin, Martin; Grimm, Oliver; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hottenga, Jouke-Jan; Langan, Camilla; Lopez, Lorna M; Hansell, Narelle K; Hwang, Kristy S; Kim, Sungeun; Laje, Gonzalo; Lee, Phil H; Liu, Xinmin; Loth, Eva; Lourdusamy, Anbarasu; Mattingsdal, Morten; Mohnke, Sebastian; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; O'Brien, Carol; Papmeyer, Martina; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rijpkema, Mark; Risacher, Shannon L; Roddey, J Cooper; Rose, Emma J; Ryten, Mina; Shen, Li; Sprooten, Emma; Strengman, Eric; Teumer, Alexander; Trabzuni, Daniah; Turner, Jessica; van Eijk, Kristel; van Erp, Theo G M; van Tol, Marie-Jose; Wittfeld, Katharina; Wolf, Christiane; Woudstra, Saskia; Aleman, Andre; Alhusaini, Saud; Almasy, Laura; Binder, Elisabeth B; Brohawn, David G; Cantor, Rita M; Carless, Melanie A; Corvin, Aiden; Czisch, Michael; Curran, Joanne E; Davies, Gail; de Almeida, Marcio A A; Delanty, Norman; Depondt, Chantal; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fagerness, Jesen; Fox, Peter T; Freimer, Nelson B; Gill, Michael; Göring, Harald H H; Hagler, Donald J; Hoehn, David; Holsboer, Florian; Hoogman, Martine; Hosten, Norbert; Jahanshad, Neda; Johnson, Matthew P; Kasperaviciute, Dalia; Kent, Jack W; Kochunov, Peter; Lancaster, Jack L; Lawrie, Stephen M; Liewald, David C; Mandl, René; Matarin, Mar; Mattheisen, Manuel; Meisenzahl, Eva; Melle, Ingrid; Moses, Eric K; Mühleisen, Thomas W; Nauck, Matthias; Nöthen, Markus M; Olvera, Rene L; Pandolfo, Massimo; Pike, G Bruce; Puls, Ralf; Reinvang, Ivar; Rentería, Miguel E; Rietschel, Marcella; Roffman, Joshua L; Royle, Natalie A; Rujescu, Dan; Savitz, Jonathan; Schnack, Hugo G; Schnell, Knut; Seiferth, Nina; Smith, Colin; Steen, Vidar M; Valdés Hernández, Maria C; Van den Heuvel, Martijn; van der Wee, Nic J; Van Haren, Neeltje E M; Veltman, Joris A; Völzke, Henry; Walker, Robert; Westlye, Lars T; Whelan, Christopher D; Agartz, Ingrid; Boomsma, Dorret I; Cavalleri, Gianpiero L; Dale, Anders M; Djurovic, Srdjan; Drevets, Wayne C; Hagoort, Peter; Hall, Jeremy; Heinz, Andreas; Jack, Clifford R; Foroud, Tatiana M; Le Hellard, Stephanie; Macciardi, Fabio; Montgomery, Grant W; Poline, Jean Baptiste; Porteous, David J; Sisodiya, Sanjay M; Starr, John M; Sussmann, Jessika; Toga, Arthur W; Veltman, Dick J; Walter, Henrik; Weiner, Michael W; Bis, Joshua C; Ikram, M Arfan; Smith, Albert V; Gudnason, Vilmundur; Tzourio, Christophe; Vernooij, Meike W; Launer, Lenore J; DeCarli, Charles; Seshadri, Sudha; Andreassen, Ole A; Apostolova, Liana G; Bastin, Mark E; Blangero, John; Brunner, Han G; Buckner, Randy L; Cichon, Sven; Coppola, Giovanni; de Zubicaray, Greig I; Deary, Ian J; Donohoe, Gary; de Geus, Eco J C; Espeseth, Thomas; Fernández, Guillén; Glahn, David C; Grabe, Hans J; Hardy, John; Hulshoff Pol, Hilleke E; Jenkinson, Mark; Kahn, René S; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Meyer-Lindenberg, Andreas; Morris, Derek W; Müller-Myhsok, Bertram; Nichols, Thomas E; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W; Potkin, Steven G; Sämann, Philipp G; Saykin, Andrew J; Schumann, Gunter; Smoller, Jordan W; Wardlaw, Joanna M; Weale, Michael E; Martin, Nicholas G; Franke, Barbara; Wright, Margaret J; Thompson, Paul M

2012-04-15

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.

PubMed

Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A; Schütt, Christine; Ravindranath, Aakash Chavan; Leuchtenberger, Stefanie; Sharma, Sapna; Kistler, Martin; Willershäuser, Monja; Brommage, Robert; Meehan, Terrence F; Mason, Jeremy; Haselimashhadi, Hamed; Hough, Tertius; Mallon, Ann-Marie; Wells, Sara; Santos, Luis; Lelliott, Christopher J; White, Jacqueline K; Sorg, Tania; Champy, Marie-France; Bower, Lynette R; Reynolds, Corey L; Flenniken, Ann M; Murray, Stephen A; Nutter, Lauryl M J; Svenson, Karen L; West, David; Tocchini-Valentini, Glauco P; Beaudet, Arthur L; Bosch, Fatima; Braun, Robert B; Dobbie, Michael S; Gao, Xiang; Herault, Yann; Moshiri, Ala; Moore, Bret A; Kent Lloyd, K C; McKerlie, Colin; Masuya, Hiroshi; Tanaka, Nobuhiko; Flicek, Paul; Parkinson, Helen E; Sedlacek, Radislav; Seong, Je Kyung; Wang, Chi-Kuang Leo; Moore, Mark; Brown, Steve D; Tschöp, Matthias H; Wurst, Wolfgang; Klingenspor, Martin; Wolf, Eckhard; Beckers, Johannes; Machicao, Fausto; Peter, Andreas; Staiger, Harald; Häring, Hans-Ulrich; Grallert, Harald; Campillos, Monica; Maier, Holger; Fuchs, Helmut; Gailus-Durner, Valerie; Werner, Thomas; Hrabe de Angelis, Martin

2018-01-18

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.

Minimum information about a marker gene sequence (MIMARKS) and minimum information about any (x) sequence (MIxS) specifications

PubMed Central

Yilmaz, Pelin; Kottmann, Renzo; Field, Dawn; Knight, Rob; Cole, James R; Amaral-Zettler, Linda; Gilbert, Jack A; Karsch-Mizrachi, Ilene; Johnston, Anjanette; Cochrane, Guy; Vaughan, Robert; Hunter, Christopher; Park, Joonhong; Morrison, Norman; Rocca-Serra, Philippe; Sterk, Peter; Arumugam, Manimozhiyan; Bailey, Mark; Baumgartner, Laura; Birren, Bruce W; Blaser, Martin J; Bonazzi, Vivien; Booth, Tim; Bork, Peer; Bushman, Frederic D; Buttigieg, Pier Luigi; Chain, Patrick S G; Charlson, Emily; Costello, Elizabeth K; Huot-Creasy, Heather; Dawyndt, Peter; DeSantis, Todd; Fierer, Noah; Fuhrman, Jed A; Gallery, Rachel E; Gevers, Dirk; Gibbs, Richard A; Gil, Inigo San; Gonzalez, Antonio; Gordon, Jeffrey I; Guralnick, Robert; Hankeln, Wolfgang; Highlander, Sarah; Hugenholtz, Philip; Jansson, Janet; Kau, Andrew L; Kelley, Scott T; Kennedy, Jerry; Knights, Dan; Koren, Omry; Kuczynski, Justin; Kyrpides, Nikos; Larsen, Robert; Lauber, Christian L; Legg, Teresa; Ley, Ruth E; Lozupone, Catherine A; Ludwig, Wolfgang; Lyons, Donna; Maguire, Eamonn; Methé, Barbara A; Meyer, Folker; Muegge, Brian; Nakielny, Sara; Nelson, Karen E; Nemergut, Diana; Neufeld, Josh D; Newbold, Lindsay K; Oliver, Anna E; Pace, Norman R; Palanisamy, Giriprakash; Peplies, Jörg; Petrosino, Joseph; Proctor, Lita; Pruesse, Elmar; Quast, Christian; Raes, Jeroen; Ratnasingham, Sujeevan; Ravel, Jacques; Relman, David A; Assunta-Sansone, Susanna; Schloss, Patrick D; Schriml, Lynn; Sinha, Rohini; Smith, Michelle I; Sodergren, Erica; Spor, Aymé; Stombaugh, Jesse; Tiedje, James M; Ward, Doyle V; Weinstock, George M; Wendel, Doug; White, Owen; Whiteley, Andrew; Wilke, Andreas; Wortman, Jennifer R; Yatsunenko, Tanya; Glöckner, Frank Oliver

2012-01-01

Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences—the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The ‘environmental packages’ apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere. PMID:21552244

Improving safety of aircraft engines: a consortium approach

NASA Astrophysics Data System (ADS)

Brasche, Lisa J. H.

1996-11-01

With over seven million departures per year, air transportation has become not a luxury, but a standard mode of transportation for the United States. A critical aspect of modern air transport is the jet engine, a complex engineered component that has enabled the rapid travel to which we have all become accustomed. One of the enabling technologies for safe air travel is nondestructive evaluation, or NDE, which includes various inspection techniques used to assess the health or integrity of a structure, component, or material. The Engine Titanium Consortium (ETC) was established in 1993 to respond to recommendations made by the Federal Aviation Administration (FAA) Titanium Rotating Components Review Team (TRCRT) for improvements in inspection of engine titanium. Several recent accomplishments of the ETC are detailed in this paper. The objective of the Engine Titanium Consortium is to provide the FAAand the manufacturers with reliable and costeffective new methods and/or improvements in mature methods for detecting cracks, inclusions, and imperfections in titanium. The consortium consists of a team of researchers from academia and industry-namely, Iowa State University, Allied Signal Propulsion Engines, General Electric Aircraft Engines, and Pratt & Whitney Engines-who work together to develop program priorities, organize a program plan, conduct the research, and implement the solutions. The true advantage of the consortium approach is that it brings together the research talents of academia and the engineering talents of industry to tackle a technology-base problem. In bringing industrial competitors together, the consortium ensures that the research results, which have safety implications and result from FAA funds, are shared and become part of the public domain.

The Complete Genome of Teredinibacter turnerae T7901: An Intracellular Endosymbiont of Marine Wood-Boring Bivalves (Shipworms)

PubMed Central

Yang, Joyce C.; Madupu, Ramana; Durkin, A. Scott; Ekborg, Nathan A.; Pedamallu, Chandra S.; Hostetler, Jessica B.; Radune, Diana; Toms, Bradley S.; Henrissat, Bernard; Coutinho, Pedro M.; Schwarz, Sandra; Field, Lauren; Trindade-Silva, Amaro E.; Soares, Carlos A. G.; Elshahawi, Sherif; Hanora, Amro; Schmidt, Eric W.; Haygood, Margo G.; Posfai, Janos; Benner, Jack; Madinger, Catherine; Nove, John; Anton, Brian; Chaudhary, Kshitiz; Foster, Jeremy; Holman, Alex; Kumar, Sanjay; Lessard, Philip A.; Luyten, Yvette A.; Slatko, Barton; Wood, Nicole; Wu, Bo; Teplitski, Max; Mougous, Joseph D.; Ward, Naomi; Eisen, Jonathan A.; Badger, Jonathan H.; Distel, Daniel L.

