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1

FORGE Canada Consortium: outcomes of a 2-year national rare-disease gene-discovery project.  

PubMed

Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE's impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally. PMID:24906018

Beaulieu, Chandree L; Majewski, Jacek; Schwartzentruber, Jeremy; Samuels, Mark E; Fernandez, Bridget A; Bernier, Francois P; Brudno, Michael; Knoppers, Bartha; Marcadier, Janet; Dyment, David; Adam, Shelin; Bulman, Dennis E; Jones, Steve J M; Avard, Denise; Nguyen, Minh Thu; Rousseau, Francois; Marshall, Christian; Wintle, Richard F; Shen, Yaoqing; Scherer, Stephen W; Friedman, Jan M; Michaud, Jacques L; Boycott, Kym M

2014-06-01

2

Independent Gene Discovery and Testing  

ERIC Educational Resources Information Center

A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

2010-01-01

3

Cancer gene discovery in mouse and man  

PubMed Central

The elucidation of the human and mouse genome sequence and developments in high-throughput genome analysis, and in computational tools, have made it possible to profile entire cancer genomes. In parallel with these advances mouse models of cancer have evolved into a powerful tool for cancer gene discovery. Here we discuss the approaches that may be used for cancer gene identification in both human and mouse and discuss how a cross-species ‘oncogenomics’ approach to cancer gene discovery represents a powerful strategy for finding genes that drive tumourigenesis. PMID:19285540

Mattison, Jenny; van der Weyden, Louise; Hubbard, Tim; Adams, David J.

2009-01-01

4

Human brain evolution: From gene discovery to phenotype discovery  

PubMed Central

The rise of comparative genomics and related technologies has added important new dimensions to the study of human evolution. Our knowledge of the genes that underwent expression changes or were targets of positive selection in human evolution is rapidly increasing, as is our knowledge of gene duplications, translocations, and deletions. It is now clear that the genetic differences between humans and chimpanzees are far more extensive than previously thought; their genomes are not 98% or 99% identical. Despite the rapid growth in our understanding of the evolution of the human genome, our understanding of the relationship between genetic changes and phenotypic changes is tenuous. This is true even for the most intensively studied gene, FOXP2, which underwent positive selection in the human terminal lineage and is thought to have played an important role in the evolution of human speech and language. In part, the difficulty of connecting genes to phenotypes reflects our generally poor knowledge of human phenotypic specializations, as well as the difficulty of interpreting the consequences of genetic changes in species that are not amenable to invasive research. On the positive side, investigations of FOXP2, along with genomewide surveys of gene-expression changes and selection-driven sequence changes, offer the opportunity for “phenotype discovery,” providing clues to human phenotypic specializations that were previously unsuspected. What is more, at least some of the specializations that have been proposed are amenable to testing with noninvasive experimental techniques appropriate for the study of humans and apes. PMID:22723367

Preuss, Todd M.

2012-01-01

5

GeneEd: Genetics, Education, Discovery  

NSDL National Science Digital Library

The GeneEd website was created by the National Library of Medicine (NLM), the National Human Genome Research Institute (NHGRI), and the National Institutes of Health (NIH) as a helpful resource for the teaching and learning of genetics. On the site, visitors can find labs and experiments, fact sheets, and teacher resources on topics including DNA forensics, genetic conditions, evolution, and biostatistics. First-time visitors will want to start their journey by looking over the Topics tab at the top of the page. There are 40 different thematic areas here consisting of articles, video clips, webcasts, and links to additional quality resources vetted by the GeneEd web team. The Labs & Experiments section includes virtual labs that explore the genetics of different organisms as well as links to resources provided by the Howard Hughes Medical Institute and Cold Spring Harbor Laboratory. Young people may also wish to take a look at the Careers in Genetics section as it features interviews with scientists that will inspire and delight.

6

Discovery project -- First of the new Louisiana cryo projects  

SciTech Connect

The Discovery Project represents the first of the new wave of NGL recovery projects to be developed in Southeast Louisiana. The Discovery Project consists of three processing segments. Phase 1 is a 350 MMscfd dew point control unit at the Larose Gas Processing Plant which was placed in operation April 1998. Phase 2 at the Larose site is a 600 MMscfd cryogenic NGL recovery facility started up in November of 1998. Much of the equipment from Phase 1 was integrated into the two train cryogenic plant in Phase 2. The demethanized product from the Larose facility is fractionated at an expanded fractionation facility in Paradis, Louisiana. This fractionator produces ethane, propane, iso and normal butanes and natural gasoline products. It is designed to handle a range of feed compositions.

Currence, K.L.; Price, B.; Coons, W.B.

1999-07-01

7

Gene Specific Co-regulation Discovery: An Improved Approach  

E-print Network

Gene Specific Co-regulation Discovery: An Improved Approach Ji Zhang, Qing Liu and Kai Xu CSIRO. Discovering gene co-regulatory relationships is a new but im- portant research problem in DNA microarray data analysis. The problem of gene specific co-regulation discovery is to, for a particular gene of in- terest

Xu, Kai "Kevin"

8

CARTaGENE Project  

Cancer.gov

Launched in October 2009, the CARTaGENE project is the largest prospective longitudinal cohort of Québec. CARTaGENE's distinguishing features are that it is a quantitative prospective cohort that has deeply phenotyped 20,000 individuals aged 40-69, the age most individuals will develop chronic disease. 37,000 individuals will be enrolled by 2014. It is an open-access infrastructure enabling researchers to investigate the genetic, environmental, and lifestyle determinants of disease in the French Canadian population. CARTaGENE has collected whole blood for DNA from 30,000 individuals.

9

Biomarker Gene Signature Discovery Integrating Network Knowledge  

PubMed Central

Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step towards a better personalized medicine. During the last decade various methods, mainly coming from the machine learning or statistical domain, have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Here we review the current state of research in this field by giving an overview about so-far proposed approaches. PMID:24832044

Cun, Yupeng; Fröhlich, Holger

2012-01-01

10

Genome-enabled Discovery of Carbon Sequestration Genes  

SciTech Connect

The fate of carbon below ground is likely to be a major factor determining the success of carbon sequestration strategies involving plants. Despite their importance, molecular processes controlling belowground C allocation and partitioning are poorly understood. This project is leveraging the Populus trichocarpa genome sequence to discover genes important to C sequestration in plants and soils. The focus is on the identification of genes that provide key control points for the flow and chemical transformations of carbon in roots, concentrating on genes that control the synthesis of chemical forms of carbon that result in slower turnover rates of soil organic matter (i.e., increased recalcitrance). We propose to enhance carbon allocation and partitioning to roots by 1) modifying the auxin signaling pathway, and the invertase family, which controls sucrose metabolism, and by 2) increasing root proliferation through transgenesis with genes known to control fine root proliferation (e.g., ANT), 3) increasing the production of recalcitrant C metabolites by identifying genes controlling secondary C metabolism by a major mQTL-based gene discovery effort, and 4) increasing aboveground productivity by enhancing drought tolerance to achieve maximum C sequestration. This broad, integrated approach is aimed at ultimately enhancing root biomass as well as root detritus longevity, providing the best prospects for significant enhancement of belowground C sequestration.

Tuskan, Gerald A [ORNL] [ORNL; Tschaplinski, Timothy J [ORNL] [ORNL; Kalluri, Udaya C [ORNL] [ORNL; Yin, Tongming [ORNL] [ORNL; Yang, Xiaohan [ORNL] [ORNL; Zhang, Xinye [ORNL] [ORNL; Engle, Nancy L [ORNL] [ORNL; Ranjan, Priya [ORNL] [ORNL; Basu, Manojit M [ORNL] [ORNL; Gunter, Lee E [ORNL] [ORNL; Jawdy, Sara [ORNL] [ORNL; Martin, Madhavi Z [ORNL] [ORNL; Campbell, Alina S [ORNL] [ORNL; DiFazio, Stephen P [ORNL] [ORNL; Davis, John M [University of Florida] [University of Florida; Hinchee, Maud [ORNL] [ORNL; Pinnacchio, Christa [U.S. Department of Energy, Joint Genome Institute] [U.S. Department of Energy, Joint Genome Institute; Meilan, R [Purdue University] [Purdue University; Busov, V. [Michigan Technological University] [Michigan Technological University; Strauss, S [Oregon State University] [Oregon State University

2009-01-01

11

Peroxidase gene discovery from the horseradish transcriptome  

PubMed Central

Background Horseradish peroxidases (HRPs) from Armoracia rusticana have long been utilized as reporters in various diagnostic assays and histochemical stainings. Regardless of their increasing importance in the field of life sciences and suggested uses in medical applications, chemical synthesis and other industrial applications, the HRP isoenzymes, their substrate specificities and enzymatic properties are poorly characterized. Due to lacking sequence information of natural isoenzymes and the low levels of HRP expression in heterologous hosts, commercially available HRP is still extracted as a mixture of isoenzymes from the roots of A. rusticana. Results In this study, a normalized, size-selected A. rusticana transcriptome library was sequenced using 454 Titanium technology. The resulting reads were assembled into 14871 isotigs with an average length of 1133 bp. Sequence databases, ORF finding and ORF characterization were utilized to identify peroxidase genes from the 14871 isotigs generated by de novo assembly. The sequences were manually reviewed and verified with Sanger sequencing of PCR amplified genomic fragments, resulting in the discovery of 28 secretory peroxidases, 23 of them previously unknown. A total of 22 isoenzymes including allelic variants were successfully expressed in Pichia pastoris and showed peroxidase activity with at least one of the substrates tested, thus enabling their development into commercial pure isoenzymes. Conclusions This study demonstrates that transcriptome sequencing combined with sequence motif search is a powerful concept for the discovery and quick supply of new enzymes and isoenzymes from any plant or other eukaryotic organisms. Identification and manual verification of the sequences of 28 HRP isoenzymes do not only contribute a set of peroxidases for industrial, biological and biomedical applications, but also provide valuable information on the reliability of the approach in identifying and characterizing a large group of isoenzymes. PMID:24666710

2014-01-01

12

A Gene-Coexpression Network for Global Discovery of  

E-print Network

A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules Joshua M. Stuart,1 * Eran Segal,2 * Daphne Koller,2 Stuart K. Kim3 To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast

Kim, Stuart

13

Standardized Plant Disease Evaluations will Enhance Resistance Gene Discovery  

Technology Transfer Automated Retrieval System (TEKTRAN)

Gene discovery and marker development using DNA based tools require plant populations with well-documented phenotypes. Related crops such as apples and pears may share a number of genes, for example resistance to common diseases, and data mining in one crop may reveal genes for the other. However, u...

14

Automated Discovery of Functional Generality of Human Gene Expression Programs  

E-print Network

expression datasets measuring the responses of human cells to infectious agents or immuneAutomated Discovery of Functional Generality of Human Gene Expression Programs Georg K. Gerber1 is the identification of expression programs, sets of co- expressed genes orchestrating normal or pathological processes

Williams, Brian C.

15

Evaluation of five ab initio gene prediction programs for the discovery of maize genes  

E-print Network

Evaluation of five ab initio gene prediction programs for the discovery of maize genes Hong Yao1 Key words: ab initio gene prediction, a1-sh2 interval, maize, maize assembled genomic islands, maizeR and Grail) were evaluated for their accuracy in predicting maize genes. Two of these programs, Gene

Schnable, Patrick S.

16

GenePath: An Intelligent Assistant to the Discovery of Genetic Pathways  

NSDL National Science Digital Library

The Baylor College of Medicine in Houston and the University of Ljubljana in Slovenia present an improved, second version of GenePath, a "web-enabled intelligent assistant for the analysis of genetic data and for discovery of genetic networks." GenePath automates the complex process of determining gene interrelationships and users may download existing projects or start new ones from scratch. The website also provides a very detailed, nicely-designed guide to running GenePath, available as a separate downloadable document.

17

Virtual Cities--A Regional Discovery Project.  

ERIC Educational Resources Information Center

Describes the "Virtual Cities" project, a virtual reality satellite teleconference with students age 12 to 17 from Canada, Italy, and the United States held during the International Council for Educational Media 1992 conference. A visual database overlaid with instructional gaming strategies provided students with the opportunity to simulate the…

Stanfel, Julie

1993-01-01

18

GWATCH: a web platform for automated gene association discovery analysis  

PubMed Central

Background As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations. Findings Here we present a dynamic web-based platform – GWATCH – that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication of candidate or putative genes suggested from other sources, limiting Bonferroni genome-wide association study (GWAS) penalties; 4) Open data release and sharing by eliminating privacy constraints (The National Human Genome Research Institute (NHGRI) Institutional Review Board (IRB), informed consent, The Health Insurance Portability and Accountability Act (HIPAA) of 1996 etc.) on unabridged results, which allows for open access comparative and meta-analysis. Conclusions GWATCH is suitable for both GWAS and whole genome sequence association datasets. We illustrate the utility of GWATCH with three large genome-wide association studies for HIV-AIDS resistance genes screened in large multicenter cohorts; however, association datasets from any study can be uploaded and analyzed by GWATCH. PMID:25374661

2014-01-01

19

Cancer Genes: Discovery and Function - Michael Dean, Ph.D.  

Cancer.gov

April 29, 2014 1:00 PM - 2:00 PM Shady Grove, Room TE408/410 + Add to Outlook Calendar Speaker: Michael Dean, Ph.D. Chief, Human Genetics Section Laboratory of Experimental Immunology, CCR, NCI Print This Page Cancer Genes: Discovery and Function

20

EST sequencing for gene discovery in Chinese hamster ovary cells  

Microsoft Academic Search

Chinese hamster ovary (CHO) cells are one of the most important cell lines in biological research, and are the most widely used host for industrial production of recombinant therapeutic proteins. Despite their extensive applications, little sequence information is available for molecular based research. To facilitate gene discovery and genetic engineering, two cDNA libraries were con- structed from three CHO cell

Katie Fraass Wlaschin; Peter Morin Nissom; Marcela de Leon Gatti; Peh Fern Ong; Sanny Arleen; Kher Shing Tan; Anette Rink; Breana Cham; Kathy Wong; Miranda Yap; Wei-Shou Hu

2005-01-01

21

Automated Discovery of Functional Generality of Human Gene Expression Programs  

Microsoft Academic Search

An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in

Georg K. Gerber; Robin D. Dowell; Tommi S. Jaakkola; David K. Gifford

2007-01-01

22

Standardized plant disease evaluations will enhance resistance gene discovery  

Technology Transfer Automated Retrieval System (TEKTRAN)

Gene discovery and marker development using DNA-based tools require plant populations with well documented phenotypes. If dissimilar phenotype evaluation methods or data scoring techniques are employed with different crops, or at different labs for the same crops, then data mining for genetic marker...

23

Discovery of genes expressed in Hydra embryogenesis  

Microsoft Academic Search

Hydra's remarkable capacity to regenerate, to proliferate asexually by budding, and to form a pattern de novo from aggregates allows studying complex cellular and molecular processes typical for embryonic development. The underlying assumption is that patterning in adult hydra tissue relies on factors and genes which are active also during early embryogenesis. Previously, we reported that in Hydra the timing

Grigory Genikhovich; Ulrich Kürn; Georg Hemmrich; Thomas C. G. Bosch

2006-01-01

24

BIOINFORMATICS Biomarker Discovery in Microarray Gene  

E-print Network

and the Gleason grading system for tumor cell differen- tiation. These ordinal scales are discrete and finite practice, pathological phenotypes are often labelled with ordinal scales rather than binary, e, these ordinal labels have been rarely treated in a principled way. This paper describes a gene selection

Ghahramani, Zoubin

25

Technology development for gene discovery and full-length sequencing  

SciTech Connect

In previous years, with support from the U.S. Department of Energy, we developed methods for construction of normalized and subtracted cDNA libraries, and constructed hundreds of high-quality libraries for production of Expressed Sequence Tags (ESTs). Our clones were made widely available to the scientific community through the IMAGE Consortium, and millions of ESTs were produced from our libraries either by collaborators or by our own sequencing laboratory at the University of Iowa. During this grant period, we focused on (1) the development of a method for preferential cloning of tissue-specific and/or rare transcripts, (2) its utilization to expedite EST-based gene discovery for the NIH Mouse Brain Molecular Anatomy Project, (3) further development and optimization of a method for construction of full-length-enriched cDNA libraries, and (4) modification of a plasmid vector to maximize efficiency of full-length cDNA sequencing by the transposon-mediated approach. It is noteworthy that the technology developed for preferential cloning of rare mRNAs enabled identification of over 2,000 mouse transcripts differentially expressed in the hippocampus. In addition, the method that we optimized for construction of full-length-enriched cDNA libraries was successfully utilized for the production of approximately fifty libraries from the developing mouse nervous system, from which over 2,500 full-ORF-containing cDNAs have been identified and accurately sequenced in their entirety either by our group or by the NIH-Mammalian Gene Collection Program Sequencing Team.

Marcelo Bento Soares

2004-07-19

26

Gene-Based Marker Systems in Plants: High Throughput Approaches for Marker Discovery and Genotyping  

Microsoft Academic Search

\\u000a Development and application of molecular markers derived from genes, commonly called genic markers or sometimes functional\\u000a markers, is gaining momentum in plant genetics and breeding. Availability of large amount of sequence data coming from genome\\/transcriptome\\u000a sequencing projects as well as advent of next generation sequencing technologies together with advances in bioinformatics\\u000a tools, marker discovery is becoming cheaper and faster. The

Rajeev K Varshney

27

Novel venom gene discovery in the platypus  

PubMed Central

Background To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. Results We identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation. Conclusions This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom. PMID:20920228

2010-01-01

28

Gene Discovery and Product Development for Grain Quality Traits  

NSDL National Science Digital Library

The composition of oils, proteins, and carbohydrates in seeds of corn, soybean, and other crops has been modified to produce grains with enhanced value. Both plant breeding and molecular technologies have been used to produce plants carrying the desired traits. Genomics-based strategies for gene discovery, coupled with high-throughput transformation processes and miniaturized, automated analytical and functionality assays, have accelerated the identification of product candidates. Molecular markerâ??based breeding strategies have been used to accelerate the process of moving trait genes into high-yielding germplasm for commercialization. These products are being tested for applications in food, feed, and industrial markets.

Barbara Mazur (DuPont Agricultural Products Experimental Station; )

1999-07-16

29

Future Mission Proposal Opportunities: Discovery, New Frontiers, and Project Prometheus  

NASA Technical Reports Server (NTRS)

The NASA Office of Space Science is expanding opportunities to propose missions to comets, asteroids, and other solar system targets. The Discovery Program continues to be popular, with two sample return missions, Stardust and Genesis, currently in operation. The New Frontiers Program, a new proposal opportunity modeled on the successful Discovery Program, begins this year with the release of its first Announcement of Opportunity. Project Prometheus, a program to develop nuclear electric power and propulsion technology intended to enable a new class of high-power, high-capability investigations, is a third opportunity to propose solar system exploration. All three classes of mission include a commitment to provide data to the Planetary Data System, any samples to the NASA Curatorial Facility at Johnson Space Center, and programs for education and public outreach.

Niebur, S. M.; Morgan, T. H.; Niebur, C. S.

2003-01-01

30

Discovery of 100-Plus Genes Tied to Autism May Improve Treatments  

MedlinePLUS

... page, please enable JavaScript. Discovery of 100-Plus Genes Tied to Autism May Improve Treatments Disorder has ... 29, 2014 Related MedlinePlus Pages Autism Spectrum Disorder Genes and Gene Therapy WEDNESDAY, Oct. 29, 2014 (HealthDay ...

31

Genome Enabled Discovery of Carbon Sequestration Genes in Poplar  

SciTech Connect

The goals of the S.H. Strauss laboratory portion of 'Genome-enabled discovery of carbon sequestration genes in poplar' are (1) to explore the functions of candidate genes using Populus transformation by inserting genes provided by Oakridge National Laboratory (ORNL) and the University of Florida (UF) into poplar; (2) to expand the poplar transformation toolkit by developing transformation methods for important genotypes; and (3) to allow induced expression, and efficient gene suppression, in roots and other tissues. As part of the transformation improvement effort, OSU developed transformation protocols for Populus trichocarpa 'Nisqually-1' clone and an early flowering P. alba clone, 6K10. Complete descriptions of the transformation systems were published (Ma et. al. 2004, Meilan et. al 2004). Twenty-one 'Nisqually-1' and 622 6K10 transgenic plants were generated. To identify root predominant promoters, a set of three promoters were tested for their tissue-specific expression patterns in poplar and in Arabidopsis as a model system. A novel gene, ET304, was identified by analyzing a collection of poplar enhancer trap lines generated at OSU (Filichkin et. al 2006a, 2006b). Other promoters include the pGgMT1 root-predominant promoter from Casuarina glauca and the pAtPIN2 promoter from Arabidopsis root specific PIN2 gene. OSU tested two induction systems, alcohol- and estrogen-inducible, in multiple poplar transgenics. Ethanol proved to be the more efficient when tested in tissue culture and greenhouse conditions. Two estrogen-inducible systems were evaluated in transgenic Populus, neither of which functioned reliably in tissue culture conditions. GATEWAY-compatible plant binary vectors were designed to compare the silencing efficiency of homologous (direct) RNAi vs. heterologous (transitive) RNAi inverted repeats. A set of genes was targeted for post transcriptional silencing in the model Arabidopsis system; these include the floral meristem identity gene (APETALA1 or AP1), auxin response factor gene (ETTIN), the gene encoding transcriptional factor of WD40 family (TRANSPARENTTESTAGLABRA1 or TTG1), and the auxin efflux carrier (PIN-FORMED2 or PIN2) gene. More than 220 transgenic lines of the 1st, 2nd and 3rd generations were analyzed for RNAi suppression phenotypes (Filichkin et. al., manuscript submitted). A total of 108 constructs were supplied by ORNL, UF and OSU and used to generate over 1,881 PCR verified transgenic Populus and over 300 PCR verified transgenic Arabidopsis events. The Populus transgenics alone required Agrobacterium co-cultivations of 124.406 explants.

Filichkin, Sergei; Etherington, Elizabeth; Ma, Caiping; Strauss, Steve

2007-02-22

32

VeryGene: linking tissue-specific genes to diseases, drugs, and beyond for knowledge discovery.  

PubMed

In addition to many other genes, tissue-specific genes (TSGs) represent a set of genes of great importance for human physiology. However, the links among TSGs, diseases, and potential therapeutic agents are often missing, hidden, or too scattered to find. There is a need to establish a knowledgebase for researchers to share this and additional information in order to speed up discovery and clinical practice. As an initiative toward systems biology, the VeryGene web server was developed to fill this gap. A significant effort has been made to integrate TSGs from two large-scale data analyses with respective information on subcellular localization, Gene Ontology, Reactome, KEGG pathway, Mouse Genome Informatics (MGI) Mammalian Phenotype, disease association, and targeting drugs. The current release carefully selected 3,960 annotated TSGs derived from 127 normal human tissues and cell types, including 5,672 gene-disease and 2,171 drug-target relationships. In addition to being a specialized source for TSGs, VeryGene can be used as a discovery tool by generating novel inferences. Some inherently useful but hidden relations among genes, diseases, drugs, and other important aspects can be inferred to form testable hypotheses. VeryGene is available online at http://www.verygene.com. PMID:21245417

Yang, Xiaoqin; Ye, Yun; Wang, Guiping; Huang, Hong; Yu, Dekuang; Liang, Shuang

2011-04-27

33

Sugarcane Functional Genomics: Gene Discovery for Agronomic Trait Development  

PubMed Central

Sugarcane is a highly productive crop used for centuries as the main source of sugar and recently to produce ethanol, a renewable bio-fuel energy source. There is increased interest in this crop due to the impending need to decrease fossil fuel usage. Sugarcane has a highly polyploid genome. Expressed sequence tag (EST) sequencing has significantly contributed to gene discovery and expression studies used to associate function with sugarcane genes. A significant amount of data exists on regulatory events controlling responses to herbivory, drought, and phosphate deficiency, which cause important constraints on yield and on endophytic bacteria, which are highly beneficial. The means to reduce drought, phosphate deficiency, and herbivory by the sugarcane borer have a negative impact on the environment. Improved tolerance for these constraints is being sought. Sugarcane's ability to accumulate sucrose up to 16% of its culm dry weight is a challenge for genetic manipulation. Genome-based technology such as cDNA microarray data indicates genes associated with sugar content that may be used to develop new varieties improved for sucrose content or for traits that restrict the expansion of the cultivated land. The genes can also be used as molecular markers of agronomic traits in traditional breeding programs. PMID:18273390

Menossi, M.; Silva-Filho, M. C.; Vincentz, M.; Van-Sluys, M.-A.; Souza, G. M.

2008-01-01

34

Sugarcane functional genomics: gene discovery for agronomic trait development.  

PubMed

Sugarcane is a highly productive crop used for centuries as the main source of sugar and recently to produce ethanol, a renewable bio-fuel energy source. There is increased interest in this crop due to the impending need to decrease fossil fuel usage. Sugarcane has a highly polyploid genome. Expressed sequence tag (EST) sequencing has significantly contributed to gene discovery and expression studies used to associate function with sugarcane genes. A significant amount of data exists on regulatory events controlling responses to herbivory, drought, and phosphate deficiency, which cause important constraints on yield and on endophytic bacteria, which are highly beneficial. The means to reduce drought, phosphate deficiency, and herbivory by the sugarcane borer have a negative impact on the environment. Improved tolerance for these constraints is being sought. Sugarcane's ability to accumulate sucrose up to 16% of its culm dry weight is a challenge for genetic manipulation. Genome-based technology such as cDNA microarray data indicates genes associated with sugar content that may be used to develop new varieties improved for sucrose content or for traits that restrict the expansion of the cultivated land. The genes can also be used as molecular markers of agronomic traits in traditional breeding programs. PMID:18273390

Menossi, M; Silva-Filho, M C; Vincentz, M; Van-Sluys, M-A; Souza, G M

2008-01-01

35

The Schistosoma mansoni gene index: gene discovery and biology by reconstruction and analysis of expressed gene sequences.  

PubMed

Expressed sequence tag (EST) sequencing and analysis is a primary research tool to identify and characterize the Schistosoma mansoni transcriptome. As part of our gene discovery effort, a total of 5,793 ESTs have been generated from clones selected randomly from complementary DNA (cDNA) libraries constructed from male and female adult worms. Assembly analysis of all the 16,813 public S. mansoni ESTs has identified 1,920 distinct tentative consensus sequences (TCs) and 5,571 nonoverlapping ESTs (singletons). Of these, 376 TCs (20%) and 1,449 singletons (26%) are unique to the SUNY/TIGR sequencing effort. Tentative consensus sequences and singletons were distributed into various categories of biological roles associated with cell structure, metabolism, protein fate, signal transduction, transcription, protein synthesis, transporters, and cell growth. The TCs and singletons represent transcripts that can be used as a resource for functional annotation of genomic sequence data, comparative sequence analysis, and cDNA clone selection for microarray projects. The utility of EST analysis is demonstrated by identifying new protease genes, which may be involved in hemoglobin degradation. PMID:12760639

Merrick, Joseph M; Osman, Ahmed; Tsai, Jennifer; Quackenbush, John; LoVerde, Philip T; Lee, Norman H

2003-04-01

36

Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS. PMID:18060051

Gwinn, Katrina; Corriveau, Roderick A.; Mitsumoto, Hiroshi; Bednarz, Kate; Brown, Robert H.; Cudkowicz, Merit; Gordon, Paul H.; Hardy, John; Kasarskis, Edward J.; Kaufmann, Petra; Miller, Robert; Sorenson, Eric; Tandan, Rup; Traynor, Bryan J.; Nash, Josefina; Sherman, Alex; Mailman, Matthew D.; Ostell, James; Bruijn, Lucie; Cwik, Valerie; Rich, Stephen S.; Singleton, Andrew; Refolo, Larry; Andrews, Jaime; Zhang, Ran; Conwit, Robin; Keller, Margaret A.

2007-01-01

37

Amyotrophic lateral sclerosis: an emerging era of collaborative gene discovery.  

PubMed

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS. PMID:18060051

Gwinn, Katrina; Corriveau, Roderick A; Mitsumoto, Hiroshi; Bednarz, Kate; Brown, Robert H; Cudkowicz, Merit; Gordon, Paul H; Hardy, John; Kasarskis, Edward J; Kaufmann, Petra; Miller, Robert; Sorenson, Eric; Tandan, Rup; Traynor, Bryan J; Nash, Josefina; Sherman, Alex; Mailman, Matthew D; Ostell, James; Bruijn, Lucie; Cwik, Valerie; Rich, Stephen S; Singleton, Andrew; Refolo, Larry; Andrews, Jaime; Zhang, Ran; Conwit, Robin; Keller, Margaret A

2007-01-01

38

Lowering the barriers from Discovery to Delivery: a JISC funded EDINA and Mimas project  

Microsoft Academic Search

Purpose – The paper aims to describe the context and the progress with the UK Discovery to Delivery project. Design\\/methodology\\/approach – Having set the scene for Discovery to Delivery, the paper describes how the project work was divided into four separate but interlinked strands. The methodologies for each strand are described and the outcomes are critically assessed. Findings – The

Fred Guy; Joy Elizabeth Palmer

2010-01-01

39

Canonical Correlation Analysis for Gene-Based Pleiotropy Discovery  

PubMed Central

Genome-wide association studies have identified a wealth of genetic variants involved in complex traits and multifactorial diseases. There is now considerable interest in testing variants for association with multiple phenotypes (pleiotropy) and for testing multiple variants for association with a single phenotype (gene-based association tests). Such approaches can increase statistical power by combining evidence for association over multiple phenotypes or genetic variants respectively. Canonical Correlation Analysis (CCA) measures the correlation between two sets of multidimensional variables, and thus offers the potential to combine these two approaches. To apply CCA, we must restrict the number of attributes relative to the number of samples. Hence we consider modules of genetic variation that can comprise a gene, a pathway or another biologically relevant grouping, and/or a set of phenotypes. In order to do this, we use an attribute selection strategy based on a binary genetic algorithm. Applied to a UK-based prospective cohort study of 4286 women (the British Women's Heart and Health Study), we find improved statistical power in the detection of previously reported genetic associations, and identify a number of novel pleiotropic associations between genetic variants and phenotypes. New discoveries include gene-based association of NSF with triglyceride levels and several genes (ACSM3, ERI2, IL18RAP, IL23RAP and NRG1) with left ventricular hypertrophy phenotypes. In multiple-phenotype analyses we find association of NRG1 with left ventricular hypertrophy phenotypes, fibrinogen and urea and pleiotropic relationships of F7 and F10 with Factor VII, Factor IX and cholesterol levels. PMID:25329069

Seoane, Jose A.; Campbell, Colin; Day, Ian N. M.; Casas, Juan P.; Gaunt, Tom R.

2014-01-01

40

A New Omics Data Resource of Pleurocybellaporrigens for Gene Discovery  

PubMed Central

Background Pleurocybellaporrigens is a mushroom-forming fungus, which has been consumed as a traditional food in Japan. In 2004, 55 people were poisoned by eating the mushroom and 17 people among them died of acute encephalopathy. Since then, the Japanese government has been alerting Japanese people to take precautions against eating the P. porrigens mushroom. Unfortunately, despite efforts, the molecular mechanism of the encephalopathy remains elusive. The genome and transcriptome sequence data of P. porrigens and the related species, however, are not stored in the public database. To gain the omics data in P. porrigens, we sequenced genome and transcriptome of its fruiting bodies and mycelia by next generation sequencing. Methodology/Principal Findings Short read sequences of genomic DNAs and mRNAs in P. porrigens were generated by Illumina Genome Analyzer. Genome short reads were de novo assembled into scaffolds using Velvet. Comparisons of genome signatures among Agaricales showed that P. porrigens has a unique genome signature. Transcriptome sequences were assembled into contigs (unigenes). Biological functions of unigenes were predicted by Gene Ontology and KEGG pathway analyses. The majority of unigenes would be novel genes without significant counterparts in the public omics databases. Conclusions Functional analyses of unigenes present the existence of numerous novel genes in the basidiomycetes division. The results mean that the omics information such as genome, transcriptome and metabolome in basidiomycetes is short in the current databases. The large-scale omics information on P. porrigens, provided from this research, will give a new data resource for gene discovery in basidiomycetes. PMID:23936076

Dohra, Hideo; Someya, Takumi; Takano, Tomoyuki; Harada, Kiyonori; Omae, Saori; Hirai, Hirofumi; Yano, Kentaro; Kawagishi, Hirokazu

2013-01-01

41

GENE CO-EXPRESSION NETWORK DISCOVERY WITH CONTROLLED STATISTICAL AND BIOLOGICAL SIGNIFICANCE  

E-print Network

GENE CO-EXPRESSION NETWORK DISCOVERY WITH CONTROLLED STATISTICAL AND BIOLOGICAL SIGNIFICANCE as a module of co- expressed genes which can be conveniently viewed as a co- expression network. Genes network. Based on the estimation of pairwise gene profile correlation, the al- gorithm provides an initial

Hero, Alfred O.

42

Gene Discovery Using Pareto Depth Sampling Distributions Gilles Fleury , Alfred Hero  

E-print Network

Gene Discovery Using Pareto Depth Sampling Distributions Gilles Fleury , Alfred Hero , Sepideh, 2004 Abstract Most methods for finding interesting gene expres- sion profiles from gene microarray data is introduced based on gene ranking according to Pareto depth in multiple discriminants. The novelty of our

Hero, Alfred O.

43

Gene expression endophenotypes: a novel approach for gene discovery in Alzheimer's disease  

Microsoft Academic Search

Uncovering the underlying genetic component of any disease is key to the understanding of its pathophysiology and may open\\u000a new avenues for development of therapeutic strategies and biomarkers. In the past several years, there has been an explosion\\u000a of genome-wide association studies (GWAS) resulting in the discovery of novel candidate genes conferring risk for complex\\u000a diseases, including neurodegenerative diseases. Despite

Nilüfer Ertekin-Taner

2011-01-01

44

Discovery and New Frontiers Project Budget Analysis Tool  

NASA Technical Reports Server (NTRS)

The Discovery and New Frontiers (D&NF) programs are multi-project, uncoupled programs that currently comprise 13 missions in phases A through F. The ability to fly frequent science missions to explore the solar system is the primary measure of program success. The program office uses a Budget Analysis Tool to perform "what-if" analyses and compare mission scenarios to the current program budget, and rapidly forecast the programs ability to meet their launch rate requirements. The tool allows the user to specify the total mission cost (fixed year), mission development and operations profile by phase (percent total mission cost and duration), launch vehicle, and launch date for multiple missions. The tool automatically applies inflation and rolls up the total program costs (in real year dollars) for comparison against available program budget. Thus, the tool allows the user to rapidly and easily explore a variety of launch rates and analyze the effect of changes in future mission or launch vehicle costs, the differing development profiles or operational durations of a future mission, or a replan of a current mission on the overall program budget. Because the tool also reports average monthly costs for the specified mission profile, the development or operations cost profile can easily be validate against program experience for similar missions. While specifically designed for predicting overall program budgets for programs that develop and operate multiple missions concurrently, the basic concept of the tool (rolling up multiple, independently-budget lines) could easily be adapted to other applications.

Newhouse, Marilyn E.

2011-01-01

45

New Discoveries From The Archean Biosphere Drilling Project (ABDP)  

NASA Astrophysics Data System (ADS)

The Archean Biosphere Drilling Project (ABDP), an international scientific drilling project involving scientists from the USA, Australia and Japan, was initiated in Pilbara Craton, Western Australia. The scientific objectives of the ABDP are the identification of microfossils and biomarkers, the clarification of geochemical environment of the early Earth, and the understanding of geophysical contribution to the co-evolution of life and environment. Through 2003 and 2004 activities, we have drilled 150 _| 300 m deep holes to recover _gfresh_h (modern weathering-free) geologic formations that range from 3.5 to 2.7 Ga in age. The drilling targets were: (1) 3.46 Ga Towers Formation, (2) mid-Archean Mosquito Formation, (3) 2.77 Ga Mt Roe Basalt, (4) 2.76 Ga Tumbiana Formation, (5) 2.74 Ga Hardey Formation. The initial investigations on the ABDP drill cores by Japanese members have already produced many exciting and interesting data and observations. 3.46 Ga Marble Bar Jasper could provide clues to the argument about the early photosynthetic cyanobacteria that have produced free oxygen and have evolved the oxygen level on the earth. There have been many ideas how the hematite in jasper was formed. Our most important discoveries are the confirmations that hematite, magnetite and siderite precipitated separately as primary minerals, and that there is a remaining texture which resembles microfossil using FE-SEM, ESCA, Laser-Raman and cathodoluminescence. Taking into account the carbon isotopic ratios of remains from _|25 to _|40 permil, these iron oxides might be biogenic. We need to identify the iron bacteria in detail to deduce the early earth_fs surface environment. In addition, the black shale of Apex Basalt overlying Marble Bar Jasper contains organic carbon from 0.7 to 5.2 percent, and the carbon isotopic ratio of which is from -26 to -30 per mil, suggesting that various microbes inhabited in the early Archean ocean. 2.77 Ga Mt Roe Basalt, which is composed of basaltic lavas interbedded with tuffs, clastic sediment and minor evaporites, well preserves the primary biogeochemical, geochemical and geophysical phenomena. The discovery of black shale with sulfide nodules is worthy of special attention. Our study suggests that the following succession of events occurred more than once, (1) eruption of amygdaloidal basaltic lava followed by eruption of tuff into shallower water, (2) deposition of sandstone and black shale, and (3) concurrent hydrothermal activity with reduced fluids altered the tuff and the lowermost clastic sediments. The extremely light carbon isotopic ratios suggest the activities of methanogene in hydrothermal veinlets and methanotroph in black shale. In addition, the wide range of sulfur isotopic ratio in black shale suggests activity of co-existing sulfate-reducing bacteria in the black shale. Occasional presence of sandstone, especially in late stage of clastic sedimentation, suggests the sedimentation near coastal environment. Stromatolite-like microtexture in the sandstone suggests the existence of photosynthetic microbes, which is supported by heavy carbon isotopic ratios (up to _|25 permil) and by the signals of hopanoids biomarker. The three dimensional geochemical data suggest the existence of marine environment from oxic at shallow site to euxinic at the deeper site. Paleomagnetic analyses suggest the episodic initiation of the earth's dynamo at about 3.5 Ga and the increase of it's momentum since at least 2.77 Ga. Taking into account the biogeochemical evidences confirmed from other ABDP cores, the increase of geomagnetic intensity might have accelerated the diversification of early life.

Nedachi, M.

2004-12-01

46

The discovery of the microphthalmia locus and its gene, Mitf  

PubMed Central

Summary The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia mutation was discovered among the descendants of a mouse that was irradiated for the purpose of mutagenesis, the mutation most likely was not radiation-induced but occurred spontaneously in one of the parents of a later breeding. Although Mitf might eventually have been identified by other molecular genetic techniques, it was first cloned from a chance transgene insertion at the microphthalmia locus. And although Mitf was found to encode a member of a well-known transcription factor family, its analysis might still be in its infancy had Mitf not turned out to be of crucial importance for the physiology and pathology of many distinct organs, including eye, ear, immune system, bone, and skin, and in particular for melanoma. In fact, near seven decades of Mitf research have led to many insights about development, function, degeneration, and malignancies of a number of specific cell types, and it is hoped that these insights will one day lead to therapies benefitting those afflicted with diseases originating in these cell types. PMID:20807369

Arnheiter, Heinz

2010-01-01

47

On Determination of Minimum Sample Size for Discovery of Temporal Gene Expression Patterns  

Microsoft Academic Search

DNA microarray technologies allow for the simultaneous monitoring of thousands of genes, which reveal important information about cellular and tissue expression phenotypes. From a viewpoint of data analysis, microarray experiments may be classified into (1) classification of patients or non-patients or more subtypes in terms of gene expressions, (2) discovery of gene expression patterns over a set of different conditions,

Fang-xiang Wu; W. J. Zhang; Anthony J. Kusalik

2006-01-01

48

Physics Discoveries  

NSDL National Science Digital Library

The Physics Discoveries section of the National Science Foundation (NSF) website brings together a "panoply of discoveries and innovations that began with NSF support." Indeed, it is quite a panoply and visitors will enjoy scrolling through the dozens of resources presented here. The projects profiled include new gene sequencing, celebrations of Marie Curie's birthday, space turbulence studies, and quantum computing. Each of these resources includes a press release, video coverage related to each project, and a set of additional websites. Visitors can also print out relevant materials and share these links via a range of social media tools.

49

Gene sequencing project identifies abnormal gene that launches rare childhood leukemia  

Cancer.gov

Research led by the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project has identified a fusion gene responsible for almost 30 percent of a rare subtype of childhood leukemia with an extremely poor prognosis. The finding offers the first evidence of a mistake that gives rise to a significant percentage of acute megakaryoblastic leukemia (AMKL) cases in children. AMKL accounts for about 10 percent of pediatric acute myeloid leukemia (AML). The discovery paves the way for desperately needed treatment advances.

50

The Gene Ontology project in 2008  

PubMed Central

The Gene Ontology (GO) project (http://www.geneontology.org/) provides a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see http://www.sequenceontology.org/). The ontologies have been extended and refined for several biological areas, and improvements to the structure of the ontologies have been implemented. To improve the quantity and quality of gene product annotations available from its public repository, the GO Consortium has launched a focused effort to provide comprehensive and detailed annotation of orthologous genes across a number of ‘reference’ genomes, including human and several key model organisms. Software developments include two releases of the ontology-editing tool OBO-Edit, and improvements to the AmiGO browser interface. PMID:17984083

2008-01-01

51

New approaches to gene discovery with animal models of obesity and diabetes.  

PubMed

DNA-based approaches to the discovery of genes contributing to the development of type 2 diabetes have not been very successful despite substantial investments of time and money. The multiple gene-gene and gene-environment interactions that influence the development of type 2 diabetes mean that DNA approaches are not the ideal tool for defining the etiology of this complex disease. Gene expression-based technologies may prove to be a more rewarding strategy to identify diabetes candidate genes. There are a number of RNA-based technologies available to identify genes that are differentially expressed in various tissues in type 2 diabetes. These include differential display polymerase chain reaction (ddPCR), suppression subtractive hybridization (SSH), and cDNA microarrays. The power of new technologies to detect differential gene expression is ideally suited to studies utilizing appropriate animal models of human disease. We have shown that the gene expression approach, in combination with an excellent animal model such as the Israeli sand rat (Psammomys obesus), can provide novel genes and pathways that may be important in the disease process and provide novel therapeutic approaches. This paper will describe a new gene discovery, beacon, a novel gene linked with energy intake. As the functional characterization of novel genes discovered in our laboratory using this approach continues, it is anticipated that we will soon be able to compile a definitive list of genes that are important in the development of obesity and type 2 diabetes. PMID:12079868

Collier, Greg; Walder, Ken; De Silva, Andrea; Tenne-Brown, Janette; Sanigorski, Andrew; Segal, David; Kantham, Lakshmi; Augert, Guy

2002-06-01

52

Discovery  

ERIC Educational Resources Information Center

All common fractions can be written in decimal form. In this Discovery article, the author suggests that teachers ask their students to calculate the decimals by actually doing the divisions themselves, and later on they can use a calculator to check their answers. This article presents a lesson based on the research of Bolt (1982).

de Mestre, Neville

2010-01-01

53

Discovery and revision of Arabidopsis genes by proteogenomics  

PubMed Central

Gene annotation underpins genome science. Most often protein coding sequence is inferred from the genome based on transcript evidence and computational predictions. While generally correct, gene models suffer from errors in reading frame, exon border definition, and exon identification. To ascertain the error rate of Arabidopsis thaliana gene models, we isolated proteins from a sample of Arabidopsis tissues and determined the amino acid sequences of 144,079 distinct peptides by tandem mass spectrometry. The peptides corresponded to 1 or more of 3 different translations of the genome: a 6-frame translation, an exon splice-graph, and the currently annotated proteome. The majority of the peptides (126,055) resided in existing gene models (12,769 confirmed proteins), comprising 40% of annotated genes. Surprisingly, 18,024 novel peptides were found that do not correspond to annotated genes. Using the gene finding program AUGUSTUS and 5,426 novel peptides that occurred in clusters, we discovered 778 new protein-coding genes and refined the annotation of an additional 695 gene models. The remaining 13,449 novel peptides provide high quality annotation (>99% correct) for thousands of additional genes. Our observation that 18,024 of 144,079 peptides did not match current gene models suggests that 13% of the Arabidopsis proteome was incomplete due to approximately equal numbers of missing and incorrect gene models. PMID:19098097

Castellana, Natalie E.; Payne, Samuel H.; Shen, Zhouxin; Stanke, Mario; Bafna, Vineet; Briggs, Steven P.

2008-01-01

54

Discovery of mammalian genes that participate in virus infection  

PubMed Central

Background Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. Results Candidate genes required for lytic reovirus infection were identified by tagged sequence mutagenesis, a process that permits rapid identification of genes disrupted by gene entrapment. One hundred fifty-one reovirus resistant clones were selected from cell libraries containing 2 × 105 independently disrupted genes, of which 111 contained mutations in previously characterized genes and functionally anonymous transcription units. Collectively, the genes associated with reovirus resistance differed from genes targeted by random gene entrapment in that known mutational hot spots were under represented, and a number of mutations appeared to cluster around specific cellular processes, including: IGF-II expression/signalling, vesicular transport/cytoskeletal trafficking and apoptosis. Notably, several of the genes have been directly implicated in the replication of reovirus and other viruses at different steps in the viral lifecycle. Conclusions Tagged sequence mutagenesis provides a rapid, genome-wide strategy to identify candidate cellular genes required for virus infection. The candidate genes provide a starting point for mechanistic studies of cellular processes that participate in the virus lifecycle and may provide targets for novel anti-viral therapies. PMID:15522117

Organ, Edward L; Sheng, Jinsong; Ruley, H Earl; Rubin, Donald H

2004-01-01

55

Molecular classification of cancer: {C}lass discovery and class prediction by gene expression monitoring  

Microsoft Academic Search

Although cancer classiÞcation has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery)or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classiÞcation based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case.A class discovery

Todd R. Golub; Donna K. Slonim; Pablo Tamayo; C. Huard; M. Gaasenbeek; Jill P. Mesirov; H. Coller; Mignon L. Loh; James R. Downing; M. A. Caligiuri; C. D. Bloomfield; Eric S. Lander

1999-01-01

56

Using the DFCI Gene Index Databases for Biological Discovery  

PubMed Central

The DFCI Gene Index Web pages provide access to analyses of ESTs and gene sequences for nearly 114 species, as well as a number of resources derived from these. Each species-specific database is presented using a common format with a home page. A variety of methods exist that allow users to search each species-specific database. Methods implemented currently include nucleotide or protein sequence queries using WU-BLAST, text-based searches using various sequence identifiers, searches by gene, tissue and library name, and searches using functional classes through Gene Ontology assignments. This protocol provides guidance for using the Gene Index Databases to extract information. PMID:20205187

Antonescu, Corina; Antonescu, Valentin; Sultana, Razvan; Quackenbush, John

2014-01-01

57

Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches  

PubMed Central

Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

2015-01-01

58

Strategic applications of gene expression: from drug discovery/development to bedside.  

PubMed

Gene expression is useful for identifying the molecular signature of a disease and for correlating a pharmacodynamic marker with the dose-dependent cellular responses to exposure of a drug. Gene expression offers utility to guide drug discovery by illustrating engagement of the desired cellular pathways/networks, as well as avoidance of acting on the toxicological pathways. Successful employment of gene-expression signatures in the later stages of drug development depends on their linkage to clinically meaningful phenotypic characteristics and requires a biologically meaningful mechanism combined with a stringent statistical rigor. Much of the success in clinical drug development is hinged on predefining the signature genes for their fitness for purposes of application. Specific examples are highlighted to illustrate the breadth and depth of the potential utility of gene-expression signatures in drug discovery and clinical development to targeted therapeutics at the bedside. PMID:23319288

Bai, Jane P F; Alekseyenko, Alexander V; Statnikov, Alexander; Wang, I-Ming; Wong, Peggy H

2013-04-01

59

Discovery of gene-regulation pathways using local causal search.  

PubMed Central

This paper reports the methods and results of a computer-based algorithm that takes as input the expression levels of a set of genes as given by DNA microarray data, and then searches for causal pathways that represent how the genes regulate each other. The algorithm uses local heuristic search and a Bayesian scoring metric. We applied the algorithm to induce causal networks from a mixture of observational and experimental gene-expression data on genes involved in galactose metabolism in the yeast Saccharomyces cerevisiae. The observational data consisted of gene-expression levels obtained from unmanipulated inverted exclamation mark degrees wild-type inverted exclamation mark +/- cells. The experimental data were produced by deleting ( inverted exclamation mark degrees knocking out inverted exclamation mark +/-) genes and measuring the expression levels of other genes. We used this data to evaluate several variations of the local search method. In each evaluation, causal relationships were predicted for all 36 pairwise combinations of nine key galactose-related genes. These predictions were then compared to the known causal relationships among these genes. PMID:12463958

Yoo, Changwon; Cooper, Gregory F.

2002-01-01

60

Discovery of mammalian genes that participate in virus infection  

Microsoft Academic Search

BACKGROUND: Viruses are obligate intracellular parasites that rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and\\/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. RESULTS: Candidate genes required for lytic reovirus infection were identified by tagged

Edward L Organ; Jinsong Sheng; H Earl Ruley; Donald H Rubin

2004-01-01

61

Speeding disease gene discovery by sequence based candidate prioritization   

E-print Network

Background: Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation ...

Adie, Euan A; Adams, Richard R; Evans, Kathryn L; Porteous, David; Pickard, Ben S

2005-03-14

62

Computational discovery of gene modules, regulatory networks and expression programs  

E-print Network

High-throughput molecular data are revolutionizing biology by providing massive amounts of information about gene expression and regulation. Such information is applicable both to furthering our understanding of fundamental ...

