Sample records for gene discovery project

  1. Pine Gene Discovery Project - Final Report - 08/31/1997 - 02/28/2001

    SciTech Connect

    Whetten, R. W.; Sederoff, R. R.; Kinlaw, C.; Retzel, E.

    2001-04-30

    Integration of pines into the large scope of plant biology research depends on study of pines in parallel with study of annual plants, and on availability of research materials from pine to plant biologists interested in comparing pine with annual plant systems. The objectives of the Pine Gene Discovery Project were to obtain 10,000 partial DNA sequences of genes expressed in loblolly pine, to determine which of those pine genes were similar to known genes from other organisms, and to make the DNA sequences and isolated pine genes available to plant researchers to stimulate integration of pines into the wider scope of plant biology research. Those objectives have been completed, and the results are available to the public. Requests for pine genes have been received from a number of laboratories that would otherwise not have included pine in their research, indicating that progress is being made toward the goal of integrating pine research into the larger molecular biology research community.

  2. FORGE Canada Consortium: Outcomes of a 2-Year National Rare-Disease Gene-Discovery Project

    PubMed Central

    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.

    2014-01-01

    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

  3. Independent Gene Discovery and Testing

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

  4. Metagenomics and novel gene discovery

    PubMed Central

    Culligan, Eamonn P; Sleator, Roy D; Marchesi, Julian R; Hill, Colin

    2014-01-01

    Metagenomics provides a means of assessing the total genetic pool of all the microbes in a particular environment, in a culture-independent manner. It has revealed unprecedented diversity in microbial community composition, which is further reflected in the encoded functional diversity of the genomes, a large proportion of which consists of novel genes. Herein, we review both sequence-based and functional metagenomic methods to uncover novel genes and outline some of the associated problems of each type of approach, as well as potential solutions. Furthermore, we discuss the potential for metagenomic biotherapeutic discovery, with a particular focus on the human gut microbiome and finally, we outline how the discovery of novel genes may be used to create bioengineered probiotics. PMID:24317337

  5. Human brain evolution: From gene discovery to phenotype discovery

    PubMed Central

    Preuss, Todd M.

    2012-01-01

    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

  6. 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.

  7. Discovery project -- First of the new Louisiana cryo projects

    SciTech Connect

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

    1999-07-01

    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.

  8. Inflammatory bowel disease gene discovery. CRADA final report

    SciTech Connect

    NONE

    1997-09-09

    The ultimate goal of this project is to identify the human gene(s) responsible for the disorder known as IBD. The work was planned in two phases. The desired products resulting from Phase 1 were BAC clone(s) containing the genetic marker(s) identified by gene/Networks, Inc. as potentially linked to IBD, plasmid subclones of those BAC(s), and new genetic markers developed from these plasmid subclones. The newly developed markers would be genotyped by gene/Networks, Inc. to ascertain evidence for linkage or non-linkage of IBD to this region. If non-linkage was indicated, the project would move to investigation of other candidate chromosomal regions. Where linkage was indicated, the project would move to Phase 2, in which a physical map of the candidate region(s) would be developed. The products of this phase would be contig(s) of BAC clones in the region exhibiting linkage to IBD, as well as plasmic subclones of the BACs and further genetic marker development. There would also be continued genotyping with new polymorphic markers during this phase. It was anticipated that clones identified and developed during these two phases would provide the physical resources for eventual disease gene discovery.

  9. Is gene discovery research or diagnosis?

    PubMed

    Samuels, Mark E; Orr, Andrew; Guernsey, Duane L; Dooley, Kent; Riddell, Christie; Hodgkinson, Kathy; Ludman, Mark; Pullman, Daryl

    2008-06-01

    The criteria that distinguish human genetic research from clinical molecular diagnosis are frequently practical rather than theoretical. They are driven by the availability and costs of the relevant technologies and the systemic level of scientific fluency in interpreting laboratory results. The guiding principle in the practice of medicine is the primacy of patient care. In the service of this overarching goal the defining characteristic of clinical diagnosis is the definition of the disease entity, even when no immediate treatment is possible. For heritable disorders caused by single-gene defects, identifying the putative causal variant is the goal of molecular diagnostics. Current technologies, costs, and standards of institutional infrastructure have not typically permitted novel gene discovery to be performed within the realm of the clinical laboratory. Discovery is usually funded by self-defined research organizations and carried out by self-defined research personnel with the primary intent of publishing findings in research journals. However, exponential improvements in technological capabilities and the concurrent decline in associated costs seem poised to recast this landscape, bringing to clinical medicine some activities now considered research. Even whole genome resequencing of individual patient DNA is within clinical reach in the foreseeable future. PMID:18496224