2009-01-01

Here we report the complete genome sequence of Teredinibacter turnerae T7901. T. turnerae is a marine gamma proteobacterium that occurs as an intracellular endosymbiont in the gills of wood-boring marine bivalves of the family Teredinidae (shipworms). This species is the sole cultivated member of an endosymbiotic consortium thought to provide the host with enzymes, including cellulases and nitrogenase, critical for digestion of wood and supplementation of the host's nitrogen-deficient diet. T. turnerae is closely related to the free-living marine polysaccharide degrading bacterium Saccharophagus degradans str. 2–40 and to as yet uncultivated endosymbionts with which it coexists in shipworm cells. Like S. degradans, the T. turnerae genome encodes a large number of enzymes predicted to be involved in complex polysaccharide degradation (>100). However, unlike S. degradans, which degrades a broad spectrum (>10 classes) of complex plant, fungal and algal polysaccharides, T. turnerae primarily encodes enzymes associated with deconstruction of terrestrial woody plant material. Also unlike S. degradans and many other eubacteria, T. turnerae dedicates a large proportion of its genome to genes predicted to function in secondary metabolism. Despite its intracellular niche, the T. turnerae genome lacks many features associated with obligate intracellular existence (e.g. reduced genome size, reduced %G+C, loss of genes of core metabolism) and displays evidence of adaptations common to free-living bacteria (e.g. defense against bacteriophage infection). These results suggest that T. turnerae is likely a facultative intracellular ensosymbiont whose niche presently includes, or recently included, free-living existence. As such, the T. turnerae genome provides insights into the range of genomic adaptations associated with intracellular endosymbiosis as well as enzymatic mechanisms relevant to the recycling of plant materials in marine environments and the production of cellulose-derived biofuels. PMID:19568419

Network-Based Identification and Prioritization of Key Regulators of Coronary Artery Disease Loci

PubMed Central

Zhao, Yuqi; Chen, Jing; Freudenberg, Johannes M.; Meng, Qingying; Rajpal, Deepak K.; Yang, Xia

2017-01-01

Objective Recent genome-wide association studies of coronary artery disease (CAD) have revealed 58 genome-wide significant and 148 suggestive genetic loci. However, the molecular mechanisms through which they contribute to CAD and the clinical implications of these findings remain largely unknown. We aim to retrieve gene subnetworks of the 206 CAD loci and identify and prioritize candidate regulators to better understand the biological mechanisms underlying the genetic associations. Approach and Results We devised a new integrative genomics approach that incorporated (1) candidate genes from the top CAD loci, (2) the complete genetic association results from the 1000 genomes-based CAD genome-wide association studies from the Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus the Coronary Artery Disease consortium, (3) tissue-specific gene regulatory networks that depict the potential relationship and interactions between genes, and (4) tissue-specific gene expression patterns between CAD patients and controls. The networks and top-ranked regulators according to these data-driven criteria were further queried against literature, experimental evidence, and drug information to evaluate their disease relevance and potential as drug targets. Our analysis uncovered several potential novel regulators of CAD such as LUM and STAT3, which possess properties suitable as drug targets. We also revealed molecular relations and potential mechanisms through which the top CAD loci operate. Furthermore, we found that multiple CAD-relevant biological processes such as extracellular matrix, inflammatory and immune pathways, complement and coagulation cascades, and lipid metabolism interact in the CAD networks. Conclusions Our data-driven integrative genomics framework unraveled tissue-specific relations among the candidate genes of the CAD genome-wide association studies loci and prioritized novel network regulatory genes orchestrating biological processes relevant to CAD. PMID:26966275

ISOL@: an Italian SOLAnaceae genomics resource.

PubMed

Chiusano, Maria Luisa; D'Agostino, Nunzio; Traini, Alessandra; Licciardello, Concetta; Raimondo, Enrico; Aversano, Mario; Frusciante, Luigi; Monti, Luigi

2008-03-26

Present-day '-omics' technologies produce overwhelming amounts of data which include genome sequences, information on gene expression (transcripts and proteins) and on cell metabolic status. These data represent multiple aspects of a biological system and need to be investigated as a whole to shed light on the mechanisms which underpin the system functionality. The gathering and convergence of data generated by high-throughput technologies, the effective integration of different data-sources and the analysis of the information content based on comparative approaches are key methods for meaningful biological interpretations. In the frame of the International Solanaceae Genome Project, we propose here ISOLA, an Italian SOLAnaceae genomics resource. ISOLA (available at http://biosrv.cab.unina.it/isola) represents a trial platform and it is conceived as a multi-level computational environment.ISOLA currently consists of two main levels: the genome and the expression level. The cornerstone of the genome level is represented by the Solanum lycopersicum genome draft sequences generated by the International Tomato Genome Sequencing Consortium. Instead, the basic element of the expression level is the transcriptome information from different Solanaceae species, mainly in the form of species-specific comprehensive collections of Expressed Sequence Tags (ESTs). The cross-talk between the genome and the expression levels is based on data source sharing and on tools that enhance data quality, that extract information content from the levels' under parts and produce value-added biological knowledge. ISOLA is the result of a bioinformatics effort that addresses the challenges of the post-genomics era. It is designed to exploit '-omics' data based on effective integration to acquire biological knowledge and to approach a systems biology view. Beyond providing experimental biologists with a preliminary annotation of the tomato genome, this effort aims to produce a trial computational environment where different aspects and details are maintained as they are relevant for the analysis of the organization, the functionality and the evolution of the Solanaceae family.

ChIP-seq and ChIP-exo profiling of Pol II, H2A.Z, and H3K4me3 in human K562 cells.

PubMed

Mchaourab, Zenab F; Perreault, Andrea A; Venters, Bryan J

2018-03-06

The human K562 chronic myeloid leukemia cell line has long served as an experimental paradigm for functional genomic studies. To systematically and functionally annotate the human genome, the ENCODE consortium generated hundreds of functional genomic data sets, such as chromatin immunoprecipitation coupled to sequencing (ChIP-seq). While ChIP-seq analyses have provided tremendous insights into gene regulation, spatiotemporal insights were limited by a resolution of several hundred base pairs. ChIP-exonuclease (ChIP-exo) is a refined version of ChIP-seq that overcomes this limitation by providing higher precision mapping of protein-DNA interactions. To study the interplay of transcription initiation and chromatin, we profiled the genome-wide locations for RNA polymerase II (Pol II), the histone variant H2A.Z, and the histone modification H3K4me3 using ChIP-seq and ChIP-exo. In this Data Descriptor, we present detailed information on parallel experimental design, data generation, quality control analysis, and data validation. We discuss how these data lay the foundation for future analysis to understand the relationship between the occupancy of Pol II and nucleosome positions at near base pair resolution.

A Central Support System Can Facilitate Implementation and Sustainability of a Classroom-Based Undergraduate Research Experience (CURE) in Genomics

PubMed Central

Lopatto, David; Hauser, Charles; Jones, Christopher J.; Paetkau, Don; Chandrasekaran, Vidya; Dunbar, David; MacKinnon, Christy; Stamm, Joyce; Alvarez, Consuelo; Barnard, Daron; Bedard, James E. J.; Bednarski, April E.; Bhalla, Satish; Braverman, John M.; Burg, Martin; Chung, Hui-Min; DeJong, Randall J.; DiAngelo, Justin R.; Du, Chunguang; Eckdahl, Todd T.; Emerson, Julia; Frary, Amy; Frohlich, Donald; Goodman, Anya L.; Gosser, Yuying; Govind, Shubha; Haberman, Adam; Hark, Amy T.; Hoogewerf, Arlene; Johnson, Diana; Kadlec, Lisa; Kaehler, Marian; Key, S. Catherine Silver; Kokan, Nighat P.; Kopp, Olga R.; Kuleck, Gary A.; Lopilato, Jane; Martinez-Cruzado, Juan C.; McNeil, Gerard; Mel, Stephanie; Nagengast, Alexis; Overvoorde, Paul J.; Parrish, Susan; Preuss, Mary L.; Reed, Laura D.; Regisford, E. Gloria; Revie, Dennis; Robic, Srebrenka; Roecklien-Canfield, Jennifer A.; Rosenwald, Anne G.; Rubin, Michael R.; Saville, Kenneth; Schroeder, Stephanie; Sharif, Karim A.; Shaw, Mary; Skuse, Gary; Smith, Christopher D.; Smith, Mary; Smith, Sheryl T.; Spana, Eric P.; Spratt, Mary; Sreenivasan, Aparna; Thompson, Jeffrey S.; Wawersik, Matthew; Wolyniak, Michael J.; Youngblom, James; Zhou, Leming; Buhler, Jeremy; Mardis, Elaine; Leung, Wilson; Threlfall, Jennifer; Elgin, Sarah C. R.

2014-01-01

In their 2012 report, the President's Council of Advisors on Science and Technology advocated “replacing standard science laboratory courses with discovery-based research courses”—a challenging proposition that presents practical and pedagogical difficulties. In this paper, we describe our collective experiences working with the Genomics Education Partnership, a nationwide faculty consortium that aims to provide undergraduates with a research experience in genomics through a scheduled course (a classroom-based undergraduate research experience, or CURE). We examine the common barriers encountered in implementing a CURE, program elements of most value to faculty, ways in which a shared core support system can help, and the incentives for and rewards of establishing a CURE on our diverse campuses. While some of the barriers and rewards are specific to a research project utilizing a genomics approach, other lessons learned should be broadly applicable. We find that a central system that supports a shared investigation can mitigate some shortfalls in campus infrastructure (such as time for new curriculum development, availability of IT services) and provides collegial support for change. Our findings should be useful for designing similar supportive programs to facilitate change in the way we teach science for undergraduates. PMID:25452493

Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome

PubMed Central

Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing; O’Connor, Timothy D.; Abecasis, Gonçalo R.; Wojcik, Genevieve L; Gignoux, Christopher R.; Gourraud, Pierre-Antoine; Lizee, Antoine; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Kenny, Eimear E.; Bustamante, Carlos; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Qin, Zhaohui S.; Preethi Boorgula, Meher; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Ruczinski, Ingo; Scott, Alan F.; Taub, Margaret A.; Vergara, Candelaria; Levin, Albert M.; Padhukasahasram, Badri; Williams, L. Keoki; Dunston, Georgia M.; Faruque, Mezbah U.; Gietzen, Kimberly; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-Youn A.; Kumar, Rajesh; Schleimer, Robert; De La Vega, Francisco M.; Shringarpure, Suyash S.; Musharoff, Shaila; Burchard, Esteban G.; Eng, Celeste; Hernandez, Ryan D.; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Maul, Pissamai; Maul, Trevor; Watson, Harold; Ilma Araujo, Maria; Riccio Oliveira, Ricardo; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Francisco Herrera-Paz, Edwin; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Marina Vasquez, Olga; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria

2017-01-01

A primary goal of The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to develop an ‘African Diaspora Power Chip’ (ADPC), a genotyping array consisting of tagging SNPs, useful in comprehensively identifying African specific genetic variation. This array is designed based on the novel variation identified in 642 CAAPA samples of African ancestry with high coverage whole genome sequence data (~30× depth). This novel variation extends the pattern of variation catalogued in the 1000 Genomes and Exome Sequencing Projects to a spectrum of populations representing the wide range of West African genomic diversity. These individuals from CAAPA also comprise a large swath of the African Diaspora population and incorporate historical genetic diversity covering nearly the entire Atlantic coast of the Americas. Here we show the results of designing and producing such a microchip array. This novel array covers African specific variation far better than other commercially available arrays, and will enable better GWAS analyses for researchers with individuals of African descent in their study populations. A recent study cataloging variation in continental African populations suggests this type of African-specific genotyping array is both necessary and valuable for facilitating large-scale GWAS in populations of African ancestry. PMID:28429804

A decision tool to guide the ethics review of a challenging breed of emerging genomic projects.