Gerber, Georg Kurt, 1970-

2007-01-01

63

Discovery of Ca2 -relevant and differentiation-associated genes  

E-print Network

are involved in ESCC, including cyclin D1, EGFR, annexin I, cystatin B, int-2, CASK and keratin 4 (Suzuki et al., 1997; Nagasawa et al., 2001; Wang et al., 2002; Xia et al., 2002). Several studies on differential gene

Tian, Weidong

64

Systematic Discovery of New Genes in the Saccharomyces cerevisiae Genome  

Microsoft Academic Search

We used genome-wide comparative analysis of predicted protein sequences to identify many novel small genes, named smORFs for small open reading frames, within the budding yeast genome. Further analysis of 117 of these new genes showed that 84 are transcribed. We extended our analysis of one smORF conserved from yeast to human. This investigation provides an updated and comprehensive annotation

Marco M. Kessler; Qiandong Zeng; Sarah Hogan; Robin Cook; Arturo J. Morales; Guillaume Cottarel

2003-01-01

65

GENOME-ENABLED DISCOVERY OF CARBON SEQUESTRATION GENES IN POPLAR  

SciTech Connect

Plants utilize carbon by partitioning the reduced carbon obtained through photosynthesis into different compartments and into different chemistries within a cell and subsequently allocating such carbon to sink tissues throughout the plant. Since the phytohormones auxin and cytokinin are known to influence sink strength in tissues such as roots (Skoog & Miller 1957, Nordstrom et al. 2004), we hypothesized that altering the expression of genes that regulate auxin-mediated (e.g., AUX/IAA or ARF transcription factors) or cytokinin-mediated (e.g., RR transcription factors) control of root growth and development would impact carbon allocation and partitioning belowground (Fig. 1 - Renewal Proposal). Specifically, the ARF, AUX/IAA and RR transcription factor gene families mediate the effects of the growth regulators auxin and cytokinin on cell expansion, cell division and differentiation into root primordia. Invertases (IVR), whose transcript abundance is enhanced by both auxin and cytokinin, are critical components of carbon movement and therefore of carbon allocation. Thus, we initiated comparative genomic studies to identify the AUX/IAA, ARF, RR and IVR gene families in the Populus genome that could impact carbon allocation and partitioning. Bioinformatics searches using Arabidopsis gene sequences as queries identified regions with high degrees of sequence similarities in the Populus genome. These Populus sequences formed the basis of our transgenic experiments. Transgenic modification of gene expression involving members of these gene families was hypothesized to have profound effects on carbon allocation and partitioning.

DAVIS J M

2007-10-11

66

The National Laboratory Gene Library Project  

SciTech Connect

The two National Laboratories at Livermore and Los Alamos have played a prominent role in the development and application of flow cytometry and sorting to chromosome classification and purification. Both laboratories began to receive numerous requests for specific human chromosomal types purified by flow sorting for gene library construction, but these requests were difficult to satisfy due to time and personnel constraints. The Department of Energy, through its Office of Health and Environmental Research, has a long-standing interest in the human genome in general and in the mutagenic and carcinogenic effects of energy-related environmental pollutants in particular. Hence, it was decided in 1983 to use the flow construct chromosome-specific gene libraries to be made available to the genetic research community. The National Laboratory Gene Library Project was envisioned as a practical way to deal with requests for sorted chromosomes, and also as a way to promote increased understanding of the human genome and the effects of mutagens and carcinogens on it. The strategy for the project was developed with the help of an advisory committee as well as suggestions and advice from many other geneticists. 4 refs., 2 tabs.

Deaven, L.L.; Van Dilla, M.A.

1988-01-01

67

iSyTE: Integrated Systems Tool for Eye Gene Discovery  

PubMed Central

Purpose. To facilitate the identification of genes associated with cataract and other ocular defects, the authors developed and validated a computational tool termed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE uses a mouse embryonic lens gene expression data set as a bioinformatics filter to select candidate genes from human or mouse genomic regions implicated in disease and to prioritize them for further mutational and functional analyses. Methods. Microarray gene expression profiles were obtained for microdissected embryonic mouse lens at three key developmental time points in the transition from the embryonic day (E)10.5 stage of lens placode invagination to E12.5 lens primary fiber cell differentiation. Differentially regulated genes were identified by in silico comparison of lens gene expression profiles with those of whole embryo body (WB) lacking ocular tissue. Results. Gene set analysis demonstrated that this strategy effectively removes highly expressed but nonspecific housekeeping genes from lens tissue expression profiles, allowing identification of less highly expressed lens disease–associated genes. Among 24 previously mapped human genomic intervals containing genes associated with isolated congenital cataract, the mutant gene is ranked within the top two iSyTE-selected candidates in approximately 88% of cases. Finally, in situ hybridization confirmed lens expression of several novel iSyTE-identified genes. Conclusions. iSyTE is a publicly available Web resource that can be used to prioritize candidate genes within mapped genomic intervals associated with congenital cataract for further investigation. Extension of this approach to other ocular tissue components will facilitate eye disease gene discovery. PMID:22323457

Lachke, Salil A.; Ho, Joshua W. K.; Kryukov, Gregory V.; O'Connell, Daniel J.; Aboukhalil, Anton; Bulyk, Martha L.; Park, Peter J.

2012-01-01

68

Methods in comparative genomics: genome correspondence, gene identification and motif discovery  

E-print Network

1 Methods in comparative genomics: genome correspondence, gene identification and motif discovery@mit.edu, nickp@genome.wi.mit.edu, bwb@genome.wi.mit.edu, bab@mit.edu, lander@wi.mit.edu (1) MIT/Whitehead Institute Center for Genome Research, 320 Charles St., Cambridge MA 02139 (2) MIT Computer Science

Kellis, Manolis

69

False discovery rate paradigms for statistical analyses of microarray gene expression data  

Microsoft Academic Search

The microarray gene expression applications have greatly stimulated the statistical research on the massive multiple hypothesis tests problem. There is now a large body of literature in this area and basically five paradigms of massive multiple tests: control of the false discovery rate (FDR), estimation of FDR, significance threshold criteria, control of family-wise error rate (FWER) or generalized FWER (gFWER),

Cheng Cheng; Stan Pounds

70

This ICBG program links the discovery of drugs and genes for agriculture with biodiversity conservation.  

E-print Network

ABSTRACT This ICBG program links the discovery of drugs and genes for agriculture with biodiversity of plants, insects and fungi will provide samples with greater activity in biological assays than samples plants, animals, fungi and bacteria (Grifo et al., 1997), and over 60% of anti-cancer and anti

Coley, Phyllis

71

Peanut EST Project: Gene discovery and marker development  

Technology Transfer Automated Retrieval System (TEKTRAN)

Aflatoxin contamination caused by Aspergillus fungi is a great concern in peanut production worldwide. Pre-harvest Aspergillii infection and aflatoxin contamination are usually severe in peanuts that are grown under drought stressed conditions. Genomic research can provide new tools to study plant-m...

72

Genomic discovery of potent chromatin insulators for human gene therapy.  

PubMed

Insertional mutagenesis and genotoxicity, which usually manifest as hematopoietic malignancy, represent major barriers to realizing the promise of gene therapy. Although insulator sequences that block transcriptional enhancers could mitigate or eliminate these risks, so far no human insulators with high functional potency have been identified. Here we describe a genomic approach for the identification of compact sequence elements that function as insulators. These elements are highly occupied by the insulator protein CTCF, are DNase I hypersensitive and represent only a small minority of the CTCF recognition sequences in the human genome. We show that the elements identified acted as potent enhancer blockers and substantially decreased the risk of tumor formation in a cancer-prone animal model. The elements are small, can be efficiently accommodated by viral vectors and have no detrimental effects on viral titers. The insulators we describe here are expected to increase the safety of gene therapy for genetic diseases. PMID:25580597

Liu, Mingdong; Maurano, Matthew T; Wang, Hao; Qi, Heyuan; Song, Chao-Zhong; Navas, Patrick A; Emery, David W; Stamatoyannopoulos, John A; Stamatoyannopoulos, George

2015-02-01

73

deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data  

PubMed Central

Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers, such as lymphomas and sarcomas. RNA-Seq (whole transcriptome shotgun sequencing) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcriptomes. However, algorithmic methods for the discovery of gene fusions using RNA-Seq data remain underdeveloped. We have developed deFuse, a novel computational method for fusion discovery in tumor RNA-Seq data. Unlike existing methods that use only unique best-hit alignments and consider only fusion boundaries at the ends of known exons, deFuse considers all alignments and all possible locations for fusion boundaries. As a result, deFuse is able to identify fusion sequences with demonstrably better sensitivity than previous approaches. To increase the specificity of our approach, we curated a list of 60 true positive and 61 true negative fusion sequences (as confirmed by RT-PCR), and have trained an adaboost classifier on 11 novel features of the sequence data. The resulting classifier has an estimated value of 0.91 for the area under the ROC curve. We have used deFuse to discover gene fusions in 40 ovarian tumor samples, one ovarian cancer cell line, and three sarcoma samples. We report herein the first gene fusions discovered in ovarian cancer. We conclude that gene fusions are not infrequent events in ovarian cancer and that these events have the potential to substantially alter the expression patterns of the genes involved; gene fusions should therefore be considered in efforts to comprehensively characterize the mutational profiles of ovarian cancer transcriptomes. PMID:21625565

McPherson, Andrew; Hormozdiari, Fereydoun; Zayed, Abdalnasser; Giuliany, Ryan; Ha, Gavin; Sun, Mark G. F.; Griffith, Malachi; Heravi Moussavi, Alireza; Senz, Janine; Melnyk, Nataliya; Pacheco, Marina; Marra, Marco A.; Hirst, Martin; Nielsen, Torsten O.; Sahinalp, S. Cenk; Huntsman, David; Shah, Sohrab P.

2011-01-01

74

Cohesin gene mutations in tumorigenesis: from discovery to clinical significance  

PubMed Central

Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3, RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister chromatids following DNA replication until its cleavage during mitosis thereby enabling faithful segregation of sister chromatids into two daughter cells. Recent cancer genomics analyses have discovered a high frequency of somatic mutations in the genes encoding the core cohesin subunits as well as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1) in a select subset of human tumors including glioblastoma, Ewing sarcoma, urothelial carcinoma, acute myeloid leukemia, and acute megakaryoblastic leukemia. Herein we review these studies including discussion of the functional significance of cohesin inactivation in tumorigenesis and potential therapeutic mechanisms to selectively target cancers harboring cohesin mutations. [BMB Reports 2014; 47(6): 299-310] PMID:24856830

Solomon, David A.; Kim, Jung-Sik; Waldman, Todd

2014-01-01

75

The Alveolate Perkinsus marinus: Biological Insights from EST Gene Discovery  

PubMed Central

Background Perkinsus marinus, a protozoan parasite of the eastern oyster Crassostrea virginica, has devastated natural and farmed oyster populations along the Atlantic and Gulf coasts of the United States. It is classified as a member of the Perkinsozoa, a recently established phylum considered close to the ancestor of ciliates, dinoflagellates, and apicomplexans, and a key taxon for understanding unique adaptations (e.g. parasitism) within the Alveolata. Despite intense parasite pressure, no disease-resistant oysters have been identified and no effective therapies have been developed to date. Results To gain insight into the biological basis of the parasite's virulence and pathogenesis mechanisms, and to identify genes encoding potential targets for intervention, we generated >31,000 5' expressed sequence tags (ESTs) derived from four trophozoite libraries generated from two P. marinus strains. Trimming and clustering of the sequence tags yielded 7,863 unique sequences, some of which carry a spliced leader. Similarity searches revealed that 55% of these had hits in protein sequence databases, of which 1,729 had their best hit with proteins from the chromalveolates (E-value ? 1e-5). Some sequences are similar to those proven to be targets for effective intervention in other protozoan parasites, and include not only proteases, antioxidant enzymes, and heat shock proteins, but also those associated with relict plastids, such as acetyl-CoA carboxylase and methyl erythrithol phosphate pathway components, and those involved in glycan assembly, protein folding/secretion, and parasite-host interactions. Conclusions Our transcriptome analysis of P. marinus, the first for any member of the Perkinsozoa, contributes new insight into its biology and taxonomic position. It provides a very informative, albeit preliminary, glimpse into the expression of genes encoding functionally relevant proteins as potential targets for chemotherapy, and evidence for the presence of a relict plastid. Further, although P. marinus sequences display significant similarity to those from both apicomplexans and dinoflagellates, the presence of trans-spliced transcripts confirms the previously established affinities with the latter. The EST analysis reported herein, together with the recently completed sequence of the P. marinus genome and the development of transfection methodology, should result in improved intervention strategies against dermo disease. PMID:20374649

2010-01-01

76

Modern plant metabolomics: advanced natural product gene discoveries, improved technologies, and future prospects.  

PubMed

Covering: 2000 to 2014Plant metabolomics has matured and modern plant metabolomics has accelerated gene discoveries and the elucidation of a variety of plant natural product biosynthetic pathways. This review covers the approximate period of 2000 to 2014, and highlights specific examples of the discovery and characterization of novel genes and enzymes associated with the biosynthesis of natural products such as flavonoids, glucosinolates, terpenoids, and alkaloids. Additional examples of the integration of metabolomics with genome-based functional characterizations of plant natural products that are important to modern pharmaceutical technology are also reviewed. This article also provides a substantial review of recent technical advances in mass spectrometry imaging, nuclear magnetic resonance imaging, integrated LC-MS-SPE-NMR for metabolite identifications, and X-ray crystallography of microgram quantities for structural determinations. The review closes with a discussion on the future prospects of metabolomics related to crop species and herbal medicine. PMID:25342293

Sumner, Lloyd W; Lei, Zhentian; Nikolau, Basil J; Saito, Kazuki

2015-01-28

77

Cameo/gem Projects and Discovery Potentiality of the Future 2? Decay Experiments  

NASA Astrophysics Data System (ADS)

The demands to the future super-sensitivity 2? decay experiments (aiming to discover the neutrinoless 2? decay or to advance restrictions on the neutrino mass to m? ? 0.01 eV) are considered and requirements to their discovery potentiality are formulated. The most realistic next generation 2? projects are reviewed and conclusion is obtained that only several of them would completely satisfy these severe demands and requirements. Nevertheless, the most of the recent projects (CAMEO, CUORE, DCBA, EXO, GEM, GENIUS, MAJORANA, MOON) could certainly reach the level of sensitivity to the neutrino mass of m? ? 0.05 eV.

Zdesenko, Yu. G.; Danevich, F. A.; Tretyak, V. I.

2004-04-01

78

Discovery of New Candidate Genes Related to Brain Development Using Protein Interaction Information  

PubMed Central

Human brain development is a dramatic process composed of a series of complex and fine-tuned spatiotemporal gene expressions. A good comprehension of this process can assist us in developing the potential of our brain. However, we have only limited knowledge about the genes and gene functions that are involved in this biological process. Therefore, a substantial demand remains to discover new brain development-related genes and identify their biological functions. In this study, we aimed to discover new brain-development related genes by building a computational method. We referred to a series of computational methods used to discover new disease-related genes and developed a similar method. In this method, the shortest path algorithm was executed on a weighted graph that was constructed using protein-protein interactions. New candidate genes fell on at least one of the shortest paths connecting two known genes that are related to brain development. A randomization test was then adopted to filter positive discoveries. Of the final identified genes, several have been reported to be associated with brain development, indicating the effectiveness of the method, whereas several of the others may have potential roles in brain development. PMID:25635857

Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

2015-01-01

79

Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery  

PubMed Central

Autoimmune diseases are often intractable because their causes are unknown. Identifying which genes contribute to these diseases may allow us to understand the pathogenesis, but it is difficult to determine which genes contribute to disease. Recently, epigenetic information has been considered to activate/deactivate disease-related genes. Thus, it may also be useful to study epigenetic information that differs between healthy controls and patients with autoimmune disease. Among several types of epigenetic information, promoter methylation is believed to be one of the most important factors. Here, we propose that principal component analysis is useful to identify specific gene promoters that are differently methylated between the normal healthy controls and patients with autoimmune disease. Full Automatic Modeling System (FAMS) was used to predict the three-dimensional structures of selected proteins and successfully inferred relatively confident structures. Several possibilities of the application to the drug discovery based on obtained structures are discussed. PMID:23855671

Ishida, Shigeharu; Umeyama, Hideaki; Iwadate, Mitsuo; Y-h, Taguchi

2014-01-01

80

MORPHIN: a web tool for human disease research by projecting model organism biology onto a human integrated gene network  

PubMed Central

Despite recent advances in human genetics, model organisms are indispensable for human disease research. Most human disease pathways are evolutionally conserved among other species, where they may phenocopy the human condition or be associated with seemingly unrelated phenotypes. Much of the known gene-to-phenotype association information is distributed across diverse databases, growing rapidly due to new experimental techniques. Accessible bioinformatics tools will therefore facilitate translation of discoveries from model organisms into human disease biology. Here, we present a web-based discovery tool for human disease studies, MORPHIN (model organisms projected on a human integrated gene network), which prioritizes the most relevant human diseases for a given set of model organism genes, potentially highlighting new model systems for human diseases and providing context to model organism studies. Conceptually, MORPHIN investigates human diseases by an orthology-based projection of a set of model organism genes onto a genome-scale human gene network. MORPHIN then prioritizes human diseases by relevance to the projected model organism genes using two distinct methods: a conventional overlap-based gene set enrichment analysis and a network-based measure of closeness between the query and disease gene sets capable of detecting associations undetectable by the conventional overlap-based methods. MORPHIN is freely accessible at http://www.inetbio.org/morphin. PMID:24861622

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

2014-01-01

81

Arctic Research Mapping Application (ARMAP) Showcases discovery level metadata for US Funded Research Projects  

NASA Astrophysics Data System (ADS)

The Arctic Research Mapping Application (ARMAP) is a suite of online applications and data services that support Arctic science by providing project tracking information (who's doing what, when and where in the region) for United States Government funded projects. Development of an interagency standard for tracking discovery level metadata for projects has been achieved through collaboration with the Alaska Data Integration work group. The US National Science Foundation plus 17 other agencies and organizations have adopted the standard with several entities successfully implementing XML based REST webservices. With ARMAP's web mapping applications and data services (http://armap.org), users can search for research projects by location, year, funding program, keyword, investigator, and discipline, among other variables. Key information about each project is displayed within the application with links to web pages that provide additional information. The ARMAP 2D mapping application has been significantly enhanced to include support for multiple projections, improved base maps, additional reference data layers, and optimization for better performance. In 2013, ship tracks for US National Science Foundation supported vessel based surveys and health care facilities have been included in ARMAP. The additional functionality of this tool will increase awareness of projects funded by numerous entities in the Arctic, enhance coordination for logistics support, help identify geographic gaps in research efforts and potentially foster more collaboration amongst researchers working in the region. Additionally, ARMAP can be used to demonstrate the effects of the International Polar Year (IPY) on funding of different research disciplines by the U.S. Government.

Gaylord, A. G.; Kassin, A.; Cody, R. P.; Manley, W. F.; Dover, M.; Score, R.; Garcia-Lavigne3, D.; Tweedie, C. E.

2013-12-01

82

Discovery of nucleotide polymorphisms in the Musa gene pool by Ecotilling.  

PubMed

Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method for the discovery and characterization of nucleotide polymorphisms in diploid and polyploid accessions of Musa. We discovered over 800 novel alleles in 80 accessions. Sequencing and band evaluation shows Ecotilling to be a robust and accurate platform for the discovery of polymorphisms in homologous and homeologous gene targets. In the process of validating the method, we identified two single nucleotide polymorphisms that may be deleterious for the function of a gene putatively important for phototropism. Evaluation of heterozygous polymorphism and haplotype blocks revealed a high level of nucleotide diversity in Musa accessions. We further applied a strategy for the simultaneous discovery of heterozygous and homozygous polymorphisms in diploid accessions to rapidly evaluate nucleotide diversity in accessions of the same genome type. This strategy can be used to develop hypotheses for inheritance patterns of nucleotide polymorphisms within and between genome types. We conclude that Ecotilling is suitable for diversity studies in Musa, that it can be considered for functional genomics studies and as tool in selecting germplasm for traditional and mutation breeding approaches. PMID:20589365

Till, Bradley J; Jankowicz-Cieslak, Joanna; Sági, László; Huynh, Owen A; Utsushi, Hiroe; Swennen, Rony; Terauchi, Ryohei; Mba, Chikelu

2010-11-01

83

Gene Expression, Single Nucleotide Variant and Fusion Transcript Discovery in Archival Material from Breast Tumors  

PubMed Central

Advantages of RNA-Seq over array based platforms are quantitative gene expression and discovery of expressed single nucleotide variants (eSNVs) and fusion transcripts from a single platform, but the sensitivity for each of these characteristics is unknown. We measured gene expression in a set of manually degraded RNAs, nine pairs of matched fresh-frozen, and FFPE RNA isolated from breast tumor with the hybridization based, NanoString nCounter (226 gene panel) and with whole transcriptome RNA-Seq using RiboZeroGold ScriptSeq V2 library preparation kits. We performed correlation analyses of gene expression between samples and across platforms. We then specifically assessed whole transcriptome expression of lincRNA and discovery of eSNVs and fusion transcripts in the FFPE RNA-Seq data. For gene expression in the manually degraded samples, we observed Pearson correlations of >0.94 and >0.80 with NanoString and ScriptSeq protocols, respectively. Gene expression data for matched fresh-frozen and FFPE samples yielded mean Pearson correlations of 0.874 and 0.783 for NanoString (226 genes) and ScriptSeq whole transcriptome protocols respectively, p<2x10-16. Specifically for lincRNAs, we observed superb Pearson correlation (0.988) between matched fresh-frozen and FFPE pairs. FFPE samples across NanoString and RNA-Seq platforms gave a mean Pearson correlation of 0.838. In FFPE libraries, we detected 53.4% of high confidence SNVs and 24% of high confidence fusion transcripts. Sensitivity of fusion transcript detection was not overcome by an increase in depth of sequencing up to 3-fold (increase from ~56 to ~159 million reads). Both NanoString and ScriptSeq RNA-Seq technologies yield reliable gene expression data for degraded and FFPE material. The high degree of correlation between NanoString and RNA-Seq platforms suggests discovery based whole transcriptome studies from FFPE material will produce reliable expression data. The RiboZeroGold ScriptSeq protocol performed particularly well for lincRNA expression from FFPE libraries, but detection of eSNV and fusion transcripts was less sensitive. PMID:24278466

Norton, Nadine; Sun, Zhifu; Asmann, Yan W.; Serie, Daniel J.; Necela, Brian M.; Bhagwate, Aditya; Jen, Jin; Eckloff, Bruce W.; Kalari, Krishna R.; Thompson, Kevin J.; Carr, Jennifer M.; Kachergus, Jennifer M.; Geiger, Xochiquetzal J.; Perez, Edith A.; Thompson, E. Aubrey

2013-01-01

84

Gene expression rule discovery and multi-objective ROC analysis using a neural-genetic hybrid.  

PubMed

Microarray data allows an unprecedented view of the biochemical mechanisms contained within a cell although deriving useful information from the data is still proving to be a difficult task. In this paper, a novel method based on a multi-objective genetic algorithm is investigated that evolves a near-optimal trade-off between Artificial Neural Network (ANN) classifier accuracy (sensitivity and specificity) and size (number of genes). This hybrid method is shown to work on four well-established gene expression data sets taken from the literature. The results provide evidence for the rule discovery ability of the hybrid method and indicate that the approach can return biologically intelligible as well as plausible results and requires no pre-filtering or pre-selection of genes. PMID:23798223

Keedwell, Ed; Narayanan, Ajit

2013-01-01

85

Transcriptome sequencing of black grouse (Tetrao tetrix) for immune gene discovery and microsatellite development.  

PubMed

The black grouse (Tetrao tetrix) is a galliform bird species that is important for both ecological studies and conservation genetics. Here, we report the sequencing of the spleen transcriptome of black grouse using 454 GS FLX Titanium sequencing. We performed a large-scale gene discovery analysis with a focus on genes that might be related to fitness in this species and also identified a large set of microsatellites. In total, we obtained 182 179 quality-filtered sequencing reads that we assembled into 9035 contigs. Using these contigs and 15 794 length-filtered (greater than 200 bp) singletons, we identified 7762 transcripts that appear to be homologues of chicken genes. A specific BLAST search with an emphasis on immune genes found 308 homologous chicken genes that have immune function, including ten major histocompatibility complex-related genes located on chicken chromosome 16. We also identified 1300 expressed sequence tag microsatellites and were able to design suitable flanking primers for 526 of these. A preliminary test of the polymorphism of the microsatellites found 10 polymorphic microsatellites of the 102 tested. Genomic resources generated in this study should greatly benefit future ecological, evolutionary and conservation genetic studies on this species. PMID:22724064

Wang, Biao; Ekblom, Robert; Castoe, Todd A; Jones, Eleanor P; Kozma, Radoslav; Bongcam-Rudloff, Erik; Pollock, David D; Höglund, Jacob

2012-04-01

86

Transcriptome sequencing of black grouse (Tetrao tetrix) for immune gene discovery and microsatellite development  

PubMed Central

The black grouse (Tetrao tetrix) is a galliform bird species that is important for both ecological studies and conservation genetics. Here, we report the sequencing of the spleen transcriptome of black grouse using 454 GS FLX Titanium sequencing. We performed a large-scale gene discovery analysis with a focus on genes that might be related to fitness in this species and also identified a large set of microsatellites. In total, we obtained 182 179 quality-filtered sequencing reads that we assembled into 9035 contigs. Using these contigs and 15 794 length-filtered (greater than 200 bp) singletons, we identified 7762 transcripts that appear to be homologues of chicken genes. A specific BLAST search with an emphasis on immune genes found 308 homologous chicken genes that have immune function, including ten major histocompatibility complex-related genes located on chicken chromosome 16. We also identified 1300 expressed sequence tag microsatellites and were able to design suitable flanking primers for 526 of these. A preliminary test of the polymorphism of the microsatellites found 10 polymorphic microsatellites of the 102 tested. Genomic resources generated in this study should greatly benefit future ecological, evolutionary and conservation genetic studies on this species. PMID:22724064

Wang, Biao; Ekblom, Robert; Castoe, Todd A.; Jones, Eleanor P.; Kozma, Radoslav; Bongcam-Rudloff, Erik; Pollock, David D.; Höglund, Jacob

2012-01-01

87

An improved procedure for gene selection from microarray experiments using false discovery rate criterion  

PubMed Central

Background A large number of genes usually show differential expressions in a microarray experiment with two types of tissues, and the p-values of a proper statistical test are often used to quantify the significance of these differences. The genes with small p-values are then picked as the genes responsible for the differences in the tissue RNA expressions. One key question is what should be the threshold to consider the p-values small. There is always a trade off between this threshold and the rate of false claims. Recent statistical literature shows that the false discovery rate (FDR) criterion is a powerful and reasonable criterion to pick those genes with differential expression. Moreover, the power of detection can be increased by knowing the number of non-differential expression genes. While this number is unknown in practice, there are methods to estimate it from data. The purpose of this paper is to present a new method of estimating this number and use it for the FDR procedure construction. Results A combination of test functions is used to estimate the number of differentially expressed genes. Simulation study shows that the proposed method has a higher power to detect these genes than other existing methods, while still keeping the FDR under control. The improvement can be substantial if the proportion of true differentially expressed genes is large. This procedure has also been tested with good results using a real dataset. Conclusion For a given expected FDR, the method proposed in this paper has better power to pick genes that show differentiation in their expression than two other well known methods. PMID:16405735

Yang, James J; Yang, Mark CK

2006-01-01

88

Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis  

PubMed Central

Background The antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin B0, a lipohexapeptide produced by the fungus Glarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. The nonribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) gene cluster responsible for pneumocandin biosynthesis from G. lozoyensis has not been elucidated to date. In this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of the G. lozoyensis wild-type strain ATCC 20868. Results The pneumocandin biosynthetic gene cluster contains a NRPS (GLNRPS4) and a PKS (GLPKS4) arranged in tandem, two cytochrome P450 monooxygenases, seven other modifying enzymes, and genes for L-homotyrosine biosynthesis, a component of the peptide core. Thus, the pneumocandin biosynthetic gene cluster is significantly more autonomous and organized than that of the recently characterized echinocandin B gene cluster. Disruption mutants of GLNRPS4 and GLPKS4 no longer produced the pneumocandins (A0 and B0), and the ?glnrps4 and ?glpks4 mutants lost antifungal activity against the human pathogenic fungus Candida albicans. In addition to pneumocandins, the G. lozoyensis genome encodes a rich repertoire of natural product-encoding genes including 24 PKSs, six NRPSs, five PKS-NRPS hybrids, two dimethylallyl tryptophan synthases, and 14 terpene synthases. Conclusions Characterization of the gene cluster provides a blueprint for engineering new pneumocandin derivatives with improved pharmacological properties. Whole genome estimation of the secondary metabolite-encoding genes from G. lozoyensis provides yet another example of the huge potential for drug discovery from natural products from the fungal kingdom. PMID:23688303

2013-01-01

89

Long Serial Analysis of Gene Expression for Gene Discovery and Transcriptome Profiling in the Widespread Marine Coccolithophore Emiliania huxleyi†  

PubMed Central

The abundant and widespread coccolithophore Emiliania huxleyi plays an important role in mediating CO2 exchange between the ocean and the atmosphere through its impact on marine photosynthesis and calcification. Here, we use long serial analysis of gene expression (SAGE) to identify E. huxleyi genes responsive to nitrogen (N) or phosphorus (P) starvation. Long SAGE is an elegant approach for examining quantitative and comprehensive gene expression patterns without a priori knowledge of gene sequences via the detection of 21-bp nucleotide sequence tags. E. huxleyi appears to have a robust transcriptional-level response to macronutrient deficiency, with 42 tags uniquely present or up-regulated twofold or greater in the N-starved library and 128 tags uniquely present or up-regulated twofold or greater in the P-starved library. The expression patterns of several tags were validated with reverse transcriptase PCR. Roughly 48% of these differentially expressed tags could be mapped to publicly available genomic or expressed sequence tag (EST) sequence data. For example, in the P-starved library a number of the tags mapped to genes with a role in P scavenging, including a putative phosphate-repressible permease and a putative polyphosphate synthetase. In short, the long SAGE analyses have (i) identified many new differentially regulated gene sequences, (ii) assigned regulation data to EST sequences with no database homology and unknown function, and (iii) highlighted previously uncharacterized aspects of E. huxleyi N and P physiology. To this end, our long SAGE libraries provide a new public resource for gene discovery and transcriptional analysis in this biogeochemically important marine organism. PMID:16391051

Dyhrman, Sonya T.; Haley, Sheean T.; Birkeland, Shanda R.; Wurch, Louie L.; Cipriano, Michael J.; McArthur, Andrew G.

2006-01-01

90

An In Vivo Functional Analysis System for Renal Gene Discovery in Drosophila Pericardial Nephrocytes  

PubMed Central

The difficulty in accessing mammalian nephrons in vivo hinders the study of podocyte biology. The Drosophila nephrocyte shares remarkable similarities to the glomerular podocyte, but the lack of a functional readout for nephrocytes makes it challenging to study this model of the podocyte, which could potentially harness the power of Drosophila genetics. Here, we present a functional analysis of nephrocytes and establish an in vivo system to screen for renal genes. We found that nephrocytes efficiently take up secreted fluorescent protein, and therefore, we generated a transgenic line carrying secreted fluorescent protein and combined it with a nephrocyte-specific driver for targeted gene knockdown, allowing the identification of genes required for nephrocyte function. To validate this system, we examined the effects of knocking down sns and duf, the Drosophila homologs of nephrin and Neph1, respectively, in pericardial nephrocytes. Knockdown of sns or duf completely abolished the accumulation of the fluorescent protein in pericardial nephrocytes. Examining the ultrastructure revealed that the formation of the nephrocyte diaphragm and lacunar structure, which is essential for protein uptake, requires sns. Our preliminary genetic screen also identified Mec2, which encodes the homolog of mammalian Podocin. Taken together, these data suggest that the Drosophila pericardial nephrocyte is a useful in vivo model to help identify genes involved in podocyte biology and facilitate the discovery of renal disease genes. PMID:23291470

Zhang, Fujian; Zhao, Ying

2013-01-01

91

Discovery of Functional Gene Variants Associated With Human Longevity: Opportunities and Challenges  

PubMed Central

Age is a major risk factor for many human diseases. Extremely long-lived individuals, such as centenarians, have managed to ward off age-related diseases and serve as human models to search for the genetic factors that influence longevity. The discovery of evolutionarily conserved pathways with major impact on life span in animal models has provided tantalizing opportunities to test the relevance of these pathways for human longevity. Here we specifically focus on the insulin/insulin-like growth factor-1 signaling as a prime candidate pathway. Coupled with the rapid advances in ultra high-throughput sequencing technologies, it is now feasible to comprehensively analyze all possible sequence variants in candidate genes segregating with a longevity phenotype and to investigate the functional consequences of the associated variants. A better understanding of the functional genes that affect healthy longevity in humans may lead to a rational basis for intervention strategies that can delay or prevent age-related diseases. PMID:22156437

Tazearslan, Cagdas; Cho, Miook

2012-01-01

92

Exploiting Pre-rRNA Processing in Diamond Blackfan Anemia Gene Discovery and Diagnosis  

PubMed Central

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre-rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre-rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre-60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene. PMID:25042156

Farrar, Jason E.; Quarello, Paola; Fisher, Ross; O’Brien, Kelly A.; Aspesi, Anna; Parrella, Sara; Henson, Adrianna L.; Seidel, Nancy E.; Atsidaftos, Eva; Prakash, Supraja; Bari, Shahla; Garelli, Emanuela; Arceci, Robert J.; Dianzani, Irma; Ramenghi, Ugo; Vlachos, Adrianna; Lipton, Jeffrey M.; Bodine, David M.; Ellis, Steven R.

2014-01-01

93

A Relational Database for the Discovery of Genes Encoding Amino Acid Biosynthetic Enzymes in Pathogenic Fungi  

PubMed Central

Fungal phytopathogens continue to cause major economic impact, either directly, through crop losses, or due to the costs of fungicide application. Attempts to understand these organisms are hampered by a lack of fungal genome sequence data. A need exists, however, to develop specific bioinformatics tools to collate and analyse the sequence data that currently is available. A web-accessible gene discovery database (http://cogeme.ex.ac.uk/biosynthesis.html) was developed as a demonstration tool for the analysis of metabolic and signal transduction pathways in pathogenic fungi using incomplete gene inventories. Using Bayesian probability to analyse the currently available gene information from pathogenic fungi, we provide evidence that the obligate pathogen Blumeria graminis possesses all amino acid biosynthetic pathways found in free-living fungi, such as Saccharomyces cerevisiae. Phylogenetic analysis was also used to deduce a gene history of succinate-semialdehyde dehydrogenase, an enzyme in the glutamate and lysine biosynthesis pathways. The database provides a tool and methodology to researchers to direct experimentation towards predicting pathway conservation in pathogenic microorganisms. PMID:18629094

Giles, Peter F.; Soanes, Darren M.

2003-01-01

94

Riboswitches: discovery of drugs that target bacterial gene-regulatory RNAs  

PubMed Central

Conspectus Riboswitches, which were discovered in the first years of the XXI century, are gene-regulatory mRNA domains that respond to the intracellular concentration of a variety of metabolites and second messengers. They control essential genes in many pathogenic bacteria, and represent a new class of biomolecular target for the development of antibiotics and chemical-biological tools. Five mechanisms of gene regulation are known for riboswitches. Most bacterial riboswitches modulate transcription termination or translation initiation in response to ligand binding. All known examples of eukaryotic riboswitches and some bacterial riboswitches control gene expression by alternative splicing. The glmS riboswitch, widespread in Gram-positive bacteria, is a catalytic RNA activated by ligand binding. Its self-cleavage destabilizes the mRNA of which it is part. Finally, one example of trans-acting riboswitch is known. Three-dimensional (3D) structures have been determined of representatives of thirteen structurally distinct riboswitch classes, providing atomic-level insight into their mechanisms of ligand recognition. While cellular and viral RNAs in general have attracted interest as potential drug targets, riboswitches show special promise due to the diversity and sophistication of small molecule recognition strategies on display in their ligand binding pockets. Moreover, uniquely among known structured RNA domains, riboswitches evolved to recognize small molecule ligands. Structural and biochemical advances in the study of riboswitches provide an impetus for the development of methods for the discovery of novel riboswitch activators and inhibitors. Recent rational drug design efforts focused on select riboswitch classes have yielded a small number of candidate antibiotic compounds, including one active in a mouse model of Staphylococcus aureus infection. The development of high-throughput methods suitable for riboswitch-specific drug discovery is ongoing. A fragment-based screening approach employing equilibrium dialysis that may be generically useful has had early success. Riboswitch-mediated gene regulation is widely employed by bacteria; however, only the thiamine pyrophosphate-responsive riboswitch has thus far been found in eukaryotes. Thus, riboswitches are particularly attractive as targets for antibacterials. Indeed, antimicrobials with previously unknown mechanisms have been found to function by binding riboswitches and leading to aberrant gene expression. PMID:21615107

Deigan, Katherine E.; Ferré-D’Amaré, Adrian R.

2011-01-01

95

141?Gene Discovery and Data Sharing in Genome Wide Association Analyses: lessons form AIDS genetic restriction genes  

PubMed Central

As genome wide association studies plus whole genome sequence analyses for complex human disease determinants are expanding, it seems useful to develop strategies to facilitate large data sharing, rapid replication and validation of provocative statistical associations that straddle the threshold for genome wide significance. At this conference, we shall announce GWATCH, (Genome Wide Association Tracks Chromosome Highway) a web based data release platform that can freely display and inspect unabridged genome tracked association data without compromising privacy or Informed Consent constrictions, allowing for rapid discovery and replication opportunities. We illustrate the utility with HIV-AIDS resistance genes screened in combined large multicenter cohort studies GWAS (MACS, HGDS, MHGS, ALLIVE, LSOCA HOMER) developed and studied over the last decades.

O'Brien, Stephen J; Svitin, Anton; Malov, Sergey; Cherkazov, Nikolay; Dobrynin, Pavel; Geerts, Paul; Troyer, Jennifer; Hendrickson-Lambert, Sher; Sezgin, Efe; Hutcheson, Holli

2014-01-01

96

Resequencing and Comparative Genomics of Stagonospora nodorum: Sectional Gene Absence and Effector Discovery  

PubMed Central

Stagonospora nodorum is an important wheat (Triticum aestivum) pathogen in many parts of the world, causing major yield losses. It was the first species in the large fungal Dothideomycete class to be genome sequenced. The reference genome sequence (SN15) has been instrumental in the discovery of genes encoding necrotrophic effectors that induce disease symptoms in specific host genotypes. Here we present the genome sequence of two further S. nodorum strains (Sn4 and Sn79) that differ in their effector repertoire from the reference. Sn79 is avirulent on wheat and produces no apparent effectors when infiltrated onto many cultivars and mapping population parents. Sn4 is pathogenic on wheat and has virulences not found in SN15. The new strains, sequenced with short-read Illumina chemistry, are compared with SN15 by a combination of mapping and de novo assembly approaches. Each of the genomes contains a large number of strain-specific genes, many of which have no meaningful similarity to any known gene. Large contiguous sections of the reference genome are absent in the two newly sequenced strains. We refer to these differences as “sectional gene absences.” The presence of genes in pathogenic strains and absence in Sn79 is added to computationally predicted properties of known proteins to produce a list of likely effector candidates. Transposon insertion was observed in the mitochondrial genomes of virulent strains where the avirulent strain retained the likely ancestral sequence. The study suggests that short-read enabled comparative genomics is an effective way to both identify new S. nodorum effector candidates and to illuminate evolutionary processes in this species. PMID:23589517

Syme, Robert Andrew; Hane, James K.; Friesen, Timothy L.; Oliver, Richard P.

2013-01-01

97

Discovery of MicroRNA169 gene copies in genomes of flowering plants through positional information.  

PubMed

Expansion and contraction of microRNA (miRNA) families can be studied in sequenced plant genomes through sequence alignments. Here, we focused on miR169 in sorghum because of its implications in drought tolerance and stem-sugar content. We were able to discover many miR169 copies that have escaped standard genome annotation methods. A new miR169 cluster was found on sorghum chromosome 1. This cluster is composed of the previously annotated sbi-MIR169o together with two newly found MIR169 copies, named sbi-MIR169t and sbi-MIR169u. We also found that a miR169 cluster on sorghum chr7 consisting of sbi-MIR169l, sbi-MIR169m, and sbi-MIR169n is contained within a chromosomal inversion of at least 500 kb that occurred in sorghum relative to Brachypodium, rice, foxtail millet, and maize. Surprisingly, synteny of chromosomal segments containing MIR169 copies with linked bHLH and CONSTANS-LIKE genes extended from Brachypodium to dictotyledonous species such as grapevine, soybean, and cassava, indicating a strong conservation of linkages of certain flowering and/or plant height genes and microRNAs, which may explain linkage drag of drought and flowering traits and would have consequences for breeding new varieties. Furthermore, alignment of rice and sorghum orthologous regions revealed the presence of two additional miR169 gene copies (miR169r and miR169s) on sorghum chr7 that formed an antisense miRNA gene pair. Both copies are expressed and target different set of genes. Synteny-based analysis of microRNAs among different plant species should lead to the discovery of new microRNAs in general and contribute to our understanding of their evolution. PMID:23348041

Calviño, Martín; Messing, Joachim

2013-01-01

98

European approach to the human gene project  

SciTech Connect

In the history of gene mapping, which extends through most of the present century, Europe has played an important role. This has continued during the evolution of the 10 International Human Gene Mapping Workshops that have been held in seven different countries since 1973. Nationally coordinated programs have been a recent development, and several European countries, including the United Kingdom and Italy, have followed the lead of the United States in investing substantial sums of money in research on the human genome. In addition, the European Community has launched a multinational program of research on Human Genome Analysis to complement the various national initiatives. The particular approach in Europe has been to support those in the field by establishing resource centers for distributing biomaterials and accessing databases, by assisting in the training of scientists, and by funding programs of research directed at present needs in both physical and genetic mapping.

Ferguson-Smith, M.A. (Cambridge Univ. (England))

1991-01-01

99

False discovery rate paradigms for statistical analyses of microarray gene expression data  

PubMed Central

The microarray gene expression applications have greatly stimulated the statistical research on the massive multiple hypothesis tests problem. There is now a large body of literature in this area and basically five paradigms of massive multiple tests: control of the false discovery rate (FDR), estimation of FDR, significance threshold criteria, control of family-wise error rate (FWER) or generalized FWER (gFWER), and empirical Bayes approaches. This paper contains a technical survey of the developments of the FDR-related paradigms, emphasizing precise formulation of the problem, concepts of error measurements, and considerations in applications. The goal is not to do an exhaustive literature survey, but rather to review the current state of the field. PMID:17597936

Cheng, Cheng; Pounds, Stan

2007-01-01

100

False discovery rate paradigms for statistical analyses of microarray gene expression data.  

PubMed

The microarray gene expression applications have greatly stimulated the statistical research on the massive multiple hypothesis tests problem. There is now a large body of literature in this area and basically five paradigms of massive multiple tests: control of the false discovery rate (FDR), estimation of FDR, significance threshold criteria, control of family-wise error rate (FWER) or generalized FWER (gFWER), and empirical Bayes approaches. This paper contains a technical survey of the developments of the FDR-related paradigms, emphasizing precise formulation of the problem, concepts of error measurements, and considerations in applications. The goal is not to do an exhaustive literature survey, but rather to review the current state of the field. PMID:17597936

Cheng, Cheng; Pounds, Stan

2007-01-01

101

Machine learning approaches for the discovery of gene-gene interactions in disease data.  

PubMed

Because of the complexity of gene-phenotype relationships machine learning approaches have considerable appeal as a strategy for modelling interactions. A number of such methods have been developed and applied in recent years with some modest success. Progress is hampered by the challenges presented by the complexity of the disease genetic data, including phenotypic and genetic heterogeneity, polygenic forms of inheritance and variable penetrance, combined with the analytical and computational issues arising from the enormous number of potential interactions. We review here recent and current approaches focusing, wherever possible, on applications to real data (particularly in the context of genome-wide association studies) and looking ahead to the further challenges posed by next generation sequencing data. PMID:22611119

Upstill-Goddard, Rosanna; Eccles, Diana; Fliege, Joerg; Collins, Andrew

2013-03-01

102

Beegle: A generic tool for disease-gene discovery based on literature mining and genomic data fusion  

E-print Network

-gene discovery is a key process with multiple applications in functional genomics and personalized medicine mining the biomedical literature and (2) it integrates data from multiple genomic sources to generate genetic disease or disorder is an important problem [1]. It has a variety of applications that could

103

Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data  

Microsoft Academic Search

Abstract. In this paper we present a new methodology,of class discovery and clustering validation tailored to the task of analyzing gene expression data. The method can best be thought of as an analysis approach, to guide and assist in the use of any of a wide range of available clustering algorithms. We call the new methodology consensus clustering, and in

Stefano Monti; Pablo Tamayo; Jill P. Mesirov; Todd R. Golub

2003-01-01

104

Heuristic Bayesian segmentation for discovery of coexpressed genes within genomic regions.  

PubMed

Segmentation aims to separate homogeneous areas from the sequential data, and plays a central role in data mining. It has applications ranging from finance to molecular biology, where bioinformatics tasks such as genome data analysis are active application fields. In this paper, we present a novel application of segmentation in locating genomic regions with coexpressed genes. We aim at automated discovery of such regions without requirement for user-given parameters. In order to perform the segmentation within a reasonable time, we use heuristics. Most of the heuristic segmentation algorithms require some decision on the number of segments. This is usually accomplished by using asymptotic model selection methods like the Bayesian information criterion. Such methods are based on some simplification, which can limit their usage. In this paper, we propose a Bayesian model selection to choose the most proper result from heuristic segmentation. Our Bayesian model presents a simple prior for the segmentation solutions with various segment numbers and a modified Dirichlet prior for modeling multinomial data. We show with various artificial data sets in our benchmark system that our model selection criterion has the best overall performance. The application of our method in yeast cell-cycle gene expression data reveals potential active and passive regions of the genome. PMID:20150667

Pehkonen, Petri; Wong, Garry; Törönen, Petri

2010-01-01

105

De Novo Assembly of Chickpea Transcriptome Using Short Reads for Gene Discovery and Marker Identification  

PubMed Central

Chickpea ranks third among the food legume crops production in the world. However, the genomic resources available for chickpea are still very limited. In the present study, the transcriptome of chickpea was sequenced with short reads on Illumina Genome Analyzer platform. We have assessed the effect of sequence quality, various assembly parameters and assembly programs on the final assembly output. We assembled ?107million high-quality trimmed reads using Velvet followed by Oases with optimal parameters into a non-redundant set of 53 409 transcripts (?100 bp), representing about 28 Mb of unique transcriptome sequence. The average length of transcripts was 523 bp and N50 length of 900 bp with coverage of 25.7 rpkm (reads per kilobase per million). At the protein level, a total of 45 636 (85.5%) chickpea transcripts showed significant similarity with unigenes/predicted proteins from other legumes or sequenced plant genomes. Functional categorization revealed the conservation of genes involved in various biological processes in chickpea. In addition, we identified simple sequence repeat motifs in transcripts. The chickpea transcripts set generated here provides a resource for gene discovery and development of functional molecular markers. In addition, the strategy for de novo assembly of transcriptome data presented here will be helpful in other similar transcriptome studies. PMID:21217129

Garg, Rohini; Patel, Ravi K.; Tyagi, Akhilesh K.; Jain, Mukesh

2011-01-01

106

The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes.  

PubMed Central

A fundamental goal of genetics and functional genomics is to identify and mutate every gene in model organisms such as Drosophila melanogaster. The Berkeley Drosophila Genome Project (BDGP) gene disruption project generates single P-element insertion strains that each mutate unique genomic open reading frames. Such strains strongly facilitate further genetic and molecular studies of the disrupted loci, but it has remained unclear if P elements can be used to mutate all Drosophila genes. We now report that the primary collection has grown to contain 1045 strains that disrupt more than 25% of the estimated 3600 Drosophila genes that are essential for adult viability. Of these P insertions, 67% have been verified by genetic tests to cause the associated recessive mutant phenotypes, and the validity of most of the remaining lines is predicted on statistical grounds. Sequences flanking >920 insertions have been determined to exactly position them in the genome and to identify 376 potentially affected transcripts from collections of EST sequences. Strains in the BDGP collection are available from the Bloomington Stock Center and have already assisted the research community in characterizing >250 Drosophila genes. The likely identity of 131 additional genes in the collection is reported here. Our results show that Drosophila genes have a wide range of sensitivity to inactivation by P elements, and provide a rationale for greatly expanding the BDGP primary collection based entirely on insertion site sequencing. We predict that this approach can bring >85% of all Drosophila open reading frames under experimental control. PMID:10471706

Spradling, A C; Stern, D; Beaton, A; Rhem, E J; Laverty, T; Mozden, N; Misra, S; Rubin, G M

1999-01-01

107

A combination of gene expression ranking and co-expression network analysis increases discovery rate in large-scale mutant screens for novel Arabidopsis thaliana abiotic stress genes.  

PubMed

As challenges to food security increase, the demand for lead genes for improving crop production is growing. However, genetic screens of plant mutants typically yield very low frequencies of desired phenotypes. Here, we present a powerful computational approach for selecting candidate genes for screening insertion mutants. We combined ranking of Arabidopsis thaliana regulatory genes according to their expression in response to multiple abiotic stresses (Multiple Stress [MST] score), with stress-responsive RNA co-expression network analysis to select candidate multiple stress regulatory (MSTR) genes. Screening of 62 T-DNA insertion mutants defective in candidate MSTR genes, for abiotic stress germination phenotypes yielded a remarkable hit rate of up to 62%; this gene discovery rate is 48-fold greater than that of other large-scale insertional mutant screens. Moreover, the MST score of these genes could be used to prioritize them for screening. To evaluate the contribution of the co-expression analysis, we screened 64 additional mutant lines of MST-scored genes that did not appear in the RNA co-expression network. The screening of these MST-scored genes yielded a gene discovery rate of 36%, which is much higher than that of classic mutant screens but not as high as when picking candidate genes from the co-expression network. The MSTR co-expression network that we created, AraSTressRegNet is publicly available at http://netbio.bgu.ac.il/arnet. This systems biology-based screening approach combining gene ranking and network analysis could be generally applicable to enhancing identification of genes regulating additional processes in plants and other organisms provided that suitable transcriptome data are available. PMID:25370817

Ransbotyn, Vanessa; Yeger-Lotem, Esti; Basha, Omer; Acuna, Tania; Verduyn, Christoph; Gordon, Michal; Chalifa-Caspi, Vered; Hannah, Matthew A; Barak, Simon

2014-11-01

108

Target discovery  

Microsoft Academic Search

Target discovery, which involves the identification and early validation of disease-modifying targets, is an essential first step in the drug discovery pipeline. Indeed, the drive to determine protein function has been stimulated, both in industry and academia, by the completion of the human genome project. In this article, we critically examine the strategies and methodologies used for both the identification

Mark A. Lindsay

2003-01-01

109

Functional Linkage between Genes That Regulate Osmotic Stress Responses and Multidrug Resistance Transporters: Challenges and Opportunities for Antibiotic Discovery  

PubMed Central

All cells need to protect themselves against the osmotic challenges of their environment by maintaining low permeability to ions across their cell membranes. This is a basic principle of cellular function, which is reflected in the interactions among ion transport and drug efflux genes that have arisen during cellular evolution. Thus, upon exposure to pore-forming antibiotics such as amphotericin B (AmB) or daptomycin (Dap), sensitive cells overexpress common resistance genes to protect themselves from added osmotic challenges. These genes share pathway interactions with the various types of multidrug resistance (MDR) transporter genes, which both preserve the native lipid membrane composition and at the same time eliminate disruptive hydrophobic molecules that partition excessively within the lipid bilayer. An increased understanding of the relationships between the genes (and their products) that regulate osmotic stress responses and MDR transporters will help to identify novel strategies and targets to overcome the current stalemate in drug discovery. PMID:24295980

2014-01-01

110

The BDGP gene disruption project: Single transposon insertions associated with 40 percent of Drosophila genes  

SciTech Connect

The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in more than 30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6,300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7,140 lines. It now includes individual lines predicted to disrupt 5,362 of the 13,666 currently annotated Drosophila genes (39 percent). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene mis-expression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool.