  10. In silico prioritisation of candidate genes for prokaryotic gene function discovery: an application of phylogenetic profiles

    Microsoft Academic Search

    Frank P. Y. Lin; Enrico W. Coiera; Ruiting Lan; Vitali Sintchenko

    2009-01-01

    BACKGROUND: In silico candidate gene prioritisation (CGP) aids the discovery of gene functions by ranking genes according to an objective relevance score. While several CGP methods have been described for identifying human disease genes, corresponding methods for prokaryotic gene function discovery are lacking. Here we present two prokaryotic CGP methods, based on phylogenetic profiles, to assist with this task. RESULTS:

  11. Genome-enabled Discovery of Carbon Sequestration Genes

    SciTech Connect

    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

    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.

  12. Peroxidase gene discovery from the horseradish transcriptome

    PubMed Central

    2014-01-01

    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

  13. A Uniform Projection Method for Motif Discovery in DNA Sequences

    E-print Network

    Zhou, Yuanyuan

    . These algorithms employ either a profile or pattern representation of a motif. In profile-based methods such GibbsDNAA Uniform Projection Method for Motif Discovery in DNA Sequences Benjamin Raphael, Lung-Tien Liu INTRODUCTION THE problem of discovering signals in a set of DNA sequences (the motif discovery problem) is well

  14. 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...

  15. A Gene-Coexpression Network for Global Discovery of

    E-print Network

    Kim, Stuart

    biological processes. DNA microarrays provide us with a first step toward the goal of uncovering gene organisms, we first associated genes from one organism with their orthologous counterparts in otherA Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules Joshua M. Stuart,1

  16. Gene Discovery in the Presence of RNA Editing Ralf Bundschuh

    E-print Network

    Bundschuh, Ralf

    Gene Discovery in the Presence of RNA Editing Ralf Bundschuh Department of Physics, Ohio State, an algorithm to Predict Insertional Editing · Performance of PIE on published data · Finding new genes as possible · Situation for mitochondrion of Physarum polycephalum: ­ six protein coding genes

  17. Antibiotic resistance gene discovery in food-producing animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous environmental reservoirs contribute to the widespread antibiotic resistance problem in human pathogens. One environmental reservoir of particular importance is the intestinal bacteria of food-producing animals. In this review I examine recent discoveries of antibiotic resistance genes in ...

  18. Discovery of Tumor Suppressor Gene Function.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.

    1995-01-01

    This is an update of a 1991 review on tumor suppressor genes written at a time when understanding of how the genes work was limited. A recent major breakthrough in the understanding of the function of tumor suppressor genes is discussed. (LZ)

  19. 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.

  20. Discovery of the DISC1 Gene

    NSDL National Science Digital Library

    2009-04-14

    Cytogenetics is the study of chromosomes and how changes in chromosome structure and number affect the individual. In this video, Professor Porteous describes the process of hunting for the DISC1 gene, a gene disrupted by a balanced translocation on chromosome 1q42.

  1. Discovery of genes expressed in Hydra embryogenesis.

    PubMed

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

    2006-01-15

    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 of expression of conserved regulatory genes, known to be involved in adult patterning, differs greatly in adults and embryos (Fröbius, A.C., Genikhovich, G., Kürn, U., Anton-Erxleben, F. and Bosch, T.C.G., 2003. Expression of developmental genes during early embryogenesis of Hydra. Dev. Genes Evol. 213, 445-455). Here, we describe an unbiased screening strategy to identify genes that are relevant to Hydra vulgaris embryogenesis. The approach yielded two sets of differentially expressed genes: one set was expressed exclusively or nearly exclusively in the embryos, while the second set was upregulated in embryos in comparison to adult polyps. Many of the genes identified in hydra embryos had no matches in the database. Among the conserved genes upregulated in embryos is the Hydra orthologue of Embryonic Ectoderm Development (HyEED). The expression pattern of HyEED in developing embryos suggests that interstitial stem cells in Hydra originate in the endoderm. Importantly, the observations uncover previously unknown differences in genes expressed by embryos and polyps and indicate that not only the timing of expression of developmental genes but also the genetic context is different in Hydra embryos compared to adults. PMID:16337937

  2. Implementation of Discovery Projects in Statistics

    ERIC Educational Resources Information Center

    Bailey, Brad; Spence, Dianna J.; Sinn, Robb

    2013-01-01

    Researchers and statistics educators consistently suggest that students will learn statistics more effectively by conducting projects through which they actively engage in a broad spectrum of tasks integral to statistical inquiry, in the authentic context of a real-world application. In keeping with these findings, we share an implementation of…