PubMed

Joly, Yann; So, Derek; Osien, Gladys; Crimi, Laura; Bobrow, Martin; Chalmers, Don; Wallace, Susan E; Zeps, Nikolajs; Knoppers, Bartha

2016-08-01

Recent projects conducted by the International Cancer Genome Consortium (ICGC) have raised the important issue of distinguishing quality assurance (QA) activities from research in the context of genomics. Research was historically defined as a systematic effort to expand a shared body of knowledge, whereas QA was defined as an effort to ascertain whether a specific project met desired standards. However, the two categories increasingly overlap due to advances in bioinformatics and the shift toward open science. As few ethics review policies take these changes into account, it is often difficult to determine the appropriate level of review. Mislabeling can result in unnecessary burdens for the investigators or, conversely, in underestimation of the risks to participants. Therefore, it is important to develop a consistent method of selecting the review process for genomics and bioinformatics projects. This paper begins by discussing two case studies from the ICGC, followed by a literature review on the distinction between QA and research and a comparative analysis of ethics review policies from Canada, the United States, the United Kingdom, and Australia. These results are synthesized into a novel two-step decision tool for researchers and policymakers, which uses traditional criteria to sort clearly defined activities while requiring the use of actual risk levels to decide more complex cases.

Challenges imposed by minor reference alleles on the identification and reporting of clinical variants from exome data.

PubMed

Koko, Mahmoud; Abdallah, Mohammed O E; Amin, Mutaz; Ibrahim, Muntaser

2018-01-15

The conventional variant calling of pathogenic alleles in exome and genome sequencing requires the presence of the non-pathogenic alleles as genome references. This hinders the correct identification of variants with minor and/or pathogenic reference alleles warranting additional approaches for variant calling. More than 26,000 Exome Aggregation Consortium (ExAC) variants have a minor reference allele including variants with known ClinVar disease alleles. For instance, in a number of variants related to clotting disorders, the phenotype-associated allele is a human genome reference allele (rs6025, rs6003, rs1799983, and rs2227564 using the assembly hg19). We highlighted how the current variant calling standards miss homozygous reference disease variants in these sites and provided a bioinformatic panel that can be used to screen these variants using commonly available variant callers. We present exome sequencing results from an individual with venous thrombosis to emphasize how pathogenic alleles in clinically relevant variants escape variant calling while non-pathogenic alleles are detected. This article highlights the importance of specialized variant calling strategies in clinical variants with minor reference alleles especially in the context of personal genomes and exomes. We provide here a simple strategy to screen potential disease-causing variants when present in homozygous reference state.

Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization.

PubMed

Zhang, Ben; Shu, Xiao-Ou; Delahanty, Ryan J; Zeng, Chenjie; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Wen, Wanqing; Long, Jirong; Li, Chun; Dunning, Alison M; Chang-Claude, Jenny; Shah, Mitul; Perkins, Barbara J; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; Floris, Giuseppe; Schmidt, Marjanka K; Rookus, Matti A; van den Hurk, Katja; de Kort, Wim L A M; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Li, Jingmei; Humphreys, Keith; Brand, Judith; Guénel, Pascal; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Benitez, Javier; Zamora, M Pilar; Perez, Jose I A; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Chenevix-Trench, Georgia; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Marchand, Loic Le; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Martens, John W M; Tilanus-Linthorst, Madeleine M A; Collée, J Margriet; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Giles, Graham G; Milne, Roger L; McLean, Catriona; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony J; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Garcia-Closas, Montserrat; Brinton, Louise; Lissowska, Jolanta; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Radice, Paolo; Bogdanova, Natalia; Antonenkova, Natalia; Dörk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Devilee, Peter; Seynaeve, Caroline; Van Asperen, Christi J; Jakubowska, Anna; Lubiński, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Hamann, Ute; Torres, Diana; Schmutzler, Rita K; Neuhausen, Susan L; Anton-Culver, Hoda; Kristensen, Vessela N; Grenaker Alnæs, Grethe I; Pierce, Brandon L; Kraft, Peter; Peters, Ulrike; Lindstrom, Sara; Seminara, Daniela; Burgess, Stephen; Ahsan, Habibul; Whittemore, Alice S; John, Esther M; Gammon, Marilie D; Malone, Kathleen E; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Pharoah, Paul D P; Simard, Jacques; Hall, Per; Hunter, David J; Easton, Douglas F; Zheng, Wei

2015-11-01

Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. We performed a meta-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients. The pooled relative risk of breast cancer was 1.17 (95% confidence interval [CI] = 1.15 to 1.19) per 10cm increase in height in the meta-analysis of prospective studies. In Mendelian randomization analysis, the odds ratio of breast cancer per 10cm increase in genetically predicted height was 1.22 (95% CI = 1.13 to 1.32) in the first consortium and 1.21 (95% CI = 1.05 to 1.39) in the second consortium. The association was found in both premenopausal and postmenopausal women but restricted to hormone receptor-positive breast cancer. Analyses of height-associated variants identified eight new loci associated with breast cancer risk after adjusting for multiple comparisons, including three loci at 1q21.2, DNAJC27, and CCDC91 at genome-wide significance level P < 5×10(-8). Our study provides strong evidence that adult height is a risk factor for breast cancer in women and certain genetic factors and biological pathways affecting adult height have an important role in the etiology of breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Salinity effect on the metabolic pathway and microbial function in phenanthrene degradation by a halophilic consortium.

PubMed

Wang, Chongyang; Huang, Yong; Zhang, Zuotao; Wang, Hui

2018-04-25

With the close relationship between saline environments and industry, polycyclic aromatic hydrocarbons (PAHs) accumulate in saline/hypersaline environments. Therefore, PAHs degradation by halotolerant/halophilic bacteria has received increasing attention. In this study, the metabolic pathway of phenanthrene degradation by halophilic consortium CY-1 was first studied which showed a single upstream pathway initiated by dioxygenation at the C1 and C2 positions, and at several downstream pathways, including the catechol pathway, gentisic acid pathway and protocatechuic acid pathway. The effects of salinity on the community structure and expression of catabolic genes were further studied by a combination of high-throughput sequencing, catabolic gene clone library and real-time PCR. Pure cultures were also isolated from consortium CY-1 to investigate the contribution made by different microbes in the PAH-degrading process. Marinobacter is the dominant genus that contributed to the upstream degradation of phenanthrene especially in high salt content. Genus Halomonas made a great contribution in transforming intermediates in the subsequent degradation of catechol by using catechol 1,2-dioxygenase (C12O). Other microbes were predicted to be mediating bacteria that were able to utilize intermediates via different downstream pathways. Salinity was investigated to have negative effects on both microbial diversity and activity of consortium CY-1 and consortium CY-1 was found with a high degree of functional redundancy in saline environments.

The autism sequencing consortium: large-scale, high-throughput sequencing in autism spectrum disorders.

PubMed

Buxbaum, Joseph D; Daly, Mark J; Devlin, Bernie; Lehner, Thomas; Roeder, Kathryn; State, Matthew W

2012-12-20

Research during the past decade has seen significant progress in the understanding of the genetic architecture of autism spectrum disorders (ASDs), with gene discovery accelerating as the characterization of genomic variation has become increasingly comprehensive. At the same time, this research has highlighted ongoing challenges. Here we address the enormous impact of high-throughput sequencing (HTS) on ASD gene discovery, outline a consensus view for leveraging this technology, and describe a large multisite collaboration developed to accomplish these goals. Similar approaches could prove effective for severe neurodevelopmental disorders more broadly. Copyright © 2012 Elsevier Inc. All rights reserved.

Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn disease susceptibility

PubMed Central

Parkes, Miles; Barrett, Jeffrey C; Prescott, Natalie; Tremelling, Mark; Anderson, Carl A; Fisher, Sheila A; Roberts, Roland G; Nimmo, Elaine R; Cummings, Fraser R; Soars, Dianne; Drummond, Hazel; Lees, Charlie W; Khawaja, Saud A; Bagnall, Richard; Burke, Denis A; Todhunter, Catherine E; Ahmad, Tariq; Onnie, Clive M; McArdle, Wendy; Strachan, David; Bethel, Graeme; Bryan, Claire; Deloukas, Panos; Forbes, Alastair; Sanderson, Jeremy; Jewell, Derek P; Satsangi, Jack; Mansfield, John C; Cardon, Lon; Mathew, Christopher G

2008-01-01

A genome-wide association scan in Crohn disease by the Wellcome Trust Case Control Consortium1 detected strong association at 6 novel loci. We tested 37 SNPs from these and other loci for association in an independent case control sample. Replication was obtained for the IRGM gene on chromosome 5q33.1 which induces autophagy (replication P = 6.6 × 10−4, combined P = 2.1 × 10−10), and for 9 other loci including NKX2-3 and gene deserts on chromosomes 1q and 5p13. PMID:17554261

Development and Characterization of Reference Materials for Genetic Testing: Focus on Public Partnerships.

PubMed

Kalman, Lisa V; Datta, Vivekananda; Williams, Mickey; Zook, Justin M; Salit, Marc L; Han, Jin Yeong

2016-11-01

Characterized reference materials (RMs) are needed for clinical laboratory test development and validation, quality control procedures, and proficiency testing to assure their quality. In this article, we review the development and characterization of RMs for clinical molecular genetic tests. We describe various types of RMs and how to access and utilize them, especially focusing on the Genetic Testing Reference Materials Coordination Program (Get-RM) and the Genome in a Bottle (GIAB) Consortium. This review also reinforces the need for collaborative efforts in the clinical genetic testing community to develop additional RMs.