Bellen, Hugo J.; Levis, Robert W.; Liao, Guochun; He, Yuchun; Carlson, Joseph W.; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P. Robin; Schulze, Karen L.; Rubin, Gerald M.; Hoskins, Roger A.; Spradling, Allan C.

2004-01-13

111

Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation  

PubMed Central

Genes co-expressed may be under similar promoter-based and/or position-based regulation. Although data on expression, position and function of human genes are available, their true integration still represents a challenge for computational biology, hampering the identification of regulatory mechanisms. We carried out an integrative analysis of genomic position, functional annotation and promoters of genes expressed in myeloid cells. Promoter analysis was conducted by a novel multi-step method for discovering putative regulatory elements, i.e. over-represented motifs, in a selected set of promoters, as compared with a background model. The combination of transcriptional, structural and functional data allowed the identification of sets of promoters pertaining to groups of genes co-expressed and co-localized in regions of the human genome. The application of motif discovery to 26 groups of genes co-expressed in myeloid cells differentiation and co-localized in the genome showed that there are more over-represented motifs in promoters of co-expressed and co-localized genes than in promoters of simply co-expressed genes (CEG). Motifs, which are similar to the binding sequences of known transcription factors, non-uniformly distributed along promoter sequences and/or occurring in highly co-expressed subset of genes were identified. Co-expressed and co-localized gene sets were grouped in two co-expressed genomic meta-regions, putatively representing functional domains of a high-level expression regulation. PMID:19059999

Coppe, Alessandro; Ferrari, Francesco; Bisognin, Andrea; Danieli, Gian Antonio; Ferrari, Sergio; Bicciato, Silvio; Bortoluzzi, Stefania

2009-01-01

112

Discovery of CTCF-Sensitive Cis-Spliced Fusion RNAs between Adjacent Genes in Human Prostate Cells.  

PubMed

Genes or their encoded products are not expected to mingle with each other unless in some disease situations. In cancer, a frequent mechanism that can produce gene fusions is chromosomal rearrangement. However, recent discoveries of RNA trans-splicing and cis-splicing between adjacent genes (cis-SAGe) support for other mechanisms in generating fusion RNAs. In our transcriptome analyses of 28 prostate normal and cancer samples, 30% fusion RNAs on average are the transcripts that contain exons belonging to same-strand neighboring genes. These fusion RNAs may be the products of cis-SAGe, which was previously thought to be rare. To validate this finding and to better understand the phenomenon, we used LNCaP, a prostate cell line as a model, and identified 16 additional cis-SAGe events by silencing transcription factor CTCF and paired-end RNA sequencing. About half of the fusions are expressed at a significant level compared to their parental genes. Silencing one of the in-frame fusions resulted in reduced cell motility. Most out-of-frame fusions are likely to function as non-coding RNAs. The majority of the 16 fusions are also detected in other prostate cell lines, as well as in the 14 clinical prostate normal and cancer pairs. By studying the features associated with these fusions, we developed a set of rules: 1) the parental genes are same-strand-neighboring genes; 2) the distance between the genes is within 30kb; 3) the 5' genes are actively transcribing; and 4) the chimeras tend to have the second-to-last exon in the 5' genes joined to the second exon in the 3' genes. We then randomly selected 20 neighboring genes in the genome, and detected four fusion events using these rules in prostate cancer and non-cancerous cells. These results suggest that splicing between neighboring gene transcripts is a rather frequent phenomenon, and it is not a feature unique to cancer cells. PMID:25658338

Qin, Fujun; Song, Zhenguo; Babiceanu, Mihaela; Song, Yansu; Facemire, Loryn; Singh, Ritambhara; Adli, Mazhar; Li, Hui

2015-02-01

113

Genome-Scale Discovery of Cell Wall Biosynthesis Genes in Populus (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)  

ScienceCinema

Wellington Muchero from Oak Ridge National Laboratory gives a talk titled "Discovery of Cell Wall Biosynthesis Genes in Populus" at the JGI 7th Annual Users Meeting: Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, California.

Muchero, Wellington [Oak Ridge National Laboratory

2013-01-22

114

Discovery of Gene Families and Alternatively Spliced Variants by RecA-Mediated Cloning  

Microsoft Academic Search

Probing the functional complexity of the human genome will require new gene cloning techniques, not only to discover intraspecies gene homologs and interspecies gene orthologs, but also to identify alternatively spliced gene variants. We report homologous cDNA cloning methods that allow cloning of gene family members, genes from different species, and alternatively spliced gene variants. We cloned human 14-3-3 gene

Hong Zeng; Elizabeth Allen; Chris W. Lehman; R. Geoffrey Sargent; Sushma Pati; David A. Zarling

2002-01-01

115

Enrico Fermi and the discovery of neutron-induced radioactivity: a project being crowned  

Microsoft Academic Search

This paper deals with the Physics Institute of via Panisperna in Rome, getting ready for investigation on neutron physics before Fermi's discovery of neutron-induced radioactivity. The importance of nuclear research had been acknowledged in the Physics Institute in Rome since 1929. The Institute had been directed towards nuclear physics since then, but from the experimental point of view, still in

Alberto De Gregorio

2005-01-01

116

GOALI: Robust and Efficient KnowledgeGOALI: Robust and Efficient Knowledge Discovery with Application in GeneDiscovery with Application in Gene  

E-print Network

Informatics, Cincinnati Children's Hospital NSF Grant # 0825710 NSF Program: Service Enterprise Engineering #12;Acute Leukemia Classification · Identify acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) based on gene expression data, which require different chemotherapy regimens · 7,192 probes

Huang, Samuel H.

117

A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules  

Microsoft Academic Search

To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast. We found 22,163 such coexpression relationships, each of which has been conserved across evolution. This conservation implies that the coexpression of these gene pairs confers a selective advantage and therefore that these genes are

Joshua M. Stuart; Eran Segal; Daphne Koller; Stuart K. Kim

2003-01-01

118

Gene discovery from Jatropha curcas by sequencing of ESTs from normalized and full-length enriched cDNA library from developing seeds  

PubMed Central

Background Jatropha curcas L. is promoted as an important non-edible biodiesel crop worldwide. Jatropha oil, which is a triacylglycerol, can be directly blended with petro-diesel or transesterified with methanol and used as biodiesel. Genetic improvement in jatropha is needed to increase the seed yield, oil content, drought and pest resistance, and to modify oil composition so that it becomes a technically and economically preferred source for biodiesel production. However, genetic improvement efforts in jatropha could not take advantage of genetic engineering methods due to lack of cloned genes from this species. To overcome this hurdle, the current gene discovery project was initiated with an objective of isolating as many functional genes as possible from J. curcas by large scale sequencing of expressed sequence tags (ESTs). Results A normalized and full-length enriched cDNA library was constructed from developing seeds of J. curcas. The cDNA library contained about 1 × 106 clones and average insert size of the clones was 2.1 kb. Totally 12,084 ESTs were sequenced to average high quality read length of 576 bp. Contig analysis revealed 2258 contigs and 4751 singletons. Contig size ranged from 2-23 and there were 7333 ESTs in the contigs. This resulted in 7009 unigenes which were annotated by BLASTX. It showed 3982 unigenes with significant similarity to known genes and 2836 unigenes with significant similarity to genes of unknown, hypothetical and putative proteins. The remaining 191 unigenes which did not show similarity with any genes in the public database may encode for unique genes. Functional classification revealed unigenes related to broad range of cellular, molecular and biological functions. Among the 7009 unigenes, 6233 unigenes were identified to be potential full-length genes. Conclusions The high quality normalized cDNA library was constructed from developing seeds of J. curcas for the first time and 7009 unigenes coding for diverse biological functions including oil biosynthesis were identified. These genes will serve as invaluable genetic resource for crop improvement in jatropha to make it an ideal and profitable crop for biodiesel production. PMID:20979643

2010-01-01

119

Discovery of Possible Gene Relationships through the Application of Self-Organizing Maps to DNA Microarray Databases  

PubMed Central

DNA microarrays and cell cycle synchronization experiments have made possible the study of the mechanisms of cell cycle regulation of Saccharomyces cerevisiae by simultaneously monitoring the expression levels of thousands of genes at specific time points. On the other hand, pattern recognition techniques can contribute to the analysis of such massive measurements, providing a model of gene expression level evolution through the cell cycle process. In this paper, we propose the use of one of such techniques –an unsupervised artificial neural network called a Self-Organizing Map (SOM)–which has been successfully applied to processes involving very noisy signals, classifying and organizing them, and assisting in the discovery of behavior patterns without requiring prior knowledge about the process under analysis. As a test bed for the use of SOMs in finding possible relationships among genes and their possible contribution in some biological processes, we selected 282 S. cerevisiae genes that have been shown through biological experiments to have an activity during the cell cycle. The expression level of these genes was analyzed in five of the most cited time series DNA microarray databases used in the study of the cell cycle of this organism. With the use of SOM, it was possible to find clusters of genes with similar behavior in the five databases along two cell cycles. This result suggested that some of these genes might be biologically related or might have a regulatory relationship, as was corroborated by comparing some of the clusters obtained with SOMs against a previously reported regulatory network that was generated using biological knowledge, such as protein-protein interactions, gene expression levels, metabolism dynamics, promoter binding, and modification, regulation and transport of proteins. The methodology described in this paper could be applied to the study of gene relationships of other biological processes in different organisms. PMID:24699245

Chavez-Alvarez, Rocio; Chavoya, Arturo; Mendez-Vazquez, Andres

2014-01-01

120

Discovery of possible gene relationships through the application of self-organizing maps to DNA microarray databases.  

PubMed

DNA microarrays and cell cycle synchronization experiments have made possible the study of the mechanisms of cell cycle regulation of Saccharomyces cerevisiae by simultaneously monitoring the expression levels of thousands of genes at specific time points. On the other hand, pattern recognition techniques can contribute to the analysis of such massive measurements, providing a model of gene expression level evolution through the cell cycle process. In this paper, we propose the use of one of such techniques--an unsupervised artificial neural network called a Self-Organizing Map (SOM)-which has been successfully applied to processes involving very noisy signals, classifying and organizing them, and assisting in the discovery of behavior patterns without requiring prior knowledge about the process under analysis. As a test bed for the use of SOMs in finding possible relationships among genes and their possible contribution in some biological processes, we selected 282 S. cerevisiae genes that have been shown through biological experiments to have an activity during the cell cycle. The expression level of these genes was analyzed in five of the most cited time series DNA microarray databases used in the study of the cell cycle of this organism. With the use of SOM, it was possible to find clusters of genes with similar behavior in the five databases along two cell cycles. This result suggested that some of these genes might be biologically related or might have a regulatory relationship, as was corroborated by comparing some of the clusters obtained with SOMs against a previously reported regulatory network that was generated using biological knowledge, such as protein-protein interactions, gene expression levels, metabolism dynamics, promoter binding, and modification, regulation and transport of proteins. The methodology described in this paper could be applied to the study of gene relationships of other biological processes in different organisms. PMID:24699245

Chavez-Alvarez, Rocio; Chavoya, Arturo; Mendez-Vazquez, Andres

2014-01-01

121

Enrico Fermi and the discovery of neutron-induced radioactivity: a project being crowned  

Microsoft Academic Search

This paper deals with the Physics Institute of via Panisperna in Rome,\\u000agetting ready for investigation on neutron physics before Fermi's discovery of\\u000aneutron-induced radioactivity. The importance of nuclear research had been\\u000aacknowledged in the Physics Institute in Rome since 1929. The Institute had\\u000abeen directed towards nuclear physics since then, but from the experimental\\u000apoint of view, still in

Alberto De Gregorio

2005-01-01

122

Knowledge Discovery Nuggets Directory  

NSDL National Science Digital Library

Knowledge Discovery Nuggets is both a web site and an associated newsletter. The newsletter focuses on the latest research, new applications, conference announcements, and news about data mining and knowledge discovery. The web site offers a large index of categorized pointers to data mining and knowledge discovery software, informative reference materials, related research projects, data sets, and much more. While somewhat difficult to navigate, Knowledge Discovery Nuggets offers an excellent place to start a data mining or knowledge discovery related search.

123

Arabidopsis thaliana Full Genome Longmer Microarrays: A Powerful Gene Discovery Tool for Agriculture and Forestry  

Microsoft Academic Search

Sequenced plant genomes provide a large reservoir of known genes with potential for use in crop and tree improvement, but assignment of specific functions to annotated genes in sequenced plant genomes remains a challenge. Furthermore, most plant genes belong to families encoding proteins with related but distinct functions. In this commentary, we discuss our development of Arabidopsis spotted whole genome

Carl J. Douglas; Jürgen Ehlting

2005-01-01

124

Single nucleotide polymorphism (SNP) discovery in mammals: a targeted-gene approach  

Microsoft Academic Search

Single nucleotide polymorphisms (SNPs) have rarely been exploited in nonhuman and nonmodel organism genetic studies. This is due partly to difficulties in finding SNPs in species where little DNA sequence data exist, as well as to a lack of robust and inexpensive genotyping methods. We have explored one SNP discovery method for molecular ecology, evolution, and conservation studies to evaluate

NICOLA AITKEN; STEVEN SMITH; CARSTEN SCHWARZ; PHILLIP A. M ORIN

2004-01-01

125

Discovery of a novel gene involved in autolysis of Clostridium cells.  

PubMed

Cell autolysis plays important physiological roles in the life cycle of clostridial cells. Understanding the genetic basis of the autolysis phenomenon of pathogenic Clostridium or solvent producing Clostridium cells might provide new insights into this important species. Genes that might be involved in autolysis of Clostridium acetobutylicum, a model clostridial species, were investigated in this study. Twelve putative autolysin genes were predicted in C. acetobutylicum DSM 1731 genome through bioinformatics analysis. Of these 12 genes, gene SMB_G3117 was selected for testing the in tracellular autolysin activity, growth profile, viable cell numbers, and cellular morphology. We found that overexpression of SMB_G3117 gene led to earlier ceased growth, significantly increased number of dead cells, and clear electrolucent cavities, while disruption of SMB_G3117 gene exhibited remarkably reduced intracellular autolysin activity. These results indicate that SMB_G3117 is a novel gene involved in cellular autolysis of C. acetobutylicum. PMID:23702687

Yang, Liejian; Bao, Guanhui; Zhu, Yan; Dong, Hongjun; Zhang, Yanping; Li, Yin

2013-06-01

126

Enrico Fermi and the discovery of neutron-induced radioactivity: a project being crowned  

E-print Network

This paper deals with the Physics Institute of via Panisperna in Rome, getting ready for investigation on neutron physics before Fermi's discovery of neutron-induced radioactivity. The importance of nuclear research had been acknowledged in the Physics Institute in Rome since 1929. The Institute had been directed towards nuclear physics since then, but from the experimental point of view, still in 1933, it was not yet engaged in nuclear experiments on account of the lack of adequate supplies. An adjustment of the equipment and supplies was undertaken, so that strong radioactive sources, Geiger-Mueller counters and Wilson chambers were finally available at the end of 1933, thanks largely to Rasetti's efforts.

Alberto De Gregorio

2005-01-27

127

Co-clustering phenome–genome for phenotype classification and disease gene discovery  

PubMed Central

Understanding the categorization of human diseases is critical for reliably identifying disease causal genes. Recently, genome-wide studies of abnormal chromosomal locations related to diseases have mapped >2000 phenotype–gene relations, which provide valuable information for classifying diseases and identifying candidate genes as drug targets. In this article, a regularized non-negative matrix tri-factorization (R-NMTF) algorithm is introduced to co-cluster phenotypes and genes, and simultaneously detect associations between the detected phenotype clusters and gene clusters. The R-NMTF algorithm factorizes the phenotype–gene association matrix under the prior knowledge from phenotype similarity network and protein–protein interaction network, supervised by the label information from known disease classes and biological pathways. In the experiments on disease phenotype–gene associations in OMIM and KEGG disease pathways, R-NMTF significantly improved the classification of disease phenotypes and disease pathway genes compared with support vector machines and Label Propagation in cross-validation on the annotated phenotypes and genes. The newly predicted phenotypes in each disease class are highly consistent with human phenotype ontology annotations. The roles of the new member genes in the disease pathways are examined and validated in the protein–protein interaction subnetworks. Extensive literature review also confirmed many new members of the disease classes and pathways as well as the predicted associations between disease phenotype classes and pathways. PMID:22735708

Hwang, TaeHyun; Atluri, Gowtham; Xie, MaoQiang; Dey, Sanjoy; Hong, Changjin; Kumar, Vipin; Kuang, Rui

2012-01-01

128

Computational discovery of DNA motifs associated with cell type-specific gene expression in Ciona  

Microsoft Academic Search

Temporally and spatially co-expressed genes are expected to be regulated by common transcription factors and therefore to share cis-regulatory elements. In the ascidian Ciona intestinalis, the whole-genome sequences and genome-scale gene expression profiles allow the use of computational techniques to investigate cis-elements that control transcription. We collected 5? flanking sequences of 50 tissue-specific genes from genome databases of C. intestinalis

Takehiro Kusakabe; Reiko Yoshida; Yoko Ikeda; Motoyuki Tsuda

2004-01-01

129

The Discovery of Zinc Fingers and Their Practical Applications in Gene Regulation: A Personal Account  

Microsoft Academic Search

An account is given of the discovery of the classical Cys2His2 (C2H2) zinc finger, arising from biochemical studies on the protein transcription factor IIIA found in Xenopus ooctyes, and of subsequent structural studies on its 3D structure and its interaction with DNA. Each finger is a self-contained domain\\u000a stabilized by a zinc ion ligated to a pair of cysteines and

Aaron Klug

130

Albert Einstein researchers' gene discovery could improve treatment for acute myeloid leukemia  

Cancer.gov

Scientists at Albert Einstein College of Medicine of Yeshiva University have discovered, in a mouse model of acute myeloid leukemia, that the gene HLX is expressed at abnormally high levels in leukemia stem cells. Gene expression is the process by which a gene synthesizes the molecule that it codes for; an "over-expressed" gene makes its product in abnormally high amounts. These findings suggest that targeting elevated HLX expression may be a promising novel strategy for treating AML. The Albert Einstein College of Medicine is home to the Albert Einstein Cancer Center.

131

Molecular Profiling of Breast Cancer Cell Lines Defines Relevant Tumor Models and Provides a Resource for Cancer Gene Discovery  

PubMed Central

Background Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes–luminal A, luminal B, ERBB2-associated, basal-like and normal-like–with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes. Methods Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA) to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression. Findings Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B) subtypes. Luminal lines displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem/progenitor-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented), and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 multi-copy deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and novel candidate breast cancer genes. Conclusions Overall, breast cancer cell lines were genetically more complex than tumors, but retained expression patterns with relevance to the luminal-basal subtype distinction. The compendium of molecular profiles defines cell lines suitable for investigations of subtype-specific pathobiology, cancer stem cell biology, biomarkers and therapies, and provides a resource for discovery of new breast cancer genes. PMID:19582160

Bocanegra, Melanie; Choi, Yoon-La; Girard, Luc; Gandhi, Jeet; Kwei, Kevin A.; Hernandez-Boussard, Tina; Wang, Pei; Gazdar, Adi F.; Minna, John D.; Pollack, Jonathan R.

2009-01-01

132

Generation of comprehensive transposon insertion mutant library for the model archaeon, Haloferax volcanii , and its use for gene discovery.  

PubMed

BackgroundArchaea share fundamental properties with bacteria and eukaryotes. Yet, they also possess unique attributes, which largely remain poorly characterized. Haloferax volcanii is an aerobic, moderately halophilic archaeon that can be grown in defined media. It serves as an excellent archaeal model organism to study the molecular mechanisms of biological processes and cellular responses to changes in the environment. Studies on haloarchaea have been impeded by the lack of efficient genetic screens that would facilitate the identification of protein functions and respective metabolic pathways.ResultsHere, we devised an insertion mutagenesis strategy that combined Mu in vitro DNA transposition and homologous-recombination-based gene targeting in H. volcanii. We generated an insertion mutant library, in which the clones contained a single genomic insertion. From the library, we isolated pigmentation-defective and auxotrophic mutants, and the respective insertions pinpointed a number of genes previously known to be involved in carotenoid and amino acid biosynthesis pathways, thus validating the performance of the methodologies used. We also identified mutants that had a transposon insertion in a gene encoding a protein of unknown or putative function, demonstrating that novel roles for non-annotated genes could be assigned.ConclusionsWe have generated, for the first time, a random genomic insertion mutant library for a halophilic archaeon and used it for efficient gene discovery. The library will facilitate the identification of non-essential genes behind any specific biochemical pathway. It represents a significant step towards achieving a more complete understanding of the unique characteristics of halophilic archaea. PMID:25488358

Kiljunen, Saija; Pajunen, Maria I; Dilks, Kieran; Storf, Stefanie; Pohlschroder, Mecky; Savilahti, Harri

2014-12-01

133

LARGE-SCALE GENE DISCOVERY IN THE PEA APHID ACYRTHOSIPHON PISUM (HEMIPTERA)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Aphids are the leading pest in agricultural crops spreading numerous plant diseases. To obtain a working overview of the genes controlling aphid survival and reproduction we chose to analyze aphid gene expression by conducting large-scale expressed sequence tag (EST) analysis using the model aphid s...

134

Systematic discovery of novel ciliary genes through functional genomics in the zebrafish  

PubMed Central

Cilia are microtubule-based hair-like organelles that play many important roles in development and physiology, and are implicated in a rapidly expanding spectrum of human diseases, collectively termed ciliopathies. Primary ciliary dyskinesia (PCD), one of the most prevalent of ciliopathies, arises from abnormalities in the differentiation or motility of the motile cilia. Despite their biomedical importance, a methodical functional screen for ciliary genes has not been carried out in any vertebrate at the organismal level. We sought to systematically discover novel motile cilia genes by identifying the genes induced by Foxj1, a winged-helix transcription factor that has an evolutionarily conserved role as the master regulator of motile cilia biogenesis. Unexpectedly, we find that the majority of the Foxj1-induced genes have not been associated with cilia before. To characterize these novel putative ciliary genes, we subjected 50 randomly selected candidates to a systematic functional phenotypic screen in zebrafish embryos. Remarkably, we find that over 60% are required for ciliary differentiation or function, whereas 30% of the proteins encoded by these genes localize to motile cilia. We also show that these genes regulate the proper differentiation and beating of motile cilia. This collection of Foxj1-induced genes will be invaluable for furthering our understanding of ciliary biology, and in the identification of new mutations underlying ciliary disorders in humans. PMID:25139857

Choksi, Semil P.; Babu, Deepak; Lau, Doreen; Yu, Xianwen; Roy, Sudipto

2014-01-01

135

SNP discovery and marker development for disease resistance candidate genes in common carp (Cyprinus carpio)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Single nucleotide polymorphisms (SNPs) in immune response genes have been reported as markers of susceptibility to infectious diseases in human and livestock. A disease caused by cyprinid herpes virus 3 (CyHV-3) is highly contagious and virulent in common carp. With the aim to investigate the gene...

136

Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling  

Microsoft Academic Search

Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients. Distinct expression profiles identified each of the

Eng-Juh Yeoh; Mary E. Ross; Sheila A. Shurtleff; W. Kent Williams; Divyen Patel; Rami Mahfouz; Fred G. Behm; Susana C. Raimondi; Mary V. Relling; Anami Patel; Cheng Cheng; Dario Campana; Dawn Wilkins; Xiaodong Zhou; Jinyan Li; Huiqing Liu; Ching-Hon Pui; William E Evans; Clayton Naeve; Limsoon Wong; James R Downing

2002-01-01

137

At the Speed of Sound: Gene Discovery in the Auditory System  

PubMed Central

As auditory genes and deafness-associated mutations are discovered at a rapid rate, exciting opportunities have arisen to uncover the molecular mechanisms underlying hearing and hearing impairment. Single genes have been identified to be pathogenic for dominant or recessive forms of nonsyndromic hearing loss, syndromic hearing loss, and, in some cases, even multiple forms of hearing loss. Modifier loci and genes have been found, and investigations into their role in the hearing process will yield valuable insight into the fundamental processes of the auditory system. PMID:11577373

Resendes, Barbara L.; Williamson, Robin E.; Morton, Cynthia C.

2001-01-01

138

De novo assembly of the common bean transcriptome using short reads for the discovery of drought-responsive genes.  

PubMed

The common bean (Phaseolus vulgaris L.) is one of the most important food legumes, far ahead of other legumes. The average grain yield of the common bean worldwide is much lower than its potential yields, primarily due to drought in the field. However, the gene network that mediates plant responses to drought stress remains largely unknown in this species. The major goals of our study are to identify a large scale of genes involved in drought stress using RNA-seq. First, we assembled 270 million high-quality trimmed reads into a non-redundant set of 62,828 unigenes, representing approximately 49 Mb of unique transcriptome sequences. Of these unigenes, 26,501 (42.2%) common bean unigenes had significant similarity with unigenes/predicted proteins from other legumes or sequenced plants. All unigenes were functionally annotated within the GO, COG and KEGG pathways. The strategy for de novo assembly of transcriptome data generated here will be useful in other legume plant transcriptome studies. Second, we identified 10,482 SSRs and 4,099 SNPs in transcripts. The large number of genetic markers provides a resource for gene discovery and development of functional molecular markers. Finally, we found differential expression genes (DEGs) between terminal drought and optimal irrigation treatments and between the two different genotypes Long 22-0579 (drought tolerant) and Naihua (drought sensitive). DEGs were confirmed by quantitative real-time PCR assays, which indicated that these genes are functionally associated with the drought-stress response. These resources will be helpful for basic and applied research for genome analysis and crop drought resistance improvement in the common bean. PMID:25275443

Wu, Jing; Wang, Lanfen; Li, Long; Wang, Shumin

2014-01-01

139

De Novo Assembly of Auricularia polytricha Transcriptome Using Illumina Sequencing for Gene Discovery and SSR Marker Identification  

PubMed Central

Auricularia polytricha (Mont.) Sacc., a type of edible black-brown mushroom with a gelatinous and modality-specific fruiting body, is in high demand in Asia due to its nutritional and medicinal properties. Illumina Solexa sequenceing technology was used to generate very large transcript sequences from the mycelium and the mature fruiting body of A. polytricha for gene discovery and molecular marker development. De novo assembly generated 36,483 ESTs with an N50 length of 636 bp. A total of 28,108 ESTs demonstrated significant hits with known proteins in the nr database, and 94.03% of the annotated ESTs showed the greatest similarity to A. delicata, a related species of A. polytricha. Functional categorization of the Gene Ontology (GO), Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed the conservation of genes involved in various biological processes in A. polytricha. Gene expression profile analysis indicated that a total of 2,057 ESTs were differentially expressed, including 1,020 ESTs that were up-regulated in the mycelium and 1,037 up-regulated in the fruiting body. Functional enrichment showed that the ESTs associated with biosynthesis, metabolism and assembly of proteins were more active in fruiting body development. The expression patterns of homologous transcription factors indicated that the molecular mechanisms of fruiting body formation and development were not exactly the same as for other agarics. Interestingly, an EST encoding tyrosinase was significantly up-regulated in the fruiting body, indicating that melanins accumulated during the processes of the formation of the black-brown color of the fruiting body in A. polytricha development. In addition, a total of 1,715 potential SSRs were detected in this transcriptome. The transcriptome analysis of A. polytricha provides valuable sequence resources and numerous molecular markers to facilitate further functional genomics studies and genetic researches on this fungus. PMID:24626227

Zhou, Yan; Chen, Lianfu; Fan, Xiuzhi; Bian, Yinbing

2014-01-01

140

Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Hepatopancreas of Microbial Challenged Mitten Crab Eriocheir sinensis  

PubMed Central

Background The Chinese mitten crab Eriocheir sinensis is an important economic crustacean and has been seriously attacked by various diseases, which requires more and more information for immune relevant genes on genome background. Recently, high-throughput RNA sequencing (RNA-seq) technology provides a powerful and efficient method for transcript analysis and immune gene discovery. Methods/Principal Findings A cDNA library from hepatopancreas of E. sinensis challenged by a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 108 cfu·mL?1) was constructed and randomly sequenced using Illumina technique. Totally 39.76 million clean reads were assembled to 70,300 unigenes. After ruling out short-length and low-quality sequences, 52,074 non-redundant unigenes were compared to public databases for homology searching and 17,617 of them showed high similarity to sequences in NCBI non-redundant protein (Nr) database. For function classification and pathway assignment, 18,734 (36.00%) unigenes were categorized to three Gene Ontology (GO) categories, 12,243 (23.51%) were classified to 25 Clusters of Orthologous Groups (COG), and 8,983 (17.25%) were assigned to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Potentially, 24, 14, 47 and 132 unigenes were characterized to be involved in Toll, IMD, JAK-STAT and MAPK pathways, respectively. Conclusions/Significance This is the first systematical transcriptome analysis of components relating to innate immune pathways in E. sinensis. Functional genes and putative pathways identified here will contribute to better understand immune system and prevent various diseases in crab. PMID:23874555

Li, Xihong; Cui, Zhaoxia; Liu, Yuan; Song, Chengwen; Shi, Guohui

2013-01-01

141

Discovery of Pituitary Adenylate Cyclase-Activating Polypeptide-Regulated Genes through Microarray Analyses in Cell Culture and In Vivo  

PubMed Central

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an evolutionarily well conserved neuropeptide with multiple functions in the nervous, endocrine, and immune systems. PACAP provides neuroprotection from ischemia and toxin exposure, is anti-inflammatory in gastric inflammatory disease and sepsis, controls proliferative signaling pathways involved in neural cell transformation, and modulates glucohomeostasis. PACAP-based, disease-targeted therapeutics might thus be both effective and benign, enhancing homeostatic responses to behavioral, metabolic, oncogenic, and inflammatory stressors. PACAP signal transduction employs synergistic regulation of calcium and cyclic adenosine monophosphate (cAMP), and noncanonical activation of both calcium- and cAMP-dependent processes. Pharmacological activation of PACAP signaling should consequently have highly specific effects even in vivo. Here, a combined cellular biochemical, pharmacologic, transcriptomic, and bioinformatic approach to understanding PACAP signal transduction by identifying PACAP target genes with oligonucleotide- and cDNA-based microarray is described. Calcium- and cAMP-dependent PACAP signaling pathways for regulation of genes encoding proteins required for neuritogenesis, changes in cell morphology, and cell survival have been traced in PC12 cells. Pharmacological experiments have linked gene expression to cell physiological responses in this system, in which gene silencing can also be employed to confirm the functional significance of induction of specific transcripts. Differential transcriptional responses to metabolic, ischemic, and other stressors in wild type compared to PACAP-deficient mice establish in principle which PACAP-responsive transcripts in culture are PACAP-dependent in vivo. Bioinformatic approaches aid in creating a pipeline for identifying neuropeptide-regulated genes, validating their cellular functions, and defining their expression in the context of neuropeptide signaling physiology, required for discovery of new targets for drug action. PMID:19076358

Eiden, Lee E.; Samal, Babru; Gerdin, Matthew J.; Mustafa, Tomris; Vaudry, David; Stroth, Nikolas

2010-01-01

142

Scienti#12;c Discovery through Advanced Computing (SciDAC-3) Partnership Project Annual Report  

SciTech Connect

The Applying Computationally Efficient Schemes for BioGeochemical Cycles ACES4BGC Project is advancing the predictive capabilities of Earth System Models (ESMs) by reducing two of the largest sources of uncertainty, aerosols and biospheric feedbacks, with a highly e#14;cient computational approach. In particular, this project is implementing and optimizing new computationally e#14;cient tracer advection algorithms for large numbers of tracer species; adding important biogeochemical interactions between the atmosphere, land, and ocean models; and applying uncertainty quanti#12;cation (UQ) techniques to constrain process parameters and evaluate uncertainties in feedbacks between biogeochemical cycles and the climate system.

Forest M. Hoffman [ORNL; Pavel B. Bochev [SNL; Philip J. Cameron-Smith [LLNL; Richard C. Easter, Jr. [PNNL; Scott M. Elliott [LANL; Steven J. Ghan [PNNL; Xiaohong Liu [formerly PNNL, U. Wyoming; Robert B. Lowrie [LANL; Donald D. Lucas [LLNL; Po-lun Ma, William J Sacks; Manish Shrivastava [PNNL; Balwinder Singh [PNNL; Timothy J. Tautges [ANL; Mark A. Taylor [SNL; Mariana Vertenstein [NCAR; Patrick H. Worley [ORNL; and; Kai Zhang [PNNL

2014-01-15

143

Stanford discovery of gene fusion in ovarian cancer could lead to earlier diagnoses:  

Cancer.gov

About 15 percent of cases of an aggressive, difficult-to-detect form of ovarian cancer contain a unique fusion between two neighboring, normally separate genes, say researchers at the Stanford University School of Medicine.

144

Biochemical genomics for gene discovery in benzylisoquinoline alkaloid biosynthesis in opium poppy and related species.  

PubMed

Benzylisoquinoline alkaloids (BIAs) are a large, diverse group of ?2500 specialized plant metabolites. Many BIAs display potent pharmacological activities, including the narcotic analgesics codeine and morphine, the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine, the antimicrobial agents sanguinarine and berberine, and the muscle relaxant (+)-tubocurarine. Opium poppy remains the sole commercial source for codeine, morphine, and a variety of semisynthetic drugs, including oxycodone and buprenorphine, derived primarily from the biosynthetic pathway intermediate thebaine. Recent advances in transcriptomics, proteomics, and metabolomics have created unprecedented opportunities for isolating and characterizing novel BIA biosynthetic genes. Here, we describe the application of next-generation sequencing and cDNA microarrays for selecting gene candidates based on comparative transcriptome analysis. We outline the basic mass spectrometric techniques to perform deep proteome and targeted metabolite analyses on BIA-producing plant tissues and provide methodologies for functionally characterizing biosynthetic gene candidates through in vitro enzyme assays and transient gene silencing in planta. PMID:22999177

Dang, Thu Thuy T; Onoyovwi, Akpevwe; Farrow, Scott C; Facchini, Peter J

2012-01-01

145

Discovery of Molecular Mechanisms of Traditional Chinese Medicinal Formula Si-Wu-Tang Using Gene Expression Microarray and Connectivity Map  

PubMed Central

To pursue a systematic approach to discovery of mechanisms of action of traditional Chinese medicine (TCM), we used microarrays, bioinformatics and the “Connectivity Map” (CMAP) to examine TCM-induced changes in gene expression. We demonstrated that this approach can be used to elucidate new molecular targets using a model TCM herbal formula Si-Wu-Tang (SWT) which is widely used for women's health. The human breast cancer MCF-7 cells treated with 0.1 µM estradiol or 2.56 mg/ml of SWT showed dramatic gene expression changes, while no significant change was detected for ferulic acid, a known bioactive compound of SWT. Pathway analysis using differentially expressed genes related to the treatment effect identified that expression of genes in the nuclear factor erythroid 2-related factor 2 (Nrf2) cytoprotective pathway was most significantly affected by SWT, but not by estradiol or ferulic acid. The Nrf2-regulated genes HMOX1, GCLC, GCLM, SLC7A11 and NQO1 were upreguated by SWT in a dose-dependent manner, which was validated by real-time RT-PCR. Consistently, treatment with SWT and its four herbal ingredients resulted in an increased antioxidant response element (ARE)-luciferase reporter activity in MCF-7 and HEK293 cells. Furthermore, the gene expression profile of differentially expressed genes related to SWT treatment was used to compare with those of 1,309 compounds in the CMAP database. The CMAP profiles of estradiol-treated MCF-7 cells showed an excellent match with SWT treatment, consistent with SWT's widely claimed use for women's diseases and indicating a phytoestrogenic effect. The CMAP profiles of chemopreventive agents withaferin A and resveratrol also showed high similarity to the profiles of SWT. This study identified SWT as an Nrf2 activator and phytoestrogen, suggesting its use as a nontoxic chemopreventive agent, and demonstrated the feasibility of combining microarray gene expression profiling with CMAP mining to discover mechanisms of actions and to identify new health benefits of TCMs. PMID:21464939

Wen, Zhining; Wang, Zhijun; Wang, Steven; Ravula, Ranadheer; Yang, Lun; Xu, Jun; Wang, Charles; Zuo, Zhong; Chow, Moses S. S.; Shi, Leming; Huang, Ying

2011-01-01

146

Project Information Form Project Title Do California Highways Act as Barriers to Gene Flow for Ground-Dwelling  

E-print Network

Project Information Form Project Title Do California Highways Act as Barriers to Gene Flow to generalize results among systems. To begin to understand how Northern California highways affect native coyotes and non-invasive sources (hair and scat) on either side of each highway and use landscape genetic

California at Davis, University of

147

Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian gene expression data  

Microsoft Academic Search

Background: A key step in the regulation of gene expression is the sequence-specific binding of transcription factors (TFs) to their DNA recognition sites. However, elucidating TF binding site (TFBS) motifs in higher eukaryotes has been challenging, even when employing cross-species sequence conservation. We hypothesized that for human and mouse, many orthologous genes expressed in a similarly tissue-specific manner in both

Bertrand R. Huber; Martha L. Bulyk

2006-01-01

148

Discovery of diversity in xylan biosynthetic genes by transcriptional profiling of a heteroxylan containing mucilaginous tissue.  

PubMed

The exact biochemical steps of xylan backbone synthesis remain elusive. In Arabidopsis, three non-redundant genes from two glycosyltransferase (GT) families, IRX9 and IRX14 from GT43 and IRX10 from GT47, are candidates for forming the xylan backbone. In other plants, evidence exists that different tissues express these three genes at widely different levels, which suggests that diversity in the makeup of the xylan synthase complex exists. Recently we have profiled the transcripts present in the developing mucilaginous tissue of psyllium (Plantago ovata Forsk). This tissue was found to have high expression levels of an IRX10 homolog, but very low levels of the two GT43 family members. This contrasts with recent wheat endosperm tissue profiling that found a relatively high abundance of the GT43 family members. We have performed an in-depth analysis of all GTs genes expressed in four developmental stages of the psyllium mucilagenous layer and in a single stage of the psyllium stem using RNA-Seq. This analysis revealed several IRX10 homologs, an expansion in GT61 (homologs of At3g18170/At3g18180), and several GTs from other GT families that are highly abundant and specifically expressed in the mucilaginous tissue. Our current hypothesis is that the four IRX10 genes present in the mucilagenous tissues have evolved to function without the GT43 genes. These four genes represent some of the most divergent IRX10 genes identified to date. Conversely, those present in the psyllium stem are very similar to those in other eudicots. This suggests these genes are under selective pressure, likely due to the synthesis of the various xylan structures present in mucilage that has a different biochemical role than that present in secondary walls. The numerous GT61 family members also show a wide sequence diversity and may be responsible for the larger number of side chain structures present in the psyllium mucilage. PMID:23761806

Jensen, Jacob K; Johnson, Nathan; Wilkerson, Curtis G

2013-01-01

149

Discovery of diversity in xylan biosynthetic genes by transcriptional profiling of a heteroxylan containing mucilaginous tissue  

PubMed Central

The exact biochemical steps of xylan backbone synthesis remain elusive. In Arabidopsis, three non-redundant genes from two glycosyltransferase (GT) families, IRX9 and IRX14 from GT43 and IRX10 from GT47, are candidates for forming the xylan backbone. In other plants, evidence exists that different tissues express these three genes at widely different levels, which suggests that diversity in the makeup of the xylan synthase complex exists. Recently we have profiled the transcripts present in the developing mucilaginous tissue of psyllium (Plantago ovata Forsk). This tissue was found to have high expression levels of an IRX10 homolog, but very low levels of the two GT43 family members. This contrasts with recent wheat endosperm tissue profiling that found a relatively high abundance of the GT43 family members. We have performed an in-depth analysis of all GTs genes expressed in four developmental stages of the psyllium mucilagenous layer and in a single stage of the psyllium stem using RNA-Seq. This analysis revealed several IRX10 homologs, an expansion in GT61 (homologs of At3g18170/At3g18180), and several GTs from other GT families that are highly abundant and specifically expressed in the mucilaginous tissue. Our current hypothesis is that the four IRX10 genes present in the mucilagenous tissues have evolved to function without the GT43 genes. These four genes represent some of the most divergent IRX10 genes identified to date. Conversely, those present in the psyllium stem are very similar to those in other eudicots. This suggests these genes are under selective pressure, likely due to the synthesis of the various xylan structures present in mucilage that has a different biochemical role than that present in secondary walls. The numerous GT61 family members also show a wide sequence diversity and may be responsible for the larger number of side chain structures present in the psyllium mucilage. PMID:23761806

Jensen, Jacob K.; Johnson, Nathan; Wilkerson, Curtis G.

2013-01-01

150

Discovery and Characterization of Two Novel Salt-Tolerance Genes in Puccinellia tenuiflora  

PubMed Central

Puccinellia tenuiflora is a monocotyledonous halophyte that is able to survive in extreme saline soil environments at an alkaline pH range of 9–10. In this study, we transformed full-length cDNAs of P. tenuiflora into Saccharomyces cerevisiae by using the full-length cDNA over-expressing gene-hunting system to identify novel salt-tolerance genes. In all, 32 yeast clones overexpressing P. tenuiflora cDNA were obtained by screening under NaCl stress conditions; of these, 31 clones showed stronger tolerance to NaCl and were amplified using polymerase chain reaction (PCR) and sequenced. Four novel genes encoding proteins with unknown function were identified; these genes had no homology with genes from higher plants. Of the four isolated genes, two that encoded proteins with two transmembrane domains showed the strongest resistance to 1.3 M NaCl. RT-PCR and northern blot analysis of P. tenuiflora cultured cells confirmed the endogenous NaCl-induced expression of the two proteins. Both of the proteins conferred better tolerance in yeasts to high salt, alkaline and osmotic conditions, some heavy metals and H2O2 stress. Thus, we inferred that the two novel proteins might alleviate oxidative and other stresses in P. tenuiflora. PMID:25238412

Li, Ying; Takano, Tetsuo; Liu, Shenkui

2014-01-01

151

Discovery of functional non-coding conserved regions in the ?-synuclein gene locus  

PubMed Central

Several single nucleotide polymorphisms (SNPs) and the Rep-1 microsatellite marker of the ?-synuclein ( SNCA) gene have consistently been shown to be associated with Parkinson’s disease, but the functional relevance is unclear. Based on these findings we hypothesized that conserved cis-regulatory elements in the SNCA genomic region regulate expression of SNCA, and that SNPs in these regions could be functionally modulating the expression of SNCA, thus contributing to neuronal demise and predisposing to Parkinson’s disease. In a pair-wise comparison of a 206kb genomic region encompassing the SNCA gene, we revealed 34 evolutionary conserved DNA sequences between human and mouse. All elements were cloned into reporter vectors and assessed for expression modulation in dual luciferase reporter assays.  We found that 12 out of 34 elements exhibited either an enhancement or reduction of the expression of the reporter gene. Three elements upstream of the SNCA gene displayed an approximately 1.5 fold (p<0.009) increase in expression. Of the intronic regions, three showed a 1.5 fold increase and two others indicated a 2 and 2.5 fold increase in expression (p<0.002). Three elements downstream of the SNCA gene showed 1.5 fold and 2.5 fold increase (p<0.0009). One element downstream of SNCA had a reduced expression of the reporter gene of 0.35 fold (p<0.0009) of normal activity. Our results demonstrate that the SNCA gene contains cis-regulatory regions that might regulate the transcription and expression of SNCA. Further studies in disease-relevant tissue types will be important to understand the functional impact of regulatory regions and specific Parkinson’s disease-associated SNPs and its function in the disease process.

Sterling, Lori; Walter, Michael; Ting, Dennis; Schüle, Birgitt

2014-01-01

152

Discovery and characterization of nutritionally regulated genes associated with muscle growth in Atlantic salmon  

PubMed Central

A genomics approach was used to identify nutritionally regulated genes involved in growth of fast skeletal muscle in Atlantic salmon (Salmo salar L.). Forward and reverse subtractive cDNA libraries were prepared comparing fish with zero growth rates to fish growing rapidly. We produced 7,420 ESTs and assembled them into nonredundant clusters prior to annotation. Contigs representing 40 potentially unrecognized nutritionally responsive candidate genes were identified. Twenty-three of the subtractive library candidates were also differentially regulated by nutritional state in an independent fasting-refeeding experiment and their expression placed in the context of 26 genes with established roles in muscle growth regulation. The expression of these genes was also determined during the maturation of a primary myocyte culture, identifying 13 candidates from the subtractive cDNA libraries with putative roles in the myogenic program. During early stages of refeeding DNAJA4, HSPA1B, HSP90A, and CHAC1 expression increased, indicating activation of unfolded protein response pathways. Four genes were considered inhibitory to myogenesis based on their in vivo and in vitro expression profiles (CEBPD, ASB2, HSP30, novel transcript GE623928). Other genes showed increased expression with feeding and highest in vitro expression during the proliferative phase of the culture (FOXD1, DRG1) or as cells differentiated (SMYD1, RTN1, MID1IP1, HSP90A, novel transcript GE617747). The genes identified were associated with chromatin modification (SMYD1, RTN1), microtubule stabilization (MID1IP1), cell cycle regulation (FOXD1, CEBPD, DRG1), and negative regulation of signaling (ASB2) and may play a role in the stimulation of myogenesis during the transition from a catabolic to anabolic state in skeletal muscle. PMID:20663983

Johnston, Ian A.

2010-01-01

153

PERMANENT GENETIC RESOURCES NOTE 1261 supported by a Discovery Project grant to J.P.E. and F.G-G. from  

E-print Network

of London. Series B, 271, 1585­1589. McMillan WO, Raff RA, Palumbi SR (1992) Population genetic consequences (1995) Population genetics software for exact tests and ecumenicism. Journal of Heredity, 86, 248PERMANENT GENETIC RESOURCES NOTE 1261 supported by a Discovery Project grant to J.P.E. and F

Uriarte, Maria

154

Natural and man-made V-gene repertoires for antibody discovery  

PubMed Central

Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety, and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of humans, mice, and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity, and composition of a repertoire impact the antibody discovery process. PMID:23162556

Finlay, William J. J.; Almagro, Juan C.

2012-01-01

155

A systems-genetics approach and data mining tool to assist in the discovery of genes underlying complex traits in Oryza sativa.  

PubMed

Many traits of biological and agronomic significance in plants are controlled in a complex manner where multiple genes and environmental signals affect the expression of the phenotype. In Oryza sativa (rice), thousands of quantitative genetic signals have been mapped to the rice genome. In parallel, thousands of gene expression profiles have been generated across many experimental conditions. Through the discovery of networks with real gene co-expression relationships, it is possible to identify co-localized genetic and gene expression signals that implicate complex genotype-phenotype relationships. In this work, we used a knowledge-independent, systems genetics approach, to discover a high-quality set of co-expression networks, termed Gene Interaction Layers (GILs). Twenty-two GILs were constructed from 1,306 Affymetrix microarray rice expression profiles that were pre-clustered to allow for improved capture of gene co-expression relationships. Functional genomic and genetic data, including over 8,000 QTLs and 766 phenotype-tagged SNPs (p-value < = 0.001) from genome-wide association studies, both covering over 230 different rice traits were integrated with the GILs. An online systems genetics data-mining resource, the GeneNet Engine, was constructed to enable dynamic discovery of gene sets (i.e. network modules) that overlap with genetic traits. GeneNet Engine does not provide the exact set of genes underlying a given complex trait, but through the evidence of gene-marker correspondence, co-expression, and functional enrichment, site visitors can identify genes with potential shared causality for a trait which could then be used for experimental validation. A set of 2 million SNPs was incorporated into the database and serve as a potential set of testable biomarkers for genes in modules that overlap with genetic traits. Herein, we describe two modules found using GeneNet Engine, one with significant overlap with the trait amylose content and another with significant overlap with blast disease resistance. PMID:23874666

Ficklin, Stephen P; Feltus, Frank Alex

2013-01-01

156

A Systems-Genetics Approach and Data Mining Tool to Assist in the Discovery of Genes Underlying Complex Traits in Oryza sativa  

PubMed Central

Many traits of biological and agronomic significance in plants are controlled in a complex manner where multiple genes and environmental signals affect the expression of the phenotype. In Oryza sativa (rice), thousands of quantitative genetic signals have been mapped to the rice genome. In parallel, thousands of gene expression profiles have been generated across many experimental conditions. Through the discovery of networks with real gene co-expression relationships, it is possible to identify co-localized genetic and gene expression signals that implicate complex genotype-phenotype relationships. In this work, we used a knowledge-independent, systems genetics approach, to discover a high-quality set of co-expression networks, termed Gene Interaction Layers (GILs). Twenty-two GILs were constructed from 1,306 Affymetrix microarray rice expression profiles that were pre-clustered to allow for improved capture of gene co-expression relationships. Functional genomic and genetic data, including over 8,000 QTLs and 766 phenotype-tagged SNPs (p-value GeneNet Engine, was constructed to enable dynamic discovery of gene sets (i.e. network modules) that overlap with genetic traits. GeneNet Engine does not provide the exact set of genes underlying a given complex trait, but through the evidence of gene-marker correspondence, co-expression, and functional enrichment, site visitors can identify genes with potential shared causality for a trait which could then be used for experimental validation. A set of 2 million SNPs was incorporated into the database and serve as a potential set of testable biomarkers for genes in modules that overlap with genetic traits. Herein, we describe two modules found using GeneNet Engine, one with significant overlap with the trait amylose content and another with significant overlap with blast disease resistance. PMID:23874666

Ficklin, Stephen P.; Feltus, Frank Alex

2013-01-01

157

Discovery of Susceptibility Gene Leads to a Family’s New Start  

Cancer.gov

Over the past 14 years, researchers in the Clinical Genetics Branch (CGB), led by Branch Chief Sharon Savage, M.D., have carried out a study of dyskeratosis congenita (DC) at the NIH Clinical Center to better understand the disorder and to identify the genes responsible for it.