  3. GWATCH: a web platform for automated gene association discovery analysis

    PubMed Central

    2014-01-01

    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

  4. Project Discovery: An Urban Middle School Reform Effort

    ERIC Educational Resources Information Center

    Shulman, Vivian; Armitage, Deirdre

    2005-01-01

    This study reports on a 5-year project to improve urban, middle-level student achievement through the implementation of two initiatives. First, teachers at a participating New York City middle school engaged in weekly curriculum-planning workshops to reformulate classroom curricula into interdisciplinary, discovery-oriented activities. Second,…

  5. SNP Marker Discovery in Koala TLR Genes

    PubMed Central

    Cui, Jian; Frankham, Greta J.; Johnson, Rebecca N.; Polkinghorne, Adam; Timms, Peter; O’Meally, Denis; Cheng, Yuanyuan; Belov, Katherine

    2015-01-01

    Toll-like receptors (TLRs) play a crucial role in the early defence against invading pathogens, yet our understanding of TLRs in marsupial immunity is limited. Here, we describe the characterisation of nine TLRs from a koala immune tissue transcriptome and one TLR from a draft sequence of the koala genome and the subsequent development of an assay to study genetic diversity in these genes. We surveyed genetic diversity in 20 koalas from New South Wales, Australia and showed that one gene, TLR10 is monomorphic, while the other nine TLR genes have between two and 12 alleles. 40 SNPs (16 non-synonymous) were identified across the ten TLR genes. These markers provide a springboard to future studies on innate immunity in the koala, a species under threat from two major infectious diseases. PMID:25799012

  6. 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...

  7. Familial Frontotemporal Dementia: From Gene Discovery to Clinical Molecular Diagnostics

    Microsoft Academic Search

    Vivianna M. Van Deerlin; Lisa H. Gill; Jennifer M. Farmer; John Q. Trojanowski

    2003-01-01

    Genetic testing is important for diagnosis and predic- tion of many diseases. The development of a clinical genetic test can be rapid for common disorders, but for rare genetic disorders this process can take years, if it occurs at all. We review the path from gene discovery to development of a clinical genetic test, using frontotem- poral dementia with parkinsonism

  8. Gene discovery and the genetic basis of calcium consumption

    PubMed Central

    Tordoff, Michael G.

    2008-01-01

    This review makes the case that gene discovery is a worthwhile approach to the study of ingestive behavior in general and to calcium appetite in particular. A description of the methods used to discover genes is provided for non-geneticists. Areas covered include the characterization of an appropriate phenotype, the choice of suitable mouse strains, the generation of a hybrid cross, interval mapping, congenic strain production, and candidate gene analysis. The approach is illustrated with an example involving mice of the C57BL/6J and PWK/PhJ strains, which differ in avidity for calcium solutions. The variation between the strains can be attributed to at least seven quantitative trait loci (QTLs). One of these QTLs is most likely accounted for by Tas1r3, which is a gene involved in the detection of sweet and umami tastes. The discovery of a novel function for a gene with no previously known role in calcium consumption illustrates the power of gene discovery methods to uncover novel mechanisms. PMID:18499198

  9. Novel venom gene discovery in the platypus

    Microsoft Academic Search

    Camilla M Whittington; Anthony T Papenfuss; Devin P Locke; Elaine R Mardis; Richard K Wilson; Sahar Abubucker; Makedonka Mitreva; Emily SW Wong; Arthur L Hsu; Philip W Kuchel; Katherine Belov; Wesley C Warren

    2010-01-01

    ABSTRACT: 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

  10. Technology development for gene discovery and full-length sequencing

    SciTech Connect

    Marcelo Bento Soares

    2004-07-19

    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.

  11. Novel venom gene discovery in the platypus

    PubMed Central

    2010-01-01

    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

  12. Gene Discovery and Product Development for Grain Quality Traits

    NSDL National Science Digital Library

    Barbara Mazur (DuPont Agricultural Products Experimental Station; )

    1999-07-16

    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.