Rapid Mineralization of Benzo[a]pyrene by a Microbial Consortium Growing on Diesel Fuel

PubMed Central

Kanaly, Robert A.; Bartha, Richard; Watanabe, Kazuya; Harayama, Shigeaki

2000-01-01

A microbial consortium which rapidly mineralized the environmentally persistent pollutant benzo[a]pyrene was recovered from soil. The consortium cometabolically converted [7-14C]benzo[a]pyrene to 14CO2 when it was grown on diesel fuel, and the extent of benzo[a]pyrene mineralization was dependent on both diesel fuel and benzo[a]pyrene concentrations. Addition of diesel fuel at concentrations ranging from 0.007 to 0.2% (wt/vol) stimulated the mineralization of 10 mg of benzo[a]pyrene per liter 33 to 65% during a 2-week incubation period. When the benzo[a]pyrene concentration was 10 to 100 mg liter−1 and the diesel fuel concentration was 0.1% (wt/vol), an inoculum containing 1 mg of cell protein per liter (small inoculum) resulted in mineralization of up to 17.2 mg of benzo[a]pyrene per liter in 16 days. This corresponded to 35% of the added radiolabel when the concentration of benzo[a]pyrene was 50 mg liter−1. A radiocarbon mass balance analysis recovered 25% of the added benzo[a]pyrene solubilized in the culture suspension prior to mineralization. Populations growing on diesel fuel most likely promoted emulsification of benzo[a]pyrene through the production of surface-active compounds. The consortium was also analyzed by PCR-denaturing gradient gel electrophoresis of 16S rRNA gene fragments, and 12 dominant bands, representing different sequence types, were detected during a 19-day incubation period. The onset of benzo[a]pyrene mineralization was compared to changes in the consortium community structure and was found to correlate with the emergence of at least four sequence types. DNA from 10 sequence types were successfully purified and sequenced, and that data revealed that eight of the consortium members were related to the class Proteobacteria but that the consortium also included members which were related to the genera Mycobacterium and Sphingobacterium. PMID:11010861

Column bioleaching of uranium embedded in granite porphyry by a mesophilic acidophilic consortium.

PubMed

Qiu, Guanzhou; Li, Qian; Yu, Runlan; Sun, Zhanxue; Liu, Yajie; Chen, Miao; Yin, Huaqun; Zhang, Yage; Liang, Yili; Xu, Lingling; Sun, Limin; Liu, Xueduan

2011-04-01

A mesophilic acidophilic consortium was enriched from acid mine drainage samples collected from several uranium mines in China. The performance of the consortium in column bioleaching of low-grade uranium embedded in granite porphyry was investigated. The influences of several chemical parameters on uranium extraction in column reactor were also investigated. A uranium recovery of 96.82% was achieved in 97 days column leaching process including 33 days acid pre-leaching stage and 64 days bioleaching stage. It was reflected that indirect leaching mechanism took precedence over direct. Furthermore, the bacterial community structure was analyzed by using Amplified Ribosomal DNA Restriction Analysis. The results showed that microorganisms on the residual surface were more diverse than that in the solution. Acidithiobacillus ferrooxidans was the dominant species in the solution and Leptospirillum ferriphilum on the residual surface. Copyright © 2011 Elsevier Ltd. All rights reserved.

A National Study on the Effects of Concussion in Collegiate Athletes and US Military Service Academy Members: The NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium Structure and Methods.

PubMed

Broglio, Steven P; McCrea, Michael; McAllister, Thomas; Harezlak, Jaroslaw; Katz, Barry; Hack, Dallas; Hainline, Brian

2017-07-01

The natural history of mild traumatic brain injury (TBI) or concussion remains poorly defined and no objective biomarker of physiological recovery exists for clinical use. The National Collegiate Athletic Association (NCAA) and the US Department of Defense (DoD) established the Concussion Assessment, Research and Education (CARE) Consortium to study the natural history of clinical and neurobiological recovery after concussion in the service of improved injury prevention, safety and medical care for student-athletes and military personnel. The objectives of this paper were to (i) describe the background and driving rationale for the CARE Consortium; (ii) outline the infrastructure of the Consortium policies, procedures, and governance; (iii) describe the longitudinal 6-month clinical and neurobiological study methodology; and (iv) characterize special considerations in the design and implementation of a multicenter trial. Beginning Fall 2014, CARE Consortium institutions have recruited and enrolled 23,533 student-athletes and military service academy students (approximately 90% of eligible student-athletes and cadets; 64.6% male, 35.4% female). A total of 1174 concussions have been diagnosed in participating subjects, with both concussion and baseline cases deposited in the Federal Interagency Traumatic Brain Injury Research (FITBIR) database. Challenges have included coordinating regulatory issues across civilian and military institutions, operationalizing study procedures, neuroimaging protocol harmonization across sites and platforms, construction and maintenance of a relational database, and data quality and integrity monitoring. The NCAA-DoD CARE Consortium represents a comprehensive investigation of concussion in student-athletes and military service academy students. The richly characterized study sample and multidimensional approach provide an opportunity to advance the field of concussion science, not only among student athletes but in all populations at risk for mild TBI.

A hybrid BAC physical map of potato: a framework for sequencing a heterozygous genome

PubMed Central

2011-01-01

Background Potato is the world's third most important food crop, yet cultivar improvement and genomic research in general remain difficult because of the heterozygous and tetraploid nature of its genome. The development of physical map resources that can facilitate genomic analyses in potato has so far been very limited. Here we present the methods of construction and the general statistics of the first two genome-wide BAC physical maps of potato, which were made from the heterozygous diploid clone RH89-039-16 (RH). Results First, a gel electrophoresis-based physical map was made by AFLP fingerprinting of 64478 BAC clones, which were aligned into 4150 contigs with an estimated total length of 1361 Mb. Screening of BAC pools, followed by the KeyMaps in silico anchoring procedure, identified 1725 AFLP markers in the physical map, and 1252 BAC contigs were anchored the ultradense potato genetic map. A second, sequence-tag-based physical map was constructed from 65919 whole genome profiling (WGP) BAC fingerprints and these were aligned into 3601 BAC contigs spanning 1396 Mb. The 39733 BAC clones that overlap between both physical maps provided anchors to 1127 contigs in the WGP physical map, and reduced the number of contigs to around 2800 in each map separately. Both physical maps were 1.64 times longer than the 850 Mb potato genome. Genome heterozygosity and incomplete merging of BAC contigs are two factors that can explain this map inflation. The contig information of both physical maps was united in a single table that describes hybrid potato physical map. Conclusions The AFLP physical map has already been used by the Potato Genome Sequencing Consortium for sequencing 10% of the heterozygous genome of clone RH on a BAC-by-BAC basis. By layering a new WGP physical map on top of the AFLP physical map, a genetically anchored genome-wide framework of 322434 sequence tags has been created. This reference framework can be used for anchoring and ordering of genomic sequences of clone RH (and other potato genotypes), and opens the possibility to finish sequencing of the RH genome in a more efficient way via high throughput next generation approaches. PMID:22142254

Cambridge Healthtech Institute's 5th Annual Conference: impact of genomics on medicine.

PubMed

Zanders, E D

2001-08-01

The recent publications in Nature and Science by the Human Genome Consortium and Celera Genomics, respectively, while being landmark achievements in themselves, have also given pause for thought. A definitive catalogue of human genes is still not available but the broad picture of how humans compare with lower organisms at the genomic level is becoming clearer. The full impact of these findings on the practice of medicine is hard to predict, but research being conducted now, in the early years of the 21st century, will form the basis of future advances in the diagnosis and treatment of disease. Exactly what this will entail is the subject of intense debate, but there are some common starting points that were discussed at this meeting in Munich. The main theme to emerge was the need to move beyond the human genome sequence towards an understanding of proteins and their interactions in complex biological pathways, thereby increasing opportunities for drug discovery through the identification of new targets. The majority of the talks were therefore devoted to the description of technological advances in the analysis of gene and protein expression (and interaction) and in the use of various methods of gene deletion in order to validate individual proteins as drug targets. Perhaps it will still be a few years before it will be possible to report on the application of genomic analyses to routine medical practice at the first point of care for patients but when that happens, the research efforts described here will have been worthwhile.

A high density physical map of chromosome 1BL supports evolutionary studies, map-based cloning and sequencing in wheat

PubMed Central

2013-01-01

Background As for other major crops, achieving a complete wheat genome sequence is essential for the application of genomics to breeding new and improved varieties. To overcome the complexities of the large, highly repetitive and hexaploid wheat genome, the International Wheat Genome Sequencing Consortium established a chromosome-based strategy that was validated by the construction of the physical map of chromosome 3B. Here, we present improved strategies for the construction of highly integrated and ordered wheat physical maps, using chromosome 1BL as a template, and illustrate their potential for evolutionary studies and map-based cloning. Results Using a combination of novel high throughput marker assays and an assembly program, we developed a high quality physical map representing 93% of wheat chromosome 1BL, anchored and ordered with 5,489 markers including 1,161 genes. Analysis of the gene space organization and evolution revealed that gene distribution and conservation along the chromosome results from the superimposition of the ancestral grass and recent wheat evolutionary patterns, leading to a peak of synteny in the central part of the chromosome arm and an increased density of non-collinear genes towards the telomere. With a density of about 11 markers per Mb, the 1BL physical map provides 916 markers, including 193 genes, for fine mapping the 40 QTLs mapped on this chromosome. Conclusions Here, we demonstrate that high marker density physical maps can be developed in complex genomes such as wheat to accelerate map-based cloning, gain new insights into genome evolution, and provide a foundation for reference sequencing. PMID:23800011

Genome-Guided Analysis of Physiological Capacities of Tepidanaerobacter acetatoxydans Provides Insights into Environmental Adaptations and Syntrophic Acetate Oxidation

PubMed Central

Niazi, Adnan; Bongcam-Rudloff, Erik; Schnürer, Anna

2015-01-01

This paper describes the genome-based analysis of Tepidanaerobacter acetatoxydans strain Re1, a syntrophic acetate-oxidising bacterium (SAOB). Principal issues such as environmental adaptations, metabolic capacities, and energy conserving systems have been investigated and the potential consequences for syntrophic acetate oxidation discussed. Briefly, in pure culture, T. acetatoxydans grows with different organic compounds and produces acetate as the main product. In a syntrophic consortium with a hydrogenotrophic methanogen, it can also reverse its metabolism and instead convert acetate to formate/H2 and CO2. It can only proceed if the product formed is continuously removed. This process generates a very small amount of energy that is scarcely enough for growth, which makes this particular syntrophy of special interest. As a crucial member of the biogas-producing community in ammonium-rich engineered AD processes, genomic features conferring ammonium resistance, bacterial defense, oxygen and temperature tolerance were found, as well as attributes related to biofilm formation and flocculation. It is likely that T. acetatoxydans can form an electrochemical gradient by putative electron-bifurcating Rnf complex and [Fe-Fe] hydrogenases, as observed in other acetogens. However, genomic deficiencies related to acetogenic metabolism and anaerobic respiration were discovered, such as the lack of formate dehydrogenase and F1F0 ATP synthase. This has potential consequences for the metabolic pathways used under SAO and non-SAO conditions. The two complete sets of bacteriophage genomes, which were found to be encoded in the genome, are also worthy of mention. PMID:25811859

Integrated physical map of bread wheat chromosome arm 7DS to facilitate gene cloning and comparative studies.