158

Discovery of Candidate Genes for Stallion Fertility from the Horse Y Chromosome  

E-print Network

proteins SPAG6 and SPAG16, A kinase (PRKA) anchor protein 4 (AKAP4) and genes encoding proteins in axonemal dynein cluster (DNAI1, DNAH5 and DNAH11 (O'Bryan and de Kretser 2006; Matzuk and Lamb 2008). Sperm motility can be affected also by deletions...

Paria, Nandina

2012-02-14

159

Gene Annotation and Drug Target Discovery in Candida albicans with a Tagged Transposon Mutant Collection  

Microsoft Academic Search

Candida albicans is the most common human fungal pathogen, causing infections that can be lethal in immunocompromised patients. Although Saccharomyces cerevisiae has been used as a model for C. albicans, it lacks C. albicans' diverse morphogenic forms and is primarily non-pathogenic. Comprehensive genetic analyses that have been instrumental for determining gene function in S. cerevisiae are hampered in C. albicans,

Julia Oh; Eula Fung; Ulrich Schlecht; Ronald W. Davis; Guri Giaever; Robert P. St. Onge; Adam Deutschbauer; Corey Nislow

2010-01-01

160

Transcriptome Analysis of Catharanthus roseus for Gene Discovery and Expression Profiling  

PubMed Central

The medicinal plant, Catharanthus roseus, accumulates wide range of terpenoid indole alkaloids, which are well documented therapeutic agents. In this study, deep transcriptome sequencing of C. roseus was carried out to identify the pathways and enzymes (genes) involved in biosynthesis of these compounds. About 343 million reads were generated from different tissues (leaf, flower and root) of C. roseus using Illumina platform. Optimization of de novo assembly involving a two-step process resulted in a total of 59,220 unique transcripts with an average length of 1284 bp. Comprehensive functional annotation and gene ontology (GO) analysis revealed the representation of many genes involved in different biological processes and molecular functions. In total, 65% of C. roseus transcripts showed homology with sequences available in various public repositories, while remaining 35% unigenes may be considered as C. roseus specific. In silico analysis revealed presence of 11,620 genic simple sequence repeats (excluding mono-nucleotide repeats) and 1820 transcription factor encoding genes in C. roseus transcriptome. Expression analysis showed roots and leaves to be actively participating in bisindole alkaloid production with clear indication that enzymes involved in pathway of vindoline and vinblastine biosynthesis are restricted to aerial tissues. Such large-scale transcriptome study provides a rich source for understanding plant-specialized metabolism, and is expected to promote research towards production of plant-derived pharmaceuticals. PMID:25072156

Sharma, Raghvendra; Sinha, Alok K.; Jain, Mukesh

2014-01-01

161

Discovery and assessment of conserved Pax6 target genes and enhancers  

PubMed Central

The characterization of transcriptional networks (TNs) is essential for understanding complex biological phenomena such as development, disease, and evolution. In this study, we have designed and implemented a procedure that combines in silico target screens with zebrafish and mouse validation, in order to identify cis-elements and genes directly regulated by Pax6. We chose Pax6 as the paradigm because of its crucial roles in organogenesis and human disease. We identified over 600 putative Pax6 binding sites and more than 200 predicted direct target genes, conserved in evolution from zebrafish to human and to mouse. This was accomplished using hidden Markov models (HMMs) generated from experimentally validated Pax6 binding sites. A small sample of genes, expressed in the neural lineage, was chosen from the predictions for RNA in situ validation using zebrafish and mouse models. Validation of DNA binding to some predicted cis-elements was also carried out using chromatin immunoprecipitation (ChIP) and zebrafish reporter transgenic studies. The results show that this combined procedure is a highly efficient tool to investigate the architecture of TNs and constitutes a useful complementary resource to ChIP and expression data sets because of its inherent spatiotemporal independence. We have identified several novel direct targets, including some putative disease genes, among them Foxp2; these will allow further dissection of Pax6 function in development and disease. PMID:21617155

Coutinho, Pedro; Pavlou, Sofia; Bhatia, Shipra; Chalmers, Kevin J.; Kleinjan, Dirk A.; van Heyningen, Veronica

2011-01-01

162

The discovery of integrated gene networks for autism and related disorders.  

PubMed

Despite considerable genetic heterogeneity underlying neurodevelopmental diseases, there is compelling evidence that many disease genes will map to a much smaller number of biological subnetworks. We developed a computational method, termed MAGI (merging affected genes into integrated networks), that simultaneously integrates protein-protein interactions and RNA-seq expression profiles during brain development to discover "modules" enriched for de novo mutations in probands. We applied this method to recent exome sequencing of 1116 patients with autism and intellectual disability, discovering two distinct modules that differ in their properties and associated phenotypes. The first module consists of 80 genes associated with Wnt, Notch, SWI/SNF, and NCOR complexes and shows the highest expression early during embryonic development (8-16 post-conception weeks [pcw]). The second module consists of 24 genes associated with synaptic function, including long-term potentiation and calcium signaling with higher levels of postnatal expression. Patients with de novo mutations in these modules are more significantly intellectually impaired and carry more severe missense mutations when compared to probands with de novo mutations outside of these modules. We used our approach to define subsets of the network associated with higher functioning autism as well as greater severity with respect to IQ. Finally, we applied MAGI independently to epilepsy and schizophrenia exome sequencing cohorts and found significant overlap as well as expansion of these modules, suggesting a core set of integrated neurodevelopmental networks common to seemingly diverse human diseases. PMID:25378250

Hormozdiari, Fereydoun; Penn, Osnat; Borenstein, Elhanan; Eichler, Evan E

2014-11-01

163

Gene Discovery in the Threatened Elkhorn Coral: 454 Sequencing of the Acropora palmata Transcriptome  

PubMed Central

Background Cnidarians, including corals and anemones, offer unique insights into metazoan evolution because they harbor genetic similarities with vertebrates beyond that found in model invertebrates and retain genes known only from non-metazoans. Cataloging genes expressed in Acropora palmata, a foundation-species of reefs in the Caribbean and western Atlantic, will advance our understanding of the genetic basis of ecologically important traits in corals and comes at a time when sequencing efforts in other cnidarians allow for multi-species comparisons. Results A cDNA library from a sample enriched for symbiont free larval tissue was sequenced on the 454 GS-FLX platform. Over 960,000 reads were obtained and assembled into 42,630 contigs. Annotation data was acquired for 57% of the assembled sequences. Analysis of the assembled sequences indicated that 83–100% of all A. palmata transcripts were tagged, and provided a rough estimate of the total number genes expressed in our samples (?18,000–20,000). The coral annotation data contained many of the same molecular components as in the Bilateria, particularly in pathways associated with oxidative stress and DNA damage repair, and provided evidence that homologs of p53, a key player in DNA repair pathways, has experienced selection along the branch separating Cnidaria and Bilateria. Transcriptome wide screens of paralog groups and transition/transversion ratios highlighted genes including: green fluorescent proteins, carbonic anhydrase, and oxidative stress proteins; and functional groups involved in protein and nucleic acid metabolism, and the formation of structural molecules. These results provide a starting point for study of adaptive evolution in corals. Conclusions Currently available transcriptome data now make comparative studies of the mechanisms underlying coral's evolutionary success possible. Here we identified candidate genes that enable corals to maintain genomic integrity despite considerable exposure to genotoxic stress over long life spans, and showed conservation of important physiological pathways between corals and bilaterians. PMID:22216101

Polato, Nicholas R.; Vera, J. Cristobal; Baums, Iliana B.

2011-01-01

164

Ultra dense array CGH and discovery of micro-copy number alterations and gene fusions in cancer genome  

PubMed Central

The characterization of molecular alterations specific to cancer facilitates the discovery of predictive and prognostic biomarkers important to targeted therapeutics. Alterations critical to cancer therapeutics include copy number alterations (CNAs) such as gene amplifications and deletions as well as genomic rearrangements resulting in gene fusions. There are two genome-wide technologies used to detect CNAs: next generation sequencing (NGS) and dense microarray based comparative genomic hybridization (aCGH). Array CGH is a mature robust technology of lower cost and more accessible than NGS. This chapter describes the protocol steps and analysis required to obtain reliable aCGH results from clinical samples. Technical options and various necessary compromises related to the nature of clinical material are considered and the consequences of these choices for data analysis and interpretation are discussed. The chapter includes brief description of the data analysis, even though analysis is often performed by bioinformaticians. Today’s cancer research requires collaboration of clinicians, molecular biologist and mathematicians. Acquaintance with the basic principles related to the extraction of the data from arrays, its normalization and the algorithms available for analysis provides a baseline for mutual understanding and communication. PMID:23412781

Przybytkowski, Ewa; Aguilar-Mahecha, Adrianan; Nabavi, Sheida; Tonellato, Peter J.; Basik, Mark

2013-01-01

165

Beyond Gene Discovery in Inflammatory Bowel Disease: The Emerging Role of Epigenetics  

PubMed Central

In the past decade, there have been fundamental advances in our understanding of genetic factors that contribute to the inflammatory bowel diseases (IBDs) Crohn’s disease and ulcerative colitis. The latest international collaborative studies have brought the number of IBD susceptibility gene loci to 163. However, genetic factors account for only a portion of overall disease variance, indicating a need to better explore gene-environment interactions in the development of IBD. Epigenetic factors can mediate interactions between the environment and the genome; their study could provide new insight into the pathogenesis of IBD. We review recent progress in identification of genetic factors associated with IBD and discuss epigenetic mechanisms that could affect development and progression of IBD. PMID:23751777

Ventham, Nicholas T.; Kennedy, Nicholas A.; Nimmo, Elaine R.; Satsangi, Jack

2013-01-01

166

Gene discovery in an invasive tephritid model pest species, the Mediterranean fruit fly, Ceratitis capitata  

PubMed Central

Background The medfly, Ceratitis capitata, is a highly invasive agricultural pest that has become a model insect for the development of biological control programs. Despite research into the behavior and classical and population genetics of this organism, the quantity of sequence data available is limited. We have utilized an expressed sequence tag (EST) approach to obtain detailed information on transcriptome signatures that relate to a variety of physiological systems in the medfly; this information emphasizes on reproduction, sex determination, and chemosensory perception, since the study was based on normalized cDNA libraries from embryos and adult heads. Results A total of 21,253 high-quality ESTs were obtained from the embryo and head libraries. Clustering analyses performed separately for each library resulted in 5201 embryo and 6684 head transcripts. Considering an estimated 19% overlap in the transcriptomes of the two libraries, they represent about 9614 unique transcripts involved in a wide range of biological processes and molecular functions. Of particular interest are the sequences that share homology with Drosophila genes involved in sex determination, olfaction, and reproductive behavior. The medfly transformer2 (tra2) homolog was identified among the embryonic sequences, and its genomic organization and expression were characterized. Conclusion The sequences obtained in this study represent the first major dataset of expressed genes in a tephritid species of agricultural importance. This resource provides essential information to support the investigation of numerous questions regarding the biology of the medfly and other related species and also constitutes an invaluable tool for the annotation of complete genome sequences. Our study has revealed intriguing findings regarding the transcript regulation of tra2 and other sex determination genes, as well as insights into the comparative genomics of genes implicated in chemosensory reception and reproduction. PMID:18500975

Gomulski, Ludvik M; Dimopoulos, George; Xi, Zhiyong; Soares, Marcelo B; Bonaldo, Maria F; Malacrida, Anna R; Gasperi, Giuliano

2008-01-01

167

Discovery of Nuclear-Encoded Genes for the Neurotoxin Saxitoxin in Dinoflagellates  

PubMed Central

Saxitoxin is a potent neurotoxin that occurs in aquatic environments worldwide. Ingestion of vector species can lead to paralytic shellfish poisoning, a severe human illness that may lead to paralysis and death. In freshwaters, the toxin is produced by prokaryotic cyanobacteria; in marine waters, it is associated with eukaryotic dinoflagellates. However, several studies suggest that saxitoxin is not produced by dinoflagellates themselves, but by co-cultured bacteria. Here, we show that genes required for saxitoxin synthesis are encoded in the nuclear genomes of dinoflagellates. We sequenced >1.2×106 mRNA transcripts from the two saxitoxin-producing dinoflagellate strains Alexandrium fundyense CCMP1719 and A. minutum CCMP113 using high-throughput sequencing technology. In addition, we used in silico transcriptome analyses, RACE, qPCR and conventional PCR coupled with Sanger sequencing. These approaches successfully identified genes required for saxitoxin-synthesis in the two transcriptomes. We focused on sxtA, the unique starting gene of saxitoxin synthesis, and show that the dinoflagellate transcripts of sxtA have the same domain structure as the cyanobacterial sxtA genes. But, in contrast to the bacterial homologs, the dinoflagellate transcripts are monocistronic, have a higher GC content, occur in multiple copies, contain typical dinoflagellate spliced-leader sequences and eukaryotic polyA-tails. Further, we investigated 28 saxitoxin-producing and non-producing dinoflagellate strains from six different genera for the presence of genomic sxtA homologs. Our results show very good agreement between the presence of sxtA and saxitoxin-synthesis, except in three strains of A. tamarense, for which we amplified sxtA, but did not detect the toxin. Our work opens for possibilities to develop molecular tools to detect saxitoxin-producing dinoflagellates in the environment. PMID:21625593

Stüken, Anke; Orr, Russell J. S.; Kellmann, Ralf; Murray, Shauna A.; Neilan, Brett A.; Jakobsen, Kjetill S.

2011-01-01

168

Gene discovery through transcriptome sequencing for the invasive mussel Limnoperna fortunei.  

PubMed

The success of the Asian bivalve Limnoperna fortunei as an invader in South America is related to its high acclimation capability. It can inhabit waters with a wide range of temperatures and salinity and handle long-term periods of air exposure. We describe the transcriptome of L. fortunei aiming to give a first insight into the phenotypic plasticity that allows non-native taxa to become established and widespread. We sequenced 95,219 reads from five main tissues of the mussel L. fortunei using Roche's 454 and assembled them to form a set of 84,063 unigenes (contigs and singletons) representing partial or complete gene sequences. We annotated 24,816 unigenes using a BLAST sequence similarity search against a NCBI nr database. Unigenes were divided into 20 eggNOG functional categories and 292 KEGG metabolic pathways. From the total unigenes, 1,351 represented putative full-length genes of which 73.2% were functionally annotated. We described the first partial and complete gene sequences in order to start understanding bivalve invasiveness. An expansion of the hsp70 gene family, seen also in other bivalves, is present in L. fortunei and could be involved in its adaptation to extreme environments, e.g. during intertidal periods. The presence of toll-like receptors gives a first insight into an immune system that could be more complex than previously assumed and may be involved in the prevention of disease and extinction when population densities are high. Finally, the apparent lack of special adaptations to extremely low O2 levels is a target worth pursuing for the development of a molecular control approach. PMID:25047650

Uliano-Silva, Marcela; Americo, Juliana Alves; Brindeiro, Rodrigo; Dondero, Francesco; Prosdocimi, Francisco; Rebelo, Mauro de Freitas

2014-01-01

169

Gene Discovery through Transcriptome Sequencing for the Invasive Mussel Limnoperna fortunei  

PubMed Central

The success of the Asian bivalve Limnoperna fortunei as an invader in South America is related to its high acclimation capability. It can inhabit waters with a wide range of temperatures and salinity and handle long-term periods of air exposure. We describe the transcriptome of L. fortunei aiming to give a first insight into the phenotypic plasticity that allows non-native taxa to become established and widespread. We sequenced 95,219 reads from five main tissues of the mussel L. fortunei using Roche’s 454 and assembled them to form a set of 84,063 unigenes (contigs and singletons) representing partial or complete gene sequences. We annotated 24,816 unigenes using a BLAST sequence similarity search against a NCBI nr database. Unigenes were divided into 20 eggNOG functional categories and 292 KEGG metabolic pathways. From the total unigenes, 1,351 represented putative full-length genes of which 73.2% were functionally annotated. We described the first partial and complete gene sequences in order to start understanding bivalve invasiveness. An expansion of the hsp70 gene family, seen also in other bivalves, is present in L. fortunei and could be involved in its adaptation to extreme environments, e.g. during intertidal periods. The presence of toll-like receptors gives a first insight into an immune system that could be more complex than previously assumed and may be involved in the prevention of disease and extinction when population densities are high. Finally, the apparent lack of special adaptations to extremely low O2 levels is a target worth pursuing for the development of a molecular control approach. PMID:25047650

Uliano-Silva, Marcela; Americo, Juliana Alves; Brindeiro, Rodrigo; Dondero, Francesco; Prosdocimi, Francisco; de Freitas Rebelo, Mauro

2014-01-01

170

Genome-wide discovery of cis-elements in promoter sequences using gene expression.  

PubMed

The availability of complete or nearly complete genome sequences, a large number of 5' expressed sequence tags, and significant public expression data allow for a more accurate identification of cis-elements regulating gene expression. We have implemented a global approach that takes advantage of available expression data, genomic sequences, and transcript information to predict cis-elements associated with specific expression patterns. The key components of our approach are: (1) precise identification of transcription start sites, (2) specific locations of cis-elements relative to the transcription start site, and (3) assessment of statistical significance for all sequence motifs. By applying our method to promoters of Arabidopsis thaliana and Mus musculus, we have identified motifs that affect gene expression under specific environmental conditions or in certain tissues. We also found that the presence of the TATA box is associated with increased variability of gene expression. Strong correlation between our results and experimentally determined motifs shows that the method is capable of predicting new functionally important cis-elements in promoter sequences. PMID:19231992

Troukhan, Maxim; Tatarinova, Tatiana; Bouck, John; Flavell, Richard B; Alexandrov, Nickolai N

2009-04-01

171

Gene Discovery and Molecular Marker Development, Based on High-Throughput Transcript Sequencing of Paspalum dilatatum Poir  

PubMed Central

Background Paspalum dilatatum Poir. (common name dallisgrass) is a native grass species of South America, with special relevance to dairy and red meat production. P. dilatatum exhibits higher forage quality than other C4 forage grasses and is tolerant to frost and water stress. This species is predominantly cultivated in an apomictic monoculture, with an inherent high risk that biotic and abiotic stresses could potentially devastate productivity. Therefore, advanced breeding strategies that characterise and use available genetic diversity, or assess germplasm collections effectively are required to deliver advanced cultivars for production systems. However, there are limited genomic resources available for this forage grass species. Results Transcriptome sequencing using second-generation sequencing platforms has been employed using pooled RNA from different tissues (stems, roots, leaves and inflorescences) at the final reproductive stage of P. dilatatum cultivar Primo. A total of 324,695 sequence reads were obtained, corresponding to c. 102 Mbp. The sequences were assembled, generating 20,169 contigs of a combined length of 9,336,138 nucleotides. The contigs were BLAST analysed against the fully sequenced grass species of Oryza sativa subsp. japonica, Brachypodium distachyon, the closely related Sorghum bicolor and foxtail millet (Setaria italica) genomes as well as against the UniRef 90 protein database allowing a comprehensive gene ontology analysis to be performed. The contigs generated from the transcript sequencing were also analysed for the presence of simple sequence repeats (SSRs). A total of 2,339 SSR motifs were identified within 1,989 contigs and corresponding primer pairs were designed. Empirical validation of a cohort of 96 SSRs was performed, with 34% being polymorphic between sexual and apomictic biotypes. Conclusions The development of genetic and genomic resources for P. dilatatum will contribute to gene discovery and expression studies. Association of gene function with agronomic traits will significantly enable molecular breeding and advance germplasm enhancement. PMID:24520314

Giordano, Andrea; Cogan, Noel O. I.; Kaur, Sukhjiwan; Drayton, Michelle; Mouradov, Aidyn; Panter, Stephen; Schrauf, Gustavo E.; Mason, John G.; Spangenberg, German C.

2014-01-01

172

The Discovery Method in Training.  

ERIC Educational Resources Information Center

In the form of a discussion between faceless people, this booklet concerns discovery learning and its advantages. Subjects covered in the discussions are: Introducing the Discovery Method; An Experiment with British Railways; The OECD Research Projects in U.S.A., Austria, and Sweden; How the Discovery Method Differs from Other Methods; Discovery…

Belbin, R. M.

173

DISCOVERY OF A LOW-MASS COMPANION TO A METAL-RICH F STAR WITH THE MARVELS PILOT PROJECT  

SciTech Connect

We report the discovery of a low-mass companion orbiting the metal-rich, main sequence F star TYC 2949-00557-1 during the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS) pilot project. The host star has an effective temperature T{sub eff} = 6135 {+-} 40 K, logg = 4.4 {+-} 0.1, and [Fe/H] = 0.32 {+-} 0.01, indicating a mass of M = 1.25 {+-} 0.09 M{sub sun} and R = 1.15 {+-} 0.15 R{sub sun}. The companion has an orbital period of 5.69449 {+-} 0.00023 days and straddles the hydrogen burning limit with a minimum mass of 64 M{sub J} , and thus may be an example of the rare class of brown dwarfs orbiting at distances comparable to those of 'Hot Jupiters'. We present relative photometry that demonstrates that the host star is photometrically stable at the few millimagnitude level on time scales of hours to years, and rules out transits for a companion of radius {approx}>0.8 R{sub J} at the 95% confidence level. Tidal analysis of the system suggests that the star and companion are likely in a double synchronous state where both rotational and orbital synchronization have been achieved. This is the first low-mass companion detected with a multi-object, dispersed, fixed-delay interferometer.

Fleming, Scott W.; Ge Jian; Mahadevan, Suvrath; Lee, Brian; Cuong Nguyen, Duy; Morehead, Robert C.; Wan Xiaoke; Zhao Bo; Liu Jian; Guo Pengcheng; Kane, Stephen R. [Department of Astronomy, University of Florida, 211 Bryant Space Science Center, Gainesville, FL 326711-2055 (United States); Eastman, Jason D.; Siverd, Robert J.; Scott Gaudi, B. [Department of Astronomy, Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Niedzielski, Andrzej [Torun Center for Astronomy, Nicolaus Copernicus University, ul. Gagarina 11, 87-100, Torun (Poland); Sivarani, Thirupathi [Indian Institute of Astrophysics, Bangalore 560034 (India); Stassun, Keivan G.; Gary, Bruce [Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235 (United States); Wolszczan, Alex [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Barnes, Rory, E-mail: scfleming@astro.ufl.ed [Department of Astronomy, University of Washington, P.O. Box 351580, Seattle, WA 98195 (United States)

2010-08-01

174

A large-scale gene discovery for the red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae).  

PubMed

The red palm weevil (RPW; Rhynchophorus ferrugineus) is a devastating pest of palms, prevalent in the Middle East as well as many other regions of the world. Here, we report a large-scale de novo complementary DNA (cDNA) sequencing effort that acquired ?5 million reads and assembled them into 26?765 contigs from 12 libraries made from samples of different RPW developmental stages based on the Roche/454 GS FLX platform. We annotated these contigs based on the publically available known insect genes and the Tribolium castaneum genome assembly. We find that over 80% of coding sequences (CDS) from the RPW contigs have high-identity homologs to known proteins with complete CDS. Gene expression analysis shows that the pupa and larval stages have the highest and lowest expression levels, respectively. In addition, we also identified more than 60?000 single nucleotide polymorphisms and 1?200 simple sequence repeat markers. This study provides the first large-scale cDNA dataset for RPW, a much-needed resource for future molecular studies. PMID:23955844

Wang, Lei; Zhang, Xiao-Wei; Pan, Lin-Lin; Liu, Wan-Fei; Wang, Da-Peng; Zhang, Guang-Yu; Yin, Yu-Xin; Yin, An; Jia, Shan-Gang; Yu, Xiao-Guang; Sun, Gao-Yuan; Hu, Song-Nian; Al-Mssallem, Ibrahim S; Yu, Jun

2013-12-01

175

Fish Suppressors of Cytokine Signaling (SOCS): Gene Discovery, Modulation of Expression and Function  

PubMed Central

The intracellular suppressors of cytokine signaling (SOCS) family members, including CISH and SOCS1 to 7 in mammals, are important regulators of cytokine signaling pathways. So far, the orthologues of all the eight mammalian SOCS members have been identified in fish, with several of them having multiple copies. Whilst fish CISH, SOCS3, and SOCS5 paralogues are possibly the result of the fish-specific whole genome duplication event, gene duplication or lineage-specific genome duplication may also contribute to some paralogues, as with the three trout SOCS2s and three zebrafish SOCS5s. Fish SOCS genes are broadly expressed and also show species-specific expression patterns. They can be upregulated by cytokines, such as IFN-?, TNF-?, IL-1?, IL-6, and IL-21, by immune stimulants such as LPS, poly I:C, and PMA, as well as by viral, bacterial, and parasitic infections in member- and species-dependent manners. Initial functional studies demonstrate conserved mechanisms of fish SOCS action via JAK/STAT pathways. PMID:22203897

Wang, Tiehui; Gorgoglione, Bartolomeo; Maehr, Tanja; Holland, Jason W.; Vecino, Jose L. González; Wadsworth, Simon; Secombes, Christopher J.

2011-01-01

176

Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71.  

PubMed

Retinitis pigmentosa is a genetically heterogeneous group of inherited ocular disorders characterized by progressive photoreceptor cell loss, night blindness, constriction of the visual field, and progressive visual disability. Homozygosity mapping and gene expression studies identified a 2 exon gene, C2ORF71. The encoded protein has no homologs and is highly expressed in the eye, where it is specifically expressed in photoreceptor cells. Two mutations were found in C2ORF71 in human RP patients: A nonsense mutation (p.W253X) in the first exon is likely to be a null allele; the second, a missense mutation (p.I201F) within a highly conserved region of the protein, leads to proteosomal degradation. Bioinformatic and functional studies identified and validated sites of lipid modification within the first three amino acids of the C2ORF71 protein. Using morpholino oligonucleotides to knockdown c2orf71 expression in zebrafish results in visual defects, confirming that C2ORF71 plays an important role in the development of normal vision. Finally, localization of C2ORF71 to primary cilia in cultured cells suggests that the protein is likely to localize to the connecting cilium or outer segment of photoreceptor cells. PMID:20398886

Nishimura, Darryl Y; Baye, Lisa M; Perveen, Rahat; Searby, Charles C; Avila-Fernandez, Almudena; Pereiro, Ines; Ayuso, Carmen; Valverde, Diana; Bishop, Paul N; Manson, Forbes D C; Urquhart, Jill; Stone, Edwin M; Slusarski, Diane C; Black, Graeme C M; Sheffield, Val C

2010-05-14

177

Discovery and Functional Analysis of a Retinitis Pigmentosa Gene, C2ORF71  

PubMed Central

Retinitis pigmentosa is a genetically heterogeneous group of inherited ocular disorders characterized by progressive photoreceptor cell loss, night blindness, constriction of the visual field, and progressive visual disability. Homozygosity mapping and gene expression studies identified a 2 exon gene, C2ORF71. The encoded protein has no homologs and is highly expressed in the eye, where it is specifically expressed in photoreceptor cells. Two mutations were found in C2ORF71 in human RP patients: A nonsense mutation (p.W253X) in the first exon is likely to be a null allele; the second, a missense mutation (p.I201F) within a highly conserved region of the protein, leads to proteosomal degradation. Bioinformatic and functional studies identified and validated sites of lipid modification within the first three amino acids of the C2ORF71 protein. Using morpholino oligonucleotides to knockdown c2orf71 expression in zebrafish results in visual defects, confirming that C2ORF71 plays an important role in the development of normal vision. Finally, localization of C2ORF71 to primary cilia in cultured cells suggests that the protein is likely to localize to the connecting cilium or outer segment of photoreceptor cells. PMID:20398886

Nishimura, Darryl Y.; Baye, Lisa M.; Perveen, Rahat; Searby, Charles C.; Avila-Fernandez, Almudena; Pereiro, Ines; Ayuso, Carmen; Valverde, Diana; Bishop, Paul N.; Manson, Forbes D.C.; Urquhart, Jill; Stone, Edwin M.; Slusarski, Diane C.; Black, Graeme C.M.; Sheffield, Val C.

2010-01-01

178

The first set of EST resource for gene discovery and marker development in pigeonpea (Cajanus cajan L.)  

PubMed Central

Background Pigeonpea (Cajanus cajan (L.) Millsp) is one of the major grain legume crops of the tropics and subtropics, but biotic stresses [Fusarium wilt (FW), sterility mosaic disease (SMD), etc.] are serious challenges for sustainable crop production. Modern genomic tools such as molecular markers and candidate genes associated with resistance to these stresses offer the possibility of facilitating pigeonpea breeding for improving biotic stress resistance. Availability of limited genomic resources, however, is a serious bottleneck to undertake molecular breeding in pigeonpea to develop superior genotypes with enhanced resistance to above mentioned biotic stresses. With an objective of enhancing genomic resources in pigeonpea, this study reports generation and analysis of comprehensive resource of FW- and SMD- responsive expressed sequence tags (ESTs). Results A total of 16 cDNA libraries were constructed from four pigeonpea genotypes that are resistant and susceptible to FW ('ICPL 20102' and 'ICP 2376') and SMD ('ICP 7035' and 'TTB 7') and a total of 9,888 (9,468 high quality) ESTs were generated and deposited in dbEST of GenBank under accession numbers GR463974 to GR473857 and GR958228 to GR958231. Clustering and assembly analyses of these ESTs resulted into 4,557 unique sequences (unigenes) including 697 contigs and 3,860 singletons. BLASTN analysis of 4,557 unigenes showed a significant identity with ESTs of different legumes (23.2-60.3%), rice (28.3%), Arabidopsis (33.7%) and poplar (35.4%). As expected, pigeonpea ESTs are more closely related to soybean (60.3%) and cowpea ESTs (43.6%) than other plant ESTs. Similarly, BLASTX similarity results showed that only 1,603 (35.1%) out of 4,557 total unigenes correspond to known proteins in the UniProt database (? 1E-08). Functional categorization of the annotated unigenes sequences showed that 153 (3.3%) genes were assigned to cellular component category, 132 (2.8%) to biological process, and 132 (2.8%) in molecular function. Further, 19 genes were identified differentially expressed between FW- responsive genotypes and 20 between SMD- responsive genotypes. Generated ESTs were compiled together with 908 ESTs available in public domain, at the time of analysis, and a set of 5,085 unigenes were defined that were used for identification of molecular markers in pigeonpea. For instance, 3,583 simple sequence repeat (SSR) motifs were identified in 1,365 unigenes and 383 primer pairs were designed. Assessment of a set of 84 primer pairs on 40 elite pigeonpea lines showed polymorphism with 15 (28.8%) markers with an average of four alleles per marker and an average polymorphic information content (PIC) value of 0.40. Similarly, in silico mining of 133 contigs with ? 5 sequences detected 102 single nucleotide polymorphisms (SNPs) in 37 contigs. As an example, a set of 10 contigs were used for confirming in silico predicted SNPs in a set of four genotypes using wet lab experiments. Occurrence of SNPs were confirmed for all the 6 contigs for which scorable and sequenceable amplicons were generated. PCR amplicons were not obtained in case of 4 contigs. Recognition sites for restriction enzymes were identified for 102 SNPs in 37 contigs that indicates possibility of assaying SNPs in 37 genes using cleaved amplified polymorphic sequences (CAPS) assay. Conclusion The pigeonpea EST dataset generated here provides a transcriptomic resource for gene discovery and development of functional markers associated with biotic stress resistance. Sequence analyses of this dataset have showed conservation of a considerable number of pigeonpea transcripts across legume and model plant species analysed as well as some putative pigeonpea specific genes. Validation of identified biotic stress responsive genes should provide candidate genes for allele mining as well as candidate markers for molecular breeding. PMID:20222972

2010-01-01

179

Challenges in Projecting Clustering Results Across Gene Expression - Profiling Datasets  

Microsoft Academic Search

Background Gene expression microarray studies for several types of cancer have been reported to identify previously unknown subtypes of tumors. For breast cancer, a molecular classification consisting of five subtypes based on gene expression microarray data has been proposed. These subtypes have been reported to exist across several breast cancer microarray studies, and they have demonstrated some association with clinical

Lara Lusa; Lisa M. McShane; James F. Reid; Loris De Cecco; Federico Ambrogi; Elia Biganzoli; Manuela Gariboldi; Marco A. Pierotti

2007-01-01

180

Project normal: Defining normal variance in mouse gene expression  

PubMed Central

The mouse has become an indispensable and versatile model organism for the study of development, genetics, behavior, and disease. The application of comprehensive gene expression profiling technologies to compare normal and diseased tissues or to assess molecular alterations resulting from various experimental interventions has the potential to provide highly detailed qualitative and quantitative descriptions of these processes. Ideally, to interpret experimental data, the magnitude and diversity of gene expression for the system under study should be well characterized, yet little is known about the normal variation of mouse gene expression in vivo. To assess natural differences in murine gene expression, we used a 5406-clone spotted cDNA microarray to quantitate transcript levels in the kidney, liver, and testis from each of 6 normal male C57BL6 mice. We used ANOVA to compare the variance across the six mice to the variance among four replicate experiments performed for each mouse tissue. For the 6 kidney samples, 102 of 3,088 genes (3.3%) exhibited a statistically significant mouse variance at a level of 0.05. In the testis, 62 of 3,252 genes (1.9%) showed statistically significant variance, and in the liver, there were 21 of 2,514 (0.8%) genes with significantly variable expression. Immune-modulated, stress-induced, and hormonally regulated genes were highly represented among the transcripts that were most variable. The expression levels of several genes varied significantly in more than one tissue. These studies help to define the baseline level of variability in mouse gene expression and emphasize the importance of replicate microarray experiments. PMID:11698685

Pritchard, Colin C.; Hsu, Li; Delrow, Jeffrey; Nelson, Peter S.

2001-01-01

181

Discovery and characterization of the first genuine avian leptin gene in the rock dove (Columba livia).  

PubMed

Leptin, the key regulator of mammalian energy balance, has been at the center of a great controversy in avian biology for the last 15 years since initial reports of a putative leptin gene (LEP) in chickens. Here, we characterize a novel LEP in rock dove (Columba livia) with low similarity of the predicted protein sequence (30% identity, 47% similarity) to the human ortholog. Searching the Sequence-Read-Archive database revealed leptin transcripts, in the dove's liver, with 2 noncoding exons preceding 2 coding exons. This unusual 4-exon structure was validated by sequencing of a GC-rich product (76% GC, 721 bp) amplified from liver RNA by RT-PCR. Sequence alignment of the dove leptin with orthologous leptins indicated that it consists of a leader peptide (21 amino acids; aa) followed by the mature protein (160 aa), which has a putative structure typical of 4-helical-bundle cytokines except that it is 12 aa longer than human leptin. Extra residues (10 aa) were located within the loop between 2 5'-helices, interrupting the amino acid motif that is conserved in tetrapods and considered essential for activation of leptin receptor (LEPR) but not for receptor binding per se. Quantitative RT-PCR of 11 tissues showed highest (P < .05) expression of LEP in the dove's liver, whereas the dove LEPR peaked (P < .01) in the pituitary. Both genes were prominently expressed in the gonads and at lower levels in tissues involved in mammalian leptin signaling (adipose; hypothalamus). A bioassay based on activation of the chicken LEPR in vitro showed leptin activity in the dove's circulation, suggesting that dove LEP encodes an active protein, despite the interrupted loop motif. Providing tools to study energy-balance control at an evolutionary perspective, our original demonstration of leptin signaling in dove predicts a more ancient role of leptin in growth and reproduction in birds, rather than appetite control. PMID:24758303

Friedman-Einat, Miriam; Cogburn, Larry A; Yosefi, Sara; Hen, Gideon; Shinder, Dmitry; Shirak, Andrey; Seroussi, Eyal

2014-09-01

182

The Fragile X Mental Retardation Syndrome 20 Years After the FMR1 Gene Discovery: an Expanding Universe of Knowledge  

PubMed Central

The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations. PMID:21912443

Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

2011-01-01

183

The fragile x mental retardation syndrome 20 years after the FMR1 gene discovery: an expanding universe of knowledge.  

PubMed

The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations. PMID:21912443

Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

2011-08-01

184

Correlated gene expression and target specificity demonstrate excitatory projection neuron diversity.  

PubMed

The neocortex contains diverse populations of excitatory neurons segregated by layer and further definable by their specific cortical and subcortical projection targets. The current study describes a systematic approach to identify molecular correlates of specific projection neuron classes in mouse primary somatosensory cortex (S1), using a combination of in situ hybridization (ISH) data mining, marker gene colocalization, and combined retrograde labeling with ISH for layer-specific marker genes. First, we identified a large set of genes with specificity for each cortical layer, and that display heterogeneous patterns within those layers. Using these genes as markers, we find extensive evidence for the covariation of gene expression and projection target specificity in layer 2/3, 5, and 6, with individual genes labeling neurons projecting to specific subsets of target structures. The combination of gene expression and target specificity imply a great diversity of projection neuron classes that is similar to or greater than that of GABAergic interneurons. The covariance of these 2 phenotypic modalities suggests that these classes are both discrete and genetically specified. PMID:24014670

Sorensen, Staci A; Bernard, Amy; Menon, Vilas; Royall, Joshua J; Glattfelder, Katie J; Desta, Tsega; Hirokawa, Karla; Mortrud, Marty; Miller, Jeremy A; Zeng, Hongkui; Hohmann, John G; Jones, Allan R; Lein, Ed S

2015-02-01

185

Discovery of copy number variants by multiplex amplifiable probe hybridization (MAPH) in candidate pigmentation genes.  

PubMed

Abstract Background: Copy Number Variants (CNVs) contribute to a large fraction of genetic diversity and some of them have been reported to offer an evolutionary advantage. Aim: To identify CNVs in pigmentary loci that could contribute to human skin pigmentation diversity. Subjects and methods: This study assessed the existence of CNVs in every exon of candidate genes: TYR, TYRP1, DCT, MC1R and SLC24A5, using the Multiplex Amplifiable Probe Hybridization technique (MAPH). This study analysed a total of 99 DNA samples of unrelated individuals from different populations. Validation and further analysis in a larger Spanish sample were performed by RT-qPCR. Results: Five CNVs were identified by MAPH: DCT exons 4 and 8, TYR exon 1 and SLC24A5 exons 1 and 4. Real-time quantitative PCR (RT-qPCR) confirmed the CNV in exon 1 of SLC24A5. This study further analysed the 5' promoter region of SLC24A5 and found another CNV in this region. However, no association was found between the CNV and the degree of pigmentation. Conclusion: Although the functional role of these structural variants in pigmentation should be the subject of future work, the results emphasize the need to consider all classes of variation (both SNPs and CNVs) when exploring the genetics of skin pigmentation. PMID:25343474

López, Saioa; García, Iker; Smith, Isabel; Sevilla, Arrate; Izagirre, Neskuts; de la Rúa, Concepción; Alonso, Santos

2014-10-24

186

The Gene Ontology's Reference Genome Project: a unified framework for functional annotation across species.  

PubMed

The Gene Ontology (GO) is a collaborative effort that provides structured vocabularies for annotating the molecular function, biological role, and cellular location of gene products in a highly systematic way and in a species-neutral manner with the aim of unifying the representation of gene function across different organisms. Each contributing member of the GO Consortium independently associates GO terms to gene products from the organism(s) they are annotating. Here we introduce the Reference Genome project, which brings together those independent efforts into a unified framework based on the evolutionary relationships between genes in these different organisms. The Reference Genome project has two primary goals: to increase the depth and breadth of annotations for genes in each of the organisms in the project, and to create data sets and tools that enable other genome annotation efforts to infer GO annotations for homologous genes in their organisms. In addition, the project has several important incidental benefits, such as increasing annotation consistency across genome databases, and providing important improvements to the GO's logical structure and biological content. PMID:19578431

2009-07-01

187

A Seriation Approach for Visualization-Driven Discovery of Co-Expression Patterns in Serial Analysis of Gene Expression (SAGE) Data  

PubMed Central

Background Serial Analysis of Gene Expression (SAGE) is a DNA sequencing-based method for large-scale gene expression profiling that provides an alternative to microarray analysis. Most analyses of SAGE data aimed at identifying co-expressed genes have been accomplished using various versions of clustering approaches that often result in a number of false positives. Principal Findings Here we explore the use of seriation, a statistical approach for ordering sets of objects based on their similarity, for large-scale expression pattern discovery in SAGE data. For this specific task we implement a seriation heuristic we term ‘progressive construction of contigs’ that constructs local chains of related elements by sequentially rearranging margins of the correlation matrix. We apply the heuristic to the analysis of simulated and experimental SAGE data and compare our results to those obtained with a clustering algorithm developed specifically for SAGE data. We show using simulations that the performance of seriation compares favorably to that of the clustering algorithm on noisy SAGE data. Conclusions We explore the use of a seriation approach for visualization-based pattern discovery in SAGE data. Using both simulations and experimental data, we demonstrate that seriation is able to identify groups of co-expressed genes more accurately than a clustering algorithm developed specifically for SAGE data. Our results suggest that seriation is a useful method for the analysis of gene expression data whose applicability should be further pursued. PMID:18787709

Morozova, Olena; Morozov, Vyacheslav; Hoffman, Brad G.; Helgason, Cheryl D.; Marra, Marco A.

2008-01-01

188

Cell Discoveries  

NSDL National Science Digital Library

In this project, students explored the world of scientists and their discoveries relating to cell research. Students were to design and build a ClarisWorks database that could answer their questions by browsing, searching, and sorting their database in a variety of ways. Students will 1) observe, compare and describe cell organelles in terms of their function, structure and operation; 2) enter and edit information in a database; 3) build and sort a student-designed database; and 4) find records in a database.

BEGIN:VCARD VERSION:2.1 FN:Shelly Peretz N:Peretz;Shelly ORG:Thornridge High School REV:2005-04-12 END:VCARD

1994-07-30

189

Genomic Resources for Gene Discovery, Functional Genome Annotation, and Evolutionary Studies of Maize and Its Close Relatives  

PubMed Central

Maize is one of the most important food crops and a key model for genetics and developmental biology. A genetically anchored and high-quality draft genome sequence of maize inbred B73 has been obtained to serve as a reference sequence. To facilitate evolutionary studies in maize and its close relatives, much like the Oryza Map Alignment Project (OMAP) (www.OMAP.org) bacterial artificial chromosome (BAC) resource did for the rice community, we constructed BAC libraries for maize inbred lines Zheng58, Chang7-2, and Mo17 and maize wild relatives Zea mays ssp. parviglumis and Tripsacum dactyloides. Furthermore, to extend functional genomic studies to maize and sorghum, we also constructed binary BAC (BIBAC) libraries for the maize inbred B73 and the sorghum landrace Nengsi-1. The BAC/BIBAC vectors facilitate transfer of large intact DNA inserts from BAC clones to the BIBAC vector and functional complementation of large DNA fragments. These seven Zea Map Alignment Project (ZMAP) BAC/BIBAC libraries have average insert sizes ranging from 92 to 148 kb, organellar DNA from 0.17 to 2.3%, empty vector rates between 0.35 and 5.56%, and genome equivalents of 4.7- to 8.4-fold. The usefulness of the Parviglumis and Tripsacum BAC libraries was demonstrated by mapping clones to the reference genome. Novel genes and alleles present in these ZMAP libraries can now be used for functional complementation studies and positional or homology-based cloning of genes for translational genomics. PMID:24037269

Wang, Chao; Shi, Xue; Liu, Lin; Li, Haiyan; Ammiraju, Jetty S.S.; Kudrna, David A.; Xiong, Wentao; Wang, Hao; Dai, Zhaozhao; Zheng, Yonglian; Lai, Jinsheng; Jin, Weiwei; Messing, Joachim; Bennetzen, Jeffrey L; Wing, Rod A.; Luo, Meizhong

2013-01-01

190

Genomic resources for gene discovery, functional genome annotation, and evolutionary studies of maize and its close relatives.  

PubMed

Maize is one of the most important food crops and a key model for genetics and developmental biology. A genetically anchored and high-quality draft genome sequence of maize inbred B73 has been obtained to serve as a reference sequence. To facilitate evolutionary studies in maize and its close relatives, much like the Oryza Map Alignment Project (OMAP) (www.OMAP.org) bacterial artificial chromosome (BAC) resource did for the rice community, we constructed BAC libraries for maize inbred lines Zheng58, Chang7-2, and Mo17 and maize wild relatives Zea mays ssp. parviglumis and Tripsacum dactyloides. Furthermore, to extend functional genomic studies to maize and sorghum, we also constructed binary BAC (BIBAC) libraries for the maize inbred B73 and the sorghum landrace Nengsi-1. The BAC/BIBAC vectors facilitate transfer of large intact DNA inserts from BAC clones to the BIBAC vector and functional complementation of large DNA fragments. These seven Zea Map Alignment Project (ZMAP) BAC/BIBAC libraries have average insert sizes ranging from 92 to 148 kb, organellar DNA from 0.17 to 2.3%, empty vector rates between 0.35 and 5.56%, and genome equivalents of 4.7- to 8.4-fold. The usefulness of the Parviglumis and Tripsacum BAC libraries was demonstrated by mapping clones to the reference genome. Novel genes and alleles present in these ZMAP libraries can now be used for functional complementation studies and positional or homology-based cloning of genes for translational genomics. PMID:24037269

Wang, Chao; Shi, Xue; Liu, Lin; Li, Haiyan; Ammiraju, Jetty S S; Kudrna, David A; Xiong, Wentao; Wang, Hao; Dai, Zhaozhao; Zheng, Yonglian; Lai, Jinsheng; Jin, Weiwei; Messing, Joachim; Bennetzen, Jeffrey L; Wing, Rod A; Luo, Meizhong

2013-11-01

191

Gene discovery in EST sequences from the wheat leaf rust fungus Puccinia triticina sexual spores, asexual spores and haustoria, compared to other rust and corn smut fungi  

PubMed Central

Background Rust fungi are biotrophic basidiomycete plant pathogens that cause major diseases on plants and trees world-wide, affecting agriculture and forestry. Their biotrophic nature precludes many established molecular genetic manipulations and lines of research. The generation of genomic resources for these microbes is leading to novel insights into biology such as interactions with the hosts and guiding directions for breakthrough research in plant pathology. Results To support gene discovery and gene model verification in the genome of the wheat leaf rust fungus, Puccinia triticina (Pt), we have generated Expressed Sequence Tags (ESTs) by sampling several life cycle stages. We focused on several spore stages and isolated haustorial structures from infected wheat, generating 17,684 ESTs. We produced sequences from both the sexual (pycniospores, aeciospores and teliospores) and asexual (germinated urediniospores) stages of the life cycle. From pycniospores and aeciospores, produced by infecting the alternate host, meadow rue (Thalictrum speciosissimum), 4,869 and 1,292 reads were generated, respectively. We generated 3,703 ESTs from teliospores produced on the senescent primary wheat host. Finally, we generated 6,817 reads from haustoria isolated from infected wheat as well as 1,003 sequences from germinated urediniospores. Along with 25,558 previously generated ESTs, we compiled a database of 13,328 non-redundant sequences (4,506 singlets and 8,822 contigs). Fungal genes were predicted using the EST version of the self-training GeneMarkS algorithm. To refine the EST database, we compared EST sequences by BLASTN to a set of 454 pyrosequencing-generated contigs and Sanger BAC-end sequences derived both from the Pt genome, and to ESTs and genome reads from wheat. A collection of 6,308 fungal genes was identified and compared to sequences of the cereal rusts, Puccinia graminis f. sp. tritici (Pgt) and stripe rust, P. striiformis f. sp. tritici (Pst), and poplar leaf rust Melampsora species, and the corn smut fungus, Ustilago maydis (Um). While extensive homologies were found, many genes appeared novel and species-specific; over 40% of genes did not match any known sequence in existing databases. Focusing on spore stages, direct comparison to Um identified potential functional homologs, possibly allowing heterologous functional analysis in that model fungus. Many potentially secreted protein genes were identified by similarity searches against genes and proteins of Pgt and Melampsora spp., revealing apparent orthologs. Conclusions The current set of Pt unigenes contributes to gene discovery in this major cereal pathogen and will be invaluable for gene model verification in the genome sequence. PMID:21435244

2011-01-01

192

National Research Council endorses human gene mapping project  

SciTech Connect

A news article discusses the Human Genome Initiative. The National Research Council, an arm of the National Academy of Sciences that is empowered by Congress to advise the federal government, is recommending a $3-billion effort to map and sequence the human genome. The committee advises appropriating $200 million each year for the project over the next 15 years. It emphasizes that funding should be generated de novo, not diverted from existing biologic and medical research efforts. As envisioned, the project would be executed in two stages: genome mapping and DNA sequencing. The first would involve preparing both physical maps, in which previously identified DNA segments are aligned in proper order on the appropriate chromosome, and genetic maps, which demonstrate the frequency with which two traits are likely to be inherited together. The recommendation paralleled provisions of two Senate bills-the science initiative bill introduced last summer by Senator Pete Domenici of New Mexico and the biotechnology bill, which senators Edward Kennedy of Massachusetts, Lawton Chiles of Florida, and Domenici introduced in December.

Not Available

1988-03-11

193

How the Serotonin Story is Being Rewritten By New Gene-Based Discoveries Principally Related to SLC6A4, the Serotonin Transporter Gene, Which Functions To Influence All Cellular Serotonin Systems  

PubMed Central

Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries in serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species; an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene; and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species. PMID:18824000

Murphy, Dennis L.; Fox, Meredith A.; Timpano, Kiara R.; Moya, Pablo; Ren-Patterson, Renee; Andrews, Anne M.; Holmes, Andrew; Lesch, Klaus-Peter; Wendland, Jens R.

2009-01-01

194

Novel Subtype-specific Genes Identify Distinct Subpopulations of Callosal Projection Neurons  

PubMed Central

Little is known about the molecular development and heterogeneity of callosal projection neurons (CPN), cortical commissural neurons that connect homotopic regions of the two cerebral hemispheres via the corpus callosum, and that are critical for bilateral integration of cortical information. Here we report on the identification of a series of genes that individually and in combination define CPN and novel CPN subpopulations during embryonic and postnatal development. We used in situ hybridization analysis, immunocytochemistry, and retrograde labeling to define the layer- and neuron type-specific distribution of these newly identified CPN genes across different stages of maturation. We demonstrate that a subset of these genes (e.g. Hspb3 and Lpl), appear specific to all CPN (in layers II/III and V–VI), while others (e.g. Nectin-3, Plexin-D1 and Dkk3) discriminate between CPN of the deep layers and those of the upper layers. Further, the data show that several genes finely subdivide CPN within individual layers and appear to label CPN subpopulations that have not been previously described using anatomical or morphological criteria. The genes identified here likely reflect the existence of distinct programs of gene expression governing the development, maturation, and function of the newly identified subpopulations of CPN. Together, these data define the first set of genes that identify and molecularly subcategorize distinct populations of callosal projection neurons, often located in distinct subdivisions of the canonical cortical laminae. PMID:19793993

Molyneaux, Bradley J.; Arlotta, Paola; Fame, Ryann M.; MacDonald, Jessica L.; MacQuarrie, Kyle L.; Macklis, Jeffrey D.