  13. Kevin Burgess' Research: Project 3 Rapid Discovery Of Catalysts Optimization For

    E-print Network

    Burgess, Kevin

    Kevin Burgess' Research: Project 3 Rapid Discovery Of Catalysts Optimization has been targeted, then discovery of catalysts to mediate those transformations tends to be a slow transformations for organic syntheses. B. Research Strategies Significance We have used the catalyst shown

  14. Distant collaboration in drug discovery: the LINK3D project.

    PubMed

    Pastor, Manuel; Benedetti, Paolo; Carotti, Angelo; Carrieri, Antonio; Díaz, Carlos; Herráiz, Cristina; Höltje, Hans-Dieter; Loza, M Isabel; Oprea, Tudor; Padín, Fernando; Pubill, Francesc; Sanz, Ferran; Stoll, Friederike

    2002-11-01

    The work describes the development of novel software supporting synchronous distant collaboration between scientists involved in drug discovery and development projects. The program allows to visualize and share data as well as to interact in real time using standard intranets and Internet resources. Direct visualization of 2D and 3D molecular structures is supported and original tools for facilitating remote discussion have been integrated. The software is multiplatform (MS-Windows, SGI-IRIX, Linux), allowing for a seamless integration of heterogeneous working environments. The project aims to support collaboration both within and between academic and industrial institutions. Since confidentiality is very important in some scenarios, special attention has been paid to security aspects. The article presents the research carried out to gather the requirements of collaborative software in the field of drug discovery and development and describes the features of the first fully functional prototype obtained. Real-world testing activities carried out on this prototype in order to guarantee its adequacy in diverse environments are also described and discussed. PMID:12825793

  15. DiscoverySchool.com : Your Genes, Your Future

    NSDL National Science Digital Library

    2007-12-12

    DiscoverSchool.com offers a lesson plan for 6-8th graders based on a Discovery Channel program Your Genes, Your Future. The lesson plan focuses on healthy behaviors rather than genetics as such, although some of the extension activities deal with genetics more directly. Students will review the benefits of eating well, exercising, and other healthy behaviors, as well as discuss the dangers of drugs, smoking, etc. Provided Web links will help students with in-class research, and educators will find useful teaching tools for creating worksheets, quizzes, and subject-specific puzzles.

  16. Similar genes discovery system (SGDS): Application for predicting possible pathways by using GO semantic similarity measure

    Microsoft Academic Search

    Jung-hsien Chiang; Shing-hua Ho; Wen-hung Wang

    2008-01-01

    This research analyzes the gene relationship according to their annotations. We present here a similar genes discovery system (SGDS), based upon semantic similarity measure of gene ontology (GO) and Entrez gene, to identify groups of similar genes. In order to validate the proposed measure, we analyze the relationships between similarity and expression correlation of pairs of genes. We explore a

  17. Genome Enabled Discovery of Carbon Sequestration Genes in Poplar

    SciTech Connect

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

    2007-02-22

    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.

  18. Sugarcane Functional Genomics: Gene Discovery for Agronomic Trait Development

    PubMed Central

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

    2008-01-01

    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

  19. Towards the Discovery of Diseases Related by Genes Using Vertex Similarity Measures

    E-print Network

    Giles, C. Lee

    Towards the Discovery of Diseases Related by Genes Using Vertex Similarity Measures Hung-Hsuan Chen--Discovering the relationships of gene to gene, gene to its related diseases, and diseases implicated in common genes is important. However, traditional biological methods can be expensive. Here, we show that the diseases

  20. Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery

    PubMed Central

    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

    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

  1. Canonical Correlation Analysis for Gene-Based Pleiotropy Discovery

    PubMed Central

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

    2014-01-01

    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

  2. High-Throughput Gene Discovery in the Rat

    PubMed Central

    Scheetz, Todd E.; Laffin, Jennifer J.; Berger, Brian; Holte, Sara; Baumes, Susan A.; Brown, Robert; Chang, Shereen; Coco, Justin; Conklin, Jim; Crouch, Keith; Donohue, Micca; Doonan, Greg; Estes, Chris; Eyestone, Mari; Fishler, Katrina; Gardiner, Jack; Guo, Lankai; Johnson, Brad; Keppel, Catherine; Kreger, Rikki; Lebeck, Mark; Marcelino, Rudy; Miljkovich, Vladan; Perdue, Mindee; Qui, Ling; Rehmann, Joshua; Reiter, Rebecca S.; Rhoads, Bridgette; Schaefer, Kelly; Smith, Christina; Sunjevaric, Ivana; Trout, Kurtis; Wu, Ning; Birkett, Clayton L.; Bischof, Jared; Gackle, Barry; Gavin, Allen; Grundstad, A. Jason; Mokrzycki, Brian; Moressi, Chris; O'Leary, Brian; Pedretti, Kevin; Roberts, Chad; Robinson, Natalie L.; Smith, Michael; Tack, Dylan; Trivedi, Nishank; Kucaba, Tamara; Freeman, Tom; Lin, Jim J.-C.; Bonaldo, Maria F.; Casavant, Thomas L.; Sheffield, Val C.; Soares, M. Bento

    2004-01-01

    The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3? ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ?50,000 rat UniGene clusters. We have identified, arrayed, and derived 5? ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI. PMID:15060017

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

    E-print Network

    Hero, Alfred O.