PubMed

Tulpová, Zuzana; Luo, Ming-Cheng; Toegelová, Helena; Visendi, Paul; Hayashi, Satomi; Vojta, Petr; Paux, Etienne; Kilian, Andrzej; Abrouk, Michaël; Bartoš, Jan; Hajdúch, Marián; Batley, Jacqueline; Edwards, David; Doležel, Jaroslav; Šimková, Hana

2018-03-08

Bread wheat (Triticum aestivum L.) is a staple food for a significant part of the world's population. The growing demand on its production can be satisfied by improving yield and resistance to biotic and abiotic stress. Knowledge of the genome sequence would aid in discovering genes and QTLs underlying these traits and provide a basis for genomics-assisted breeding. Physical maps and BAC clones associated with them have been valuable resources from which to generate a reference genome of bread wheat and to assist map-based gene cloning. As a part of a joint effort coordinated by the International Wheat Genome Sequencing Consortium, we have constructed a BAC-based physical map of bread wheat chromosome arm 7DS consisting of 895 contigs and covering 94% of its estimated length. By anchoring BAC contigs to one radiation hybrid map and three high resolution genetic maps, we assigned 73% of the assembly to a distinct genomic position. This map integration, interconnecting a total of 1713 markers with ordered and sequenced BAC clones from a minimal tiling path, provides a tool to speed up gene cloning in wheat. The process of physical map assembly included the integration of the 7DS physical map with a whole-genome physical map of Aegilops tauschii and a 7DS Bionano genome map, which together enabled efficient scaffolding of physical-map contigs, even in the non-recombining region of the genetic centromere. Moreover, this approach facilitated a comparison of bread wheat and its ancestor at BAC-contig level and revealed a reconstructed region in the 7DS pericentromere. Copyright © 2018. Published by Elsevier B.V.

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

PubMed Central

Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

2016-01-01

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID:27379672

REPORT OF THE NIH TASK FORCE ON RESEARCH STANDARDS FOR CHRONIC LOW BACK PAIN

PubMed Central

Deyo, Richard A.; Dworkin, Samuel F.; Amtmann, Dagmar; Andersson, Gunnar; Borenstein, David; Carragee, Eugene; Carrino, John; Chou, Roger; Cook, Karon; DeLitto, Anthony; Goertz, Christine; Khalsa, Partap; Loeser, John; Mackey, Sean; Panagis, James; Rainville, James; Tosteson, Tor; Turk, Dennis; Von Korff, Michael; Weiner, Debra K.

2014-01-01

Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients’ lives. Such cLBP is often termed non-specific, and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The NIH Pain Consortium therefore charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research participants (drawing heavily on the PROMIS methodology); reporting “responder analyses” in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect the RTF recommendations will become a dynamic document, and undergo continual improvement. Perspective A Task Force was convened by the NIH Pain Consortium, with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimal dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. PMID:24787228

The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.

PubMed

Amos, Christopher I; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R; Gayther, Simon A; Casey, Graham; Hunter, David J; Sellers, Thomas A; Gruber, Stephen B; Dunning, Alison M; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A; Hazelett, Dennis J; Bojesen, Stig E; Caga-Anan, Charlisse; Haiman, Christopher A; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E; Couch, Fergus J; Forman, Judith L; Giles, Graham G; Conti, David V; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske-Hohlfeld, Irene; Hicks, Belynda D; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline; Soucy, Penny; Manz, Judith; Cunningham, Julie M; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel; Lindström, Sara; Adams, Marcia; McKay, James D; Phelan, Catherine M; Benlloch, Sara; Kelemen, Linda E; Brennan, Paul; Riggan, Marjorie; O'Mara, Tracy A; Shen, Hongbing; Shi, Yongyong; Thompson, Deborah J; Goodman, Marc T; Nielsen, Sune F; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L; Shelford, Tameka; Edlund, Christopher K; Taylor, Jack A; Field, John K; Park, Sue K; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J; Marchini, Jonathan; Amin Al Olama, Ali; Peters, Ulrike; Eeles, Rosalind A; Seldin, Michael F; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C; Pharoah, Paul D P; Chenevix-Trench, Georgia; Chanock, Stephen J; Simard, Jacques; Easton, Douglas F

2017-01-01

Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126-35. ©2016 AACR. ©2016 American Association for Cancer Research.

The OncoArray Consortium: a Network for Understanding the Genetic Architecture of Common Cancers

PubMed Central

Amos, Christopher I.; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R.; Gayther, Simon A.; Casey, Graham; Hunter, David J.; Sellers, Thomas A.; Gruber, Stephen B.; Dunning, Alison M.; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B.; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A.; Hazelett, Dennis J.; Bojesen, Stig E.; Caga-Anan, Charlisse; Haiman, Christopher A.; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J.; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E.; Couch, Fergus J.; Forman, Judith L.; Giles, Graham G.; Conti, David V.; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske, Irene; Hicks, Belynda D.; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline B.; Soucy, Penny; Manz, Judith; Cunningham, Julie M.; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel M.; Lindström, Sara; Adams, Marcia; McKay, James D.; Phelan, Catherine M.; Benlloch, Sara; Kelemen, Linda E.; Brennan, Paul; Riggan, Marjorie; O’Mara, Tracy A.; Shen, Hongbin; Shi, Yongyong; Thompson, Deborah J.; Goodman, Marc T.; Nielsen, Sune F.; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L.; Shelford, Tameka; Edlund, Christopher K.; Taylor, Jack A.; Field, John K.; Park, Sue K.; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J.; Marchini, Jonathan; Al Olama, Ali Amin; Peters, Ulrike; Eeles, Rosalind A.; Seldin, Michael F.; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C.; Pharoah, Paul D.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Simard, Jacques; Easton, Douglas F.

2016-01-01

Background Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. Methods The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Impact Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. PMID:27697780

Association between polygenic risk for schizophrenia, neurocognition and social cognition across development

PubMed Central

Germine, L; Robinson, E B; Smoller, J W; Calkins, M E; Moore, T M; Hakonarson, H; Daly, M J; Lee, P H; Holmes, A J; Buckner, R L; Gur, R C; Gur, R E

2016-01-01

Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8–21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk. Schizophrenia polygenic risk was estimated for each participant based on summary statistics from the most recent schizophrenia genome-wide association analysis (Psychiatric Genomics Consortium 2014). After correction for multiple comparisons, greater schizophrenia polygenic risk was significantly associated with reduced speed of emotion identification and verbal reasoning. These associations were significant by age 9 years and there was no evidence of interaction between schizophrenia polygenic risk and age on neurocognitive performance. We then looked at the association between schizophrenia polygenic risk and emotion identification speed in the Harvard/MGH Brain Genomics Superstruct Project sample (695 participants ages 18–35 years), where we replicated the association between schizophrenia polygenic risk and emotion identification speed. These analyses provide evidence for a replicable association between polygenic risk for schizophrenia and a specific aspect of social cognition. Our findings indicate that individual differences in genetic risk for schizophrenia are linked with the development of aspects of social cognition and potentially verbal reasoning, and that these associations emerge relatively early in development. PMID:27754483

Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

PubMed

Kirby, Marie K; Ramaker, Ryne C; Roberts, Brian S; Lasseigne, Brittany N; Gunther, David S; Burwell, Todd C; Davis, Nicholas S; Gulzar, Zulfiqar G; Absher, Devin M; Cooper, Sara J; Brooks, James D; Myers, Richard M

2017-04-17

Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer. We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models. We identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues. DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

Comparative fine mapping of the Wax 1 (W1) locus in hexaploid wheat.

PubMed

Lu, Ping; Qin, Jinxia; Wang, Guoxin; Wang, Lili; Wang, Zhenzhong; Wu, Qiuhong; Xie, Jingzhong; Liang, Yong; Wang, Yong; Zhang, Deyun; Sun, Qixin; Liu, Zhiyong

2015-08-01

By applying comparative genomics analyses, a high-density genetic linkage map of the Wax 1 ( W1 ) locus was constructed as a framework for map-based cloning. Glaucousness is described as the scattering effect of visible light from wax deposited on the cuticle of plant aerial organs. In wheat, the wax on leaves and stems is mainly controlled by two sets of genes: glaucousness loci (W1 and W2) and non-glaucousness loci (Iw1 and Iw2). Bulked segregant analysis (BSA) and simple sequence repeat (SSR) mapping showed that Wax1 (W1) is located on chromosome arm 2BS between markers Xgwm210 and Xbarc35. By applying comparative genomics analyses, colinearity genomic regions of the W1 locus on wheat 2BS were identified in Brachypodium distachyon chromosome 5, rice chromosome 4 and sorghum chromosome 6, respectively. Four STS markers were developed using the Triticum aestivum cv. Chinese Spring 454 contig sequences and the International Wheat Genome Sequencing Consortium (IWGSC) survey sequences. W1 was mapped into a 0.93 cM genetic interval flanked by markers XWGGC3197 and XWGGC2484, which has synteny with genomic regions of 56.5 kb in Brachypodium, 390 kb in rice and 31.8 kb in sorghum. The fine genetic map can serve as a framework for chromosome landing, physical mapping and map-based cloning of the W1 in wheat.

Association between polygenic risk for schizophrenia, neurocognition and social cognition across development.

PubMed

Germine, L; Robinson, E B; Smoller, J W; Calkins, M E; Moore, T M; Hakonarson, H; Daly, M J; Lee, P H; Holmes, A J; Buckner, R L; Gur, R C; Gur, R E

2016-10-18

Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8-21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk. Schizophrenia polygenic risk was estimated for each participant based on summary statistics from the most recent schizophrenia genome-wide association analysis (Psychiatric Genomics Consortium 2014). After correction for multiple comparisons, greater schizophrenia polygenic risk was significantly associated with reduced speed of emotion identification and verbal reasoning. These associations were significant by age 9 years and there was no evidence of interaction between schizophrenia polygenic risk and age on neurocognitive performance. We then looked at the association between schizophrenia polygenic risk and emotion identification speed in the Harvard/MGH Brain Genomics Superstruct Project sample (695 participants ages 18-35 years), where we replicated the association between schizophrenia polygenic risk and emotion identification speed. These analyses provide evidence for a replicable association between polygenic risk for schizophrenia and a specific aspect of social cognition. Our findings indicate that individual differences in genetic risk for schizophrenia are linked with the development of aspects of social cognition and potentially verbal reasoning, and that these associations emerge relatively early in development.

A Description of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) Common Data Analysis Pipeline

PubMed Central

Rudnick, Paul A.; Markey, Sanford P.; Roth, Jeri; Mirokhin, Yuri; Yan, Xinjian; Tchekhovskoi, Dmitrii V.; Edwards, Nathan J.; Thangudu, Ratna R.; Ketchum, Karen A.; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Stein, Stephen E.

2016-01-01

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has produced large proteomics datasets from the mass spectrometric interrogation of tumor samples previously analyzed by The Cancer Genome Atlas (TCGA) program. The availability of the genomic and proteomic data is enabling proteogenomic study for both reference (i.e., contained in major sequence databases) and non-reference markers of cancer. The CPTAC labs have focused on colon, breast, and ovarian tissues in the first round of analyses; spectra from these datasets were produced from 2D LC-MS/MS analyses and represent deep coverage. To reduce the variability introduced by disparate data analysis platforms (e.g., software packages, versions, parameters, sequence databases, etc.), the CPTAC Common Data Analysis Platform (CDAP) was created. The CDAP produces both peptide-spectrum-match (PSM) reports and gene-level reports. The pipeline processes raw mass spectrometry data according to the following: (1) Peak-picking and quantitative data extraction, (2) database searching, (3) gene-based protein parsimony, and (4) false discovery rate (FDR)-based filtering. The pipeline also produces localization scores for the phosphopeptide enrichment studies using the PhosphoRS program. Quantitative information for each of the datasets is specific to the sample processing, with PSM and protein reports containing the spectrum-level or gene-level (“rolled-up”) precursor peak areas and spectral counts for label-free or reporter ion log-ratios for 4plex iTRAQ™. The reports are available in simple tab-delimited formats and, for the PSM-reports, in mzIdentML. The goal of the CDAP is to provide standard, uniform reports for all of the CPTAC data, enabling comparisons between different samples and cancer types as well as across the major ‘omics fields. PMID:26860878

Genetically decreased vitamin D and risk of Alzheimer disease.