2009-01-01

195

Importing statistical measures into Artemis enhances gene identification in the Leishmania genome project  

PubMed Central

Background Seattle Biomedical Research Institute (SBRI) as part of the Leishmania Genome Network (LGN) is sequencing chromosomes of the trypanosomatid protozoan species Leishmania major. At SBRI, chromosomal sequence is annotated using a combination of trained and untrained non-consensus gene-prediction algorithms with ARTEMIS, an annotation platform with rich and user-friendly interfaces. Results Here we describe a methodology used to import results from three different protein-coding gene-prediction algorithms (GLIMMER, TESTCODE and GENESCAN) into the ARTEMIS sequence viewer and annotation tool. Comparison of these methods, along with the CODONUSAGE algorithm built into ARTEMIS, shows the importance of combining methods to more accurately annotate the L. major genomic sequence. Conclusion An improvised and powerful tool for gene prediction has been developed by importing data from widely-used algorithms into an existing annotation platform. This approach is especially fruitful in the Leishmania genome project where there is large proportion of novel genes requiring manual annotation. PMID:12793912

Aggarwal, Gautam; Worthey, EA; McDonagh, Paul D; Myler, Peter J

2003-01-01

196

Novel enabling technologies of gene isolation and plant transformation for improved crop protection  

SciTech Connect

Meeting the needs of agricultural producers requires the continued development of improved transgenic crop protection products. The completed project focused on developing novel enabling technologies of gene discovery and plant transformation to facilitate the generation of such products.

Torok, Tamas

2013-02-04

197

TOXICOGENOMICS DRUG DISCOVERY AND THE PATHOLOGIST  

EPA Science Inventory

Toxicogenomics, drug discovery, and pathologist. The field of toxicogenomics, which currently focuses on the application of large-scale differential gene expression (DGE) data to toxicology, is starting to influence drug discovery and development in the pharmaceutical indu...

198

Discovery and evaluation of candidate sex-determining genes and xenobiotics in the gonads of lake sturgeon (Acipenser fulvescens).  

PubMed

Modern pyrosequencing has the potential to uncover many interesting aspects of genome evolution, even in lineages where genomic resources are scarce. In particular, 454 pyrosequencing of nonmodel species has been used to characterize expressed sequence tags, xenobiotics, gene ontologies, and relative levels of gene expression. Herein, we use pyrosequencing to study the evolution of genes expressed in the gonads of a polyploid fish, the lake sturgeon (Acipenser fulvescens). Using 454 pyrosequencing of transcribed genes, we produced more than 125 MB of sequence data from 473,577 high-quality sequencing reads. Sequences that passed stringent quality control thresholds were assembled into 12,791 male contigs and 32,629 female contigs. Average depth of coverage was 4.2 x for the male assembly and 5.5x for the female assembly. Analytical rarefaction indicates that our assemblies include most of the genes expressed in lake sturgeon gonads. Over 86,700 sequencing reads were assigned gene ontologies, many to general housekeeping genes like protein, RNA, and ion binding genes. We searched specifically for sex determining genes and documented significant sex differences in the expression of two genes involved in animal sex determination, DMRT1 and TRA-1. DMRT1 is the master sex determining gene in birds and in medaka (Oryzias latipes) whereas TRA-1 helps direct sexual differentiation in nematodes. We also searched the lake sturgeon assembly for evidence of xenobiotic organisms that may exist as endosymbionts. Our results suggest that exogenous parasites (trematodes) and pathogens (protozoans) apparently have infected lake sturgeon gonads, and the trematodes have horizontally transferred some genes to the lake sturgeon genome. PMID:20386959

Hale, Matthew C; Jackson, James R; Dewoody, J Andrew

2010-07-01

199

Discovery and evaluation of candidate sex-determining genes and xenobiotics in the gonads of lake sturgeon ( Acipenser fulvescens )  

Microsoft Academic Search

Modern pyrosequencing has the potential to uncover many interesting aspects of genome evolution, even in lineages where genomic\\u000a resources are scarce. In particular, 454 pyrosequencing of nonmodel species has been used to characterize expressed sequence\\u000a tags, xenobiotics, gene ontologies, and relative levels of gene expression. Herein, we use pyrosequencing to study the evolution\\u000a of genes expressed in the gonads of

Matthew C. HaleJames; James R. Jackson; J. Andrew DeWoody

2010-01-01

200

Integration of Cot Analysis, DNA Cloning, and High-Throughput Sequencing Facilitates Genome Characterization and Gene Discovery  

Microsoft Academic Search

Cot-based sequence discovery represents a powerful means by which both low-copy and repetitive sequences can be selectively and efficiently fractionated, cloned, and characterized. Based upon the results of a Cot analysis, hydroxyapatite chromatography was used to fractionate sorghum (Sorghum bicolor) genomic DNA into highly repetitive (HR), moderately repetitive (MR), and single\\/low-copy (SL) sequence components that were consequently cloned to produce

Daniel G. Peterson; Stefan R. Schulze; Erica B. Sciara; Scott A. Lee; John E. Bowers; Alexander Nagel; Ning Jiang; Deanne C. Tibbitts; Susan R. Wessler; Andrew H. Paterson

2002-01-01

201

Guided Discoveries.  

ERIC Educational Resources Information Center

Presented are four mathematical discoveries made by students on an arithmetical function using the Fibonacci sequence. Discussed is the nature of the role of the teacher in directing the students' discovery activities. (KR)

Ehrlich, Amos

1991-01-01

202

Relationships between inhibitory activity against a cancer cell line panel, profiles of plants collected, and compound classes isolated in an anticancer drug discovery project.  

PubMed

In an attempt to determine the relationships between the plant profiles (country of collection, taxonomy, plant part) and the compound classes isolated with cytotoxic activity against a panel of human tumor cell lines, the data compiled from a 15-year anticancer drug-discovery project were subjected to an analysis of variance (ANOVA). The results indicate significant trends in cytotoxic activity relative to collection location, taxonomy, plant part, and compound classes isolated. Plant collections were made in tropical forests in six countries, with collections from Ecuador resulting in higher activity than those from Indonesia and Peru. Interestingly, collections from Florida were not statistically different than those from the countries with higher biodiversity. One hundred and forty-five families were represented in the collections, with the Clusiaceae, Elaeocarpaceae, Meliaceae, and Rubiaceae having low ED50 (half maximal effective dose) values. Especially active genera included Aglaia, Casearia, Exostema, Mallotus, and Trichosanthes. Roots and below-ground plant materials were significantly more active than above-ground materials. Cucurbitacins, flavaglines, anthraquinones, fatty acids, tropane alkaloids, lignans, and sesquiterpenoids were significantly more active than xanthones and oligorhamnosides. The results from this study should serve as a guide for future plant collection endeavors for anticancer drug discovery. PMID:17193321

Balunas, Marcy J; Jones, William P; Chin, Young-Won; Mi, Qiuwen; Farnsworth, Norman R; Soejarto, Djaja D; Cordell, Geoffrey A; Swanson, Steven M; Pezzuto, John M; Chai, Hee-Byung; Kinghorn, A Douglas

2006-08-01

203

A Comparison of Digital Gene Expression Profiling and Methyl DNA Immunoprecipitation as Methods for Gene Discovery in Honeybee (Apis mellifera) Behavioural Genomic Analyses  

PubMed Central

The honey bee has a well-organized system of division of labour among workers. Workers typically progress through a series of discrete behavioural castes as they age, and this has become an important case study for exploring how dynamic changes in gene expression can influence behaviour. Here we applied both digital gene expression analysis and methyl DNA immunoprecipitation analysis to nurse, forager and reverted nurse bees (nurses that have returned to the nursing state after a period spent foraging) from the same colony in order to compare the outcomes of these different forms of genomic analysis. A total of 874 and 710 significantly differentially expressed genes were identified in forager/nurse and reverted nurse/forager comparisons respectively. Of these, 229 genes exhibited reversed directions of gene expression differences between the forager/nurse and reverted nurse/forager comparisons. Using methyl-DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) we identified 366 and 442 significantly differentially methylated genes in forager/nurse and reverted nurse/forager comparisons respectively. Of these, 165 genes were identified as differentially methylated in both comparisons. However, very few genes were identified as both differentially expressed and differentially methylated in our comparisons of nurses and foragers. These findings confirm that changes in both gene expression and DNA methylation are involved in the nurse and forager behavioural castes, but the different analytical methods reveal quite distinct sets of candidate genes. PMID:24040006

Guan, Cui; Barron, Andrew B.; He, Xu Jiang; Wang, Zi Long; Yan, Wei Yu; Zeng, Zhi Jiang

2013-01-01

204

Discovery of Genes Related to Witches Broom Disease in Paulownia tomentosa × Paulownia fortunei by a De Novo Assembled Transcriptome  

PubMed Central

In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches’ Broom (PaWB) disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene’s roles in the developmental process and in PaWB disease resistance. PMID:24278262

Liu, Rongning; Dong, Yanpeng; Fan, Guoqiang; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Niu, Suyan

2013-01-01

205

Immune gene discovery by expressed sequence tag (EST) analysis of hemocytes in the ridgetail white prawn Exopalaemon carinicauda  

PubMed Central

The ridgetail white prawn Exopalaemon carinicauda is one of the most important commercial species in eastern China. However, little information of immune genes in E. carinicauda has been reported. To identify distinctive genes associated with immunity, an expressed sequence tag (EST) library was constructed from hemocytes of E. carinicauda. A total of 3411 clones were sequenced, yielding 2853 ESTs and the average sequence length is 436 bp. The cluster and assembly analysis yielded 1053 unique sequences including 329 contigs and 724 singletons. Blast analysis identified 593 (56.3%) of the unique sequences as orthologs of genes from other organisms (E-value < 1e-5). Based on the COG and Gene Ontology (GO), 593 unique sequences were classified. Through comparison with previous studies, 153 genes assembled from 367 ESTs have been identified as possibly involved in defense or immune functions. These genes are categorized into seven categories according to their putative functions in shrimp immune system: antimicrobial peptides, prophenoloxidase activating system, antioxidant defense systems, chaperone proteins, clottable proteins, pattern recognition receptors and other immune-related genes. According to EST abundance, the major immune-related genes were thioredoxin (141, 4.94% of all ESTs) and calmodulin (14, 0.49% of all ESTs). The EST sequences of E. carinicauda hemocytes provide important information of the immune system and lay the groundwork for development of molecular markers related to disease resistance in prawn species. PMID:23092732

Duan, Yafei; Liu, Ping; Li, Jitao; Li, Jian; Chen, Ping

2013-01-01

206

Coupled Transcriptome and Proteome Analysis of Human Lymphotropic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes  

SciTech Connect

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

Dresang, Lindsay R.; Teuton, Jeremy R.; Feng, Huichen; Jacobs, Jon M.; Camp, David G.; Purvine, Samuel O.; Gritsenko, Marina A.; Li, Zhihua; Smith, Richard D.; Sugden, Bill; Moore, Patrick S.; Chang, Yuan

2011-12-20

207

Discovery of genes related to witches broom disease in Paulownia tomentosa × Paulownia fortunei by a De Novo assembled transcriptome.  

PubMed

In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches' Broom (PaWB) disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene's roles in the developmental process and in PaWB disease resistance. PMID:24278262

Liu, Rongning; Dong, Yanpeng; Fan, Guoqiang; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Niu, Suyan

2013-01-01

208

The first set of expressed sequence tags (EST) from the medicinal mushroom Agaricus subrufescens delivers resource for gene discovery and marker development.  

PubMed

Agaricus subrufescens is one of the most important culinary-medicinal cultivable mushrooms with potentially high-added-value products and extended agronomical valorization. The development of A. subrufescens-related technologies is hampered by, among others, the lack of suitable molecular tools. Thus, this mushroom is considered as a genomic orphan species with a very limited number of available molecular markers or sequences. To fill this gap, this study reports the generation and analysis of the first set of expressed sequence tags (EST) for A. subrufescens. cDNA fragments obtained from young sporophores (SP) and vegetative mycelium in liquid culture (CL) were sequenced using 454 pyrosequencing technology. After assembly process, 4,989 and 5,125 sequences were obtained in SP and CL libraries, respectively. About 87% of the EST had significant similarity with Agaricus bisporus-predicted proteins, and 79% correspond to known proteins. Functional categorization according to Gene Ontology could be assigned to 49% of the sequences. Some gene families potentially involved in bioactive compound biosynthesis could be identified. A total of 232 simple sequence repeats (SSRs) were identified, and a set of 40 EST-SSR polymorphic markers were successfully developed. This EST dataset provides a new resource for gene discovery and molecular marker development. It constitutes a solid basis for further genetic and genomic studies in A. subrufescens. PMID:24917377

Foulongne-Oriol, Marie; Lapalu, Nicolas; Férandon, Cyril; Spataro, Cathy; Ferrer, Nathalie; Amselem, Joelle; Savoie, Jean-Michel

2014-09-01

209

Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes.  

PubMed

The mechanisms generating precise connections between specific thalamic nuclei and cortical areas remain poorly understood. Using axon tracing analysis of ephrin/Eph mutant mice, we provide in vivo evidence that Eph receptors in the thalamus and ephrins in the cortex control intra-areal topographic mapping of thalamocortical (TC) axons. In addition, we show that the same ephrin/Eph genes unexpectedly control the inter-areal specificity of TC projections through the early topographic sorting of TC axons in an intermediate target, the ventral telencephalon. Our results constitute the first identification of guidance cues involved in inter-areal specificity of TC projections and demonstrate that the same set of mapping labels is used differentially for the generation of topographic specificity of TC projections between and within individual cortical areas. PMID:12895420

Dufour, Audrey; Seibt, Julie; Passante, Lara; Depaepe, Vanessa; Ciossek, Thomas; Frisén, Jonas; Kullander, Klas; Flanagan, John G; Polleux, Franck; Vanderhaeghen, Pierre

2003-07-31

210

Discovery of Genes Related to Insecticide Resistance in Bactrocera dorsalis by Functional Genomic Analysis of a De Novo Assembled Transcriptome  

PubMed Central

Insecticide resistance has recently become a critical concern for control of many insect pest species. Genome sequencing and global quantization of gene expression through analysis of the transcriptome can provide useful information relevant to this challenging problem. The oriental fruit fly, Bactrocera dorsalis, is one of the world's most destructive agricultural pests, and recently it has been used as a target for studies of genetic mechanisms related to insecticide resistance. However, prior to this study, the molecular data available for this species was largely limited to genes identified through homology. To provide a broader pool of gene sequences of potential interest with regard to insecticide resistance, this study uses whole transcriptome analysis developed through de novo assembly of short reads generated by next-generation sequencing (NGS). The transcriptome of B. dorsalis was initially constructed using Illumina's Solexa sequencing technology. Qualified reads were assembled into contigs and potential splicing variants (isotigs). A total of 29,067 isotigs have putative homologues in the non-redundant (nr) protein database from NCBI, and 11,073 of these correspond to distinct D. melanogaster proteins in the RefSeq database. Approximately 5,546 isotigs contain coding sequences that are at least 80% complete and appear to represent B. dorsalis genes. We observed a strong correlation between the completeness of the assembled sequences and the expression intensity of the transcripts. The assembled sequences were also used to identify large numbers of genes potentially belonging to families related to insecticide resistance. A total of 90 P450-, 42 GST-and 37 COE-related genes, representing three major enzyme families involved in insecticide metabolism and resistance, were identified. In addition, 36 isotigs were discovered to contain target site sequences related to four classes of resistance genes. Identified sequence motifs were also analyzed to characterize putative polypeptide translational products and associate them with specific genes and protein functions. PMID:22879883

Hsu, Ju-Chun; Wu, Wen-Jer; Feng, Hai-Tung; Haymer, David S.; Chen, Chien-Yu

2012-01-01

211

Discovery of dominant and dormant genes from expression data using a novel generalization of SNR for multi-class problems  

Microsoft Academic Search

BACKGROUND: The Signal-to-Noise-Ratio (SNR) is often used for identification of biomarkers for two-class problems and no formal and useful generalization of SNR is available for multiclass problems. We propose innovative generalizations of SNR for multiclass cancer discrimination through introduction of two indices, Gene Dominant Index and Gene Dormant Index (GDIs). These two indices lead to the concepts of dominant and

Yu-shuen Tsai; Chin-teng Lin; George C. Tseng; I-fang Chung; Nikhil Ranjan Pal

2008-01-01

212

High Throughput Screening of Co-Expressed Gene Pairs with Controlled False Discovery Rate (FDR) and Minimum Acceptable Strength (MAS)  

Microsoft Academic Search

Many exploratory microarray data analysis tools such as gene clustering and relevance networks rely on detecting pairwise gene co-expression. Traditional screening of pairwise co-expression either controls bio- logical significance or statistical significance, but not both. The former approach does not provide stochastic error control, and the later approach screens many co-expressions with excessively low correlation. We have designed and implemented

Dongxiao Zhu; Alfred O. Hero; Zhaohui S. Qin; Anand Swaroop

2005-01-01

213

De Novo Assembly, Gene Annotation, and Marker Discovery in Stored-Product Pest Liposcelis entomophila (Enderlein) Using Transcriptome Sequences  

PubMed Central

Background As a major stored-product pest insect, Liposcelis entomophila has developed high levels of resistance to various insecticides in grain storage systems. However, the molecular mechanisms underlying resistance and environmental stress have not been characterized. To date, there is a lack of genomic information for this species. Therefore, studies aimed at profiling the L. entomophila transcriptome would provide a better understanding of the biological functions at the molecular levels. Methodology/Principal Findings We applied Illumina sequencing technology to sequence the transcriptome of L. entomophila. A total of 54,406,328 clean reads were obtained and that de novo assembled into 54,220 unigenes, with an average length of 571 bp. Through a similarity search, 33,404 (61.61%) unigenes were matched to known proteins in the NCBI non-redundant (Nr) protein database. These unigenes were further functionally annotated with gene ontology (GO), cluster of orthologous groups of proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A large number of genes potentially involved in insecticide resistance were manually curated, including 68 putative cytochrome P450 genes, 37 putative glutathione S-transferase (GST) genes, 19 putative carboxyl/cholinesterase (CCE) genes, and other 126 transcripts to contain target site sequences or encoding detoxification genes representing eight types of resistance enzymes. Furthermore, to gain insight into the molecular basis of the L. entomophila toward thermal stresses, 25 heat shock protein (Hsp) genes were identified. In addition, 1,100 SSRs and 57,757 SNPs were detected and 231 pairs of SSR primes were designed for investigating the genetic diversity in future. Conclusions/Significance We developed a comprehensive transcriptomic database for L. entomophila. These sequences and putative molecular markers would further promote our understanding of the molecular mechanisms underlying insecticide resistance or environmental stress, and will facilitate studies on population genetics for psocids, as well as providing useful information for functional genomic research in the future. PMID:24244605

Wei, Dan-Dan; Chen, Er-Hu; Ding, Tian-Bo; Chen, Shi-Chun; Dou, Wei; Wang, Jin-Jun

2013-01-01

214

De Novo Assembly and Discovery of Genes That Are Involved in Drought Tolerance in Tibetan Sophora moorcroftiana  

PubMed Central

Sophora moorcroftiana, a Leguminosae shrub species that is restricted to the arid and semi-arid regions of the Qinghai-Tibet Plateau, is an ecologically important foundation species and exhibits substantial drought tolerance in the Plateau. There are no functional genomics resources in public databases for understanding the molecular mechanism underlying the drought tolerance of S. moorcroftiana. Therefore, we performed a large-scale transcriptome sequencing of this species under drought stress using the Illumina sequencing technology. A total of 62,348,602 clean reads were obtained. The assembly of the clean reads resulted in 146,943 transcripts, including 66,026 unigenes. In the assembled sequences, 1534 transcription factors were identified and classified into 23 different common families, and 9040 SSR loci, from di- to hexa-nucleotides, whose repeat number is greater than five, were presented. In addition, we performed a gene expression profiling analysis upon dehydration treatment. The results indicated significant differences in the gene expression profiles among the control, mild stress and severe stress. In total, 4687, 5648 and 5735 genes were identified from the comparison of mild versus control, severe versus control and severe versus mild stress, respectively. Based on the differentially expressed genes, a Gene Ontology annotation analysis indicated many dehydration-relevant categories, including ‘response to water ‘stimulus’ and ‘response to water deprivation’. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes pathway analysis uncovered some important pathways, such as ‘metabolic pathways’ and ‘plant hormone signal transduction’. In addition, the expression patterns of 25 putative genes that are involved in drought tolerance resulting from quantitative real-time PCR were consistent with their transcript abundance changes as identified by RNA-seq. The globally sequenced genes covered a considerable proportion of the S. moorcroftiana transcriptome, and the expression results may be useful to further extend the knowledge on the drought tolerance of this plant species that survives under Plateau conditions. PMID:25559297

Li, Huie; Yao, Weijie; Fu, Yaru; Li, Shaoke; Guo, Qiqiang

2015-01-01

215

Discovery of genes related to insecticide resistance in Bactrocera dorsalis by functional genomic analysis of a de novo assembled transcriptome.  

PubMed

Insecticide resistance has recently become a critical concern for control of many insect pest species. Genome sequencing and global quantization of gene expression through analysis of the transcriptome can provide useful information relevant to this challenging problem. The oriental fruit fly, Bactrocera dorsalis, is one of the world's most destructive agricultural pests, and recently it has been used as a target for studies of genetic mechanisms related to insecticide resistance. However, prior to this study, the molecular data available for this species was largely limited to genes identified through homology. To provide a broader pool of gene sequences of potential interest with regard to insecticide resistance, this study uses whole transcriptome analysis developed through de novo assembly of short reads generated by next-generation sequencing (NGS). The transcriptome of B. dorsalis was initially constructed using Illumina's Solexa sequencing technology. Qualified reads were assembled into contigs and potential splicing variants (isotigs). A total of 29,067 isotigs have putative homologues in the non-redundant (nr) protein database from NCBI, and 11,073 of these correspond to distinct D. melanogaster proteins in the RefSeq database. Approximately 5,546 isotigs contain coding sequences that are at least 80% complete and appear to represent B. dorsalis genes. We observed a strong correlation between the completeness of the assembled sequences and the expression intensity of the transcripts. The assembled sequences were also used to identify large numbers of genes potentially belonging to families related to insecticide resistance. A total of 90 P450-, 42 GST-and 37 COE-related genes, representing three major enzyme families involved in insecticide metabolism and resistance, were identified. In addition, 36 isotigs were discovered to contain target site sequences related to four classes of resistance genes. Identified sequence motifs were also analyzed to characterize putative polypeptide translational products and associate them with specific genes and protein functions. PMID:22879883

Hsu, Ju-Chun; Chien, Ting-Ying; Hu, Chia-Cheng; Chen, Mei-Ju May; Wu, Wen-Jer; Feng, Hai-Tung; Haymer, David S; Chen, Chien-Yu

2012-01-01

216

Tissue microarrays in drug discovery  

Microsoft Academic Search

Advances in molecular methods have massively facilitated the discovery of potential molecular targets for gene-specific therapy. Accelerated lead discovery has at the same time generated a massive demand for thorough validation of such putative targets. Very often human tissue analysis is needed for this purpose. However, the need to analyse large numbers of well-characterized human tissues constitutes a major bottleneck

Ronald Simon; Kenneth Hillan; Guido Sauter

2003-01-01

217

Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families.  

PubMed

Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function. PMID:25558065

Alazami, Anas M; Patel, Nisha; Shamseldin, Hanan E; Anazi, Shamsa; Al-Dosari, Mohammed S; Alzahrani, Fatema; Hijazi, Hadia; Alshammari, Muneera; Aldahmesh, Mohammed A; Salih, Mustafa A; Faqeih, Eissa; Alhashem, Amal; Bashiri, Fahad A; Al-Owain, Mohammed; Kentab, Amal Y; Sogaty, Sameera; Al Tala, Saeed; Temsah, Mohamad-Hani; Tulbah, Maha; Aljelaify, Rasha F; Alshahwan, Saad A; Seidahmed, Mohammed Zain; Alhadid, Adnan A; Aldhalaan, Hesham; AlQallaf, Fatema; Kurdi, Wesam; Alfadhel, Majid; Babay, Zainab; Alsogheer, Mohammad; Kaya, Namik; Al-Hassnan, Zuhair N; Abdel-Salam, Ghada M H; Al-Sannaa, Nouriya; Al Mutairi, Fuad; El Khashab, Heba Y; Bohlega, Saeed; Jia, Xiaofei; Nguyen, Henry C; Hammami, Rakad; Adly, Nouran; Mohamed, Jawahir Y; Abdulwahab, Firdous; Ibrahim, Niema; Naim, Ewa A; Al-Younes, Banan; Meyer, Brian F; Hashem, Mais; Shaheen, Ranad; Xiong, Yong; Abouelhoda, Mohamed; Aldeeri, Abdulrahman A; Monies, Dorota M; Alkuraya, Fowzan S

2015-01-13

218

Discovery of a Linear Peptide for Improving Tumor Targeting of Gene Products and Treatment of Distal Tumors by IL-12 Gene Therapy  

PubMed Central

Like many effective therapeutics, interleukin-12 (IL-12) therapy often causes side effects. Tumor targeted delivery may improve the efficacy and decrease the toxicity of systemic IL-12 treatments. In this study, a novel targeting approach was investigated. A secreted alkaline phosphatase (SEAP) reporter gene-based screening process was used to identify a mini-peptide which can be produced in vivo to target gene products to tumors. The coding region for the best peptide was inserted into an IL-12 gene to determine the antitumor efficacy. Affinity chromatography, mass spectrometry analysis, and binding studies were used to identify a receptor for this peptide. We discovered that the linear peptide VNTANST increased the tumor accumulation of the reporter gene products in five independent tumor models including one human xenogeneic model. The product from VNTANST-IL-12 fusion gene therapy increased accumulation of IL-12 in the tumor environment, and in three tumor models, VNTANST-IL-12 gene therapy inhibited distal tumor growth. In a spontaneous lung metastasis model, inhibition of metastatic tumor growth was improved compared to wild-type IL-12 gene therapy, and in a squamous cell carcinoma model, toxic liver lesions were reduced. The receptor for VNTANST was identified as vimentin. These results show the promise of using VNTANST to improve IL-12 treatments. PMID:21386825

Cutrera, Jeffry; Dibra, Denada; Xia, Xueqing; Hasan, Azeem; Reed, Scott; Li, Shulin

2011-01-01

219

Transcriptome-based discovery of pathways and genes related to resistance against Fusarium head blight in wheat landrace Wangshuibai  

PubMed Central

Background Fusarium head blight (FHB), caused mainly by Fusarium graminearum (Fg) Schwabe (teleomorph: Gibberellazeae Schwble), brings serious damage to wheat production. Chinese wheat landrace Wangshuibai is one of the most important resistance sources in the world. The knowledge of mechanism underlying its resistance to FHB is still limited. Results To get an overview of transcriptome characteristics of Wangshuibai during infection by Fg, a high-throughput RNA sequencing based on next generation sequencing (NGS) technology (Illumina) were performed. Totally, 165,499 unigenes were generated and assigned to known protein databases including NCBI non-redundant protein database (nr) (82,721, 50.0%), Gene Ontology (GO) (38,184, 23.1%), Swiss-Prot (50,702, 30.6%), Clusters of orthologous groups (COG) (51,566, 31.2%) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) (30,657, 18.5%), as determined by Blastx search. With another NGS based platform, a digital gene expression (DGE) system, gene expression in Wangshuibai and its FHB susceptible mutant NAUH117 was profiled and compared at two infection stages by inoculation of Fg at 24 and 48 hour, with the aim of identifying genes involved in FHB resistance. Conclusion Pathogen-related proteins such as PR5, PR14 and ABC transporter and JA signaling pathway were crucial for FHB resistance, especially that mediated by Fhb1. ET pathway and ROS/NO pathway were not activated in Wangshuibai and may be not pivotal in defense to FHB. Consistent with the fact that in NAUH117 there presented a chromosome fragment deletion, which led to its increased FHB susceptibility, in Wangshuibai, twenty out of eighty-nine genes showed changed expression patterns upon the infection of Fg. The up-regulation of eight of them was confirmed by qRT-PCR, revealing they may be candidate genes for Fhb1 and need further functional analysis to confirm their roles in FHB resistance. PMID:23514540

2013-01-01

220

High-Throughput Sequence Analysis of Turbot (Scophthalmus maximus) Transcriptome Using 454-Pyrosequencing for the Discovery of Antiviral Immune Genes  

PubMed Central

Background Turbot (Scophthalmus maximus L.) is an important aquacultural resource both in Europe and Asia. However, there is little information on gene sequences available in public databases. Currently, one of the main problems affecting the culture of this flatfish is mortality due to several pathogens, especially viral diseases which are not treatable. In order to identify new genes involved in immune defense, we conducted 454-pyrosequencing of the turbot transcriptome after different immune stimulations. Methodology/Principal Findings Turbot were injected with viral stimuli to increase the expression level of immune-related genes. High-throughput deep sequencing using 454-pyrosequencing technology yielded 915,256 high-quality reads. These sequences were assembled into 55,404 contigs that were subjected to annotation steps. Intriguingly, 55.16% of the deduced protein was not significantly similar to any sequences in the databases used for the annotation and only 0.85% of the BLASTx top-hits matched S. maximus protein sequences. This relatively low level of annotation is possibly due to the limited information for this specie and other flatfish in the database. These results suggest the identification of a large number of new genes in turbot and in fish in general. A more detailed analysis showed the presence of putative members of several innate and specific immune pathways. Conclusions/Significance To our knowledge, this study is the first transcriptome analysis using 454-pyrosequencing for turbot. Previously, there were only 12,471 EST and less of 1,500 nucleotide sequences for S. maximus in NCBI database. Our results provide a rich source of data (55,404 contigs and 181,845 singletons) for discovering and identifying new genes, which will serve as a basis for microarray construction, gene expression characterization and for identification of genetic markers to be used in several applications. Immune stimulation in turbot was very effective, obtaining an enormous variety of sequences belonging to genes involved in the defense mechanisms. PMID:22629298

Pereiro, Patricia; Balseiro, Pablo; Romero, Alejandro; Dios, Sonia; Forn-Cuni, Gabriel; Fuste, Berta; Planas, Josep V.; Beltran, Sergi; Novoa, Beatriz; Figueras, Antonio

2012-01-01

221

Toxins and drug discovery.  

PubMed

Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process. PMID:25448391

Harvey, Alan L

2014-12-15

222

Discovery of Novel Leaf Rust Responsive microRNAs in Wheat and Prediction of Their Target Genes  

PubMed Central

MicroRNAs are endogenous small noncoding RNAs which play critical roles in gene regulation. Few wheat (Triticum aestivum L.) miRNA sequences are available in miRBase repertoire and knowledge of their biological functions related to biotic stress is limited. We identified 52 miRNAs, belonging to 19 families, from next-generation transcriptome sequence data based on homology search. One wheat specific novel miRNA was identified but could not be ascribed or assigned to any known miRNA family. Differentially expressed 22 miRNAs were found between susceptible and resistant wheat near-isogenic lines inoculated with leaf rust pathogen Puccinia triticina and compared with mock inoculated controls. Most miRNAs were more upregulated in susceptible NIL compared to resistant NIL. We identified 1306 potential target genes for these 52 miRNAs with vital roles in response to stimuli, signaling, and diverse metabolic and cellular processes. Gene ontology analysis showed 66, 20, and 35 target genes to be categorized into biological process, molecular function, and cellular component, respectively. A miRNA-mediated regulatory network revealed relationships among the components of the targetome. The present study provides insight into potential miRNAs with probable roles in leaf rust pathogenesis and their target genes in wheat which establish a foundation for future studies. PMID:25180085

Kumar, Dhananjay; Singh, Dharmendra; Kanodia, Pulkit; Prabhu, Kumble Vinod; Kumar, Manish; Mukhopadhyay, Kunal

2014-01-01

223

De Novo Transcriptome Analysis of an Aerial Microalga Trentepohlia jolithus: Pathway Description and Gene Discovery for Carbon Fixation and Carotenoid Biosynthesis  

PubMed Central

Background Algae in the order Trentepohliales have a broad geographic distribution and are generally characterized by the presence of abundant ?-carotene. The many monographs published to date have mainly focused on their morphology, taxonomy, phylogeny, distribution and reproduction; molecular studies of this order are still rare. High-throughput RNA sequencing (RNA-Seq) technology provides a powerful and efficient method for transcript analysis and gene discovery in Trentepohlia jolithus. Methods/Principal Findings Illumina HiSeq 2000 sequencing generated 55,007,830 Illumina PE raw reads, which were assembled into 41,328 assembled unigenes. Based on NR annotation, 53.28% of the unigenes (22,018) could be assigned to gene ontology classes with 54 subcategories and 161,451 functional terms. A total of 26,217 (63.44%) assembled unigenes were mapped to 128 KEGG pathways. Furthermore, a set of 5,798 SSRs in 5,206 unigenes and 131,478 putative SNPs were identified. Moreover, the fact that all of the C4 photosynthesis genes exist in T. jolithus suggests a complex carbon acquisition and fixation system. Similarities and differences between T. jolithus and other algae in carotenoid biosynthesis are also described in depth. Conclusions/Significance This is the first broad transcriptome survey for T. jolithus, increasing the amount of molecular data available for the class Ulvophyceae. As well as providing resources for functional genomics studies, the functional genes and putative pathways identified here will contribute to a better understanding of carbon fixation and fatty acid and carotenoid biosynthesis in T. jolithus. PMID:25254555

Li, Qianqian; Liu, Jianguo; Zhang, Litao; Liu, Qian

2014-01-01

224

Analysis of Temporal-spatial Co-variation within Gene Expression Microarray Data in an  

E-print Network

as defined by Gene Ontology at lower false discovery rates. This new methodology builds on the advantages of LCM to isolate pure phenotypic populations within complex tissues and allows improved abil- ity of these models. The Gene Ontology project [1, 7] can help to incorporate the known biological details of gene

Ehler, Martin

225

STARNET 2: a web-based tool for accelerating discovery of gene regulatory networks using microarray co-expression data  

Microsoft Academic Search

Background: Although expression microarrays have become a standard tool used by biologists, analysis of data produced by microarray experiments may still present challenges. Comparison of data from different platforms, organisms, and labs may involve complicated data processing, and inferring relationships between genes remains difficult. Results: STARNET 2 is a new web-based tool that allows post hoc visual analysis of correlations

Daniel Jupiter; Hailin Chen; Vincent VanBuren

2009-01-01

226

Gene discovery for comparative biology of parasitic and non-parasitic plants. A five-week molecular research immersion  

Microsoft Academic Search

As part of an NSF-funded initiative, biology students, primarily those in the early stages of their degree program, were recruited to participate in ongoing research alongside principle investigators. In this example, ten students were given five weeks of intensive training in molecular research methods, with the objective of cloning genes involved in core metabolic processes in the parasitic plant Cuscuta

Mark A. Schoenbeck

227

SNP discovery and development of genetic markers for mapping immune response genes in common carp (Cyprinus carpio)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Single nucleotide polymorphisms (SNPs) in immune response genes have been reported as markers for susceptibility to infectious diseases in human and livestock. A disease caused by cyprinid herpesvirus 3 (CyHV-3) is highly contagious and virulent in common carp (Cyprinus carpio). With the aim to de...

228

Functional Gene-Guided Discovery of Type II Polyketides from Culturable Actinomycetes Associated with Soft Coral Scleronephthya sp  

PubMed Central

Compared with the actinomycetes in stone corals, the phylogenetic diversity of soft coral-associated culturable actinomycetes is essentially unexplored. Meanwhile, the knowledge of the natural products from coral-associated actinomycetes is very limited. In this study, thirty-two strains were isolated from the tissue of the soft coral Scleronephthya sp. in the East China Sea, which were grouped into eight genera by 16S rDNA phylogenetic analysis: Micromonospora, Gordonia, Mycobacterium, Nocardioides, Streptomyces, Cellulomonas, Dietzia and Rhodococcus. 6 Micromonospora strains and 4 Streptomyces strains were found to be with the potential for producing aromatic polyketides based on the analysis of KS? (ketoacyl-synthase) gene in the PKS II (type II polyketides synthase) gene cluster. Among the 6 Micromonospora strains, angucycline cyclase gene was amplified in 2 strains (A5-1 and A6-2), suggesting their potential in synthesizing angucyclines e.g. jadomycin. Under the guidance of functional gene prediction, one jadomycin B analogue (7b, 13-dihydro-7-O-methyl jadomycin B) was detected in the fermentation broth of Micromonospora sp. strain A5-1. This study highlights the phylogenetically diverse culturable actinomycetes associated with the tissue of soft coral Scleronephthya sp. and the potential of coral-derived actinomycetes especially Micromonospora in producing aromatic polyketides. PMID:22880121

Sun, Wei; Peng, Chongsheng; Zhao, Yunyu; Li, Zhiyong

2012-01-01

229

Gene discovery in the finger leather coral Sinularia notanda by construction and sequencing of a normalized cDNA libary.  

PubMed

The transplantation of coral fragments is one of methods that restore coral communities. To form coral colonies, the fragmented corals initiated skeletal extension from the cut-edge of fragment then success the settlement. To better understand the molecular events underlying fragment adhesion and settlement, we constructed a normalized cDNA library and generated and annotated expressed sequence tags (ESTs) from the fragmented adult polyps of soft coral Sinularia notanda. We generated 3251 high-quality ESTs with an average length of 580bp and the EST cluster and assembly analyses produced 2796 unigenes, including 2487 singletons and 309 contigs. Of the known genes, 55 genes were selected to be involved in polyp fragment adhesion and settlement based on Gene Ontology (GO) classification. Notably, two EST clones were identified to show homology with galaxin gene which was demonstrated as coral specific calcifying protein of organic matrix. These EST sequences can provide utility as molecular markers in molecular and genetic studies of S. notanda and other soft coral. PMID:25450166

Kim, Jae-Woo; Kim, Seong Ho; Jung, Min-Min; Kim, Heung Soo; Han, Seock-Jung; Moon, Tae Seok; Kim, Bong-Seok; Nam, Bo-Hye; Park, Chan-Il

2014-11-01

230

Discovery of single nucleotide polymorphisms in candidate genes associated with fertility and production traits in Holstein cattle  

PubMed Central

Background Identification of single nucleotide polymorphisms (SNPs) for specific genes involved in reproduction might improve reliability of genomic estimates for these low-heritability traits. Semen from 550 Holstein bulls of high (? 1.7; n?=?288) or low (? ?2; n?=?262) daughter pregnancy rate (DPR) was genotyped for 434 candidate SNPs using the Sequenom MassARRAY® system. Three types of SNPs were evaluated: SNPs previously reported to be associated with reproductive traits or physically close to genetic markers for reproduction, SNPs in genes that are well known to be involved in reproductive processes, and SNPs in genes that are differentially expressed between physiological conditions in a variety of tissues associated in reproductive function. Eleven reproduction and production traits were analyzed. Results A total of 40 SNPs were associated (P?genes involved in the endocrine system, cell signaling, immune function and inhibition of apoptosis. A total of 10 genes were regulated by estradiol. In addition, 22 SNPs were associated with heifer conception rate, 33 with cow conception rate, 36 with productive life, 34 with net merit, 23 with milk yield, 19 with fat yield, 13 with fat percent, 19 with protein yield, 22 with protein percent, and 13 with somatic cell score. The allele substitution effect for SNPs associated with heifer conception rate, cow conception rate, productive life and net merit were in the same direction as for DPR. Allele substitution effects for several SNPs associated with production traits were in the opposite direction as DPR. Nonetheless, there were 29 SNPs associated with DPR that were not negatively associated with production traits. Conclusion SNPs in a total of 40 genes associated with DPR were identified as well as SNPs for other traits. It might be feasible to include these SNPs into genomic tests of reproduction and other traits. The genes associated with DPR are likely to be important for understanding the physiology of reproduction. Given the large number of SNPs associated with DPR that were not negatively associated with production traits, it should be possible to select for DPR without compromising production. PMID:23759029

2013-01-01

231

A Novel Biclustering Algorithm for the Discovery of Meaningful Biological Correlations between microRNAs and their Target Genes  

PubMed Central

Background microRNAs (miRNAs) are a class of small non-coding RNAs which have been recognized as ubiquitous post-transcriptional regulators. The analysis of interactions between different miRNAs and their target genes is necessary for the understanding of miRNAs' role in the control of cell life and death. In this paper we propose a novel data mining algorithm, called HOCCLUS2, specifically designed to bicluster miRNAs and target messenger RNAs (mRNAs) on the basis of their experimentally-verified and/or predicted interactions. Indeed, existing biclustering approaches, typically used to analyze gene expression data, fail when applied to miRNA:mRNA interactions since they usually do not extract possibly overlapping biclusters (miRNAs and their target genes may have multiple roles), extract a huge amount of biclusters (difficult to browse and rank on the basis of their importance) and work on similarities of feature values (do not limit the analysis to reliable interactions). Results To overcome these limitations, HOCCLUS2 i) extracts possibly overlapping biclusters, to catch multiple roles of both miRNAs and their target genes; ii) extracts hierarchically organized biclusters, to facilitate bicluster browsing and to distinguish between universe and pathway-specific miRNAs; iii) extracts highly cohesive biclusters, to consider only reliable interactions; iv) ranks biclusters according to the functional similarities, computed on the basis of Gene Ontology, to facilitate bicluster analysis. Conclusions Our results show that HOCCLUS2 is a valid tool to support biologists in the identification of context-specific miRNAs regulatory modules and in the detection of possibly unknown miRNAs target genes. Indeed, results prove that HOCCLUS2 is able to extract cohesiveness-preserving biclusters, when compared with competitive approaches, and statistically confirm (at a confidence level of 99%) that mRNAs which belong to the same biclusters are, on average, more functionally similar than mRNAs which belong to different biclusters. Finally, the hierarchy of biclusters provides useful insights to understand the intrinsic hierarchical organization of miRNAs and their potential multiple interactions on target genes. PMID:23815553

2013-01-01

232

Generation of expressed sequence tags under cadmium stress for gene discovery and development of molecular markers in chickpea.  

PubMed

Chickpea is the world's third most important legume crop and belongs to Fabaceae family but suffered from severe yield loss due to various biotic and abiotic stresses. Development of modern genomic tools such as molecular markers and identification of resistant genes associated with these stresses facilitate improvement in chickpea breeding towards abiotic stress tolerance. In this study, 1597 high-quality expressed sequence tags (ESTs) were generated from a cDNA library of variety Pusa 1105 root tissue after cadmium (Cd) treatment. Assembly of ESTs resulted in a total of 914 unigenes of which putative homology was obtained for 38.8 % of unigenes after BLASTX search. In terms of species distribution, majority of sequences found similarity with Medicago truncatula followed by Glycine max, Vitis vinifera and Populus trichocarpa and Pisum sativum sequences. Functional annotation was assigned using Blast2Go, and the Gene Ontology (GO) terms were categorized into biological process, molecular function and cellular component. Approximately 10.83 % of unigenes were assigned at least one GO term. Moreover, in the distribution of transcripts into various biological pathways, 20 of the annotated transcripts were assigned to ten pathways in KEGG database. A majority of the genes were found to be involved in sulphur and nitrogen metabolism. In the quantitative real-time PCR analysis, five of the transcription factors and three of the transporter genes were found to be highly expressed after Cd treatment. Besides, the utility of ESTs was demonstrated by exploiting them for the development of 83 genic molecular markers including EST-simple sequence repeats and intron targeted polymorphism that would assist in tagging of genes related to metal stress for future prospects. PMID:24414095

Gaur, Rashmi; Bhatia, Sabhyata; Gupta, Meetu

2014-07-01

233

Transcriptome profiling of the testis reveals genes involved in spermatogenesis and marker discovery in the oriental fruit fly, Bactrocera dorsalis.  

PubMed

The testis is a highly specialized tissue that plays a vital role in ensuring fertility by producing spermatozoa, which are transferred to the female during mating. Spermatogenesis is a complex process, resulting in the production of mature sperm, and involves significant structural and biochemical changes in the seminiferous epithelium of the adult testis. The identification of genes involved in spermatogenesis of Bactrocera dorsalis (Hendel) is critical for a better understanding of its reproductive development. In this study, we constructed a cDNA library of testes from male B.?dorsalis adults at different ages, and performed de novo transcriptome sequencing to produce a comprehensive transcript data set, using Illumina sequencing technology. The analysis yielded 52?016?732 clean reads, including a total of 4.65?Gb of nucleotides. These reads were assembled into 47?677 contigs (average 443?bp) and then clustered into 30?516 unigenes (average 756?bp). Based on BLAST hits with known proteins in different databases, 20?921 unigenes were annotated with a cut-off E-value of 10(-5) . The transcriptome sequences were further annotated using the Clusters of Orthologous Groups, Gene Orthology and the Kyoto Encyclopedia of Genes and Genomes databases. Functional genes involved in spermatogenesis were analysed, including cell cycle proteins, metalloproteins, actin, and ubiquitin and antihyperthermia proteins. Several testis-specific genes were also identified. The transcripts database will help us to understand the molecular mechanisms underlying spermatogenesis in B.?dorsalis. Furthermore, 2913 simple sequence repeats and 151?431 single nucleotide polymorphisms were identified, which will be useful for investigating the genetic diversity of B.?dorsalis in the future. PMID:25255964

Wei, D; Li, H-M; Yang, W-J; Wei, D-D; Dou, W; Huang, Y; Wang, J-J

2015-02-01

234

Scientific Discovery for All  

ERIC Educational Resources Information Center

The scientific discovery process comes alive for 70 minority students each year at Uniondale High School in New York where students have won top awards for "in-house" projects. Uniondale High School is in a middle-income school district where over 95% of students are from minority groups. Founded in 2000, the Uniondale High School Research Program…

Zaikowski, Lori; Lichtman, Paul; Quarless, Duncan

2007-01-01

235

Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies  

NASA Astrophysics Data System (ADS)

Current techniques for three-dimensional (3D) optical microscopy (deconvolution, confocal microscopy, and optical coherence tomography) generate 3D data by ``optically sectioning'' the specimen. This places severe constraints on the maximum thickness of a specimen that can be imaged. We have developed a microscopy technique that uses optical projection tomography (OPT) to produce high-resolution 3D images of both fluorescent and nonfluorescent biological specimens with a thickness of up to 15 millimeters. OPT microscopy allows the rapid mapping of the tissue distribution of RNA and protein expression in intact embryos or organ systems and can therefore be instrumental in studies of developmental biology or gene function.

Sharpe, James; Ahlgren, Ulf; Perry, Paul; Hill, Bill; Ross, Allyson; Hecksher-Sørensen, Jacob; Baldock, Richard; Davidson, Duncan

2002-04-01

236

Transcriptome Analysis of the Portunus trituberculatus: De Novo Assembly, Growth-Related Gene Identification and Marker Discovery  

PubMed Central

Background The swimming crab, Portunus trituberculatus, is an important farmed species in China, has been attracting extensive studies, which require more and more genome background knowledge. To date, the sequencing of its whole genome is unavailable and transcriptomic information is also scarce for this species. In the present study, we performed de novo transcriptome sequencing to produce a comprehensive transcript dataset for major tissues of Portunus trituberculatus by the Illumina paired-end sequencing technology. Results Total RNA was isolated from eyestalk, gill, heart, hepatopancreas and muscle. Equal quantities of RNA from each tissue were pooled to construct a cDNA library. Using the Illumina paired-end sequencing technology, we generated a total of 120,137 transcripts with an average length of 1037 bp. Further assembly analysis showed that all contigs contributed to 87,100 unigenes, of these, 16,029 unigenes (18.40% of the total) can be matched in the GenBank non-redundant database. Potential genes and their functions were predicted by GO, KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literature, many putative genes with fundamental roles in growth and muscle development, including actin, myosin, tropomyosin, troponin and other potentially important candidate genes were identified for the first time in this specie. Furthermore, 22,673 SSRs and 66,191 high-confidence SNPs were identified in this EST dataset. Conclusion The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in Portunus trituberculatus. The data will also instruct future functional studies to manipulate or select for genes influencing growth that should find practical applications in aquaculture breeding programs. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will be essential for accelerating aquaculture breeding programs with this species. PMID:24722690

Lv, Jianjian; Liu, Ping; Gao, Baoquan; Wang, Yu; Wang, Zheng; Chen, Ping; Li, Jian

2014-01-01

237

Discovery of genes implicated in whirling disease infection and resistance in rainbow trout using genome-wide expression profiling  

PubMed Central

Background Whirling disease, caused by the pathogen Myxobolus cerebralis, afflicts several salmonid species. Rainbow trout are particularly susceptible and may suffer high mortality rates. The disease is persistent and spreading in hatcheries and natural waters of several countries, including the U.S.A., and the economic losses attributed to whirling disease are substantial. In this study, genome-wide expression profiling using cDNA microarrays was conducted for resistant Hofer and susceptible Trout Lodge rainbow trout strains following pathogen exposure with the primary objective of identifying specific genes implicated in whirling disease resistance. Results Several genes were significantly up-regulated in skin following pathogen exposure for both the resistant and susceptible rainbow trout strains. For both strains, response to infection appears to be linked with the interferon system. Expression profiles for three genes identified with microarrays were confirmed with qRT-PCR. Ubiquitin-like protein 1 was up-regulated over 100 fold and interferon regulating factor 1 was up-regulated over 15 fold following pathogen exposure for both strains. Expression of metallothionein B, which has known roles in inflammation and immune response, was up-regulated over 5 fold in the resistant Hofer strain but was unchanged in the susceptible Trout Lodge strain following pathogen exposure. Conclusion The present study has provided an initial view into the genetic basis underlying immune response and resistance of rainbow trout to the whirling disease parasite. The identified genes have allowed us to gain insight into the molecular mechanisms implicated in salmonid immune response and resistance to whirling disease infection. PMID:18218127

Baerwald, Melinda R; Welsh, Amy B; Hedrick, Ronald P; May, Bernie

2008-01-01

238

Discovery of bacterial polyhydroxyalkanoate synthase (PhaC)-encoding genes from seasonal Baltic Sea ice and cold estuarine waters.  