PubMed

Mokry, Lauren E; Ross, Stephanie; Morris, John A; Manousaki, Despoina; Forgetta, Vincenzo; Richards, J Brent

2016-12-13

To test whether genetically decreased vitamin D levels are associated with Alzheimer disease (AD) using mendelian randomization (MR), a method that minimizes bias due to confounding or reverse causation. We selected single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels (p < 5 × 10 -8 ) from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) Consortium (N = 33,996) to act as instrumental variables for the MR study. We measured the effect of each of these SNPs on 25OHD levels in the Canadian Multicentre Osteoporosis Study (CaMos; N = 2,347) and obtained the corresponding effect estimates for each SNP on AD risk from the International Genomics of Alzheimer's Project (N = 17,008 AD cases and 37,154 controls). To produce MR estimates, we weighted the effect of each SNP on AD by its effect on 25OHD and meta-analyzed these estimates using a fixed-effects model to provide a summary effect estimate. The SUNLIGHT Consortium identified 4 SNPs to be genome-wide significant for 25OHD, which described 2.44% of the variance in 25OHD in CaMos. All 4 SNPs map to genes within the vitamin D metabolic pathway. MR analyses demonstrated that a 1-SD decrease in natural log-transformed 25OHD increased AD risk by 25% (odds ratio 1.25, 95% confidence interval 1.03-1.51, p = 0.021). After sensitivity analysis in which we removed SNPs possibly influenced by pleiotropy and population stratification, the results were largely unchanged. Our results provide evidence supporting 25OHD as a causal risk factor for AD. These findings provide further rationale to understand the effect of vitamin D supplementation on cognition and AD risk in randomized controlled trials. © 2016 American Academy of Neurology.

A Description of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) Common Data Analysis Pipeline.

PubMed

Rudnick, Paul A; Markey, Sanford P; Roth, Jeri; Mirokhin, Yuri; Yan, Xinjian; Tchekhovskoi, Dmitrii V; Edwards, Nathan J; Thangudu, Ratna R; Ketchum, Karen A; Kinsinger, Christopher R; Mesri, Mehdi; Rodriguez, Henry; Stein, Stephen E

2016-03-04

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has produced large proteomics data sets from the mass spectrometric interrogation of tumor samples previously analyzed by The Cancer Genome Atlas (TCGA) program. The availability of the genomic and proteomic data is enabling proteogenomic study for both reference (i.e., contained in major sequence databases) and nonreference markers of cancer. The CPTAC laboratories have focused on colon, breast, and ovarian tissues in the first round of analyses; spectra from these data sets were produced from 2D liquid chromatography-tandem mass spectrometry analyses and represent deep coverage. To reduce the variability introduced by disparate data analysis platforms (e.g., software packages, versions, parameters, sequence databases, etc.), the CPTAC Common Data Analysis Platform (CDAP) was created. The CDAP produces both peptide-spectrum-match (PSM) reports and gene-level reports. The pipeline processes raw mass spectrometry data according to the following: (1) peak-picking and quantitative data extraction, (2) database searching, (3) gene-based protein parsimony, and (4) false-discovery rate-based filtering. The pipeline also produces localization scores for the phosphopeptide enrichment studies using the PhosphoRS program. Quantitative information for each of the data sets is specific to the sample processing, with PSM and protein reports containing the spectrum-level or gene-level ("rolled-up") precursor peak areas and spectral counts for label-free or reporter ion log-ratios for 4plex iTRAQ. The reports are available in simple tab-delimited formats and, for the PSM-reports, in mzIdentML. The goal of the CDAP is to provide standard, uniform reports for all of the CPTAC data to enable comparisons between different samples and cancer types as well as across the major omics fields.

DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

PubMed Central

Joubert, Bonnie R.; Felix, Janine F.; Yousefi, Paul; Bakulski, Kelly M.; Just, Allan C.; Breton, Carrie; Reese, Sarah E.; Markunas, Christina A.; Richmond, Rebecca C.; Xu, Cheng-Jian; Küpers, Leanne K.; Oh, Sam S.; Hoyo, Cathrine; Gruzieva, Olena; Söderhäll, Cilla; Salas, Lucas A.; Baïz, Nour; Zhang, Hongmei; Lepeule, Johanna; Ruiz, Carlos; Ligthart, Symen; Wang, Tianyuan; Taylor, Jack A.; Duijts, Liesbeth; Sharp, Gemma C.; Jankipersadsing, Soesma A.; Nilsen, Roy M.; Vaez, Ahmad; Fallin, M. Daniele; Hu, Donglei; Litonjua, Augusto A.; Fuemmeler, Bernard F.; Huen, Karen; Kere, Juha; Kull, Inger; Munthe-Kaas, Monica Cheng; Gehring, Ulrike; Bustamante, Mariona; Saurel-Coubizolles, Marie José; Quraishi, Bilal M.; Ren, Jie; Tost, Jörg; Gonzalez, Juan R.; Peters, Marjolein J.; Håberg, Siri E.; Xu, Zongli; van Meurs, Joyce B.; Gaunt, Tom R.; Kerkhof, Marjan; Corpeleijn, Eva; Feinberg, Andrew P.; Eng, Celeste; Baccarelli, Andrea A.; Benjamin Neelon, Sara E.; Bradman, Asa; Merid, Simon Kebede; Bergström, Anna; Herceg, Zdenko; Hernandez-Vargas, Hector; Brunekreef, Bert; Pinart, Mariona; Heude, Barbara; Ewart, Susan; Yao, Jin; Lemonnier, Nathanaël; Franco, Oscar H.; Wu, Michael C.; Hofman, Albert; McArdle, Wendy; Van der Vlies, Pieter; Falahi, Fahimeh; Gillman, Matthew W.; Barcellos, Lisa F.; Kumar, Ashish; Wickman, Magnus; Guerra, Stefano; Charles, Marie-Aline; Holloway, John; Auffray, Charles; Tiemeier, Henning W.; Smith, George Davey; Postma, Dirkje; Hivert, Marie-France; Eskenazi, Brenda; Vrijheid, Martine; Arshad, Hasan; Antó, Josep M.; Dehghan, Abbas; Karmaus, Wilfried; Annesi-Maesano, Isabella; Sunyer, Jordi; Ghantous, Akram; Pershagen, Göran; Holland, Nina; Murphy, Susan K.; DeMeo, Dawn L.; Burchard, Esteban G.; Ladd-Acosta, Christine; Snieder, Harold; Nystad, Wenche; Koppelman, Gerard H.; Relton, Caroline L.; Jaddoe, Vincent W.V.; Wilcox, Allen; Melén, Erik; London, Stephanie J.

2016-01-01

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10−16). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure. PMID:27040690

Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: evidence from the International Consortium for Prostate Cancer Genetics (ICPCG).

PubMed

Jin, Guangfu; Lu, Lingyi; Cooney, Kathleen A; Ray, Anna M; Zuhlke, Kimberly A; Lange, Ethan M; Cannon-Albright, Lisa A; Camp, Nicola J; Teerlink, Craig C; Fitzgerald, Liesel M; Stanford, Janet L; Wiley, Kathleen E; Isaacs, Sarah D; Walsh, Patrick C; Foulkes, William D; Giles, Graham G; Hopper, John L; Severi, Gianluca; Eeles, Ros; Easton, Doug; Kote-Jarai, Zsofia; Guy, Michelle; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Whittemore, Alice S; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Catalona, William J; Zheng, S Lilly; Ostrander, Elaine A; Isaacs, William B; Xu, Jianfeng

2012-07-01

Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.

Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: evidence from the International Consortium for Prostate Cancer Genetics (ICPCG)

PubMed Central

Jin, Guangfu; Lu, Lingyi; Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.; Lange, Ethan M.; Cannon-Albright, Lisa A.; Camp, Nicola J.; Teerlink, Craig C.; FitzGerald, Liesel M.; Stanford, Janet L.; Wiley, Kathleen E.; Walsh, Patrick C.; Foulkes, William D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; Eeles, Ros; Easton, Doug; Kote-Jarai, Zsofia; Guy, Michelle; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Catalona, William J.; Zheng, S. Lilly; Isaacs, William B.

2012-01-01

Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case–control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case–control GWAS are also associated with disease risk in HPC families. PMID:22198737

Implementing a screening tool for identifying patients at risk for hereditary breast and ovarian cancer: a statewide initiative.

PubMed

Brannon Traxler, L; Martin, Monique L; Kerber, Alice S; Bellcross, Cecelia A; Crane, Barbara E; Green, Victoria; Matthews, Roland; Paris, Nancy M; Gabram, Sheryl G A

2014-10-01

The Georgia Breast Cancer Genomic Health Consortium is a partnership created with funding from the Centers for Disease Control and Prevention (CDC) to the Georgia Department of Public Health to reduce cancer disparities among high-risk minority women. The project addresses young women at increased risk for hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts. The consortium provides education and collects surveillance data using the breast cancer genetics referral screening tool (B-RST) available at www.BreastCancerGeneScreen.org . The HBOC educational protocol was presented to 73 staff in 6 public health centers. Staff used the tool during the collection of medical history. Further family history assessments and testing for mutations in the BRCA1/2 genes were facilitated if appropriate. Data was collected from November 2012 through December 2013, including 2,159 screened women. The majority of patients identified as black/African American and were 18-49 years old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110 patients who agreed to be contacted provided a detailed family history. A total of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1 patient was positive for a BRCA2 mutation, and 1 patient was found to carry a variant of uncertain significance. The introduction of genomics practice within public health departments has provided access to comprehensive cancer care for uninsured individuals. The successful implementation of the B-RST into public health centers demonstrates the opportunity for integration of HBOC screening into primary care practices.

Federating clinical data from six pediatric hospitals: process and initial results for microbiology from the PHIS+ consortium.

PubMed

Gouripeddi, Ramkiran; Warner, Phillip B; Mo, Peter; Levin, James E; Srivastava, Rajendu; Shah, Samir S; de Regt, David; Kirkendall, Eric; Bickel, Jonathan; Korgenski, E Kent; Precourt, Michelle; Stepanek, Richard L; Mitchell, Joyce A; Narus, Scott P; Keren, Ron

2012-01-01

Microbiology study results are necessary for conducting many comparative effectiveness research studies. Unlike core laboratory test results, microbiology results have a complex structure. Federating and integrating microbiology data from six disparate electronic medical record systems is challenging and requires a team of varied skills. The PHIS+ consortium which is partnership between members of the Pediatric Research in Inpatient Settings (PRIS) network, the Children's Hospital Association and the University of Utah, have used "FURTHeR' for federating laboratory data. We present our process and initial results for federating microbiology data from six pediatric hospitals.

Department of Defense prostate cancer clinical trials consortium: a new instrument for prostate cancer clinical research.