PubMed

Polyhydroxyalkanoates (PHAs) are macromolecules produced by bacteria as means for storing carbon and energy in intracellular granules. PHAs have physical properties similar to those of plastics and have become of interest to industry as materials for environmentally friendly bioplastic production. There is an ongoing search for new PHA-producing bacterial strains and PHA-synthesizing enzymes tolerating extreme conditions to find ways of producing PHAs at cold temperatures and high solute concentrations. Moreover, the study of PHA producers in the sea-ice biome can aid in understanding the microbial ecology of carbon cycling in ice-associated ecosystems. In this study, PHA producers and PHA synthase genes were examined under the extreme environmental conditions of sea ice and cold seawater to find evidence of PHA production in an environment requiring adaptation to high salinity and cold temperatures. Sea ice and cold estuarine water samples were collected from the northern Baltic Sea and evidence of PHA production was gathered, using microscopy with Nile Blue A staining of PHA-granules and PCR assays detecting PHA-synthesis genes. The PHA granules and PHA synthases were found at all sampling locations, in both sea ice and water, and throughout the sampling period spanning over 10 years. Our study shows, for the first time, that PHA synthesis occurs in Baltic Sea cold-adapted bacteria in their natural environment, which makes the Baltic Sea and its cold environments an interesting choice in the quest for PHA-synthesizing bacteria and synthesis genes. PMID:25280551

Pärnänen, Katariina; Karkman, Antti; Virta, Marko; Eronen-Rasimus, Eeva; Kaartokallio, Hermanni

2015-01-01

239

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.  

PubMed

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756

Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Del Vecchio, Lucia; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Battaglia, Giovanni Giorgio; Garozzo, Maurizio; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; P?czek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Ma?gorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J; Novak, Jan; Julian, Bruce A; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P; Gharavi, Ali G

2014-11-01

240

Schistosoma mansoni genome project: an update  

Microsoft Academic Search

A schistosome genome project was initiated by the World Health Organization in 1994 with the notion that the best prospects for identifying new targets for drugs, vaccines, and diagnostic development lie in schistosome gene discovery, development of chromosome maps, whole genome sequencing and genome analysis. Schistosoma mansoni has a haploid genome of 270 Mb contained on 8 pairs of chromosomes.

Philip T. LoVerde; Hirohisa Hirai; Joseph M. Merrick; Norman H. Lee; Najib El-Sayed

2004-01-01

241

Transcriptome Analysis of the Oriental River Prawn, Macrobrachium nipponense Using 454 Pyrosequencing for Discovery of Genes and Markers  

PubMed Central

Background The oriental river prawn, Macrobrachium nipponense, is an economically and nutritionally important species of the Palaemonidae family of decapod crustaceans. To date, the sequencing of its whole genome is unavailable as a non-model organism. Transcriptomic information is also scarce for this species. In this study, we performed de novo transcriptome sequencing to produce the first comprehensive expressed sequence tag (EST) dataset for M. nipponense using high-throughput sequencing technologies. Methodology and Principal Findings Total RNA was isolated from eyestalk, gill, heart, ovary, testis, hepatopancreas, muscle, and embryos at the cleavage, gastrula, nauplius and zoea stages. Equal quantities of RNA from each tissue and stage were pooled to construct a cDNA library. Using 454 pyrosequencing technology, we generated a total of 984,204 high quality reads (338.59Mb) with an average length of 344 bp. Clustering and assembly of these reads produced a non-redundant set of 81,411 unique sequences, comprising 42,551 contigs and 38,860 singletons. All of the unique sequences were involved in the molecular function (30,425), cellular component (44,112) and biological process (67,679) categories by GO analysis. Potential genes and their functions were predicted by KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literature, many putative genes involved in sex determination, including DMRT1, FTZ-F1, FOXL2, FEM1 and other potentially important candidate genes, were identified for the first time in this prawn. Furthermore, 6,689 SSRs and 18,107 high-confidence SNPs were identified in this EST dataset. Conclusions The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in M. nipponense. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will be essential for accelerating aquaculture breeding programs with this species. PMID:22745820

Ma, Keyi; Qiu, Gaofeng; Feng, Jianbin; Li, Jiale

2012-01-01

242

Gene Discovery for Enzymes Involved in Limonene Modification or Utilization by the Mountain Pine Beetle-Associated Pathogen Grosmannia clavigera  

PubMed Central

To successfully colonize and eventually kill pine trees, Grosmannia clavigera (Gs cryptic species), the main fungal pathogen associated with the mountain pine beetle (Dendroctonus ponderosae), has developed multiple mechanisms to overcome host tree chemical defenses, of which terpenoids are a major component. In addition to a monoterpene efflux system mediated by a recently discovered ABC transporter, Gs has genes that are highly induced by monoterpenes and that encode enzymes that modify or utilize monoterpenes [especially (+)-limonene]. We showed that pine-inhabiting Ophiostomale fungi are tolerant to monoterpenes, but only a few, including Gs, are known to utilize monoterpenes as a carbon source. Gas chromatography-mass spectrometry (GC-MS) revealed that Gs can modify (+)-limonene through various oxygenation pathways, producing carvone, p-mentha-2,8-dienol, perillyl alcohol, and isopiperitenol. It can also degrade (+)-limonene through the C-1-oxygenated pathway, producing limonene-1,2-diol as the most abundant intermediate. Transcriptome sequencing (RNA-seq) data indicated that Gs may utilize limonene 1,2-diol through beta-oxidation and then valine and tricarboxylic acid (TCA) metabolic pathways. The data also suggested that at least two gene clusters, located in genome contigs 108 and 161, were highly induced by monoterpenes and may be involved in monoterpene degradation processes. Further, gene knockouts indicated that limonene degradation required two distinct Baeyer-Villiger monooxygenases (BVMOs), an epoxide hydrolase and an enoyl coenzyme A (enoyl-CoA) hydratase. Our work provides information on enzyme-mediated limonene utilization or modification and a more comprehensive understanding of the interaction between an economically important fungal pathogen and its host's defense chemicals. PMID:24837377

Wang, Ye; Lim, Lynette; Madilao, Lina; Lah, Ljerka; Bohlmann, Joerg

2014-01-01

243

Gene discovery for enzymes involved in limonene modification or utilization by the mountain pine beetle-associated pathogen Grosmannia clavigera.  

PubMed

To successfully colonize and eventually kill pine trees, Grosmannia clavigera (Gs cryptic species), the main fungal pathogen associated with the mountain pine beetle (Dendroctonus ponderosae), has developed multiple mechanisms to overcome host tree chemical defenses, of which terpenoids are a major component. In addition to a monoterpene efflux system mediated by a recently discovered ABC transporter, Gs has genes that are highly induced by monoterpenes and that encode enzymes that modify or utilize monoterpenes [especially (+)-limonene]. We showed that pine-inhabiting Ophiostomale fungi are tolerant to monoterpenes, but only a few, including Gs, are known to utilize monoterpenes as a carbon source. Gas chromatography-mass spectrometry (GC-MS) revealed that Gs can modify (+)-limonene through various oxygenation pathways, producing carvone, p-mentha-2,8-dienol, perillyl alcohol, and isopiperitenol. It can also degrade (+)-limonene through the C-1-oxygenated pathway, producing limonene-1,2-diol as the most abundant intermediate. Transcriptome sequencing (RNA-seq) data indicated that Gs may utilize limonene 1,2-diol through beta-oxidation and then valine and tricarboxylic acid (TCA) metabolic pathways. The data also suggested that at least two gene clusters, located in genome contigs 108 and 161, were highly induced by monoterpenes and may be involved in monoterpene degradation processes. Further, gene knockouts indicated that limonene degradation required two distinct Baeyer-Villiger monooxygenases (BVMOs), an epoxide hydrolase and an enoyl coenzyme A (enoyl-CoA) hydratase. Our work provides information on enzyme-mediated limonene utilization or modification and a more comprehensive understanding of the interaction between an economically important fungal pathogen and its host's defense chemicals. PMID:24837377

Wang, Ye; Lim, Lynette; Madilao, Lina; Lah, Ljerka; Bohlmann, Joerg; Breuil, Colette

2014-08-01

244

Insights into shell deposition in the Antarctic bivalve Laternula elliptica: gene discovery in the mantle transcriptome using 454 pyrosequencing  

PubMed Central

Background The Antarctic clam, Laternula elliptica, is an infaunal stenothermal bivalve mollusc with a circumpolar distribution. It plays a significant role in bentho-pelagic coupling and hence has been proposed as a sentinel species for climate change monitoring. Previous studies have shown that this mollusc displays a high level of plasticity with regard to shell deposition and damage repair against a background of genetic homogeneity. The Southern Ocean has amongst the lowest present-day CaCO3 saturation rate of any ocean region, and is predicted to be among the first to become undersaturated under current ocean acidification scenarios. Hence, this species presents as an ideal candidate for studies into the processes of calcium regulation and shell deposition in our changing ocean environments. Results 454 sequencing of L. elliptica mantle tissue generated 18,290 contigs with an average size of 535 bp (ranging between 142 bp-5.591 kb). BLAST sequence similarity searching assigned putative function to 17% of the data set, with a significant proportion of these transcripts being involved in binding and potentially of a secretory nature, as defined by GO molecular function and biological process classifications. These results indicated that the mantle is a transcriptionally active tissue which is actively proliferating. All transcripts were screened against an in-house database of genes shown to be involved in extracellular matrix formation and calcium homeostasis in metazoans. Putative identifications were made for a number of classical shell deposition genes, such as tyrosinase, carbonic anhydrase and metalloprotease 1, along with novel members of the family 2 G-Protein Coupled Receptors (GPCRs). A membrane transport protein (SEC61) was also characterised and this demonstrated the utility of the clam sequence data as a resource for examining cold adapted amino acid substitutions. The sequence data contained 46,235 microsatellites and 13,084 Single Nucleotide Polymorphisms(SNPs/INDELS), providing a resource for population and also gene function studies. Conclusions This is the first 454 data from an Antarctic marine invertebrate. Sequencing of mantle tissue from this non-model species has considerably increased resources for the investigation of the processes of shell deposition and repair in molluscs in a changing environment. A number of promising candidate genes were identified for functional analyses, which will be the subject of further investigation in this species and also used in model-hopping experiments in more tractable and economically important model aquaculture species, such as Crassostrea gigas and Mytilus edulis. PMID:20529341

2010-01-01

245

From amplification to gene in thyroid cancer: a high-resolution mapped bacterial-artificial-chromosome resource for cancer chromosome aberrations guides gene discovery after comparative genome hybridization.  

PubMed Central

Chromosome rearrangements associated with neoplasms provide a rich resource for definition of the pathways of tumorigenesis. The power of comparative genome hybridization (CGH) to identify novel genes depends on the existence of suitable markers, which are lacking throughout most of the genome. We now report a general approach that translates CGH data into higher-resolution genomic-clone data that are then used to define the genes located in aneuploid regions. We used CGH to study 33 thyroid-tumor DNAs and two tumor-cell-line DNAs. The results revealed amplifications of chromosome band 2p21, with less-intense amplification on 2p13, 19q13.1, and 1p36 and with least-intense amplification on 1p34, 1q42, 5q31, 5q33-34, 9q32-34, and 14q32. To define the 2p21 region amplified, a dense array of 373 FISH-mapped chromosome 2 bacterial artificial chromosomes (BACs) was constructed, and 87 of these were hybridized to a tumor-cell line. Four BACs carried genomic DNA that was amplified in these cells. The maximum amplified region was narrowed to 3-6 Mb by multicolor FISH with the flanking BACs, and the minimum amplicon size was defined by a contig of 420 kb. Sequence analysis of the amplified BAC 1D9 revealed a fragment of the gene, encoding protein kinase C epsilon (PKCepsilon), that was then shown to be amplified and rearranged in tumor cells. In summary, CGH combined with a dense mapped resource of BACs and large-scale sequencing has led directly to the definition of PKCepsilon as a previously unmapped candidate gene involved in thyroid tumorigenesis. PMID:9683604

Chen, X; Knauf, J A; Gonsky, R; Wang, M; Lai, E H; Chissoe, S; Fagin, J A; Korenberg, J R

1998-01-01

246

Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project  

PubMed Central

The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed, resulted in the identification of >44,000 variations, both substitutions and indels (insertions and deletions), which have been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets revealed 122 gene loci with coding substitutions of which 97 were non-synonymous. The haplotype (A3-B7-DR15; PGF cell line) designated as the new MHC reference sequence, has been incorporated into the human genome assembly (NCBI35 and subsequent builds), and constitutes the largest single-haplotype sequence of the human genome to date. The extensive variation and annotation data derived from the analysis of seven further haplotypes have been made publicly available and provide a framework and resource for future association studies of all MHC-associated diseases and transplant medicine. PMID:18193213

Horton, Roger; Gibson, Richard; Coggill, Penny; Miretti, Marcos; Allcock, Richard J.; Almeida, Jeff; Forbes, Simon; Gilbert, James G. R.; Halls, Karen; Harrow, Jennifer L.; Hart, Elizabeth; Howe, Kevin; Jackson, David K.; Palmer, Sophie; Roberts, Anne N.; Sims, Sarah; Stewart, C. Andrew; Traherne, James A.; Trevanion, Steve; Wilming, Laurens; Rogers, Jane; de Jong, Pieter J.; Elliott, John F.; Sawcer, Stephen; Todd, John A.; Trowsdale, John

2008-01-01

247

Lignification in Sugarcane: Biochemical Characterization, Gene Discovery, and Expression Analysis in Two Genotypes Contrasting for Lignin Content1[W  

PubMed Central

Sugarcane (Saccharum spp.) is currently one of the most efficient crops in the production of first-generation biofuels. However, the bagasse represents an additional abundant lignocellulosic resource that has the potential to increase the ethanol production per plant. To achieve a more efficient conversion of bagasse into ethanol, a better understanding of the main factors affecting biomass recalcitrance is needed. Because several studies have shown a negative effect of lignin on saccharification yield, the characterization of lignin biosynthesis, structure, and deposition in sugarcane is an important goal. Here, we present, to our knowledge, the first systematic study of lignin deposition during sugarcane stem development, using histological, biochemical, and transcriptional data derived from two sugarcane genotypes with contrasting lignin contents. Lignin amount and composition were determined in rind (outer) and pith (inner) tissues throughout stem development. In addition, the phenolic metabolome was analyzed by ultra-high-performance liquid chromatography-mass spectrometry, which allowed the identification of 35 compounds related to the phenylpropanoid pathway and monolignol biosynthesis. Furthermore, the Sugarcane EST Database was extensively surveyed to identify lignin biosynthetic gene homologs, and the expression of all identified genes during stem development was determined by quantitative reverse transcription-polymerase chain reaction. Our data provide, to our knowledge, the first in-depth characterization of lignin biosynthesis in sugarcane and form the baseline for the rational metabolic engineering of sugarcane feedstock for bioenergy purposes. PMID:24144790

Bottcher, Alexandra; Cesarino, Igor; Brombini dos Santos, Adriana; Vicentini, Renato; Mayer, Juliana Lischka Sampaio; Vanholme, Ruben; Morreel, Kris; Goeminne, Geert; Moura, Jullyana Cristina Magalhães Silva; Nobile, Paula Macedo; Carmello-Guerreiro, Sandra Maria; Antonio dos Anjos, Ivan; Creste, Silvana; Boerjan, Wout; Landell, Marcos Guimarães de Andrade; Mazzafera, Paulo

2013-01-01

248

Lignification in sugarcane: biochemical characterization, gene discovery, and expression analysis in two genotypes contrasting for lignin content.  

PubMed

Sugarcane (Saccharum spp.) is currently one of the most efficient crops in the production of first-generation biofuels. However, the bagasse represents an additional abundant lignocellulosic resource that has the potential to increase the ethanol production per plant. To achieve a more efficient conversion of bagasse into ethanol, a better understanding of the main factors affecting biomass recalcitrance is needed. Because several studies have shown a negative effect of lignin on saccharification yield, the characterization of lignin biosynthesis, structure, and deposition in sugarcane is an important goal. Here, we present, to our knowledge, the first systematic study of lignin deposition during sugarcane stem development, using histological, biochemical, and transcriptional data derived from two sugarcane genotypes with contrasting lignin contents. Lignin amount and composition were determined in rind (outer) and pith (inner) tissues throughout stem development. In addition, the phenolic metabolome was analyzed by ultra-high-performance liquid chromatography-mass spectrometry, which allowed the identification of 35 compounds related to the phenylpropanoid pathway and monolignol biosynthesis. Furthermore, the Sugarcane EST Database was extensively surveyed to identify lignin biosynthetic gene homologs, and the expression of all identified genes during stem development was determined by quantitative reverse transcription-polymerase chain reaction. Our data provide, to our knowledge, the first in-depth characterization of lignin biosynthesis in sugarcane and form the baseline for the rational metabolic engineering of sugarcane feedstock for bioenergy purposes. PMID:24144790

Bottcher, Alexandra; Cesarino, Igor; Santos, Adriana Brombini dos; Vicentini, Renato; Mayer, Juliana Lischka Sampaio; Vanholme, Ruben; Morreel, Kris; Goeminne, Geert; Moura, Jullyana Cristina Magalhães Silva; Nobile, Paula Macedo; Carmello-Guerreiro, Sandra Maria; Anjos, Ivan Antonio dos; Creste, Silvana; Boerjan, Wout; Landell, Marcos Guimarães de Andrade; Mazzafera, Paulo

2013-12-01

249

Array-Based Gene Discovery with Three Unrelated Subjects Shows SCARB2/LIMP-2 Deficiency Causes Myoclonus Epilepsy and Glomerulosclerosis  

PubMed Central

Action myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies. PMID:18308289

Berkovic, Samuel F.; Dibbens, Leanne M.; Oshlack, Alicia; Silver, Jeremy D.; Katerelos, Marina; Vears, Danya F.; Lüllmann-Rauch, Renate; Blanz, Judith; Zhang, Ke Wei; Stankovich, Jim; Kalnins, Renate M.; Dowling, John P.; Andermann, Eva; Andermann, Frederick; Faldini, Enrico; D'Hooge, Rudi; Vadlamudi, Lata; Macdonell, Richard A.; Hodgson, Bree L.; Bayly, Marta A.; Savige, Judy; Mulley, John C.; Smyth, Gordon K.; Power, David A.; Saftig, Paul; Bahlo, Melanie

2008-01-01

250

Development of an integrated transcript sequence database and a gene expression atlas for gene discovery and analysis in switchgrass (Panicum virgatum L.).  

PubMed

Switchgrass (Panicum virgatum L.) is a perennial C4 grass with the potential to become a major bioenergy crop. To help realize this potential, a set of RNA-based resources were developed. Expressed sequence tags (ESTs) were generated from two tetraploid switchgrass genotypes, Alamo AP13 and Summer VS16. Over 11.5 million high-quality ESTs were generated with 454 sequencing technology, and an additional 169 079 Sanger sequences were obtained from the 5' and 3' ends of 93 312 clones from normalized, full-length-enriched cDNA libraries. AP13 and VS16 ESTs were assembled into 77 854 and 30 524 unique transcripts (unitranscripts), respectively, using the Newbler and pave programs. Published Sanger-ESTs (544 225) from Alamo, Kanlow, and 15 other cultivars were integrated with the AP13 and VS16 assemblies to create a universal switchgrass gene index (PviUT1.2) with 128 058 unitranscripts, which were annotated for function. An Affymetrix cDNA microarray chip (Pvi_cDNAa520831) containing 122 973 probe sets was designed from PviUT1.2 sequences, and used to develop a Gene Expression Atlas for switchgrass (PviGEA). The PviGEA contains quantitative transcript data for all major organ systems of switchgrass throughout development. We developed a web server that enables flexible, multifaceted analyses of PviGEA transcript data. The PviGEA was used to identify representatives of all known genes in the phenylpropanoid-monolignol biosynthesis pathway. PMID:23289674

Zhang, Ji-Yi; Lee, Yi-Ching; Torres-Jerez, Ivone; Wang, Mingyi; Yin, Yanbin; Chou, Wen-Chi; He, Ji; Shen, Hui; Srivastava, Avinash C; Pennacchio, Christa; Lindquist, Erika; Grimwood, Jane; Schmutz, Jeremy; Xu, Ying; Sharma, Manoj; Sharma, Rita; Bartley, Laura E; Ronald, Pamela C; Saha, Malay C; Dixon, Richard A; Tang, Yuhong; Udvardi, Michael K

2013-04-01

251

Discovery of Potential New Gene Variants and Inflammatory Cytokine Associations with Fibromyalgia Syndrome by Whole Exome Sequencing  

PubMed Central

Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play a role in the disorder, we performed complete exome sequencing on a subset of FMS patients. Out of 150 nuclear families (trios) DNA from 19 probands was subjected to complete exome sequencing. Since >80,000 SNPs were found per proband, the data were further filtered, including analysis of those with stop codons, a rare frequency (<2.5%) in the 1000 Genomes database, and presence in at least 2/19 probands sequenced. Two nonsense mutations, W32X in C11orf40 and Q100X in ZNF77 among 150 FMS trios had a significantly elevated frequency of transmission to affected probands (p?=?0.026 and p?=?0.032, respectively) and were present in a subset of 13% and 11% of FMS patients, respectively. Among 9 patients bearing more than one of the variants we have described, 4 had onset of symptoms between the ages of 10 and 18. The subset with the C11orf40 mutation had elevated plasma levels of the inflammatory cytokines, MCP-1 and IP-10, compared with unaffected controls or FMS patients with the wild-type allele. Similarly, patients with the ZNF77 mutation have elevated levels of the inflammatory cytokine, IL-12, compared with controls or patients with the wild type allele. Our results strongly implicate an inflammatory basis for FMS, as well as specific cytokine dysregulation, in at least 35% of our FMS cohort. PMID:23762283

Wu, Xiwei; Mao, Allen; Chang, Frances; Deng, Xutao; Gao, Harry; Ouyang, Ching; Dery, Kenneth J.; Le, Keith; Longmate, Jeffrey; Marek, Claudia; St. Amand, R. Paul; Krontiris, Theodore G.; Shively, John E.

2013-01-01

252

Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel.  

PubMed

Many drugs inhibit the human ether-a-go-go-related gene (HERG) cardiac K+ channel. This leads to action potential prolongation on the cellular level, a prolongation of the QT interval on the electrocardiogram, and sometimes cardiac arrhythmia. To date, no activators of this channel have been reported. Here, we describe the in vitro electrophysiological effects of (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluoro-phenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid (RPR260243), a novel activator of HERG. Using patch-clamp electrophysiology, we found that RPR260243 dramatically slowed current deactivation when applied to cells stably expressing HERG. The effects of RPR260243 on HERG channel deactivation were temperature- and voltage-dependent and occurred over the concentration range of 1 to 30 microM. RPR260243-modified HERG currents were inhibited by dofetilide (IC50 = 58 nM). RPR260243 had little effect on HERG current amplitude and no significant effects on steady-state activation parameters or on channel inactivation processes. RPR260243 displayed no activator-like effects on other voltage-dependent ion channels, including the closely related erg3 K+ channel. RPR260243 enhanced the delayed rectifier current in guinea pig myocytes but, when administered alone, had little effect on action potential parameters in these cells. However, RPR260243 completely reversed the action potential-prolonging effects of dofetilide in this preparation. Using the Langendorff heart method, we found that 5 microM RPR260243 increased T-wave amplitude, prolonged the PR interval, and shortened the QT interval. We believe RPR260243 represents the first known HERG channel activator and that the drug works primarily by inhibiting channel closure, leading to a persistent HERG channel current upon repolarization. Compounds like RPR260243 will be useful for studying the physiological role of HERG and may one day find use in treating cardiac disease. PMID:15548764

Kang, Jiesheng; Chen, Xiao-Liang; Wang, Hongge; Ji, Junzhi; Cheng, Hsien; Incardona, Josephine; Reynolds, William; Viviani, Fabrice; Tabart, Michel; Rampe, David

2005-03-01

253

Discovery and molecular mapping of a new gene conferring resistance to stem rust, Sr53, derived from Aegilops geniculata and characterization of spontaneous translocation stocks with reduced alien chromatin  

Technology Transfer Automated Retrieval System (TEKTRAN)

This study reports the discovery and molecular mapping of a resistance gene effective against stem rust races RKQQC and TTKSK (Ug99) derived from Aegilops geniculata (2n=4x=28, UgUgMgMg). Two populations from the crosses TA5599 (T5DL-5MgL.5MgS)/TA3809 (ph1b mutant in Chinese Spring background) and T...

254

Characterization of Capsicum annuum Genetic Diversity and Population Structure Based on Parallel Polymorphism Discovery with a 30K Unigene Pepper GeneChip  

PubMed Central

The widely cultivated pepper, Capsicum spp., important as a vegetable and spice crop world-wide, is one of the most diverse crops. To enhance breeding programs, a detailed characterization of Capsicum diversity including morphological, geographical and molecular data is required. Currently, molecular data characterizing Capsicum genetic diversity is limited. The development and application of high-throughput genome-wide markers in Capsicum will facilitate more detailed molecular characterization of germplasm collections, genetic relationships, and the generation of ultra-high density maps. We have developed the Pepper GeneChip® array from Affymetrix for polymorphism detection and expression analysis in Capsicum. Probes on the array were designed from 30,815 unigenes assembled from expressed sequence tags (ESTs). Our array design provides a maximum redundancy of 13 probes per base pair position allowing integration of multiple hybridization values per position to detect single position polymorphism (SPP). Hybridization of genomic DNA from 40 diverse C. annuum lines, used in breeding and research programs, and a representative from three additional cultivated species (C. frutescens, C. chinense and C. pubescens) detected 33,401 SPP markers within 13,323 unigenes. Among the C. annuum lines, 6,426 SPPs covering 3,818 unigenes were identified. An estimated three-fold reduction in diversity was detected in non-pungent compared with pungent lines, however, we were able to detect 251 highly informative markers across these C. annuum lines. In addition, an 8.7 cM region without polymorphism was detected around Pun1 in non-pungent C. annuum. An analysis of genetic relatedness and diversity using the software Structure revealed clustering of the germplasm which was confirmed with statistical support by principle components analysis (PCA) and phylogenetic analysis. This research demonstrates the effectiveness of parallel high-throughput discovery and application of genome-wide transcript-based markers to assess genetic and genomic features among Capsicum annuum. PMID:23409153

Hill, Theresa A.; Ashrafi, Hamid; Reyes-Chin-Wo, Sebastian; Yao, JiQiang; Stoffel, Kevin; Truco, Maria-Jose; Kozik, Alexander; Michelmore, Richard W.; Van Deynze, Allen

2013-01-01

255

Space Discovery.  

ERIC Educational Resources Information Center

Describes one teacher's experience taking Space Discovery courses that were sponsored by the United States Space Foundation (USSF). These courses examine the history of space science, theory of orbits and rocketry, the effects of living in outer space on humans, and space weather. (DDR)

Blackman, Joan

1998-01-01

256

Accidental Discoveries  

NSDL National Science Digital Library

In this activity, students research scientific discoveries that happened by accident in the past, and learn how gamma-rays were discovered by 20th century scientists. In the process, students develop an understanding that science theories change in the face of new evidence. This acitivity is part of the "Swift: Eyes Through Time" collection that is available on the Teacher's Domain website.

257

Fear conditioning leads to alteration in specific genes expression in cortical and thalamic neurons that project to the lateral amygdala.  

PubMed

RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala (LA) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNAs from the dissected neurons were subjected to microarray analysis. The levels of selected RNAs detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA. The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical-LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory-related disorders. We monitored gene expression after fear conditioning learning in thalamus-lateral amygdala (LA) and cortex-LA brain pathways. We detected genes that are specifically increased after fear learning and that encode proteins that function as regulators of protein synthesis, maturation and degradation in thalamus-LA pathway and regulators of transcription in the cortex-LA pathway. These findings provide insights into the molecular mechanisms involved in fear memory formation. PMID:25352022

Katz, Ira K; Lamprecht, Raphael

2015-02-01

258

Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project.  

PubMed

Iron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOE?4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases. PMID:20817350

Lehmann, Donald J; Schuur, Maaike; Warden, Donald R; Hammond, Naomi; Belbin, Olivia; Kölsch, Heike; Lehmann, Michael G; Wilcock, Gordon K; Brown, Kristelle; Kehoe, Patrick G; Morris, Chris M; Barker, Rachel; Coto, Eliecer; Alvarez, Victoria; Deloukas, Panos; Mateo, Ignacio; Gwilliam, Rhian; Combarros, Onofre; Arias-Vásquez, Alejandro; Aulchenko, Yurii S; Ikram, M Arfan; Breteler, Monique M; van Duijn, Cornelia M; Oulhaj, Abderrahim; Heun, Reinhard; Cortina-Borja, Mario; Morgan, Kevin; Robson, Kathryn; Smith, A David

2012-01-01

259

Mathematics Discoveries  

NSDL National Science Digital Library

What is math for anyway? Ever hear that question from your students? Bookmark this National Science Foundation link and begin to share news of important math-related discoveries and developments. Sample: "Math Could Aid in Curing Cancer" or, perhaps closer to the middle school mindset: "Cloaking Device Concept Moves Beyond Theory: Applied mathematician Graeme Milton brings the dream of cloaking devices portrayed in Star Trek and Harry Potter closer to reality."

2009-01-01

260

Concept Discovery in a Scientific Domain Concept Discovery in a  

E-print Network

that subjects make. #12;Concept Discovery in a Scientific Domain 3 In 1965 Jacques Monod and François Jacob were in molecular biology was used. This task was based upon one set of experiments that Jacob and Monod used of the most important questions in biology: Monod and Jacob discovered a mechanism for how genes

Dunbar, Kevin N.

261

The Hubble Space Telescope Extragalactic Distance Scale Key Project. 1: The discovery of Cepheids and a new distance to M81  

Microsoft Academic Search

We report on the discovery of 30 new Cepheids in the nearby galaxy M81 based on observations using the Hubble Space Telescope (HST). The periods of these Cepheids lie in the range of 10-55 days, based on 18 independent epochs using the HST wide-band F555W filter. The HST F555W and F785LP data have been transformed to the Cousins standard V

Wendy L. Freedman; Shaun M. Hughes; Barry F. Madore; Jeremy R. Mould; Myung Gyoon Lee; Peter Stetson; Robert C. Kennicutt; Anne Turner; Laura Ferrarese; Holland Ford; John A. Graham; Robert Hill; John G. Hoessel; John Huchra; Garth D. Illingworth

1994-01-01

262

The Extragalactic Distance Scale Key Project. III. The Discovery of Cepheids and a New Distance to M101 Using the Hubble Space Telescope  

Microsoft Academic Search

We report on the discovery of 29 Cepheid variables in the galaxy M101 using the original Wide Field Camera (WFC) and the new Wide Field and Planetary Camera 2 (WFPC2) on the Hubble Space Telescope. We observed a field in M101 at 17 independent epochs in V (F555W), five epochs in I (F785LP\\/ F814W), and one epoch in B (F439W),

Daniel D. Kelson; Garth D. Illingworth; Wendy F. Freedman; John A. Graham; Robert Hill; Barry F. Madore; Abhijit Saha; Peter B. Stetson; Robert C. Kennicutt Jr.; Jeremy R. Mould; Shaun M. Hughes; Laura Ferrarese; Randy Phelps; Anne Turner; Kem H. Cook; Holland Ford; John G. Hoessel; John Huchra

1996-01-01

263

Discovery Channel: Science Fair Central  

NSDL National Science Digital Library

The Discovery Channel promotes student participation in science fairs at this appealing, vibrant website. Users can find a terrific, thorough guide to creating science fair projects, including project ideas and lists of books and external web sites for students to utilize during their research. Students can find tip sheets for projects in many science subjects including astronomy, chemistry, and earth science. Educators can discover how to organize a science fair and parents can learn how to get involved with their children's projects. This site is a great way to excite children about science and scientific investigations.

264

Harry Stottlemier's Discovery [Revised Edition].  

ERIC Educational Resources Information Center

"Harry Stottlemeier's Discovery" is the student book for the project in philosophical thinking described in SO 008 123-126. It offers a model of dialogue -- both of children with one another and of children with adults. The story is set among a classroom of children who begin to understand the basics of logical reasoning when Harry, who isn't…

Lipman, Matthew

265

Trypanosoma cruzi: a putative vacuolar ATP synthase subunit and a CAAX prenyl protease-encoding gene, as examples of gene identification in genome projects.  

PubMed

An international genome program has been initiated to increase the knowledge about the Trypanosoma cruzi genome and thereby find effective tools to treat Chagas' disease. We here report the molecular characterization of two novel genes found in the course of this project. Two of the open reading frames (ORF) identified in the sequencing of the third smallest chromosome of the CL Brener strain of T. cruzi were selected for further molecular characterization due to their similarity to genes with interesting functions in other organisms and their potential as targets to combat the parasite. The first ORF (402 bp) showed homology to a 14-kDa vacuolar ATP synthase subunit F from a variety of organisms, such as yeast, rat, bovine, human, and a number of prokaryotes. The second ORF (1188 bp) resembled a CAAX prenyl protease-encoding gene, identified in different organisms, including Homo sapiens, Saccharomyces cerevisiae, and Arabidopsis thaliana, as well as several prokaryotes. RT-PCR from T. cruzi total epimastigote RNA allowed us to isolate the complete transcripts of these genes. Furthermore, screening of an available normalized cDNA library derived from the same stage of the parasite confirmed that both genes are expressed at least in the epimastigote stage of T. cruzi. Comparison of the putative T. cruzi proteins to their counterparts in other organisms revealed significant protein sequence conservation over large evolutionary distances. Computer analysis revealed the presence of several motifs in both proteins, possibly related to the regulation and localization of these proteins in the parasite. PMID:10964645

Porcel, B M; Aslund, L; Pettersson, U; Andersson, B

2000-07-01

266

Discovery's Edge  

NSDL National Science Digital Library

The Mayo Clinic is one of the most well-respected medical facilities in the world, so it makes sense for them to have a great online publication to celebrate their work. Designed as a general interest publication, Discovery's Edge offers "insight into the process and progress of medical science in support of the world's largest group medical practice." Visitors can explore the user-friendly site by clicking through recent stories such as, "Putting the hurt on tobacco addiction" and "Genomics: The dawn of a new medical era.� In the Features Archive users can browse through some recent triumphs, including reports on asthma triggers and the future of biomechanics. Visitors can also browse the complete online archive or sign up to receive each new edition via email or RSS feed.

267

Discovery Scarp  

NASA Technical Reports Server (NTRS)

One of the most prominent lobate scarps (Discovery Scarp), photographed by Mariner 10 during it's first encounter with Mercury, is located at the center of this image (extending from the top to near bottom). This scarp is about 350 kilometers long and transects two craters 35 and 55 kilometers in diameter. The maximum height of the scarp south of the 55-kilometer crater is about 3 kilometers. Notice the shallow older crater (near the center of the image) perched on the crest of the scarp. (FDS 17389 and 27399)

The Mariner 10 mission, managed by the Jet Propulsion Laboratory for NASA's Office of Space Science, explored Venus in February 1974 on the way to three encounters with Mercury-in March and September 1974 and in March 1975. The spacecraft took more than 7,000 photos of Mercury, Venus, the Earth and the Moon.

Image Credit: NASA/JPL/Northwestern University

1974-01-01

268

High Cognitive Complexity and the Making of Major Scientific Discoveries  

Microsoft Academic Search

This essay is derived from insights developed from a complex research project about major discoveries in the basic biomedical sciences of Britain, France, Germany and the United States during the entire twentieth century. Focusing on 291 major discoveries, that study was designed to understand the organizational and laboratory context in which major discoveries occurred.2 In the process of conducting the

J. Rogers Hollingsworth

269

Open PHACTS: semantic interoperability for drug discovery.  

PubMed

Open PHACTS is a public-private partnership between academia, publishers, small and medium sized enterprises and pharmaceutical companies. The goal of the project is to deliver and sustain an 'open pharmacological space' using and enhancing state-of-the-art semantic web standards and technologies. It is focused on practical and robust applications to solve specific questions in drug discovery research. OPS is intended to facilitate improvements in drug discovery in academia and industry and to support open innovation and in-house non-public drug discovery research. This paper lays out the challenges and how the Open PHACTS project is hoping to address these challenges technically and socially. PMID:22683805

Williams, Antony J; Harland, Lee; Groth, Paul; Pettifer, Stephen; Chichester, Christine; Willighagen, Egon L; Evelo, Chris T; Blomberg, Niklas; Ecker, Gerhard; Goble, Carole; Mons, Barend

2012-11-01

270

High-resolution mapping of the S -locus in Turnera leads to the discovery of three genes tightly associated with the S -alleles  

Microsoft Academic Search

While the breeding system known as distyly has been used as a model system in genetics, and evolutionary biology for over\\u000a a century, the genes determining this system remain unknown. To positionally clone genes determining distyly, a high-resolution\\u000a map of the S-locus region of Turnera has been constructed using segregation data from 2,013 backcross progeny. We discovered three putative genes

Jonathan J. D. Labonne; Alina Goultiaeva; Joel S. Shore

2009-01-01

271

Evolution of hedgehog and hedgehog-related genes, their origin from Hog proteins in ancestral eukaryotes and discovery of a novel Hint motif  

PubMed Central

Background The Hedgehog (Hh) signaling pathway plays important roles in human and animal development as well as in carcinogenesis. Hh molecules have been found in both protostomes and deuterostomes, but curiously the nematode Caenorhabditis elegans lacks a bona-fide Hh. Instead a series of Hh-related proteins are found, which share the Hint/Hog domain with Hh, but have distinct N-termini. Results We performed extensive genome searches such as the cnidarian Nematostella vectensis and several nematodes to gain further insights into Hh evolution. We found six genes in N. vectensis with a relationship to Hh: two Hh genes, one gene with a Hh N-terminal domain fused to a Willebrand factor type A domain (VWA), and three genes containing Hint/Hog domains with distinct novel N-termini. In the nematode Brugia malayi we find the same types of hh-related genes as in C. elegans. In the more distantly related Enoplea nematodes Xiphinema and Trichinella spiralis we find a bona-fide Hh. In addition, T. spiralis also has a quahog gene like C. elegans, and there are several additional hh-related genes, some of which have secreted N-terminal domains of only 15 to 25 residues. Examination of other Hh pathway components revealed that T. spiralis - like C. elegans - lacks some of these components. Extending our search to all eukaryotes, we recovered genes containing a Hog domain similar to Hh from many different groups of protists. In addition, we identified a novel Hint gene family present in many eukaryote groups that encodes a VWA domain fused to a distinct Hint domain we call Vint. Further members of a poorly characterized Hint family were also retrieved from bacteria. Conclusion In Cnidaria and nematodes the evolution of hh genes occurred in parallel to the evolution of other genes that contain a Hog domain but have different N-termini. The fact that Hog genes comprising a secreted N-terminus and a Hog domain are found in many protists indicates that this gene family must have arisen in very early eukaryotic evolution, and gave rise eventually to hh and hh-related genes in animals. The results indicate a hitherto unsuspected ability of Hog domain encoding genes to evolve new N-termini. In one instance in Cnidaria, the Hh N-terminal signaling domain is associated with a VWA domain and lacks a Hog domain, suggesting a modular mode of evolution also for the N-terminal domain. The Hog domain proteins, the inteins and VWA-Vint proteins are three families of Hint domain proteins that evolved in parallel in eukaryotes. PMID:18334026

Bürglin, Thomas R

2008-01-01

272

Environmental Regulation of Plant Gene Expression: An Rt-qPCR Laboratory Project for an Upper-Level Undergraduate Biochemistry or Molecular Biology Course  

ERIC Educational Resources Information Center

We present a novel laboratory project employing "real-time" RT-qPCR to measure the effect of environment on the expression of the "FLOWERING LOCUS C" gene, a key regulator of floral timing in "Arabidopsis thaliana" plants. The project requires four 3-hr laboratory sessions and is aimed at upper-level undergraduate…

Eickelberg, Garrett J.; Fisher, Alison J.

2013-01-01

273

Genes  

NSDL National Science Digital Library

Illustration of the placement of genes in a chromosome. A gene can be defined as a region of DNA that controls a hereditary characteristic. It usually corresponds to a sequence used in the production of a specific protein or RNA. A gene carries biological information in a form that must be copied and transmitted from each cell to all its progeny. This includes the entire functional unit: coding DNA sequences, non-coding regulatory DNA sequences, and introns. Genes can be as short as 1000 base pairs or as long as several hundred thousand base pairs. It can even be carried by more than one chromosome. The estimate for the number of genes in humans has decreased as our knowledge has increased. As of 2001, humans are thought to have between 30,000 and 40,000 genes.

Access Excellence

2005-03-12

274

Studying human disease genes in Caenorhabditis elegans: a molecular genetics laboratory project.  

PubMed

Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether Caenorhabditis elegans can be a useful model system for studying genes associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned gene. They confirmed the genetic deletion with nested polymerase chain reaction and performed a bioinformatics analysis to predict how the deletion would affect the encoded mRNA and protein. Students also performed RNA interference (RNAi) against their assigned gene and evaluated whether RNAi caused a phenotype similar to that of the genetic deletion. As a capstone activity, students prepared scientific posters in which they presented their data, evaluated whether C. elegans was a useful model system for studying their assigned genes, and proposed future directions. Assessment showed gains in understanding genotype versus phenotype, RNAi, common bioinformatics tools, and the utility of model organisms. PMID:22665589

Cox-Paulson, Elisabeth A; Grana, Theresa M; Harris, Michelle A; Batzli, Janet M

2012-01-01

275

Human Lung Project: Evaluating Variance of Gene Expression in the Human Lung  

PubMed Central

Nondiseased tissue is an important reference for microarray studies of pulmonary disease. We obtained 23 single lungs from multiorgan donors at time of procurement. Donors varied in age, sex, smoking history, and ethnicity. Lungs were dissected into upper and lower lobe peripheral sections for RNA extraction. Microarray analysis was performed using Affymetrix Hu-133 Plus 2.0 arrays. We observed that the relative variability of gene expression increased rapidly from technical (lowest), to regional, to population (highest). In addition, age and sex have measurable effects on gene expression. Gene expression variability is heterogeneously distributed among biologic categories. We conclude that gene expression variability is greater between individuals than within individuals and that population variability is the most important factor in the study design of microarray experiments of the human lung. Classes of genes with high population variability are biologically important and provide a novel perspective into lung physiology and pathobiology. Our study represents the first comprehensive analysis of nondiseased lung tissue. The generation of this robust dataset has important implications for the design and implementation of future comparative expression analysis with pulmonary disease states. PMID:16498083

Gruber, Michael P.; Coldren, Christopher D.; Woolum, Malcolm D.; Cosgrove, Gregory P.; Zeng, Chan; Barón, Anna E.; Moore, Mark D.; Cool, Carlyne D.; Worthen, G. Scott; Brown, Kevin K.; Geraci, Mark W.

2006-01-01

276

From Genes to Proteins to Behavior: A Laboratory Project That Enhances Student Understanding in Cell and Molecular Biology  

PubMed Central

In the laboratory, students can actively explore concepts and experience the nature of scientific research. We have devised a 5-wk laboratory project in our introductory college biology course whose aim was to improve understanding in five major concepts that are central to basic cellular, molecular biology, and genetics while teaching molecular biology techniques. The project was focused on the production of adenine in Saccharomyces cerevisiae and investigated the nature of mutant red colonies of this yeast. Students created red mutants from a wild-type strain, amplified the two genes capable of giving rise to the red phenotype, and then analyzed the nucleotide sequences. A quiz assessing student understanding in the five areas was given at the start and the end of the course. Analysis of the quiz showed significant improvement in each of the areas. These areas were taught in the laboratory and the classroom; therefore, students were surveyed to determine whether the laboratory played a role in their improved understanding of the five areas. Student survey data demonstrated that the laboratory did have an important role in their learning of the concepts. This project simulated steps in a research project and could be adapted for an advanced course in genetics. PMID:19952098

Silveira, Linda A.

2009-01-01

277

High-resolution mapping of the S-locus in Turnera leads to the discovery of three genes tightly associated with the S-alleles.  

PubMed

While the breeding system known as distyly has been used as a model system in genetics, and evolutionary biology for over a century, the genes determining this system remain unknown. To positionally clone genes determining distyly, a high-resolution map of the S-locus region of Turnera has been constructed using segregation data from 2,013 backcross progeny. We discovered three putative genes tightly linked with the S-locus. An N-acetyltransferase (TkNACE) flanks the S-locus at 0.35 cM while a sulfotransferase (TkST1) and a non-LTR retroelement (TsRETRO) show complete linkage to the S-locus. An assay of population samples of six species revealed that TsRETRO, initially discovered in diploid Turnera subulata, is also associated with the S-allele in tetraploid T. subulata and diploid Turnera scabra. The sulfotransferase gene shows some level of differential expression in long versus short styles, indicating it might be involved in some aspect of distyly. The complete linkage of TkST1 and TsRETRO to the S-locus suggests that both genes may reside within, or in the immediate vicinity of the S-locus. Chromosome walking has been initiated using one of the genes discovered in the present study to identify the genes determining distyly. PMID:19283410

Labonne, Jonathan J D; Goultiaeva, Alina; Shore, Joel S

2009-06-01

278

Environmental regulation of plant gene expression: an RT-qPCR laboratory project for an upper-level undergraduate biochemistry or molecular biology course.  

PubMed

We present a novel laboratory project employing "real-time" RT-qPCR to measure the effect of environment on the expression of the FLOWERING LOCUS C gene, a key regulator of floral timing in Arabidopsis thaliana plants. The project requires four 3-hr laboratory sessions and is aimed at upper-level undergraduate students in biochemistry or molecular biology courses. The project provides students with hands-on experience with RT-qPCR, the current "gold standard" for gene expression analysis, including detailed data analysis using the common 2-??CT method. Moreover, it provides a convenient starting point for many inquiry-driven projects addressing diverse questions concerning ecological biochemistry, naturally occurring genetic variation, developmental biology, and the regulation of gene expression in nature. PMID:24038665

Eickelberg, Garrett J; Fisher, Alison J

2013-01-01

279

Discovery of gene cluster for mycosporine-like amino acid biosynthesis from Actinomycetales microorganisms and production of a novel mycosporine-like amino acid by heterologous expression.  

PubMed

Mycosporines and mycosporine-like amino acids (MAAs), including shinorine (mycosporine-glycine-serine) and porphyra-334 (mycosporine-glycine-threonine), are UV-absorbing compounds produced by cyanobacteria, fungi, and marine micro- and macroalgae. These MAAs have the ability to protect these organisms from damage by environmental UV radiation. Although no reports have described the production of MAAs and the corresponding genes involved in MAA biosynthesis from Gram-positive bacteria to date, genome mining of the Gram-positive bacterial database revealed that two microorganisms belonging to the order Actinomycetales, Actinosynnema mirum DSM 43827 and Pseudonocardia sp. strain P1, possess a gene cluster homologous to the biosynthetic gene clusters identified from cyanobacteria. When the two strains were grown in liquid culture, Pseudonocardia sp. accumulated a very small amount of MAA-like compound in a medium-dependent manner, whereas A. mirum did not produce MAAs under any culture conditions, indicating that the biosynthetic gene cluster of A. mirum was in a cryptic state in this microorganism. In order to characterize these biosynthetic gene clusters, each biosynthetic gene cluster was heterologously expressed in an engineered host, Streptomyces avermitilis SUKA22. Since the resultant transformants carrying the entire biosynthetic gene cluster controlled by an alternative promoter produced mainly shinorine, this is the first confirmation of a biosynthetic gene cluster for MAA from Gram-positive bacteria. Furthermore, S. avermitilis SUKA22 transformants carrying the biosynthetic gene cluster for MAA of A. mirum accumulated not only shinorine and porphyra-334 but also a novel MAA. Structure elucidation revealed that the novel MAA is mycosporine-glycine-alanine, which substitutes l-alanine for the l-serine of shinorine. PMID:24907338

Miyamoto, Kiyoko T; Komatsu, Mamoru; Ikeda, Haruo

2014-08-01

280

A new set of ESTs and cDNA clones from full-length and normalized libraries for gene discovery and functional characterization in citrus  

PubMed Central

Background Interpretation of ever-increasing raw sequence information generated by modern genome sequencing technologies faces multiple challenges, such as gene function analysis and genome annotation. Indeed, nearly 40% of genes in plants encode proteins of unknown function. Functional characterization of these genes is one of the main challenges in modern biology. In this regard, the availability of full-length cDNA clones may fill in the gap created between sequence information and biological knowledge. Full-length cDNA clones facilitate functional analysis of the corresponding genes enabling manipulation of their expression in heterologous systems and the generation of a variety of tagged versions of the native protein. In addition, the development of full-length cDNA sequences has the power to improve the quality of genome annotation. Results We developed an integrated method to generate a new normalized EST collection enriched in full-length and rare transcripts of different citrus species from multiple tissues and developmental stages. We constructed a total of 15 cDNA libraries, from which we isolated 10,898 high-quality ESTs representing 6142 different genes. Percentages of redundancy and proportion of full-length clones range from 8 to 33, and 67 to 85, respectively, indicating good efficiency of the approach employed. The new EST collection adds 2113 new citrus ESTs, representing 1831 unigenes, to the collection of citrus genes available in the public databases. To facilitate functional analysis, cDNAs were introduced in a Gateway-based cloning vector for high-throughput functional analysis of genes in planta. Herein, we describe the technical methods used in the library construction, sequence analysis of clones and the overexpression of CitrSEP, a citrus homolog to the Arabidopsis SEP3 gene, in Arabidopsis as an example of a practical application of the engineered Gateway vector for functional analysis. Conclusion The new EST collection denotes an important step towards the identification of all genes in the citrus genome. Furthermore, public availability of the cDNA clones generated in this study, and not only their sequence, enables testing of the biological function of the genes represented in the collection. Expression of the citrus SEP3 homologue, CitrSEP, in Arabidopsis results in early flowering, along with other phenotypes resembling the over-expression of the Arabidopsis SEPALLATA genes. Our findings suggest that the members of the SEP gene family play similar roles in these quite distant plant species. PMID:19747386

Marques, M Carmen; Alonso-Cantabrana, Hugo; Forment, Javier; Arribas, Raquel; Alamar, Santiago; Conejero, Vicente; Perez-Amador, Miguel A

2009-01-01

281

Gene Testing for Hereditary Ataxia  

MedlinePLUS

... FAQ NATIONAL ATAXIA FOUNDATION FREQUENTLY ASKED QUESTIONS ABOUT... Gene Testing for Hereditary Ataxia This fact sheet provides ... onset. For which of the hereditary ataxias is gene testing available? Discovery of specific ataxia genes makes ...

282

Mapping Our Genes--The Genome Projects: How Big, How Fast?  

ERIC Educational Resources Information Center

Scientific and technical journals in biology and medicine in recent years have extensively covered a debate about whether and how to determine the function and order of human genes on human chromosomes and when to determine the sequence of molecular building blocks that comprise DNA in those chromosomes. In 1987, these issues rose to become part…

Congress of the U.S., Washington, DC. Office of Technology Assessment.

283

A functional gene discovery in the Fas-mediated pathway to apoptosis by analysis of transiently expressed randomized hybrid-ribozyme libraries  

Microsoft Academic Search

The sequence of much of the human genome is now available and the next goal is to identify functional genes and to clarify their roles. We have recently developed a novel system for isolation of genes in the Fas- and TNF-a-mediated pathways to apoptosis using poly(A)-connected hammerhead ribozyme libraries with randomized substrate-binding arms at both the 5¢ and 3¢ ends

Hiroaki Kawasaki; Kazunari Taira

2002-01-01

284

Discovery of a Strongly-Interrelated Gene Network in Corals under Constant Darkness by Correlation Analysis after Wavelet Transform on Complex Network Model  

PubMed Central

Coral reefs occupy a relatively small portion of sea area, yet serve as a crucial source of biodiversity by establishing harmonious ecosystems with marine plants and animals. Previous researches mainly focused on screening several key genes induced by stress. Here we proposed a novel method—correlation analysis after wavelet transform of complex network model, to explore the effect of light on gene expression in the coral Acropora millepora based on microarray data. In this method, wavelet transform and the conception of complex network were adopted, and 50 key genes with large differences were finally captured, including both annotated genes and novel genes without accurate annotation. These results shed light on our understanding of coral's response toward light changes and the genome-wide interaction among genes under the control of biorhythm, and hence help us to better protect the coral reef ecosystems. Further studies are needed to explore how functional connections are related to structural connections, and how connectivity arises from the interactions within and between different systems. The method introduced in this study for analyzing microarray data will allow researchers to explore genome-wide interaction network with their own dataset and understand the relevant biological processes. PMID:24651851

Zhou, Xilong; Liu, Xuefeng; Zhang, Zhaobao; Wang, Xumin; Liu, Tao; Liu, Guiming

2014-01-01

285

Discovery of a strongly-interrelated gene network in corals under constant darkness by correlation analysis after wavelet transform on complex network model.  

PubMed

Coral reefs occupy a relatively small portion of sea area, yet serve as a crucial source of biodiversity by establishing harmonious ecosystems with marine plants and animals. Previous researches mainly focused on screening several key genes induced by stress. Here we proposed a novel method--correlation analysis after wavelet transform of complex network model, to explore the effect of light on gene expression in the coral Acropora millepora based on microarray data. In this method, wavelet transform and the conception of complex network were adopted, and 50 key genes with large differences were finally captured, including both annotated genes and novel genes without accurate annotation. These results shed light on our understanding of coral's response toward light changes and the genome-wide interaction among genes under the control of biorhythm, and hence help us to better protect the coral reef ecosystems. Further studies are needed to explore how functional connections are related to structural connections, and how connectivity arises from the interactions within and between different systems. The method introduced in this study for analyzing microarray data will allow researchers to explore genome-wide interaction network with their own dataset and understand the relevant biological processes. PMID:24651851

Liu, Longlong; Qu, Jieqiong; Zhou, Xilong; Liu, Xuefeng; Zhang, Zhaobao; Wang, Xumin; Liu, Tao; Liu, Guiming

2014-01-01

286

Analysis of expressed sequence tags from Actinidia: applications of a cross species EST database for gene discovery in the areas of flavor, health, color and ripening  

PubMed Central

Background Kiwifruit (Actinidia spp.) are a relatively new, but economically important crop grown in many different parts of the world. Commercial success is driven by the development of new cultivars with novel consumer traits including flavor, appearance, healthful components and convenience. To increase our understanding of the genetic diversity and gene-based control of these key traits in Actinidia, we have produced a collection of 132,577 expressed sequence tags (ESTs). Results The ESTs were derived mainly from four Actinidia species (A. chinensis, A. deliciosa, A. arguta and A. eriantha) and fell into 41,858 non redundant clusters (18,070 tentative consensus sequences and 23,788 EST singletons). Analysis of flavor and fragrance-related gene families (acyltransferases and carboxylesterases) and pathways (terpenoid biosynthesis) is presented in comparison with a chemical analysis of the compounds present in Actinidia including esters, acids, alcohols and terpenes. ESTs are identified for most genes in color pathways controlling chlorophyll degradation and carotenoid biosynthesis. In the health area, data are presented on the ESTs involved in ascorbic acid and quinic acid biosynthesis showing not only that genes for many of the steps in these pathways are represented in the database, but that genes encoding some critical steps are absent. In the convenience area, genes related to different stages of fruit softening are identified. Conclusion This large EST resource will allow researchers to undertake the tremendous challenge of understanding the molecular basis of genetic diversity in the Actinidia genus as well as provide an EST resource for comparative fruit genomics. The various bioinformatics analyses we have undertaken demonstrates the extent of coverage of ESTs for genes encoding different biochemical pathways in Actinidia. PMID:18655731

Crowhurst, Ross N; Gleave, Andrew P; MacRae, Elspeth A; Ampomah-Dwamena, Charles; Atkinson, Ross G; Beuning, Lesley L; Bulley, Sean M; Chagne, David; Marsh, Ken B; Matich, Adam J; Montefiori, Mirco; Newcomb, Richard D; Schaffer, Robert J; Usadel, Björn; Allan, Andrew C; Boldingh, Helen L; Bowen, Judith H; Davy, Marcus W; Eckloff, Rheinhart; Ferguson, A Ross; Fraser, Lena G; Gera, Emma; Hellens, Roger P; Janssen, Bart J; Klages, Karin; Lo, Kim R; MacDiarmid, Robin M; Nain, Bhawana; McNeilage, Mark A; Rassam, Maysoon; Richardson, Annette C; Rikkerink, Erik HA; Ross, Gavin S; Schröder, Roswitha; Snowden, Kimberley C; Souleyre, Edwige JF; Templeton, Matt D; Walton, Eric F; Wang, Daisy; Wang, Mindy Y; Wang, Yanming Y; Wood, Marion; Wu, Rongmei; Yauk, Yar-Khing; Laing, William A

2008-01-01

287

Moments of Discovery: A Pulsar Discovery  

NSDL National Science Digital Library

This online exhibit from the American Institute of Physics contains the history of the discovery of the first optical pulsar in the Crab Nebula. It includes both a transcription of the conversation at the moment of the discovery and commentary by the astronomers who made the discovery and by Philip Morrison. MP3 files of the conversations, commentary, and ideas for use by teachers are included.

2008-02-15

288

EXPOSING STUDENTS AND TEACHERS TO SCIENCE WITH SHORT TERM BARLEY GENE MAPPING PROJECTS.  

Technology Transfer Automated Retrieval System (TEKTRAN)

Many universities sponsor science research programs during the summers to provide hands-on laboratory experience to high school students and teachers. Our objective was to design a project that exposes the students to the full range of research, from developing and testing a hypothesis through prese...

289

Discovery and Characterization of a Silent Gene Cluster that Produces Azaphilones from Aspergillus niger ATCC 1015 Reveal a Hydroxylation-Mediated Pyran-Ring Formation  

PubMed Central

SUMMARY Azaphilones are a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibits a broad range of bioactivities. While widespread among various fungi, their biosynthesis has not been thoroughly elucidated. By activation of a silent (aza) gene cluster in Aspergillus niger ATCC 1015, we have discovered six new azaphilone compounds, azanigerones A-F (1, 3-7). Transcriptional analysis and deletion of a key polyketide synthase (PKS) gene further confirmed the involvement of the aza gene cluster. The biosynthetic pathway was shown to involve the convergent actions of a highly-reducing and a non-reducing PKSs. Most significantly, in vitro reaction of a key flavin-dependent monooxygenase encoded in the cluster with an early benzaldehyde intermediate revealed its roles in hydroxylation and pyran-ring formation to afford the characteristic bicylic core shared by azaphilones. PMID:22921072

Zabala, Angelica O.; Xu, Wei; Chooi, Yit-Heng; Tang, Yi

2012-01-01

290

Exons, Introns and Talking Genes: The Sience Behind the Human Genome Project  

SciTech Connect

This book presents in simple terms the basis of molecular genetics and how it is used to obtain an understanding of the human genome. The author's central focus is the transistion of genetics from statistics to experimental manipulations, and he offers analogies that help readers visualize the genome, thereby avoiding conventional scientific presentations. He illustrates how genetics is used in scientific laboratories, in courtrooms, and in hospitals. Little is presented about the complex social and ethical issues raised by the Human Genome project.

Jacobson, K.B.

1993-01-01

291

Next-generation pyrosequencing of gonad transcriptomes in the polyploid lake sturgeon (Acipenser fulvescens): the relative merits of normalization and rarefaction in gene discovery  

Microsoft Academic Search

BACKGROUND: Next-generation sequencing technologies have been applied most often to model organisms or species closely related to a model. However, these methods have the potential to be valuable in many wild organisms, including those of conservation concern. We used Roche 454 pyrosequencing to characterize gene expression in polyploid lake sturgeon (Acipenser fulvescens) gonads. RESULTS: Titration runs on a Roche 454

Matthew C Hale; Cory R McCormick; James R Jackson; J Andrew DeWoody

2009-01-01

292

Code-assisted discovery of TAL effector targets in bacterial leaf streak of rice reveals contrast with bacterial blight and a novel susceptibility gene  

Technology Transfer Automated Retrieval System (TEKTRAN)

Transcription activator-like (TAL) effectors found in Xanthomonas spp. promote bacterial growth and plant susceptibility by binding specific DNA sequences or, effector-binding elements (EBEs), and inducing host gene expression. In this study, we have found substantially different transcriptional pro...

293

A Genome-wide Analysis of Admixture in Uyghurs and a High-Density Admixture Map for Disease-Gene Discovery  

E-print Network

, and it will enable studies of diseases showing differences in genetic risk between EUR and EAS populations features.1 Genetic studies have found that extant Uyghur populations represent an admixture of eastern, in a recent study, that both East-Asian (EAS) and European (EUR) ancestries contribute to the current gene

Xu, Shuhua

294

Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin  

Technology Transfer Automated Retrieval System (TEKTRAN)

An accurate and precisely annotated genome assembly is a fundamental requirement for functional genomic analysis. Here, the complete DNA sequence and gene annotation of mouse Chromosome 11 was used to test the efficacy of large-scale sequencing for mutation identification. We re-sequenced the 14,000...

295

Detection and Discovery of Crustacean Parasites in Blue Crabs (Callinectes sapidus) by Using 18S rRNA Gene-Targeted Denaturing High-Performance Liquid Chromatography? †  

PubMed Central

Recently, we described a novel denaturing high-performance liquid chromatography (DHPLC) approach useful for initial detection and identification of crustacean parasites. Because this approach utilizes general primers targeted to conserved regions of the 18S rRNA gene, a priori genetic sequence information on eukaryotic parasites is not required. This distinction provides a significant advantage over specifically targeted PCR assays that do not allow for the detection of unknown or unsuspected parasites. However, initial field evaluations of the DHPLC assay suggested that because of PCR-biased amplification of dominant host genes it was not possible to detect relatively rare parasite genes in infected crab tissue. Here, we describe the use of a peptide nucleic acid (PNA) PCR hybridization blocking probe in association with DHPLC (PNA-PCR DHPLC) to overcome inherent PCR bias associated with amplification of rare target genes by use of generic primers. This approach was utilized to detect infection of blue crabs (Callinectes sapidus) by the parasitic dinoflagellate Hematodinium sp. Evaluation of 76 crabs caught in Wassaw Sound, GA, indicated a 97% correspondence between detection of the parasite by use of a specific PCR diagnostic assay and that by use of PNA-PCR DHPLC. During these studies, we discovered one crab with an association with a previously undescribed protist symbiont. Phylogenetic analysis of the amplified symbiont 18S rRNA gene indicated that it is most closely related to the free-living kinetoplastid parasite Procryptobia sorokini. To our knowledge, this is the first report of this parasite group in a decapod crab and of this organism exhibiting a presumably parasitic life history. PMID:18502913

Troedsson, Christofer; Lee, Richard F.; Walters, Tina; Stokes, Vivica; Brinkley, Karrie; Naegele, Verena; Frischer, Marc E.

2008-01-01

296

An EU Project on gene flow analysis between crop and wild forms of lettuce and chicory in the context of GMO biosafety: first results in lettuce  

Microsoft Academic Search

An EU project is presented that aims at detecting gene flow between crop and wild forms of lettuce and chicory and possible consequences for the ecology of the wild forms in the light of GMO biosafety assessment. Two novel molecular marker systems, the retrotransposon-based SSAP and the disease resistance gene-based NBS-profiling, were successfully developed for testing their ability to trace

Wiel van de C. C. M; Gerard van der Linden; Nijs den J. C. M; Andrew Flavell; Naeem Syed; Rikke Jorgensen; Francois Felber; Ivan Scotti; J. N. A. M. Rouppe van der Voort; J. Peleman

2003-01-01

297

Antarctic macrozooplankton of the southwest Atlantic sector and Bellingshausen Sea: Baseline historical distributions ( Discovery Investigations, 1928-1935) related to temperature and food, with projections for subsequent ocean warming  

NASA Astrophysics Data System (ADS)

Since the Discovery Investigations of the 1920s and 1930s, seawater temperatures have increased in the Atlantic sector by ˜1 °C; greater than the global mean rise. The aims of this paper were first to rescue the Discovery macrozooplankton data, second to provide quantitative "baseline" distribution maps, relating these to indices of temperature and food. Our third aim was to use the relationships we derived between abundance and temperature to project the potential affect of a 1 °C warming on the Discovery era distribution patterns. Based on the 1 m ringnet data retrieved from 615 stations (Nov-March), four taxa comprised >90% of the Antarctic macrozooplankton abundance: Rhincalanus gigas, Thysanoessa spp., Euphausia superba, and Chaetognaths. Most of the taxa, especially the more abundant ones, were warm water species penetrating into Antarctica and thus total macrozooplankton abundance decreased about 100-fold from 50°S to 70°S. While temperature correlated best with distribution at this large scale, food availability (proxied by a present-day satellite-based Chlorophyll a climatology) had a secondary effect, with the major euphausiids Euphausia superba and Thysanoessa spp. concentrated in high chl a areas. A modelled uniform 1 °C temperature rise produced a poleward shift for all taxa, but the Antarctic continent blocked this re-adjustment for the high latitude species, constricting their predicted range. More widespread polar/sub-polar species were predicted to increase their penetration into Antarctica by 4-12° in latitude, whereas the poleward shift in potential range of sub-Antarctic taxa were limited by the steep temperature gradient across the Antarctic Polar Front (APF). However, within the Scotia Sea the relatively warm temperatures of the northern Antarctic Zone, abundant food due to iron fertilisation and intense eddy activity provide a "gateway" for northern species to penetrate south of the APF. Our model predictions, based on measured distributional ranges and observed temperature increases, provide a yardstick with which to compare modern day data compilations and assess the potential effects of future temperature increases.

Mackey, A. P.; Atkinson, A.; Hill, S. L.; Ward, P.; Cunningham, N. J.; Johnston, N. M.; Murphy, E. J.

2012-01-01

298

Discovery in chemistry  

SciTech Connect

The question, ''Where do axioms and postulates originate.'' is addressed. The article assumes that they are acquired by inductive logic and are new ideas or discoveries. How discoveries happen in chemistry is the topic of the talk.

Holley, C.E. Jr.

1982-12-01

299

NCI DTP Discovery Services  

Cancer.gov

Discovery Services Home Discovery Development Pathways Grants/Contracts Books/Publications Site Search Data Search What's New FAQs Repositories Synthetics, Natural Products, Radiolabeled Materials, Biologics Reference Standards and Reagents, Tumor Repository Animal

300

Discovery of a Dicer-Independent, Cell-Type Dependent Alternate Targeting Sequence Generator: Implications in Gene Silencing & Pooled RNAi Screens  

PubMed Central

There is an acceptance that plasmid-based delivery of interfering RNA always generates the intended targeting sequences in cells, making it as specific as its synthetic counterpart. However, recent studies have reported on cellular inefficiencies of the former, especially in light of emerging gene discordance at inter-screen level and across formats. Focusing primarily on the TRC plasmid-based shRNA hairpins, we reasoned that alleged specificities were perhaps compromised due to altered processing; resulting in a multitude of random interfering sequences. For this purpose, we opted to study the processing of hairpin TRCN#40273 targeting CTTN; which showed activity in a miRNA-21 gain-of-function shRNA screen, but inactive when used as an siRNA duplex. Using a previously described walk-through method, we identified 36 theoretical cleavage variants resulting in 78 potential siRNA duplexes targeting 53 genes. We synthesized and tested all of them. Surprisingly, six duplexes targeting ASH1L, DROSHA, GNG7, PRKCH, THEM4, and WDR92 scored as active. QRT-PCR analysis on hairpin transduced reporter cells confirmed knockdown of all six genes, besides CTTN; revealing a surprising 7 gene-signature perturbation by this one single hairpin. We expanded our qRT-PCR studies to 26 additional cell lines and observed unique knockdown profiles associated with each cell line tested; even for those lacking functional DICER1 gene suggesting no obvious dependence on dicer for shRNA hairpin processing; contrary to published models. Taken together, we report on a novel dicer independent, cell-type dependent mechanism for non-specific RNAi gene silencing we coin Alternate Targeting Sequence Generator (ATSG). In summary, ATSG adds another dimension to the already complex interpretation of RNAi screening data, and provides for the first time strong evidence in support of arrayed screening, and questions the scientific merits of performing pooled RNAi screens, where deconvolution of up to genome-scale pools is indispensable for target identification. PMID:24987961

Bhinder, Bhavneet; Shum, David; Li, Mu; Ibáñez, Glorymar; Vlassov, Alexander V.; Magdaleno, Susan; Djaballah, Hakim

2014-01-01

301

The Alabama Drug Discovery Alliance: A Collaborative Partnership to Facilitate Academic Drug Discovery  

PubMed Central

The Alabama Drug Discovery Alliance is a collaboration between the University of Alabama at Birmingham and Southern Research Institute that aims to support the discovery and development of therapeutic molecules that address an unmet medical need. The alliance builds on the expertise present at both institutions and has the dedicated commitment of their respective technology transfer and intellectual property offices to guide any commercial opportunities that may arise from the supported efforts. Although most projects involve high throughput screening, projects at any stage in the drug discovery and development pathway are eligible for support. Irrespective of the target and stage of any project, well-functioning interdisciplinary teams are crucial to a project’s progress. These teams consist of investigators with a wide variety of expertise from both institutions to contribute to the program’s success. PMID:21448756

Everts, Maaike; Knight, W. Blaine; Harris, David R.; Secrist, John A.; Whitley, Richard J.

2011-01-01

302

Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes.  

PubMed

Lafora disease (LD) is an autosomal recessive and fatal form of progressive myoclonus epilepsy. LD patients manifest myoclonus and tonic-clonic seizures, visual hallucinations, and progressive neurologic deterioration beginning at 12 to 15 years of age. The two genes known to be associated with LD are EPM2A and NHLRC1. Mutations in at least one other as yet unknown gene also cause LD. The EMP2A encodes a protein phosphatase and NHLRC1 encodes an ubiquitin ligase. These two proteins interact with each other and, as a complex, are thought to regulate critical neuronal functions. Nearly 100 distinct mutations have been discovered in the two genes in over 200 independent LD families. Nearly half of them are missense mutations, and the deletion mutations account for one-quarter. Several reports have provided functional data for the mutant proteins and a few also provide genotype-phenotype correlations. In this review we provide an update on the spectrum of EPM2A and NHLRC1 mutations, and discuss their distribution in the patient population, genotype-phenotype correlations, and on the possible effect of disease mutations on the cellular functions of LD proteins. PMID:19267391

Singh, Shweta; Ganesh, Subramaniam

2009-05-01

303

Discovery of miR-mRNA interactions via simultaneous Bayesian inference of gene networks and clusters using sequence-based predictions and expression data.  

PubMed

MicroRNAs (miRs) are known to interfere with mRNA expression, and much work has been put into predicting and inferring miR-mRNA interactions. Both sequence-based interaction predictions as well as interaction inference based on expression data have been proven somewhat successful; furthermore, models that combine the two methods have had even more success. In this paper, I further refine and enrich the methods of miRmRNA interaction discovery by integrating a Bayesian clustering algorithm into a model of prediction-enhanced miR-mRNA target inference, creating an algorithm called PEACOAT, which is written in the R language. I show that PEACOAT improves the inference of miR-mRNA target interactions using both simulated data and a data set of microarrays from samples of multiple myeloma patients. In simulated networks of 25 miRs and mRNAs, our methods using clustering can improve inference in roughly two-thirds of cases, and in the multiple myeloma data set, KEGG pathway enrichment was found to be more significant with clustering than without. Our findings are consistent with previous work in clustering of non-miR genetic networks and indicate that there could be a significant advantage to clustering of miR and mRNA expression data as a part of interaction inference. PMID:23846182

Godsey, Brian

2013-01-01

304

Dirigent proteins in conifer defense: gene discovery, phylogeny, and differential wound- and insect-induced expression of a family of DIR and DIR-like genes in spruce (Picea spp.).  

PubMed

The outer stem tissues of conifers provide a durable constitutive and inducible defense barrier consisting of suberized or lignified periderm, sclereids, a network of terpenoid-filled resin ducts, and phenolic phloem parenchyma cells. Microarray gene expression profiling of Sitka spruce (Picea sitchensis) bark attacked by stem-boring weevils (Pissodes strobi) or through mechanical wounding demonstrated significant accumulation of transcripts resembling dirigent protein (DIR) genes. To investigate this gene family and its spatial and temporal patterns of expression in conifer defense, we isolated cDNAs representing 19 unique DIR and DIR-like genes from Sitka spruce, white spruce (P. glauca), and interior spruce (P. glauca x engelmannii). Sequence alignments also identified a large number of DIR-like proteins in other plant species, which share several conserved protein motifs with known DIR proteins. Phylogenetic analysis of 72 DIR and DIR-like proteins suggests five distinct subfamilies, DIR-a and four DIR-like subfamilies (DIR-b, DIR-c, DIR-d and DIR-e). Previously characterized members of the DIR-a subfamily direct stereoselective phenolic coupling reactions in the formation of lignans and possibly lignins. The spruce genes identified here are members of the DIR-a and DIR-b subfamilies. Using gene-specific quantitative real-time PCR we measured constitutive expression for six DIR-a genes and three DIR-like genes in different stem tissues, green shoot tips, and roots of Sitka spruce. DIR-like genes revealed ubiquitous high expression in all tissues. In contrast, the six DIR-a genes showed a gradient of transcript abundance in stem tissues with highest levels in the outer cortex and lowest levels in the inner xylem. Gene-specific transcript profiling of six DIR-a genes confirmed rapid and strong accumulation (up to 500-fold) in wound- and weevil-induced stem bark and xylem. These findings suggest a role for spruce DIR genes in constitutive and induced phenolic defense mechanisms against stem-boring insects. PMID:16463097

Ralph, Steven; Park, Ji-Young; Bohlmann, Jörg; Mansfield, Shawn D

2006-01-01

305

Antibody informatics for drug discovery.  

PubMed

More and more antibody therapeutics are being approved every year, mainly due to their high efficacy and antigen selectivity. However, it is still difficult to identify the antigen, and thereby the function, of an antibody if no other information is available. There are obstacles inherent to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii) antibody numbering and IMGT. Here, we review "antibody informatics," which may integrate the above three fields so that bridging the gaps between industrial needs and academic solutions can be accelerated. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID:25110827

Shirai, Hiroki; Prades, Catherine; Vita, Randi; Marcatili, Paolo; Popovic, Bojana; Xu, Jianqing; Overington, John P; Hirayama, Kazunori; Soga, Shinji; Tsunoyama, Kazuhisa; Clark, Dominic; Lefranc, Marie-Paule; Ikeda, Kazuyoshi

2014-11-01

306

Discovery of a novel neuroprotective compound, AS1219164, by high-throughput chemical screening of a newly identified apoptotic gene marker.  

PubMed

We have reported that tacrolimus (FK506), an immunosuppressive drug, and diclofenac, a non-steroidal anti-inflammatory drug, possess different modes of neuroprotective action. FK506 suppresses only thapsigargin-induced apoptosis in neuroblastoma SH-SY5Y cells while diclofenac reverses tunicamycin-induced as well as thapsigargin-induced apoptosis. The aim of this study is to discover novel compounds that exert neuroprotective properties by using the transcriptional response of a newly identified gene, which was regulated by both FK506 and diclofenac, as a surrogate screening marker in high-throughput chemical screening and characterize the compounds in comparison with FK506 and diclofenac. Using a microarray with 4504 human cDNAs and quantitative RT-PCR, two genes as apoptotic markers, transmembrane protein 100 (TMEM100) and limb-bud and heart (LBH), were identified because the thapsigargin-induced elevations in their mRNA levels were reversed by both FK506 and diclofenac. A luciferase reporter assay with a TMEM100 promoter region was applied to high-throughput chemical screening. AS1219164, {3-[(E)-2-{5-[(E)-2-pyridin-4-ylvinyl]pyridin-3-yl} vinyl]aniline}, suppressed thapsigargin-induced transactivation of the TMEM100 gene and reversed thapsigargin-induced increases in TMEM100 and LBH mRNA levels in SH-SY5Y cells, similar to the effects of FK506 and diclofenac. Furthermore, AS1219164 protected against SH-SY5Y cell death induced by four apoptotic agents including thapsigargin, similar to diclofenac, but was more potent than diclofenac, while FK506 only showed protective effects against thapsigargin-induced cell death. In conclusion, a novel neuroprotecitve compound, AS1219164, was discovered by high-throughput chemical screening using a reporter assay with the TMEM100 gene promoter regulated by both FK506 and diclofenac. Reporter assay using the promoter region of a gene under pharmacological and physiological transcriptional regulation would be well suit for use in high-throughput chemical screening. PMID:21824470

Yamazaki, Takao; Muramoto, Masakazu; Okitsu, Osamu; Morikawa, Noriyuki; Kita, Yasuhiro

2011-11-01

307

Discovery of Western European R1b1a2 Y Chromosome Variants in 1000 Genomes Project Data: An Online Community Approach  

PubMed Central

The authors have used an online community approach, and tools that were readily available via the Internet, to discover genealogically and therefore phylogenetically relevant Y-chromosome polymorphisms within core haplogroup R1b1a2-L11/S127 (rs9786076). Presented here is the analysis of 135 unrelated L11 derived samples from the 1000 Genomes Project. We were able to discover new variants and build a much more complex phylogenetic relationship for L11 sub-clades. Many of the variants were further validated using PCR amplification and Sanger sequencing. The identification of these new variants will help further the understanding of population history including patrilineal migrations in Western and Central Europe where R1b1a2 is the most frequent haplogroup. The fine-grained phylogenetic tree we present here will also help to refine historical genetic dating studies. Our findings demonstrate the power of citizen science for analysis of whole genome sequence data. PMID:22911832

Rocca, Richard A.; Magoon, Gregory; Reynolds, David F.; Krahn, Thomas; Tilroe, Vincent O.; Op den Velde Boots, Peter M.; Grierson, Andrew J.

2012-01-01

308

Motif Discovery in Tissue-Specific Regulatory Sequences Using Directed Information  

Microsoft Academic Search

Motif discovery for the identification of functional regulatory elements underlying gene expression is a challeng- ing problem. Sequence inspection often leads to discovery of novel motifs (including transcription factor sites) with p reviously uncharacterized function in gene expression. Coupled with the complexity underlying tissue-specific gene expression, th ere are several motifs that are putatively responsible for expression in a certain

Arvind Rao; Alfred O. Hero III; David J. States; James Douglas Engel

2007-01-01

309

Project Exploration  

NSDL National Science Digital Library

Chicago-based Project Exploration "is the living classroom that involves students and the public in scientific discovery, by connecting kids and families to interactive exhibits, labs, unique science programs and real scientists." Project Exploration focuses on reaching city kids, but every kid (and teachers) should check out this wonderful Web site. Visitors will find tons of activities and features to explore, such as Project Exploration's paleontological expeditions (past and present) and the Mesozoic Garden -- created for the 2003 Chicago Flower and Garden Show. Teachers will also find lesson plans tucked here and there among Project Exploration's dizzying assortment of Web features.

Lyon, Gabrielle; Sereno, Paul

1999-01-01

310

The human genome project: Cracking the genetic code of life  

SciTech Connect

This book presents a description of the human genome project and a good orientation to the science and opinions in the field. Also included is a chronology of discovery from the physical and chemical organization of cells through to genes and how the chronology exempliefies the transformation of thought and attitudes in Western society. Both the interested layman and the scientist who may be contemplating a new research area are targeted.

Lee, T.F.

1991-01-01

311

Project COLD.  

ERIC Educational Resources Information Center

Describes Project COLD (Climate, Ocean, Land, Discovery) a scientific study of the Polar Regions, a collection of 35 modules used within the framework of existing subjects: oceanography, biology, geology, meterology, geography, social science. Includes a partial list of topics and one activity (geodesic dome) from a module. (Author/SK)

Kazanjian, Wendy C.

1982-01-01

312

DFCI Gene Index Project: Interactive Data Maps for Plant, Animal, Protist, and Fungi Organisims from the Dana-Farber Cancer Institute  

DOE Data Explorer

Funding for the Dana-Farber Cancer Institute (DFCI) Gene Index Project ended and the database was taken down in July of 2014. However, this record links you to the "tombstone" page where you will find FTP addresses for the software tools and the data created.

313

Discovery and validation of gene-linked diagnostic SNP markers for assessing hybridization between Largemouth bass (Micropterus salmoides) and Florida bass (M. floridanus).  

PubMed

Efforts to improve recreational fisheries have included widespread stocking of Micropterus floridanus outside its native range of peninsular Florida. Hybridization of Florida bass (M. floridanus) with largemouth bass (Micropterus salmoides) has now dramatically expanded beyond a naturally occurring intergrade zone in the southeast U.S. In recent years, there has been growing interest in protecting the genetic integrity of native basses and assessing the impact and nature of M. salmoides/M. floridanus introgression from the standpoint of hatchery and sport-fishery managers, fish biologists, ecologists and evolutionary biologists. Here, we conducted RNA-seq-based sequencing of the transcriptomes of M. salmoides, M. floridanus and their F1 hybrid and identified a set of 3674 SNP markers with fixed-allelic differences from 2112 unique genes. We then developed a subset of 25 of these markers into a single diagnostic multiplex assay and validated its capacity for assessing integrity and hybridization in hatchery and wild populations of largemouth and Florida bass. The availability of this resource, high-quality transcriptomes and a large set of gene-linked SNPs, should greatly facilitate functional and population genomics studies in these key species and allow the identification of traits and processes under selection during introgressive hybridization. PMID:25047482

Li, Chao; Gowan, Spencer; Anil, Ammu; Beck, Benjamin H; Thongda, Wilawan; Kucuktas, Huseyin; Kaltenboeck, Ludmilla; Peatman, Eric

2014-07-21

314

Parallel discovery of Alzheimer's therapeutics.  

PubMed

As the prevalence of Alzheimer's disease (AD) grows, so do the costs it imposes on society. Scientific, clinical, and financial interests have focused current drug discovery efforts largely on the single biological pathway that leads to amyloid deposition. This effort has resulted in slow progress and disappointing outcomes. Here, we describe a "portfolio approach" in which multiple distinct drug development projects are undertaken simultaneously. Although a greater upfront investment is required, the probability of at least one success should be higher with "multiple shots on goal," increasing the efficiency of this undertaking. However, our portfolio simulations show that the risk-adjusted return on investment of parallel discovery is insufficient to attract private-sector funding. Nevertheless, the future cost savings of an effective AD therapy to Medicare and Medicaid far exceed this investment, suggesting that government funding is both essential and financially beneficial. PMID:24944190

Lo, Andrew W; Ho, Carole; Cummings, Jayna; Kosik, Kenneth S

2014-06-18

315

The ERGOTM genome analysis and discovery system  

Microsoft Academic Search

The ERGOTM (http:\\/\\/ergo.integratedgenomics.com\\/ ERGO\\/) genome analysis and discovery suite is an integration of biological data from genomics, bio- chemistry, high-throughput expression profiling, genetics and peer-reviewed journals to achieve a comprehensive analysis of genes and genomes. Far beyond any conventional systems that facilitate functional assignments, ERGO combines pattern- based analysis with comparative genomics by visua- lizing genes within the context of

Ross A. Overbeek; Niels Larsen; Theresa Walunas; Mark D'souza; Gordon D. Pusch; Evgeni Selkov Jr.; Konstantinos Liolios; Viktor Joukov; Denis Kaznadzey; Iain Anderson; Anamitra Bhattacharyya; Henry Burd; Warren Gardner; Paul Hanke; Vinayak Kapatral; Natalia Mikhailova; Olga Vassieva; Andrei Osterman; Veronika Vonstein; Michael Fonstein; Natalia Ivanova; Nikos Kyrpides

2003-01-01

316

Transcriptome Analysis of Androgenic Gland for Discovery of Novel Genes from the Oriental River Prawn, Macrobrachium nipponense, Using Illumina Hiseq 2000  

PubMed Central

Background The oriental river prawn, Macrobrachium nipponense, is an important aquaculture species in China, even in whole of Asia. The androgenic gland produces hormones that play crucial roles in sexual differentiation to maleness. This study is the first de novo M. nipponense transcriptome analysis using cDNA prepared from mRNA isolated from the androgenic gland. Illumina/Solexa was used for sequencing. Methodology and Principal Finding The total volume of RNA sample was more than 5 ug. We generated 70,853,361 high quality reads after eliminating adapter sequences and filtering out low-quality reads. A total of 78,408 isosequences were obtained by clustering and assembly of the clean reads, producing 57,619 non-redundant transcripts with an average length of 1244.19 bp. In total 70,702 isosequences were matched to the Nr database, additional analyses were performed by GO (33,203), KEGG (17,868), and COG analyses (13,817), identifying the potential genes and their functions. A total of 47 sex-determination related gene families were identified from the M. nipponense androgenic gland transcriptome based on the functional annotation of non-redundant transcripts and comparisons with the published literature. Furthermore, a total of 40 candidate novel genes were found, that may contribute to sex-determination based on their extremely high expression levels in the androgenic compared to other sex glands,. Further, 437 SSRs and 65,535 high-confidence SNPs were identified in this EST dataset from which 14 EST-SSR markers have been isolated. Conclusion Our study provides new sequence information for M. nipponense, which will be the basis for further genetic studies on decapods crustaceans. More importantly, this study dramatically improves understanding of sex-determination mechanisms, and advances sex-determination research in all crustacean species. The huge number of potential SSR and SNP markers isolated from the transcriptome may shed the lights on research in many fields, including the evolution and molecular ecology of Macrobrachium species. PMID:24204682

Jin, Shubo; Fu, Hongtuo; Zhou, Qiao; Sun, Shengming; Jiang, Sufei; Xiong, Yiwei; Gong, Yongsheng; Qiao, Hui; Zhang, Wenyi

2013-01-01

317

Discovery of a novel functional leptin protein (LEP) in zebra finches: evidence for the existence of an authentic avian leptin gene predominantly expressed in the brain and pituitary.  

PubMed

Leptin (LEP) is reported to play important roles in controlling energy balance in vertebrates, including birds. However, it remains an open question whether an authentic "LEP gene" exists and functions in birds. Here, we identified and characterized a LEP gene (zebra finch LEP [zbLEP]) encoding a 172-amino acid precursor in zebra finches. Despite zbLEP showing limited amino acid sequence identity (26%-29%) to human and mouse LEPs, synteny analysis proved that zbLEP is orthologous to mammalian LEP. Using a pAH32 luciferase reporter system and Western blot analysis, we demonstrated that the recombinant zbLEP protein could potently activate finch and chicken LEP receptors (zbLEPR; cLEPR) expressed in human embryonic kidney 293 cells and enhance signal transducer and activator of transcription 3 phosphorylation, further indicating that zbLEP is a functional ligand for avian LEPRs. Interestingly, quantitative real-time RT-PCR revealed that zbLEP mRNA is expressed nearly exclusively in the pituitary and various brain regions but undetectable in adipose tissue and liver, whereas zbLEPR mRNA is widely expressed in adult finch tissues examined with abundant expression noted in pituitary, implying that unlike mammalian LEP, finch LEP may not act as an adipocyte-derived signal to control energy balance. As in finches, a LEP highly homologous to zbLEP was also identified in budgerigar genome. Strikingly, finch and budgerigar LEPs show little homology with chicken LEP (cLEP) previously reported, suggesting that the so-called cLEP is incorrect. Collectively, our data provide convincing evidence for the existence of an authentic functional LEP in avian species and suggest an important role of brain- and pituitary-derived LEP played in vertebrates. PMID:24823393

Huang, Guian; Li, Juan; Wang, Hongning; Lan, Xinyu; Wang, Yajun

2014-09-01

318

A transcriptomic analysis of striped catfish (Pangasianodon hypophthalmus) in response to salinity adaptation: De novo assembly, gene annotation and marker discovery.  

PubMed

The striped catfish (Pangasianodon hypophthalmus) culture industry in the Mekong Delta in Vietnam has developed rapidly over the past decade. The culture industry now however, faces some significant challenges, especially related to climate change impacts notably from predicted extensive saltwater intrusion into many low topographical coastal provinces across the Mekong Delta. This problem highlights a need for development of culture stocks that can tolerate more saline culture environments as a response to expansion of saline water-intruded land. While a traditional artificial selection program can potentially address this need, understanding the genomic basis of salinity tolerance can assist development of more productive culture lines. The current study applied a transcriptomic approach using Ion PGM technology to generate expressed sequence tag (EST) resources from the intestine and swim bladder from striped catfish reared at a salinity level of 9ppt which showed best growth performance. Total sequence data generated was 467.8Mbp, consisting of 4,116,424 reads with an average length of 112bp. De novo assembly was employed that generated 51,188 contigs, and allowed identification of 16,116 putative genes based on the GenBank non-redundant database. GO annotation, KEGG pathway mapping, and functional annotation of the EST sequences recovered with a wide diversity of biological functions and processes. In addition, more than 11,600 simple sequence repeats were also detected. This is the first comprehensive analysis of a striped catfish transcriptome, and provides a valuable genomic resource for future selective breeding programs and functional or evolutionary studies of genes that influence salinity tolerance in this important culture species. PMID:24841517

Thanh, Nguyen Minh; Jung, Hyungtaek; Lyons, Russell E; Chand, Vincent; Tuan, Nguyen Viet; Thu, Vo Thi Minh; Mather, Peter

2014-06-01

319

Biological simulations in drug discovery.  

PubMed

Simulation of biological processes, systems and organs is a necessary complement to genetic and molecular sequencing. Using the heart as an example, the authors describe the way in which such modelling can be used in drug discovery, development and assessment. The technology is readily applicable to other organs and systems as well; models of neurones and neuronal systems, the pancreas and the lungs have already been developed. Ultimately, a virtual corpus is feasible. Genes can only specify the properties of the proteins they code for, and any integrative properties of the system must be 'computed' by their interactions-Sydney Brenner PMID:10234145

Noble; Levin; Scott

1999-01-01

320

Final report on LDRD project : elucidating performance of proton-exchange-membrane fuel cells via computational modeling with experimental discovery and validation.  

SciTech Connect

In this report, we document the accomplishments in our Laboratory Directed Research and Development project in which we employed a technical approach of combining experiments with computational modeling and analyses to elucidate the performance of hydrogen-fed proton exchange membrane fuel cells (PEMFCs). In the first part of this report, we document our focused efforts on understanding water transport in and removal from a hydrogen-fed PEMFC. Using a transparent cell, we directly visualized the evolution and growth of liquid-water droplets at the gas diffusion layer (GDL)/gas flow channel (GFC) interface. We further carried out a detailed experimental study to observe, via direct visualization, the formation, growth, and instability of water droplets at the GDL/GFC interface using a specially-designed apparatus, which simulates the cathode operation of a PEMFC. We developed a simplified model, based on our experimental observation and data, for predicting the onset of water-droplet instability at the GDL/GFC interface. Using a state-of-the-art neutron imaging instrument available at NIST (National Institute of Standard and Technology), we probed liquid-water distribution inside an operating PEMFC under a variety of operating conditions and investigated effects of evaporation due to local heating by waste heat on water removal. Moreover, we developed computational models for analyzing the effects of micro-porous layer on net water transport across the membrane and GDL anisotropy on the temperature and water distributions in the cathode of a PEMFC. We further developed a two-phase model based on the multiphase mixture formulation for predicting the liquid saturation, pressure drop, and flow maldistribution across the PEMFC cathode channels. In the second part of this report, we document our efforts on modeling the electrochemical performance of PEMFCs. We developed a constitutive model for predicting proton conductivity in polymer electrolyte membranes and compared model prediction with experimental data obtained in our laboratory and from literature. Moreover, we developed a one-dimensional analytical model for predicting electrochemical performance of an idealized PEMFC with small surface over-potentials. Furthermore, we developed a multi-dimensional computer model, which is based on the finite-element method and a fully-coupled implicit solution scheme via Newton's technique, for simulating the performance of PEMFCs. We demonstrated utility of our finite-element model by comparing the computed current density distribution and overall polarization with those measured using a segmented cell. In the last part of this report, we document an exploratory experimental study on MEA (membrane electrode assembly) degradation.

Wang, Chao Yang (Pennsylvania State University, University Park, PA); Pasaogullari, Ugur (Pennsylvania State University, University Park, PA); Noble, David R.; Siegel, Nathan P.; Hickner, Michael A.; Chen, Ken Shuang

2006-11-01

321

Breeding Specialty Starch Maize Using Exotic Genetic Resources for Gene Discovery of Novel Alleles and Modifiers with Materials Generated from the USDA-ARS GEM Project  

Technology Transfer Automated Retrieval System (TEKTRAN)

Amylomaize VII, a class of High Amylose Maize with at least 70% of the kernel starch composed of the linear amylose polymer, has had numerous food and industrial applications including the manufacturing of biodegradable plastics, adhesives and candies. More recently it has been found to be a signi...

322

Gene-targeted microfluidic cultivation validated by isolation of a gut bacterium listed in Human Microbiome Project's Most Wanted taxa  

PubMed Central

This paper describes a microfluidics-based workflow for genetically targeted isolation and cultivation of microorganisms from complex clinical samples. Data sets from high-throughput sequencing suggest the existence of previously unidentified bacterial taxa and functional genes with high biomedical importance. Obtaining isolates of these targets, preferably in pure cultures, is crucial for advancing understanding of microbial genetics and physiology and enabling physical access to microbes for further applications. However, the majority of microbes have not been cultured, due in part to the difficulties of both identifying proper growth conditions and characterizing and isolating each species. We describe a method that enables genetically targeted cultivation of microorganisms through a combination of microfluidics and on- and off-chip assays. This method involves (i) identification of cultivation conditions for microbes using growth substrates available only in small quantities as well as the correction of sampling bias using a “chip wash” technique; and (ii) performing on-chip genetic assays while also preserving live bacterial cells for subsequent scale-up cultivation of desired microbes, by applying recently developed technology to create arrays of individually addressable replica microbial cultures. We validated this targeted approach by cultivating a bacterium, here referred to as isolate microfluidicus 1, from a human cecal biopsy. Isolate microfluidicus 1 is, to our knowledge, the first successful example of targeted cultivation of a microorganism from the high-priority group of the Human Microbiome Project’s “Most Wanted” list, and, to our knowledge, the first cultured representative of a previously unidentified genus of the Ruminococcaceae family. PMID:24965364

Ma, Liang; Kim, Jungwoo; Hatzenpichler, Roland; Karymov, Mikhail A.; Hubert, Nathaniel; Hanan, Ira M.; Chang, Eugene B.; Ismagilov, Rustem F.

2014-01-01

323

A Generic Tool for Transcription Factor Target Gene Discovery in Arabidopsis Cell Suspension Cultures Based on Tandem Chromatin Affinity Purification1[W][OPEN  

PubMed Central

Genome-wide identification of transcription factor (TF) binding sites is pivotal to our understanding of gene expression regulation. Although much progress has been made in the determination of potential binding regions of proteins by chromatin immunoprecipitation, this method has some inherent limitations regarding DNA enrichment efficiency and antibody necessity. Here, we report an alternative strategy for assaying in vivo TF-DNA binding in Arabidopsis (Arabidopsis thaliana) cells by tandem chromatin affinity purification (TChAP). Evaluation of TChAP using the E2Fa TF and comparison with traditional chromatin immunoprecipitation and single chromatin affinity purification illustrates the suitability of TChAP and provides a resource for exploring the E2Fa transcriptional network. Integration with transcriptome, cis-regulatory element, functional enrichment, and coexpression network analyses demonstrates the quality of the E2Fa TChAP sequencing data and validates the identification of new direct E2Fa targets. TChAP enhances both TF target mapping throughput, by circumventing issues related to antibody availability, and output, by improving DNA enrichment efficiency. PMID:24453163

Verkest, Aurine; Abeel, Thomas; Heyndrickx, Ken S.; Van Leene, Jelle; Lanz, Christa; Van De Slijke, Eveline; De Winne, Nancy; Eeckhout, Dominique; Persiau, Geert; Van Breusegem, Frank; Inzé, Dirk; Vandepoele, Klaas; De Jaeger, Geert

2014-01-01

324

Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions.  

PubMed

Anthelmintic resistance has a great impact on livestock production systems worldwide, is an emerging concern in companion animal medicine, and represents a threat to our ongoing ability to control human soil-transmitted helminths. The Consortium for Anthelmintic Resistance and Susceptibility (CARS) provides a forum for scientists to meet and discuss the latest developments in the search for molecular markers of anthelmintic resistance. Such markers are important for detecting drug resistant worm populations, and indicating the likely impact of the resistance on drug efficacy. The molecular basis of resistance is also important for understanding how anthelmintics work, and how drug resistant populations arise. Changes to target receptors, drug efflux and other biological processes can be involved. This paper reports on the CARS group meeting held in August 2013 in Perth, Australia. The latest knowledge on the development of molecular markers for resistance to each of the principal classes of anthelmintics is reviewed. The molecular basis of resistance is best understood for the benzimidazole group of compounds, and we examine recent work to translate this knowledge into useful diagnostics for field use. We examine recent candidate-gene and whole-genome approaches to understanding anthelmintic resistance and identify markers. We also look at drug transporters in terms of providing both useful markers for resistance, as well as opportunities to overcome resistance through the targeting of the transporters themselves with inhibitors. Finally, we describe the tools available for the application of the newest high-throughput sequencing technologies to the study of anthelmintic resistance. PMID:25516826

Kotze, Andrew C; Hunt, Peter W; Skuce, Philip; von Samson-Himmelstjerna, Georg; Martin, Richard J; Sager, Heinz; Krücken, Jürgen; Hodgkinson, Jane; Lespine, Anne; Jex, Aaron R; Gilleard, John S; Beech, Robin N; Wolstenholme, Adrian J; Demeler, Janina; Robertson, Alan P; Charvet, Claude L; Neveu, Cedric; Kaminsky, Ronald; Rufener, Lucien; Alberich, Melanie; Menez, Cecile; Prichard, Roger K

2014-12-01

325

Schistosoma mansoni genome project: an update.  

PubMed

A schistosome genome project was initiated by the World Health Organization in 1994 with the notion that the best prospects for identifying new targets for drugs, vaccines, and diagnostic development lie in schistosome gene discovery, development of chromosome maps, whole genome sequencing and genome analysis. Schistosoma mansoni has a haploid genome of 270 Mb contained on 8 pairs of chromosomes. It is estimated that the S. mansoni genome contains between 15000 and 25000 genes. There are approximately 16689 ESTs obtained from diverse libraries representing different developmental stages of S. mansoni, deposited in the NCBI EST database. More than half of the deposited sequences correspond to genes of unknown function. Approximately 40-50% of the sequences form unique clusters, suggesting that approximately 20-25% of the total schistosome genes have been discovered. Efforts to develop low resolution chromosome maps are in progress. There is a genome sequencing program underway that will provide 3X sequence coverage of the S. mansoni genome that will result in approximately 95% gene discovery. The genomics era has provided the resources to usher in the era of functional genomics that will involve microarrays to focus on specific metabolic pathways, proteomics to identify relevant proteins and protein-protein interactions to understand critical parasite pathways. Functional genomics is expected to accelerate the development of control and treatment strategies for schistosomiasis. PMID:15081950

LoVerde, Philip T; Hirai, Hirohisa; Merrick, Joseph M; Lee, Norman H; El-Sayed, Najib

2004-06-01

326

Implications for powering biomarker discovery studies.  

PubMed

This study examined variations in gene expression between FFPE blocks within tumors of individual patients. Microarray data were used to measure tumor heterogeneity within and between patients and disease states. Data were used to determine the number of samples needed to power biomarker discovery studies. Bias and variation in gene expression were assessed at the intrapatient and interpatient levels and between adenocarcinoma and squamous samples. A mixed-model analysis of variance was fitted to gene expression data and model signatures to assess the statistical significance of observed variations within and between samples and disease states. Sample size analysis, adjusted for sample heterogeneity, was used to determine the number of samples required to support biomarker discovery studies. Variation in gene expression was observed between blocks taken from a single patient. However, this variation was considerably less than differences between histological characteristics. This degree of block-to-block variation still permits biomarker discovery using either macrodissected tumors or whole FFPE sections, provided that intratumor heterogeneity is taken into account. Failure to consider intratumor heterogeneity may result in underpowered biomarker studies that may result in either the generation of longer gene signatures or the inability to identify a viable biomarker. Moreover, the results of this study indicate that a single biopsy sample is suitable for applying a biomarker in non-small-cell lung cancer. PMID:22251612

Dibben, Sian M; Holt, Robert J; Davison, Timothy S; Wilson, Claire L; Taylor, Janet; Paul, Ian; McManus, Kieran; Kelly, Paul J; Proutski, Vitali; Harkin, D Paul; Kerr, Peter; Fennell, Dean A; James, Jacqueline A; Kennedy, Richard D

2012-01-01

327

"Eureka, Eureka!" Discoveries in Science  

ERIC Educational Resources Information Center

Accidental discoveries have been of significant value in the progress of science. Although accidental discoveries are more common in pharmacology and chemistry, other branches of science have also benefited from such discoveries. While most discoveries are the result of persistent research, famous accidental discoveries provide a fascinating…

Agarwal, Pankaj

2011-01-01

328

Topology Discovery Using Cisco Discovery Protocol  

E-print Network

In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology of CDP-based networks. Our experiments show that the physical topology of the network including links that are in Forwarding Block state can be discovered.

Rodriguez, Sergio R

2009-01-01

329

Accelerating scientific discovery : 2007 annual report.  