PubMed

Morris, Michael J; Basch, Ethan M; Wilding, George; Hussain, Maha; Carducci, Michael A; Higano, Celestia; Kantoff, Philip; Oh, William K; Small, Eric J; George, Daniel; Mathew, Paul; Beer, Tomasz M; Slovin, Susan F; Ryan, Charles; Logothetis, Christopher; Scher, Howard I

2009-01-01

In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >or=1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.

Genome-Wide SNP Detection, Validation, and Development of an 8K SNP Array for Apple

PubMed Central

Chagné, David; Crowhurst, Ross N.; Troggio, Michela; Davey, Mark W.; Gilmore, Barbara; Lawley, Cindy; Vanderzande, Stijn; Hellens, Roger P.; Kumar, Satish; Cestaro, Alessandro; Velasco, Riccardo; Main, Dorrie; Rees, Jasper D.; Iezzoni, Amy; Mockler, Todd; Wilhelm, Larry; Van de Weg, Eric; Gardiner, Susan E.; Bassil, Nahla; Peace, Cameron

2012-01-01

As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica) breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of ‘Golden Delicious’, SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional), and genomic selection in apple. PMID:22363718

Public-Private Partnerships in Cloud-Computing Services in the Context of Genomic Research.

PubMed

Granados Moreno, Palmira; Joly, Yann; Knoppers, Bartha Maria

2017-01-01

Public-private partnerships (PPPs) have been increasingly used to spur and facilitate innovation in a number of fields. In healthcare, the purpose of using a PPP is commonly to develop and/or provide vaccines and drugs against communicable diseases, mainly in developing or underdeveloped countries. With the advancement of technology and of the area of genomics, these partnerships also focus on large-scale genomic research projects that aim to advance the understanding of diseases that have a genetic component and to develop personalized treatments. This new focus has created new forms of PPPs that involve information technology companies, which provide computing infrastructure and services to store, analyze, and share the massive amounts of data genomic-related projects produce. In this article, we explore models of PPPs proposed to handle, protect, and share the genomic data collected and to further develop genomic-based medical products. We also identify the reasons that make these models suitable and the challenges they have yet to overcome. To achieve this, we describe the details and complexities of MSSNG, International Cancer Genome Consortium, and 100,000 Genomes Project, the three PPPs that focus on large-scale genomic research to better understand the genetic components of autism, cancer, rare diseases, and infectious diseases with the intention to find appropriate treatments. Organized as PPP and employing cloud-computing services, the three projects have advanced quickly and are likely to be important sources of research and development for future personalized medicine. However, there still are unresolved matters relating to conflicts of interest, commercialization, and data control. Learning from the challenges encountered by past PPPs allowed us to establish that developing guidelines to adequately manage personal health information stored in clouds and ensuring the protection of data integrity and privacy would be critical steps in the development of future PPPs.

Public–Private Partnerships in Cloud-Computing Services in the Context of Genomic Research

PubMed Central

Granados Moreno, Palmira; Joly, Yann; Knoppers, Bartha Maria

2017-01-01

Public–private partnerships (PPPs) have been increasingly used to spur and facilitate innovation in a number of fields. In healthcare, the purpose of using a PPP is commonly to develop and/or provide vaccines and drugs against communicable diseases, mainly in developing or underdeveloped countries. With the advancement of technology and of the area of genomics, these partnerships also focus on large-scale genomic research projects that aim to advance the understanding of diseases that have a genetic component and to develop personalized treatments. This new focus has created new forms of PPPs that involve information technology companies, which provide computing infrastructure and services to store, analyze, and share the massive amounts of data genomic-related projects produce. In this article, we explore models of PPPs proposed to handle, protect, and share the genomic data collected and to further develop genomic-based medical products. We also identify the reasons that make these models suitable and the challenges they have yet to overcome. To achieve this, we describe the details and complexities of MSSNG, International Cancer Genome Consortium, and 100,000 Genomes Project, the three PPPs that focus on large-scale genomic research to better understand the genetic components of autism, cancer, rare diseases, and infectious diseases with the intention to find appropriate treatments. Organized as PPP and employing cloud-computing services, the three projects have advanced quickly and are likely to be important sources of research and development for future personalized medicine. However, there still are unresolved matters relating to conflicts of interest, commercialization, and data control. Learning from the challenges encountered by past PPPs allowed us to establish that developing guidelines to adequately manage personal health information stored in clouds and ensuring the protection of data integrity and privacy would be critical steps in the development of future PPPs. PMID:28164085

Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies.

PubMed

Mocellin, Simone; Tropea, Saveria; Benna, Clara; Rossi, Carlo Riccardo

2018-02-19

Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma. We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10 -6 ; top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10 -6 ; top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10 -7 ; top gene RORA, gene P value = 2.0 × 10 -6 ), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for breast cancer (PER1, RORC). Our findings, based on the largest series ever utilized for ARTP-based gene and pathway analysis, support the hypothesis that circadian pathway genetic variation is involved in cancer predisposition.

Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease

PubMed Central

Wang, Kai; Zhang, Haitao; Kugathasan, Subra; Annese, Vito; Bradfield, Jonathan P.; Russell, Richard K.; Sleiman, Patrick M.A.; Imielinski, Marcin; Glessner, Joseph; Hou, Cuiping; Wilson, David C.; Walters, Thomas; Kim, Cecilia; Frackelton, Edward C.; Lionetti, Paolo; Barabino, Arrigo; Van Limbergen, Johan; Guthery, Stephen; Denson, Lee; Piccoli, David; Li, Mingyao; Dubinsky, Marla; Silverberg, Mark; Griffiths, Anne; Grant, Struan F.A.; Satsangi, Jack; Baldassano, Robert; Hakonarson, Hakon

2009-01-01

Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 × 10−5). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies. PMID:19249008

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

PubMed Central

Pharoah, Paul D. P.; Tsai, Ya-Yu; Ramus, Susan J.; Phelan, Catherine M.; Goode, Ellen L.; Lawrenson, Kate; Price, Melissa; Fridley, Brooke L.; Tyrer, Jonathan P.; Shen, Howard; Weber, Rachel; Karevan, Rod; Larson, Melissa C.; Song, Honglin; Tessier, Daniel C.; Bacot, François; Vincent, Daniel; Cunningham, Julie M.; Dennis, Joe; Dicks, Ed; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Armasu, Sebastian M.; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brenton, James D.; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Campbell, Ian; Carney, Michael E; Carvalho, Renato S.; Chang-Claude, Jenny; Chen, Y. Anne; Chen, Zhihua; Chow, Wong-Ho; Cicek, Mine S.; Coetzee, Gerhard; Cook, Linda S.; Cramer, Daniel W.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David; Flanagan, James; Gao, Yu-Tang; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham; Gjyshi, Anxhela; Gore, Martin; Gronwald, Jacek; Guo, Qi; Halle, Mari K; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Estrid; Høgdall, Claus K.; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Kalli, Kimberly R.; Karlan, Beth Y.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne Krüger; Konecny, Gottfried E.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Nathan; Lee, Janet; Leminen, Arto; Lim, Boon Kiong; Lissowska, Jolanta; Lubiński, Jan; Lundvall, Lene; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara; Orlow, Irene; Paul, James; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jenny; Pike, Malcolm C; Poole, Elizabeth M; Qu, Xiaotao; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo; Rzepecka, Iwona K; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shen, Hui; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Sieh, Weiva; Southey, Melissa C.; Spellman, Paul; Tajima, Kazuo; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S.; van Altena, Anne M.; Berg, David Van Den; Vergote, Ignace; Vierkant, Robert A.; Vitonis, Allison F.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Goodman, Marc T.; Hall, Per; Easton, Douglas F; Pearce, Celeste L; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin; Monteiro, Alvaro N.A.; Gayther, Simon A.; Schildkraut, Joellen M.; Sellers, Thomas A.

2013-01-01

Genome wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC) with another two loci being close to genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the United Kingdom. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. Follow-up genotyping was carried out in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 previously near genome-wide significance and identified three novel loci associated with risk; two loci associated with all EOC subtypes, at 8q21 (rs11782652, P=5.5×10-9) and 10p12 (rs1243180; P=1.8×10-8), and another locus specific to the serous subtype at 17q12 (rs757210; P=8.1×10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility that implicates CHMP4C in the pathogenesis of ovarian cancer. PMID:23535730

Conceptualizing a Genomics Software Institute (GSI)

PubMed Central

Gilbert, Jack A.; Catlett, Charlie; Desai, Narayan; Knight, Rob; White, Owen; Robbins, Robert; Sankaran, Rajesh; Sansone, Susanna-Assunta; Field, Dawn; Meyer, Folker

2012-01-01

Microbial ecology has been enhanced greatly by the ongoing ‘omics revolution, bringing half the world's biomass and most of its biodiversity into analytical view for the first time; indeed, it feels almost like the invention of the microscope and the discovery of the new world at the same time. With major microbial ecology research efforts accumulating prodigious quantities of sequence, protein, and metabolite data, we are now poised to address environmental microbial research at macro scales, and to begin to characterize and understand the dimensions of microbial biodiversity on the planet. What is currently impeding progress is the need for a framework within which the research community can develop, exchange and discuss predictive ecosystem models that describe the biodiversity and functional interactions. Such a framework must encompass data and metadata transparency and interoperation; data and results validation, curation, and search; application programming interfaces for modeling and analysis tools; and human and technical processes and services necessary to ensure broad adoption. Here we discuss the need for focused community interaction to augment and deepen established community efforts, beginning with the Genomic Standards Consortium (GSC), to create a science-driven strategic plan for a Genomic Software Institute (GSI). PMID:22675605

The genome sequence of the plant pathogen Xylella fastidiosa. The Xylella fastidiosa Consortium of the Organization for Nucleotide Sequencing and Analysis.