SciTech Connect

As a gateway for scientific discovery, the Argonne Leadership Computing Facility (ALCF) works hand in hand with the world's best computational scientists to advance research in a diverse span of scientific domains, ranging from chemistry, applied mathematics, and materials science to engineering physics and life sciences. Sponsored by the U.S. Department of Energy's (DOE) Office of Science, researchers are using the IBM Blue Gene/L supercomputer at the ALCF to study and explore key scientific problems that underlie important challenges facing our society. For instance, a research team at the University of California-San Diego/ SDSC is studying the molecular basis of Parkinson's disease. The researchers plan to use the knowledge they gain to discover new drugs to treat the disease and to identify risk factors for other diseases that are equally prevalent. Likewise, scientists from Pratt & Whitney are using the Blue Gene to understand the complex processes within aircraft engines. Expanding our understanding of jet engine combustors is the secret to improved fuel efficiency and reduced emissions. Lessons learned from the scientific simulations of jet engine combustors have already led Pratt & Whitney to newer designs with unprecedented reductions in emissions, noise, and cost of ownership. ALCF staff members provide in-depth expertise and assistance to those using the Blue Gene/L and optimizing user applications. Both the Catalyst and Applications Performance Engineering and Data Analytics (APEDA) teams support the users projects. In addition to working with scientists running experiments on the Blue Gene/L, we have become a nexus for the broader global community. In partnership with the Mathematics and Computer Science Division at Argonne National Laboratory, we have created an environment where the world's most challenging computational science problems can be addressed. Our expertise in high-end scientific computing enables us to provide guidance for applications that are transitioning to petascale as well as to produce software that facilitates their development, such as the MPICH library, which provides a portable and efficient implementation of the MPI standard--the prevalent programming model for large-scale scientific applications--and the PETSc toolkit that provides a programming paradigm that eases the development of many scientific applications on high-end computers.

Beckman, P.; Dave, P.; Drugan, C.

2008-11-14

330

Serendipity and Scientific Discovery.  

ERIC Educational Resources Information Center

The discovery of penicillin is cited in a discussion of the role of serendipity as it relates to scientific discovery. The importance of sagacity as a personality trait is noted. Successful researchers have questioning minds, are willing to view data from several perspectives, and recognize and appreciate the unexpected. (JW)

Rosenman, Martin F.

1988-01-01

331

Where is the Discovery in Literature-Based Discovery?  

NASA Astrophysics Data System (ADS)

This chapter addresses the core of literature-based discovery (LBD), namely, what is discovery and how is the generation of discovery confirmed. The chapter starts with definitions of discovery and innovation, especially in the LBD context, and then proceeds to describe radical discovery and LBD. It then describes the vetting necessary to confirm the presence of discovery. Finally, the chapter concludes with a few examples where use of more comprehensive vetting techniques would have been prudent before discovery was reported. The LBD focus is on open discovery systems (start with a problem, discover a solution, or vice versa) exclusively.

Kostoff, R. N.

332

Wyre Community Discovery Centre Wyre Community Discovery  

E-print Network

boiler and the building must be carefully considered. Ideally have an all-year-round need to balance use wood chip boiler provides heating and hot water to the Discovery Centre. The boiler is fuelled using contractor to chip and store locally-sourced timber. Hot water from the boiler is stored in an accumulator

333

Discovery Park Undergraduate Research Internship Projects  

E-print Network

expression in largemouth bass tissues exposed to different chemicals · Manufacture 3-D composite materials whether or not to license the technologies · Transform gold nanorods into molecular probes to detect technologies. -Due to the rapid advance of computing, sensing, and communication technologies, large

334

THEMOSELYSNOWFLAKESPONGE A USC LIBRARIES DISCOVERY FELLOW PROJECT  

E-print Network

. Mosely has discovered a relative of Menger's original fractal--the Mosely Snowflake Sponge. USC Libraries to assemble a level one Mosely Snowflake Sponge, a smaller variant of the level three fractal under. She designed and developed the methods for creating the Mosely Snowflake Sponge. ABOUT MARGARET

Valero-Cuevas, Francisco

335

Discovery Channel Telescope software key technologies  

NASA Astrophysics Data System (ADS)

The Discovery Channel Telescope (DCT) is a 4.3-meter astronomical research telescope being built in northern Arizona as a partnership between Discovery Communications and Lowell Observatory. The project software team has designed and partially implemented a component-based system. We describe here the key features of that design (state-based components that respond to signals) and detail specific implementation technologies we expect to be of most interest: examples of the Command Pattern, State Pattern, and XML-based configuration file handling using LabVIEW classes and shared variables with logging and alarming features.

Lotz, Paul J.

2010-07-01

336

Discovery Channel Telescope software development overview  

NASA Astrophysics Data System (ADS)

The Discovery Channel Telescope (DCT) is a 4.3-meter astronomical research telescope being built in northern Arizona as a partnership between Discovery Communications and Lowell Observatory. We present an overview of the current status of the project software effort, including the iterative development process (including planning, requirements management and traceability, design, code, test, issue tracking, and version control), our experience with management and design techniques and tools the team uses that support the effort, key features of the component-based architectural design, and implementation examples that leverage new LabVIEW-based technologies.

Lotz, Paul J.; Greenspan, Daniel; Godwin, Ryan; Taylor, Philip

2010-07-01

337

Viral surveillance and discovery  

PubMed Central

The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health. PMID:23602435

Lipkin, Walter Ian; Firth, Cadhla

2014-01-01

338

DEGAS: De Novo Discovery of Dysregulated Pathways in Human Diseases  

E-print Network

DEGAS: De Novo Discovery of Dysregulated Pathways in Human Diseases Igor Ulitsky1¤a *, Akshay: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression a small number of the genes in human disease-related pathways show consistent dysregulation in sick

Shamir, Ron

339

The requirements discovery process  

SciTech Connect

Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirement process. This paper provides a high-level overview of the requirements discovery process.

Bahill, A.T. [Univ. of Arizona, Tucson, AZ (United States). Systems and Industrial Engineering; Dean, F.F. [Sandia National Lab., Albuquerque, NM (United States)

1997-02-01

340

Platforms for antibiotic discovery.  

PubMed

The spread of resistant bacteria, leading to untreatable infections, is a major public health threat but the pace of antibiotic discovery to combat these pathogens has slowed down. Most antibiotics were originally isolated by screening soil-derived actinomycetes during the golden era of antibiotic discovery in the 1940s to 1960s. However, diminishing returns from this discovery platform led to its collapse, and efforts to create a new platform based on target-focused screening of large libraries of synthetic compounds failed, in part owing to the lack of penetration of such compounds through the bacterial envelope. This article considers strategies to re-establish viable platforms for antibiotic discovery. These include investigating untapped natural product sources such as uncultured bacteria, establishing rules of compound penetration to enable the development of synthetic antibiotics, developing species-specific antibiotics and identifying prodrugs that have the potential to eradicate dormant persisters, which are often responsible for hard-to-treat infections. PMID:23629505

Lewis, Kim

2013-05-01

341

CoMoDis: composite motif discovery in mammalian genomes  

PubMed Central

Specificity of mammalian gene regulatory regions is achieved to a large extent through the combinatorial binding of sets of transcription factors to distinct binding sites, discrete combinations of which are often referred to as regulatory modules. Identification and subsequent characterization of gene regulatory modules will be a key step in assembling transcriptional regulatory networks from gene expression profiling data, with the ultimate goal of unravelling the regulatory codes that govern gene expression in various cell types. Here we describe the new bioinformatics tool, Composite Motif Discovery (CoMoDis), which streamlines computational identification of novel regulatory modules starting from a single seed motif. Seed motifs represent binding sites conserved across mammalian species. CoMoDis facilitates novel motif discovery by automating the extraction of DNA sequences flanking seed motifs and streamlining downstream motif discovery using a variety of tools, including several that utilize phylogenetic conservation criteria. CoMoDis is available at . PMID:17130158

Donaldson, Ian J.; Göttgens, Berthold

2007-01-01

342

History of Saturn Discoveries  

NSDL National Science Digital Library

In this lesson, learners will use History of Discovery cards and interpretive skits to examine how scientists throughout history have explored Saturn. The lesson enables students to discern the multicultural nature of scientific inquiry and to see how technology improvements increase our ability to solve scientific mysteries. The lesson also prepares students to create and interpret their own timelines spanning the years 1610 to 2010. The timelines depict scientists, technologies, and discoveries. This is lesson 4 of 6 in the Saturn Educators Guide.

343

Discovery Collection: Marine Animals  

NSDL National Science Digital Library

Marine Animals is one of the AMNH Education Department's many collections of specimens and artifacts gathered the world over by explorers and scientists. In its online Discovery Collection form, Marine Animals includes photographs of 20 specimens with classification and distribution details, an interactive key that guides you through specimen identification, an activity where students select and identify a specimen photograph using the interactive identification key and an Educator's Guide with suggestions for how to use the Marine Animals Discovery Collection in the classroom.

Lisa Breslof

344

Discovery Collection: Oyster Shells  

NSDL National Science Digital Library

Oyster Shells is one of the AMNH Education Department's many collections of specimens and artifacts gathered the world over by explorers and scientists. In its online Discovery Collection form, Oyster Shells includes photographs of 15 specimens with classification and distribution details, an interactive key that guides you through specimen identification, an activity where students select and identify a specimen photograph using the interactive identification key and an Educator's Guide with suggestions for how to use the Oyster Shells Discovery Collection in the classroom.

Breslof, Lisa; Schiller, William

345

3 Supernova Discoveries  

Microsoft Academic Search

The Nearby Supernova Factory reports the discovery of 3 supernovae in images obtained on Aug 09 and Aug 24 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery

C. Baltay; A. Bauer; D. Rabinowitz; R. Scalzo; G. Rigaudier; E. Pecontal; C. Buton; Y. Copin; E. Gangler; G. Smadja; C. Tao; P. Antilogus; R. Pain; R. Pereira; C. Wu; G. Aldering; C. Aragon; S. Bailey; S. Bongard; M. Childress; S. Loken; P. Nugent; S. Perlmutter; K. Runge; R. C. Thomas; B. A. Weaver; D. Birchall; J. Cough; J. Holtzman

2007-01-01

346

9 Supernova Discoveries  

Microsoft Academic Search

The Nearby Supernova Factory reports the discovery of 9 supernovae in images obtained Sep 26 through Oct 12 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes

P. Antilogus; S. Bailey; R. Pain; R. Pereira; C. Wu; G. Aldering; C. Aragon; S. Bongard; M. Childress; S. Loken; P. Nugent; S. Perlmutter; K. Runge; R. C. Thomas; B. A. Weaver; C. Baltay; A. Bauer; D. Rabinowitz; R. Scalzo; G. Rigaudier; E. Pecontal; C. Buton; Y. Copin; E. Gangler; G. Smadja; C. Tao; D. Birchall; J. Cough; J. Holtzman

2007-01-01

347

4 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

4 Supernova Discoveries The Nearby Supernova Factory reports the discovery of 4 supernovae in images obtained Jul 13 through Jul 14 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each.

Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Birchall, D.; Holtzman, J.

2007-07-01

348

6 Supernova Discoveries  

Microsoft Academic Search

The Nearby Supernova Factory reports the discovery of 6 supernovae in images obtained Aug 31 through Sep 01 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes

C. Buton; Y. Copin; E. Gangler; G. Smadja; C. Tao; P. Antilogus; S. Bailey; R. Pain; R. Pereira; C. Wu; G. Aldering; C. Aragon; S. Bongard; M. Childress; S. Loken; P. Nugent; S. Perlmutter; K. Runge; R. C. Thomas; B. A. Weaver; C. Baltay; A. Bauer; D. Rabinowitz; R. Scalzo; G. Rigaudier; E. Pecontal; D. Birchall; J. Cough; J. Holtzman

2007-01-01

349

2 Supernova Discoveries  

Microsoft Academic Search

The Nearby Supernova Factory reports the discovery of 2 supernovae in images obtained Aug 22 through Aug 24 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes

G. Aldering; C. Aragon; S. Bailey; S. Bongard; M. Childress; S. Loken; P. Nugent; S. Perlmutter; K. Runge; R. C. Thomas; B. A. Weaver; C. Baltay; A. Bauer; D. Rabinowitz; R. Scalzo; G. Rigaudier; E. Pecontal; C. Buton; Y. Copin; E. Gangler; G. Smadja; C. Tao; P. Antilogus; R. Pain; R. Pereira; C. Wu; D. Birchall; J. Cough; J. Holtzman

2007-01-01

350

4 Supernova Discoveries  

Microsoft Academic Search

The Nearby Supernova Factory reports the discovery of 4 supernovae in images obtained Aug 15 through Aug 19 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes

C. Buton; Y. Copin; E. Gangler; G. Smadja; C. Tao; P. Antilogus; R. Pain; R. Pereira; C. Wu; G. Aldering; C. Aragon; S. Bailey; S. Bongard; M. Childress; S. Loken; P. Nugent; S. Perlmutter; K. Runge; R. C. Thomas; B. A. Weaver; C. Baltay; A. Bauer; D. Rabinowitz; R. Scalzo; G. Rigaudier; E. Pecontal; D. Birchall; J. Cough; J. Holtzman

2007-01-01

351

Gene discovery and engineering for biomass degradation  

Technology Transfer Automated Retrieval System (TEKTRAN)

The eventual depletion of the world’s fossil fuel reserves has generated intense interest in alternatives. Lignocellulosic biomass represents a viable source for our future fuel and chemical feedstock needs. Hemicellulose is the second most common component of biomass. It is composed primarily of...

352

Gene discovery in the Acanthamoeba castellanii genome  

SciTech Connect

Acanthamoeba castellanii is a free-living amoeba found in soil, freshwater, and marine environments and an important predator of bacteria. Acanthamoeba castellanii is also an opportunistic pathogen of clinical interest, responsible for several distinct diseases in humans. In order to provide a genomic platform for the study of this ubiquitous and important protist, we generated a sequence survey of approximately 0.5 x coverage of the genome. The data predict that A. castellanii exhibits a greater biosynthetic capacity than the free-living Dictyostelium discoideum and the parasite Entamoeba histolytica, providing an explanation for the ability of A. castellanii to inhabit adversity of environments. Alginate lyase may provide access to bacteria within biofilms by breaking down the biofilm matrix, and polyhydroxybutyrate depolymerase may facilitate utilization of the bacterial storage compound polyhydroxybutyrate as a food source. Enzymes for the synthesis and breakdown of cellulose were identified, and they likely participate in encystation and excystation as in D. discoideum. Trehalose-6-phosphate synthase is present, suggesting that trehalose plays a role in stress adaptation. Detection and response to a number of stress conditions is likely accomplished with a large set of signal transduction histidine kinases and a set of putative receptorserine/threonine kinases similar to those found in E. histolytica. Serine, cysteine and metalloproteases were identified, some of which are likely involved in pathogenicity.

Anderson, Iain J.; Watkins, Russell F.; Samuelson, John; Spencer,David F.; Majoros, William H.; Gray, Michael W.; Loftus, Brendan J.

2005-08-01

353

Integrated analysis of gene expression and copy number data on gene shaving using independent component analysis.  

PubMed

DNA microarray gene expression and microarray-based comparative genomic hybridization (aCGH) have been widely used for biomedical discovery. Because of the large number of genes and the complex nature of biological networks, various analysis methods have been proposed. One such method is "gene shaving," a procedure which identifies subsets of the genes with coherent expression patterns and large variation across samples. Since combining genomic information from multiple sources can improve classification and prediction of diseases, in this paper we proposed a new method, "ICA gene shaving" (ICA, independent component analysis), for jointly analyzing gene expression and copy number data. First we used ICA to analyze joint measurements, gene expression and copy number, of a biological system and project the data onto statistically independent biological processes. Next, we used these results to identify patterns of variation in the data and then applied an iterative shaving method. We investigated the properties of our proposed method by analyzing both simulated and real data. We demonstrated that the robustness of our method to noise using simulated data. Using breast cancer data, we showed that our method is superior to the Generalized Singular Value Decomposition (GSVD) gene shaving method for identifying genes associated with breast cancer. PMID:21519112

Sheng, Jinhua; Deng, Hong-Wen; Calhoun, Vince D; Wang, Yu-Ping

2011-01-01

354

Knowledge discovery by accuracy maximization  

PubMed Central

Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold’s topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan’s presidency and not from its beginning. PMID:24706821

Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

2014-01-01

355

Advancing drug discovery for schizophrenia  

PubMed Central

Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, “Advancing Drug Discovery for Schizophrenia” was held March 9–11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia. PMID:22032400

Marder, Stephen R.; Roth, Bryan; Sullivan, Patrick F.; Scolnick, Edward M.; Nestler, Eric J.; Geyer, Mark A.; Welnberger, Daniel R.; Karayiorgou, Maria; Guidotti, Alessandro; Gingrich, Jay; Akbarian, Schahram; Buchanan, Robert W.; Lieberman, Jeffrey A.; Conn, P. Jeffrey; Haggarty, Stephen J.; Law, Amanda J.; Campbell, Brian; Krystal, John H.; Moghaddam, Bita; Saw, Akira; Caron, Marc G.; George, Susan R.; Allen, John A.; Solis, Michelle

2013-01-01

356

A Gene Recommender Algorithm to Identify Coexpressed Genes in C. elegans  

E-print Network

A Gene Recommender Algorithm to Identify Coexpressed Genes in C. elegans Art B. Owen,1,4 Josh is for the discovery of new genes with similar function to a given list of genes (the query) already known to have closely related function. We have developed an algorithm, called the gene recommender, that ranks genes

Stuart, Josh

357

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements  

EPA Science Inventory

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, ...

358

MICROARRAY QUALITY CONTROL PROJECT: A COMPREHENSIVE GENE EXPRESSION TECHNOLOGY SURVEY DEMONSTRATES MEASURABLE CONSISTENCY AND CONCORDANT RESULTS BETWEEN PLATFORMS  

EPA Science Inventory

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, h...

359

Moments of Discovery  

NSDL National Science Digital Library

Even the most cursory explorations into how scientific discoveries are made reveals that many of these discoveries are tinged with a certain serendipity and circumstances that are not immediately attributable to a wholly reasoned and logical progression of methodical experiments. Presented by the American Institute of Physics, this online multimedia exhibit tells the story of two important 20th century scientific discoveries: the discovery of nuclear fission and the detection of the first optical pulsar. The discovery of nuclear fission section contains audio clips from some of those responsible for this scientific endeavor, including Enrico Fermi, Arthur Holly Compton, and Otto Hahn. One particularly noteworthy clip features Compton's firsthand recollection of the first successful self-sustaining nuclear chain reaction under the bleacher of Stagg Field on the campus of the University of Chicago. The second exhibit hones in on the detection of the first optical pulsar, and includes clips from Philip Morrison, John Cocke, and Michael Disney. The site is rounded out by a set of teachers' guides designed to complement these online exhibits.

360

Development Status of the WetLab-2 Project: New Tools for On-orbit Real-time Quantitative Gene Expression.  

NASA Technical Reports Server (NTRS)

The primary objective of NASA Ames Research Centers WetLab-2 Project is to place on the ISS a research platform to facilitate gene expression analysis via quantitative real-time PCR (qRT-PCR) of biological specimens grown or cultured on orbit. The WetLab-2 equipment will be capable of processing multiple sample types ranging from microbial cultures to animal tissues dissected on-orbit. In addition to the logistical benefits of in-situ sample processing and analysis, conducting qRT-PCR on-orbit eliminates the confounding effects on gene expression of reentry stresses and shock acting on live cells and organisms. The system can also validate terrestrial analyses of samples returned from ISS by providing quantitative on-orbit gene expression benchmarking prior to sample return. The ability to get on orbit data will provide investigators with the opportunity to adjust experimental parameters for subsequent trials based on the real-time data analysis without need for sample return and re-flight. Finally, WetLab-2 can be used for analysis of air, surface, water, and clinical samples to monitor environmental contaminants and crew health. The verification flight of the instrument is scheduled to launch on SpaceX-5 in Aug. 2014.Progress to date: The WetLab-2 project completed a thorough study of commercially available qRT-PCR systems and performed a downselect based on both scientific and engineering requirements. The selected instrument, the Cepheid SmartCycler, has advantages including modular design (16 independent PCR modules), low power consumption, and rapid ramp times. The SmartCycler has multiplex capabilities, assaying up to four genes of interest in each of the 16 modules. The WetLab-2 team is currently working with Cepheid to modify the unit for housing within an EXPRESS rack locker on the ISS. This will enable the downlink of data to the ground and provide uplink capabilities for programming, commanding, monitoring, and instrument maintenance. The project is currently designing a module that will lyse the cells and extract RNA of sufficient quality for use in qRT-PCR reactions while using a housekeeping gene to normalize RNA concentration and integrity. Current testing focuses on two promising commercial products and chemistries that allow for RNA extraction with minimal complexity and crew time.

Jung, Jimmy; Parra, Macarena P.; Almeida, Eduardo; Boone, Travis; Chinn, Tori; Ricco, Antonio; Souza, Kenneth; Hyde, Liz; Rukhsana, Yousuf; Richey, C. Scott

2013-01-01

361

Science Fun with Electricity...Discoveries and Innovations.  

ERIC Educational Resources Information Center

This project manual is written for 4-H member children who are in the fifth grade or older. This project is designed to familiarize members with the scientific history concerning the discovery and application of electric energy through the 1800's. Readers can conduct experiments similar to the ones performed by the scientists and inventors of that…

Horton, Robert L.

362

Exploring the Planets: Discovery  

NSDL National Science Digital Library

This site describes what early civilizations knew about our solar system and how astronomy developed over the centuries. The early theories describing the movements of the planets, development of the first telescopes, and discoveries of the planets Uranus, Neptune and Pluto are some of the topics addressed in Discovery. Here you will find the Pluto discovery plate, the photographic plate taken the day Pluto's position was discovered by Clyde Tombaugh. Other topics covered at this site include: the Renaissance with the ideas of Copernicus and Kepler; the age of the telescope, which traces its development; Galileo, who is credited with discovering the moons of Jupiter, phases of Venus, and the craters on the Moon; and planetary satellites.

363

DiscoveryResources.org  

NSDL National Science Digital Library

An interesting site that is packed full of up-to-date info, discoveryresources.org is "where you will find the most up-to-date information, resources and news available about electronic discovery...(the site) offers much needed resources for legal professionals who seek to understand the many new technological and legal challenges associated with electronic discovery." As fast as the technology revolution is booming, so too is are all of the legal strings attached. This site seeks to provide professionals in the field with a means to stay up on discovery news. With links to Legal News, Featured Articles, a weblog, and a Reading Room, there is lots of useful information on this unique site.

364

Physical activity correlates with glutamate receptor gene expression in spinally-projecting RVLM neurons: a laser capture microdissection study.  

PubMed

Physical inactivity is an important risk factor in the development of cardiovascular disease. The rostral ventrolateral portion of the medulla (RVLM) is composed of heterogeneous populations of neurons that are involved in the regulation of the cardiovascular system. Because of functional heterogeneity, studying the changes in the gene expression of this specific population of neurons within the RVLM is challenging. In the present study, a fluorescent retrograde tracer was injected into the spinal cord to specifically label bulbospinal RVLM neurons in sedentary and active rats. Laser capture microdissection (LCM) was then employed to collect the fluorescently labeled neurons from sections encompassing the rostrocaudal extent of the RVLM. RNA extracted from the neurons was used in qRT-PCR analysis. Changes in gene expression levels of glutamate and GABA receptor subunits were compared between sedentary and physically active rats. GLUR3 subunit showed a significant negative correlation between total running distance and its relative gene expression in active rats. There were no significant difference in the gene expression of NMDA (NR1, NR2A, NR2B, NR2C and NR2D), AMPA (GLUR1, GLUR2 and GLUR3) and GABAA (GABAA1 and GABAA2) receptor subunits. Overall, the present study demonstrates the feasibility of utilizing LCM to investigate the gene expression changes in a specific population of neurons in the RVLM. Correlation studies suggest that physical activity could contribute to neuroplasticity in the RVLM. PMID:25173073

Subramanian, Madhan; Holt, Avril G; Mueller, Patrick J

2014-10-17

365

Pathway to Discovery  

NSDL National Science Digital Library

This interactive, online module allows learners to study the history of the discovery of black holes. Learners may work independently or in small groups to complete the activity. By completing this activity students learn the history of the discovery of black holes. This activity is a subsection of the "Is a Black Hole Really A Hole?" within the online exploration "No Escape: The Truth about Black Holes." Detailed teacher pages, identified as Teaching Tips on the title page of the activity, provide science background information, lesson plan ideas, related resources, and alignment with national education standards.

366

Titanic: Discovery Channel  

NSDL National Science Digital Library

RMS Titanic raised a 23- by 14-foot section of the Titanic's outer hull this week, and the Discovery Channel, who helped sponsor the expedition, will be webcasting live from the interior of the Titanic via robot cameras August 16 at 8:00 and 10:00 p.m. (Eastern Time). In addition to their live webcase, the Discovery Channel site (discussed in the December 5, 1997 issue of the Scout Report) features virtual reality tours of sections of the Titanic before and after its crash, quicktime videos of the expeditions, a computer animated simulation of the crash, and more.

367

4 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 4 supernovae in images obtained Aug 15 through Aug 19 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Birchall, D.; Cough, J.; Holtzman, J.

2007-08-01

368

11 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 11 supernovae in images obtained Jun 30 through Jul 08 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Birchall, D.; Holtzman, J.

2007-07-01

369

4 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 4 supernovae in images obtained Aug 31 through Sep 10 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Aldering, G.; Aragon, C.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Bailey, S.; Pain, R.; Pereira, R.; Wu, C.; Birchall, D.; Cough, J.; Holtzman, J.

2007-09-01

370

2 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 2 supernovae in images obtained Jul 26 through Jul 28 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Birchall, D.; Holtzman, J.

2007-07-01

371

2 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 2 supernovae in images obtained Jul 18 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Birchall, D.; Holtzman, J.

2007-07-01

372

4 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 4 supernovae in images obtained Aug 24 through Aug 26 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Birchall, D.; Cough, J.; Holtzman, J.

2007-09-01

373

6 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 6 supernovae in images obtained Aug 31 through Sep 01 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Bailey, S.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Birchall, D.; Cough, J.; Holtzman, J.

2007-09-01

374

3 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 3 supernovae in images obtained Aug 19 through Aug 20 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Birchall, D.; Cough, J.; Holtzman, J.

2007-08-01

375

9 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 9 supernovae in images obtained Sep 26 through Oct 12 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Antilogus, P.; Bailey, S.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Birchall, D.; Cough, J.; Holtzman, J.

2007-10-01

376

4 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 4 supernovae in images obtained Jul 18 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Birchall, D.; Holtzman, J.

2007-07-01

377

3 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 3 supernovae in images obtained on Aug 09 and Aug 24 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Birchall, D.; Cough, J.; Holtzman, J.

2007-08-01

378

4 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 4 supernovae in images obtained Sep 01 through Sep 02 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Bailey, S.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Birchall, D.; Cough, J.; Holtzman, J.

2007-09-01

379

2 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 2 supernovae in images obtained Aug 22 through Aug 24 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Birchall, D.; Cough, J.; Holtzman, J.

2007-08-01

380

2 Supernova Discoveries  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of 2 supernovae in images obtained Aug 03 and Aug 05 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST Consortium. Spectra (range 320-1000 nm) obtained with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope were used to classify each. R-band discovery magnitudes and J2000.0 coordinates are derived from comparison with the USNO-B1.0 catalog.

Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Birchall, D.; Holtzman, J.

2007-08-01

381

Scientists Find Gene They Say Affects Flu Shot Response  

MedlinePLUS

... on this page, please enable JavaScript. Scientists Find Gene They Say Affects Flu Shot Response Discovery could ... Thursday, December 11, 2014 Related MedlinePlus Pages Flu Genes and Gene Therapy Immunization THURSDAY, Dec. 11, 2014 ( ...

382

STS-114: Discovery Propulsion System Modification Briefing  

NASA Technical Reports Server (NTRS)

A briefing on the propulsion system modification of the STS-114 Discovery is presented. June Malone, NASA Public Affairs, introduces the panel who consists of: Sandy Coleman, External Tank Project Manager, Neil Otte, External Tank Chief Engineer, and Tom Williams, Solid Rocket Booster, Deputy Project Manager. Neil Otte presents charts on new requirements for foam debris reduction on the external tank. He also presents charts describing the Forward Bipod Redesign, LO2 Feedline Bellows Location, LH2 Intertank Flange Location, and In-Flight Imagery. Tom Williams presents charts describing Solid Rocket Booster Activities and Return to Flight efforts.

2005-01-01

383

PTF weekly SN discovery report, December 31, 2011  

NASA Astrophysics Data System (ADS)

The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf/ ; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 5 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B ), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org ).

Gal-Yam, A.; Arcavi, I.; Yaron, O.; Xu, D.; Nugent, P.; Pan, Y.-C.

2011-12-01

384

PTF weekly SN discovery report, December 8, 2011  

NASA Astrophysics Data System (ADS)

The PTF (ATEL #1964, #3253; http://www.astro.caltech.edu/ptf/ ; Law et al. 2009, PASP, 121, 1395; Rau et al. 2009, PASP, 121, 1334) reports the discovery of 25 new supernovae. PTF discoveries are made by autonomous PTF software (Bloom et al. 2011, http://adsabs.harvard.edu/abs/2011arXiv1106.5491B), as well as by the Galaxy Zoo Supernova Project (Smith et al. 2011, MNRAS, 412, 1309; http://supernova.galaxyzoo.org).

Gal-Yam, Avishay; Yaron, O.; Ben-Ami, S.; Nugent, P. E.; Groot, P.; Tandulkar, S.; Horesh, E. Bellm. A.; Cao, Y.; Levitan, D.; Sesar, B.; Hook, I.; Pan, Y.-C.; Kandrashoff, M.; Blanchard, P.; Silverman, J.; Cenko, S. B.; Miller, A.; Filippenko, A. V.; Clubb, K. I.

2011-12-01

385

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

PubMed Central

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

2011-01-01

386

Birds. Nature Discovery I.  

ERIC Educational Resources Information Center

The birds of New England and their particular habitats are explored in this guide which is part of a series of Nature Discovery publications. The materials are designed to directly supplement the natural science curricula and to complement other subject areas including social studies, language arts, music, and art. The program is designed for…

Stone, Sally F.

387

The Discovery of America  

ERIC Educational Resources Information Center

Discusses a model for explaining the spread of human population explosion on North American continent since its discovery 12,000 years ago. The model may help to map the spread of Homo sapiens throughout the New World by using the extinction chronology of the Pleistocene megafauna. (Author/PS)

Martin, Paul S.

1973-01-01

388

discoveries in drugs and  

E-print Network

New discoveries in drugs and medicinal products are happening rapidly.One of the greatest that developing new drugs requires an enormous amount of time and money. On av- erage, introducing a new drug product to market takes approximately 15 years and $650 million. A drug product consists of therapeutics

Glasser, Benjamin J.

389

Takeda's Oncology Discovery Strategy.  

PubMed

Takeda's Oncology Discovery Strategy is tightly integrated and focused on first and fast-best-in-class products and product combinations. Core areas of expertise include hormones, protein homeostasis, biotherapeutics and signal transduction. Strategic imperatives for research success are understanding of unmet needs, focus on biological expertise in foundational areas of leadership and flexibility to adapt to new information. PMID:23493743

DeSchuytner, Brian; Kuvalanka, Kyle; Hibner, Barbara; Bolen, Joseph

2013-04-01

390

Discovery Education: A Definition.  

ERIC Educational Resources Information Center

Discovery Education is based on the writings of Henry David Thoreau, an early champion of experiential learning. After 2 months of preparation, 10th-grade students spent 4 days in the wilderness reenacting a piece of history, such as the Lewis and Clark Expedition. The interdisciplinary approach always included journal-writing. Students gained…

Wilson, Harold C.

2002-01-01

391

Frequent Subgraph Discovery  

Microsoft Academic Search

Over the years, frequent itemset discovery algorithms have been used to solve various interesting problems. As data mining techniques are being increasingly applied to non-traditional domains, existing approaches for finding frequent itemsets cannot be used as they cannot model the requirement of these domains. An alternate way of modeling the objects in these data sets, is to use a graph

Michihiro Kuramochi; George Karypis

2001-01-01

392

Synthetic Biology of Antimicrobial Discovery  

E-print Network

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future ...

Zakeri, Bijan

393

The Human Genome Project and biology education  

SciTech Connect

Within the last several years, biologists celebrated the fortieth anniversary of the Watson-Crick model of DNA and the fiftieth anniversary of the demonstration that DNA is the genetic material, discoveries that began a pervasive and ongoing revolution in biology and medicine. Nobelist Joshua Lederberg, for example, called the work of Avery`s group {open_quotes}the most important discovery in biology in the twentieth century.{close_quotes} This early work on DNA also contributed to a revolution in biology education, beginning in the 1960s. Like the biological revolution that is its counterpart, however, the educational revolution is incomplete, in part because the science continues to evolve, but primarily because scientists and science educators have not yet responded completely to the challenges of genetics and molecular biology. These challenges are made even more obvious by the scope and visibility of the Human Genome Project, the international project intended to map and sequence all human genes. Science educators face 4 challenges discussed in this article and using the Genome project as an example: teach for conceptual understanding; the nature of science; the personal and social impact of science and technology; the principles of technology.

McInerney, J.D. [Biological Sciences Curriculum Study, Colorado Springs, CO (United States)

1995-12-01

394

Genetic basis of olfactory cognition: extremely high level of DNA sequence polymorphism in promoter regions of the human olfactory receptor genes revealed using the 1000 Genomes Project dataset  

PubMed Central

The molecular mechanism of olfactory cognition is very complicated. Olfactory cognition is initiated by olfactory receptor proteins (odorant receptors), which are activated by olfactory stimuli (ligands). Olfactory receptors are the initial player in the signal transduction cascade producing a nerve impulse, which is transmitted to the brain. The sensitivity to a particular ligand depends on the expression level of multiple proteins involved in the process of olfactory cognition: olfactory receptor proteins, proteins that participate in signal transduction cascade, etc. The expression level of each gene is controlled by its regulatory regions, and especially, by the promoter [a region of DNA about 100–1000 base pairs long located upstream of the transcription start site (TSS)]. We analyzed single nucleotide polymorphisms using human whole-genome data from the 1000 Genomes Project and revealed an extremely high level of single nucleotide polymorphisms in promoter regions of olfactory receptor genes and HLA genes. We hypothesized that the high level of polymorphisms in olfactory receptor promoters was responsible for the diversity in regulatory mechanisms controlling the expression levels of olfactory receptor proteins. Such diversity of regulatory mechanisms may cause the great variability of olfactory cognition of numerous environmental olfactory stimuli perceived by human beings (air pollutants, human body odors, odors in culinary etc.). In turn, this variability may provide a wide range of emotional and behavioral reactions related to the vast variety of olfactory stimuli. PMID:24715883

Ignatieva, Elena V.; Levitsky, Victor G.; Yudin, Nikolay S.; Moshkin, Mikhail P.; Kolchanov, Nikolay A.

2014-01-01

395

Advanced Energy Projects, FY 1993  

NASA Astrophysics Data System (ADS)

AEP has been supporting research on novel materials for energy technology, renewable and biodegradable materials, new uses for scientific discoveries, alternate pathways to energy efficiency, alternative energy sources, innovative approaches to waste treatment and reduction, etc. The summaries are grouped according to projects active in FY 1993, Phase 1 SBIR projects, and Phase 2 SBIR projects. Investigator and institutional indexes are included.

1993-09-01

396

Discovery: Gear & Gadgets Videos  

NSDL National Science Digital Library

Do you want to learn about soy surfboards? How text messages might save lives? Or about how a therapeutic war game might help veterans? All of this and much more is available on the Discovery Channel's Gear & Gadgets website. Each video is a few minutes in length, and visitors can search through the collection of 31 videos by name or subject. Users can use the Show Me toolbar to look for clips, existing playlists, and full episodes. The Tech videos are informative, and visitors would do well to look at Underwater Turbines Pump Out Energy and Truckin' From Diesel to Veg Oil. Finally, the site also includes updates from other Discovery video channels, including clips on new medical technologies and aerospace innovations.

397

National Science Foundation: Discoveries  

NSDL National Science Digital Library

Everyday, research sponsored by the National Science Foundation (NSF) turns up a new discovery, an interesting facet of a scientific endeavor, and sometimes, just something that might delight and amaze even the casual observer. Recently the NSF created this website to serve as a clearinghouse of information about the work they sponsor. The "Discoveries" site can be searched in its entirety, or visitors can just peruse the chronological list that's front and center on their homepage. Over in the "Research Areas" section, visitors can wander through "Biology", "Education", "Nanoscience", and eight other topical areas. Some summaries that might be of particular interest include "Mysteries of the Unregulated Internet" and "The Bizarre Creatures of Madagascar". Also, it's worth nothing that parties who enjoy the site can sign up for their RSS feed here.

398

Discovery of charm  

SciTech Connect

In my talk I will cover the period 1973 to 1976 which saw the discoveries of the J/psi and psi' resonances and most of the Psion spectroscopy, the tau lepton and the D/sup 0/,D/sup +/ charmed meson doublet. Occasionally I will refer briefly to more recent results. Since this conference is on the history of the weak-interactions I will deal primarily with the properties of naked charm and in particular the weakly decaying doublet of charmed mesons. Most of the discoveries I will mention were made with the SLAC-LBL Magnetic Detector or MARK I which we operated at SPEAR from 1973 to 1976. 27 references.

Goldhaber, G.

1984-11-01

399

A Supernova Discovery  

NASA Astrophysics Data System (ADS)

The Nearby Supernova Factory reports the discovery of supernova SNF20070731-005 in images obtained Jul 31.5 UTC using the QUEST-II camera on the Palomar Oschin 48-inch telescope, operated by the Palomar-QUEST consortium. An R-band discovery magnitude of 18.3 and J2000.0 coordinates RA 03:16:31.37 DEC 15:27:40.7 are derived from comparison with the USNO-B1.0 catalog. A spectrum (range 320-1000 nm) obtained Aug 08.6 UTC with the SuperNova Integral Field Spectrograph on the University of Hawaii 2.2-meter telescope was used for classification.

Aldering, G.; Aragon, C.; Bailey, S.; Bongard, S.; Childress, M.; Loken, S.; Nugent, P.; Perlmutter, S.; Runge, K.; Thomas, R. C.; Weaver, B. A.; Baltay, C.; Bauer, A.; Rabinowitz, D.; Scalzo, R.; Rigaudier, G.; Pecontal, E.; Buton, C.; Copin, Y.; Gangler, E.; Smadja, G.; Tao, C.; Antilogus, P.; Pain, R.; Pereira, R.; Wu, C.; Birchall, D.; Holtzman, J.

2007-08-01

400

Challenges of Antibacterial Discovery  

PubMed Central

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort. PMID:21233508

Silver, Lynn L.

2011-01-01

401

UniGene  

NSDL National Science Digital Library

Created by the National Center for Biotechnology Information, UniGene is "an experimental system for automatically partitioning GenBank sequences into a non-redundant set of gene-oriented clusters." In addition to gene sequences, this Web site also offers thousands of novel expressed sequence tag (EST) sequences, a useful gene discovery resource. Organisms currently cataloged include human, rat, mouse, cow, zebrafish, clawed frog, fruitfly, mosquito, wheat, rice, barley, maize, and cress. Users may also access the Digital Differential Display to compare gene expression fingerprints for cancer cells and their normal counterparts. Other Web site features include query tips, FAQs, and relevant external links.

402

Discoveries in Photosynthesis  

NASA Astrophysics Data System (ADS)

"Life Is Bottled Sunshine" [Wynwood Reade, Martyrdom of Man, 1924]. This inspired phrase is a four-word summary of the significance of photosynthesis for life on earth. The study of photosynthesis has attracted the attention of a legion of biologists, biochemists, chemists and physicists for over 200 years. Discoveries in Photosynthesis presents a sweeping overview of the history of photosynthesis investigations, and detailed accounts of research progress in all aspects of the most complex bioenergetic process in living organisms.

Govindjee; Beatty, J. T.; Gest, H.; Allen, J. F.

403

Discovery management workshop  

NASA Technical Reports Server (NTRS)

Two dozen participants assembled under the direction of the NASA Solar System Exploration Division (SEED) April 13-15, 1993. Participants supported the goals of cheaper and faster solar system exploration. The workshop concluded that the Discovery Program concept and goals are viable. Management concerns are articulated in the final report. Appendix A includes lists of participants in alphabetical order, by functional area, and by organization type. Appendix B includes the agenda for the meeting.

1993-01-01

404

The discovery of quarks.  

PubMed

Quarks are widely recognized today as being among the elementary particles of which matter is composed. The key evidence for their existence came from a series of inelastic electron-nucleon scattering experiments conducted between 1967 and 1973 at the Stanford Linear Accelerator Center. Other theoretical and experimental advances of the 1970s confirmed this discovery, leading to the present standard model of elementary particle physics. PMID:17736758

Riordan, M

1992-05-29

405

Planetary Science Resource Discoveries  

NSDL National Science Digital Library

Planetary Science Research Discoveries (PSRD) is an educational site sharing the latest research on meteorites, planets, and other solar system bodies being made by NASA-sponsored scientists. The web site is supported by the Cosmochemistry Program of NASA's Science Mission Directorate and by Hawai'i Space Grant Consortium. The site features useful links related to planetary and space sciences. Links to internal pages as well as other sites are searchable by topic. The site also includes a glossary.

G. J. Taylor

406

Discovery concepts for Mars  

NASA Technical Reports Server (NTRS)

Two focused Mars missions that would fit within the guidelines for the proposed Discovery line are discussed. The first mission would deal with the issue of the escape of the atmosphere (Mars') to space. A complete understanding of this topic is crucial to deciphering the evolution of the atmosphere, climate change, and volatile inventories. The second mission concerns the investigation of remanent magnetization of the crust and its relationship to the ionosphere and the atmosphere.

Luhmann, J. G.; Russell, C. T.; Brace, L. H.; Nagy, A. F.; Jakosky, B. M.; Barth, C. A.; Waite, J. H.

1992-01-01

407

Discovery as a process  

SciTech Connect

The three great myths, which form a sort of triumvirate of misunderstanding, are the Eureka! myth, the hypothesis myth, and the measurement myth. These myths are prevalent among scientists as well as among observers of science. The Eureka! myth asserts that discovery occurs as a flash of insight, and as such is not subject to investigation. This leads to the perception that discovery or deriving a hypothesis is a moment or event rather than a process. Events are singular and not subject to description. The hypothesis myth asserts that proper science is motivated by testing hypotheses, and that if something is not experimentally testable then it is not scientific. This myth leads to absurd posturing by some workers conducting empirical descriptive studies, who dress up their study with a ``hypothesis`` to obtain funding or get it published. Methods papers are often rejected because they do not address a specific scientific problem. The fact is that many of the great breakthroughs in silence involve methods and not hypotheses or arise from largely descriptive studies. Those captured by this myth also try to block funding for those developing methods. The third myth is the measurement myth, which holds that determining what to measure is straightforward, so one doesn`t need a lot of introspection to do science. As one ecologist put it to me ``Don`t give me any of that philosophy junk, just let me out in the field. I know what to measure.`` These myths lead to difficulties for scientists who must face peer review to obtain funding and to get published. These myths also inhibit the study of science as a process. Finally, these myths inhibit creativity and suppress innovation. In this paper I first explore these myths in more detail and then propose a new model of discovery that opens the supposedly miraculous process of discovery to doser scrutiny.

Loehle, C.

1994-05-01

408

Evaluating HapMap SNP data transferability in a large-scale genotyping project involving 175 cancer-associated genes  

Microsoft Academic Search

One of the many potential uses of the HapMap project is its application to the investigation of complex disease aetiology\\u000a among a wide range of populations. This study aims to assess the transferability of HapMap SNP data to the Spanish population\\u000a in the context of cancer research. We have carried out a genotyping study in Spanish subjects involving 175 candidate

Gloria Ribas; Anna González-Neira; Antonio Salas; Roger L. Milne; Ana Vega; Begoña Carracedo; Emilio González; Eva Barroso; Lara P. Fernández; Patricio Yankilevich; Mercedes Robledo; Ángel Carracedo; Javier Benítez

2006-01-01

409

The language of discovery  

PubMed Central

Discovery, as a public attribution, and discovering, the act of conducting research, are experiences that entail “languaging” the unknown. This distinguishing property of language ? its ability to bring forth, out of the unspoken realm, new knowledge, original ideas, and novel thinking – is essential to the discovery process. In sharing their ideas and views, scientists create co?negotiated linguistic distinctions that prompt the revision of established mental maps and the adoption of new ones. While scientific mastery entails command of the conversational domain unique to a specific discipline, there is an emerging conversational domain that must be mastered that goes beyond the language unique to any particular specialty. Mastery of this new conversational domain gives researchers access to their hidden mental maps that limit their ways of thinking about and doing science. The most effective scientists use language to recontextualize their approach to problem?solving, which triggers new insights (previously unavailable) that result in new discoveries. While language is not a replacement for intuition and other means of knowing, when we try to understand what’s outside of language we have to use language to do so. PMID:21688238

Souba, Wiley

2011-01-01

410

Human genome project and mutation research: A mating that needs to happen  

SciTech Connect

The Human Genome Project has been in existence for several years. It has created a wealth of resources in the form of genetic and physical maps, innovative technologies, instrumentation, and information. It is driving the future of gene discovery, as well as disease diagnosis, amelioration, and treatment. Despite the successes in the project, the mutation research community has, in general, been slow to capitalize on the infrastructure and resources that have been created. This should not continue as there are now available some key technologies and resources that are ripe for exploitation. 19 refs.

Carrano, A.V. [Lawrence Livermore National Lab., CA (United States)

1994-12-31

411

Retrotransposition of gene transcripts leads to structural variation in mammalian genomes  

PubMed Central

Background Retroposed processed gene transcripts are an important source of material for new gene formation on evolutionary timescales. Most prior work on gene retrocopy discovery compared copies in reference genome assemblies to their source genes. Here, we explore gene retrocopy insertion polymorphisms (GRIPs) that are present in the germlines of individual humans, mice, and chimpanzees, and we identify novel gene retrocopy insertions in cancerous somatic tissues that are absent from patient-matched non-cancer genomes. Results Through analysis of whole-genome sequence data, we found evidence for 48 GRIPs in the genomes of one or more humans sequenced as part of the 1,000 Genomes Project and The Cancer Genome Atlas, but which were not in the human reference assembly. Similarly, we found evidence for 755 GRIPs at distinct locations in one or more of 17 inbred mouse strains but which were not in the mouse reference assembly, and 19 GRIPs across a cohort of 10 chimpanzee genomes, which were not in the chimpanzee reference genome assembly. Many of these insertions are new members of existing gene families whose source genes are highly and widely expressed, and the majority have detectable hallmarks of processed gene retrocopy formation. We estimate the rate of novel gene retrocopy insertions in humans and chimps at roughly one new gene retrocopy insertion for every 6,000 individuals. Conclusions We find that gene retrocopy polymorphisms are a widespread phenomenon, present a multi-species analysis of these events, and provide a method for their ascertainment. PMID:23497673

2013-01-01

412

Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene  

PubMed Central

To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundació ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19–1.44); P=9.74 × 10?9). PMID:24495969

Ruiz, A; Heilmann, S; Becker, T; Hernández, I; Wagner, H; Thelen, M; Mauleón, A; Rosende-Roca, M; Bellenguez, C; Bis, J C; Harold, D; Gerrish, A; Sims, R; Sotolongo-Grau, O; Espinosa, A; Alegret, M; Arrieta, J L; Lacour, A; Leber, M; Becker, J; Lafuente, A; Ruiz, S; Vargas, L; Rodríguez, O; Ortega, G; Dominguez, M-A; Mayeux, R; Haines, J L; Pericak-Vance, M A; Farrer, L A; Schellenberg, G D; Chouraki, V; Launer, L J; van Duijn, C; Seshadri, S; Antúnez, C; Breteler, M M; Serrano-Ríos, M; Jessen, F; Tárraga, L; Nöthen, M M; Maier, W; Boada, M; Ramírez, A

2014-01-01

413

Discovery and Classification in Astronomy  

NASA Astrophysics Data System (ADS)

Three decades after Martin Harwit's pioneering Cosmic Discovery (1981), and following on the recent IAU Symposium "Accelerating the Rate of Astronomical Discovery,” we have revisited the problem of discovery in astronomy, emphasizing new classes of objects. 82 such classes have been identified and analyzed, including 22 in the realm of the planets, 36 in the realm of the stars, and 24 in the realm of the galaxies. We find an extended structure of discovery, consisting of detection, interpretation and understanding, each with its own nuances and a microstructure including conceptual, technological and social roles. This is true with a remarkable degree of consistency over the last 400 years of telescopic astronomy, ranging from Galileo's discovery of satellites, planetary rings and star clusters, to the discovery of quasars and pulsars. Telescopes have served as "engines of discovery” in several ways, ranging from telescope size and sensitivity (planetary nebulae and spiral galaxies), to specialized detectors (TNOs) and the opening of the electromagnetic spectrum for astronomy (pulsars, pulsar planets, and most active galaxies). A few classes (radiation belts, the solar wind and cosmic rays), were initially discovered without the telescope. Classification also plays an important role in discovery. While it might seem that classification marks the end of discovery, or a post-discovery phase, in fact it often marks the beginning, even a pre-discovery phase. Nowhere is this more clearly seen than in the classification of stellar spectra, long before dwarfs, giants and supergiants were known, or their evolutionary sequence recognized. Classification may also be part of a post-discovery phase, as in the MK system of stellar classification, constructed after the discovery of stellar luminosity classes. Some classes are declared rather than discovered, as in the case of gas and ice giant planets, and, infamously, Pluto as a dwarf planet.

Dick, Steven J.

2012-01-01

414

Discovery of alpha-defensins in basal mammals.  

PubMed

Alpha-defensins are essential molecules of the innate immune system that have broad spectrum antimicrobial activity against a range of bacteria and viruses. To date, alpha-defensins have only been identified in the Euarchontoglires branch of the mammals. This has led to speculation that alpha-defensins may be specific to this group, a somewhat surprising finding, given their importance in the immune system. The mammalian genome project provided us with the opportunity to search for alpha-defensins in previously unexamined mammalian superorders. Using hidden Markov model (HMM) profile searching, we report the discovery of alpha-defensins in the African savanna elephant, the lesser hedgehog tenrec, and the nine-banded armadillo genomes representing two of the most basal mammalian superorders, Afrotheria and Xenarthra. Furthermore, we identify an alpha-defensin-like gene in the gray short-tailed opossum, suggesting that alpha-defensins may have evolved much earlier than previously thought, before the divergence of placental mammals and marsupials approximately 130 mya. PMID:17367857

Lynn, David J; Bradley, Daniel G

2007-01-01

415

Your Genes, Your Choices  

MedlinePLUS

Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

416