PubMed

Simpson, A J; Reinach, F C; Arruda, P; Abreu, F A; Acencio, M; Alvarenga, R; Alves, L M; Araya, J E; Baia, G S; Baptista, C S; Barros, M H; Bonaccorsi, E D; Bordin, S; Bové, J M; Briones, M R; Bueno, M R; Camargo, A A; Camargo, L E; Carraro, D M; Carrer, H; Colauto, N B; Colombo, C; Costa, F F; Costa, M C; Costa-Neto, C M; Coutinho, L L; Cristofani, M; Dias-Neto, E; Docena, C; El-Dorry, H; Facincani, A P; Ferreira, A J; Ferreira, V C; Ferro, J A; Fraga, J S; França, S C; Franco, M C; Frohme, M; Furlan, L R; Garnier, M; Goldman, G H; Goldman, M H; Gomes, S L; Gruber, A; Ho, P L; Hoheisel, J D; Junqueira, M L; Kemper, E L; Kitajima, J P; Krieger, J E; Kuramae, E E; Laigret, F; Lambais, M R; Leite, L C; Lemos, E G; Lemos, M V; Lopes, S A; Lopes, C R; Machado, J A; Machado, M A; Madeira, A M; Madeira, H M; Marino, C L; Marques, M V; Martins, E A; Martins, E M; Matsukuma, A Y; Menck, C F; Miracca, E C; Miyaki, C Y; Monteriro-Vitorello, C B; Moon, D H; Nagai, M A; Nascimento, A L; Netto, L E; Nhani, A; Nobrega, F G; Nunes, L R; Oliveira, M A; de Oliveira, M C; de Oliveira, R C; Palmieri, D A; Paris, A; Peixoto, B R; Pereira, G A; Pereira, H A; Pesquero, J B; Quaggio, R B; Roberto, P G; Rodrigues, V; de M Rosa, A J; de Rosa, V E; de Sá, R G; Santelli, R V; Sawasaki, H E; da Silva, A C; da Silva, A M; da Silva, F R; da Silva, W A; da Silveira, J F; Silvestri, M L; Siqueira, W J; de Souza, A A; de Souza, A P; Terenzi, M F; Truffi, D; Tsai, S M; Tsuhako, M H; Vallada, H; Van Sluys, M A; Verjovski-Almeida, S; Vettore, A L; Zago, M A; Zatz, M; Meidanis, J; Setubal, J C

2000-07-13

Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range of economically important plant diseases. Here we report the complete genome sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis--a serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305-base-pair (bp) circular chromosome and two plasmids of 51,158 bp and 1,285 bp. We can assign putative functions to 47% of the 2,904 predicted coding regions. Efficient metabolic functions are predicted, with sugars as the principal energy and carbon source, supporting existence in the nutrient-poor xylem sap. The mechanisms associated with pathogenicity and virulence involve toxins, antibiotics and ion sequestration systems, as well as bacterium-bacterium and bacterium-host interactions mediated by a range of proteins. Orthologues of some of these proteins have only been identified in animal and human pathogens; their presence in X. fastidiosa indicates that the molecular basis for bacterial pathogenicity is both conserved and independent of host. At least 83 genes are bacteriophage-derived and include virulence-associated genes from other bacteria, providing direct evidence of phage-mediated horizontal gene transfer.

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.

PubMed

Pharoah, Paul D P; Tsai, Ya-Yu; Ramus, Susan J; Phelan, Catherine M; Goode, Ellen L; Lawrenson, Kate; Buckley, Melissa; Fridley, Brooke L; Tyrer, Jonathan P; Shen, Howard; Weber, Rachel; Karevan, Rod; Larson, Melissa C; Song, Honglin; Tessier, Daniel C; Bacot, François; Vincent, Daniel; Cunningham, Julie M; Dennis, Joe; Dicks, Ed; Aben, Katja K; Anton-Culver, Hoda; Antonenkova, Natalia; Armasu, Sebastian M; Baglietto, Laura; Bandera, Elisa V; Beckmann, Matthias W; Birrer, Michael J; Bloom, Greg; Bogdanova, Natalia; Brenton, James D; Brinton, Louise A; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Campbell, Ian; Carney, Michael E; Carvalho, Renato S; Chang-Claude, Jenny; Chen, Y Anne; Chen, Zhihua; Chow, Wong-Ho; Cicek, Mine S; Coetzee, Gerhard; Cook, Linda S; Cramer, Daniel W; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Edwards, Robert; Ekici, Arif B; Fasching, Peter A; Fenstermacher, David; Flanagan, James; Gao, Yu-Tang; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham; Gjyshi, Anxhela; Gore, Martin; Gronwald, Jacek; Guo, Qi; Halle, Mari K; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Estrid; Høgdall, Claus K; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Kalli, Kimberly R; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne Krüger; Konecny, Gottfried E; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Nathan; Lee, Janet; Leminen, Arto; Lim, Boon Kiong; Lissowska, Jolanta; Lubiński, Jan; Lundvall, Lene; Lurie, Galina; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Nakanishi, Toru; Narod, Steven A; Ness, Roberta B; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara; Orlow, Irene; Paul, James; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jenny; Pike, Malcolm C; Poole, Elizabeth M; Qu, Xiaotao; Risch, Harvey A; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo; Rzepecka, Iwona K; Salvesen, Helga B; Schwaab, Ira; Severi, Gianluca; Shen, Hui; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Sieh, Weiva; Southey, Melissa C; Spellman, Paul; Tajima, Kazuo; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S; van Altena, Anne M; van den Berg, David; Vergote, Ignace; Vierkant, Robert A; Vitonis, Allison F; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wik, Elisabeth; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Yang, Hannah P; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Goodman, Marc T; Hall, Per; Easton, Douglas F; Pearce, Celeste L; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin; Monteiro, Alvaro N A; Gayther, Simon A; Schildkraut, Joellen M; Sellers, Thomas A

2013-04-01

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

Multiple Phenotype Association Tests Using Summary Statistics in Genome-Wide Association Studies

PubMed Central

Liu, Zhonghua; Lin, Xihong

2017-01-01

Summary We study in this paper jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. PMID:28653391

Multiple phenotype association tests using summary statistics in genome-wide association studies.

PubMed

Liu, Zhonghua; Lin, Xihong

2018-03-01

We study in this article jointly testing the associations of a genetic variant with correlated multiple phenotypes using the summary statistics of individual phenotype analysis from Genome-Wide Association Studies (GWASs). We estimated the between-phenotype correlation matrix using the summary statistics of individual phenotype GWAS analyses, and developed genetic association tests for multiple phenotypes by accounting for between-phenotype correlation without the need to access individual-level data. Since genetic variants often affect multiple phenotypes differently across the genome and the between-phenotype correlation can be arbitrary, we proposed robust and powerful multiple phenotype testing procedures by jointly testing a common mean and a variance component in linear mixed models for summary statistics. We computed the p-values of the proposed tests analytically. This computational advantage makes our methods practically appealing in large-scale GWASs. We performed simulation studies to show that the proposed tests maintained correct type I error rates, and to compare their powers in various settings with the existing methods. We applied the proposed tests to a GWAS Global Lipids Genetics Consortium summary statistics data set and identified additional genetic variants that were missed by the original single-trait analysis. © 2017, The International Biometric Society.

Transcriptome interrogation of human myometrium identifies differentially expressed sense-antisense pairs of protein-coding and long non-coding RNA genes in spontaneous labor at term

PubMed Central

Romero, Roberto; Tarca, Adi; Chaemsaithong, Piya; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Jia, Hui; Hassan, Sonia S.; Kalita, Cynthia A.; Cai, Juan; Yeo, Lami; Lipovich, Leonard

2014-01-01

Objective The mechanisms responsible for normal and abnormal parturition are poorly understood. Myometrial activation leading to regular uterine contractions is a key component of labor. Dysfunctional labor (arrest of dilatation and/or descent) is a leading indication for cesarean delivery. Compelling evidence suggests that most of these disorders are functional in nature, and not the result of cephalopelvic disproportion. The methodology and the datasets afforded by the post-genomic era provide novel opportunities to understand and target gene functions in these disorders. In 2012, the ENCODE Consortium elucidated the extraordinary abundance and functional complexity of long non-coding RNA genes in the human genome. The purpose of the study was to identify differentially expressed long non-coding RNA genes in human myometrium in women in spontaneous labor at term. Materials and Methods Myometrium was obtained from women undergoing cesarean deliveries who were not in labor (n=19) and women in spontaneous labor at term (n=20). RNA was extracted and profiled using an Illumina® microarray platform. The analysis of the protein coding genes from this study has been previously reported. Here, we have used computational approaches to bound the extent of long non-coding RNA representation on this platform, and to identify co-differentially expressed and correlated pairs of long non-coding RNA genes and protein-coding genes sharing the same genomic loci. Results Upon considering more than 18,498 distinct lncRNA genes compiled nonredundantly from public experimental data sources, and interrogating 2,634 that matched Illumina microarray probes, we identified co-differential expression and correlation at two genomic loci that contain coding-lncRNA gene pairs: SOCS2-AK054607 and LMCD1-NR_024065 in women in spontaneous labor at term. This co-differential expression and correlation was validated by qRT-PCR, an independent experimental method. Intriguingly, one of the two lncRNA genes differentially expressed in term labor had a key genomic structure element, a splice site that lacked evolutionary conservation beyond primates. Conclusions We provide for the first time evidence for coordinated differential expression and correlation of cis-encoded antisense lncRNAs and protein-coding genes with known, as well as novel roles in pregnancy in the myometrium of women in spontaneous labor at term. PMID:24168098

Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior.

PubMed

Tielbeek, Jorim J; Johansson, Ada; Polderman, Tinca J C; Rautiainen, Marja-Riitta; Jansen, Philip; Taylor, Michelle; Tong, Xiaoran; Lu, Qing; Burt, Alexandra S; Tiemeier, Henning; Viding, Essi; Plomin, Robert; Martin, Nicholas G; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant; Beaver, Kevin M; Waldman, Irwin; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Perry, John R B; Munafò, Marcus; LoParo, Devon; Paunio, Tiina; Tiihonen, Jari; Mous, Sabine E; Pappa, Irene; de Leeuw, Christiaan; Watanabe, Kyoko; Hammerschlag, Anke R; Salvatore, Jessica E; Aliev, Fazil; Bigdeli, Tim B; Dick, Danielle; Faraone, Stephen V; Popma, Arne; Medland, Sarah E; Posthuma, Danielle

2017-12-01

Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = -0.52, P = .005) was detected. The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.

A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC)

PubMed Central

Patel, Ashokkumar A.; Gilbertson, John R.; Showe, Louise C.; London, Jack W.; Ross, Eric; Ochs, Michael F.; Carver, Joseph; Lazarus, Andrea; Parwani, Anil V.; Dhir, Rajiv; Beck, J. Robert; Liebman, Michael; Garcia, Fernando U.; Prichard, Jeff; Wilkerson, Myra; Herberman, Ronald B.; Becich, Michael J.

2007-01-01

Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer-specific biomarkers and encourage collaborative research efforts among the participating centers. Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions’ IRB/HIPAA standards. Results: Currently, this “virtual biorepository” has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semi-automated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium’s web site. Conclusions: The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy. PMID:19455246

The three-dimensional genome organization of Drosophila melanogaster through data integration.

PubMed

Li, Qingjiao; Tjong, Harianto; Li, Xiao; Gong, Ke; Zhou, Xianghong Jasmine; Chiolo, Irene; Alber, Frank

2017-07-31

Genome structures are dynamic and non-randomly organized in the nucleus of higher eukaryotes. To maximize the accuracy and coverage of three-dimensional genome structural models, it is important to integrate all available sources of experimental information about a genome's organization. It remains a major challenge to integrate such data from various complementary experimental methods. Here, we present an approach for data integration to determine a population of complete three-dimensional genome structures that are statistically consistent with data from both genome-wide chromosome conformation capture (Hi-C) and lamina-DamID experiments. Our structures resolve the genome at the resolution of topological domains, and reproduce simultaneously both sets of experimental data. Importantly, this data deconvolution framework allows for structural heterogeneity between cells, and hence accounts for the expected plasticity of genome structures. As a case study we choose Drosophila melanogaster embryonic cells, for which both data types are available. Our three-dimensional genome structures have strong predictive power for structural features not directly visible in the initial data sets, and reproduce experimental hallmarks of the D. melanogaster genome organization from independent and our own imaging experiments. Also they reveal a number of new insights about genome organization and its functional relevance, including the preferred locations of heterochromatic satellites of different chromosomes, and observations about homologous pairing that cannot be directly observed in the original Hi-C or lamina-DamID data. Our approach allows systematic integration of Hi-C and lamina-DamID data for complete three-dimensional genome structure calculation, while also explicitly considering genome structural variability.