    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

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

    Microsoft Academic Search

    Nilüfer Ertekin-Taner

    2011-01-01

    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

  5. RIKEN Center for Sustainable Resource Science Gene Discovery Research Group

    E-print Network

    Fukai, Tomoki

    Research Unit Regulatory Network Research Unit Plant Proteomics Research Unit Metabolomics Research Group Metabolic Systems Research Team Environmental Metabolic Aanalysis Research team Metabolome Informatics Divison Chemical Bank Unit for Drug Discovery Platform Seed Compounds Exploratory Unit for Drug Discovery

  6. RIKEN Center for Sustainable Resource Science Gene Discovery Research Group

    E-print Network

    Fukai, Tomoki

    Network Research Unit Plant Proteomics Research Unit Metabolomics Research Group Metabolic Systems Research Team Environmental Metabolic Aanalysis Research team Metabolome Informatics Research Team Unit for Drug Discovery Platform Seed Compounds Exploratory Unit for Drug Discovery Platform

  7. 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.

  8. 78 FR 69363 - Lake Tahoe Basin Management Unit, California, Heavenly Mountain Resort Epic Discovery Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ...DEPARTMENT OF AGRICULTURE Forest Service Lake Tahoe Basin Management Unit, California...Resort Epic Discovery Project AGENCY: Lake Tahoe Basin Management Unit, Forest Service...expanding needs and expectations of visitors to Lake Tahoe, better support the...

  9. Discovery of novel genes and gene isoforms by integrating transcriptomic and proteomic profiling from mouse liver.

    PubMed

    Wu, Peng; Zhang, Hongyu; Lin, Weiran; Hao, Yunwei; Ren, Liangliang; Zhang, Chengpu; Li, Ning; Wei, Handong; Jiang, Ying; He, Fuchu

    2014-05-01

    Comprehensively identifying gene expression in both transcriptomic and proteomic levels of one tissue is a prerequisite for a deeper understanding of its biological functions. Alternative splicing and RNA editing, two main forms of transcriptional processing, play important roles in transcriptome and proteome diversity and result in multiple isoforms for one gene, which are hard to identify by mass spectrometry (MS)-based proteomics approach due to the relative lack of isoform information in standard protein databases. In our study, we employed MS and RNA-Seq in parallel into mouse liver tissue and captured a considerable catalogue of both transcripts and proteins that, respectively, covered 60 and 34% of protein-coding genes in Ensembl. We then developed a bioinformatics workflow for building a customized protein database that for the first time included new splicing-derived peptides and RNA-editing-caused peptide variants, allowing us to more completely identify protein isoforms. Using this experimentally determined database, we totally identified 150 peptides not present in standard biological databases at false discovery rate of <1%, corresponding to 72 novel splicing isoforms, 43 new genetic regions, and 15 RNA-editing sites. Of these, 11 randomly selected novel events passed experimental verification by PCR and Sanger sequencing. New discoveries of gene products with high confidence in two omics levels demonstrated the robustness and effectiveness of our approach and its potential application into improve genome annotation. All the MS data have been deposited to the iProx ( http://ww.iprox.org ) with the identifier IPX00003601. PMID:24717071

  10. Discovery

    ERIC Educational Resources Information Center

    de Mestre, Neville

    2010-01-01

    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).

  11. Discovery and revision of Arabidopsis genes by proteogenomics.

    PubMed

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

    2008-12-30

    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

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

    Microsoft Academic Search

    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

    Although cancer classiŢcation 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 classiŢcation based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case.A class discovery

  13. Using the DFCI Gene Index Databases for Biological Discovery

    PubMed Central

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

    2014-01-01

    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

  14. Prioritization of neurodevelopmental disease genes by discovery of new mutations.

    PubMed

    Hoischen, Alexander; Krumm, Niklas; Eichler, Evan E

    2014-06-01

    Advances in genome sequencing technologies have begun to revolutionize neurogenetics, allowing the full spectrum of genetic variation to be better understood in relation to disease. Exome sequencing of hundreds to thousands of samples from patients with autism spectrum disorder, intellectual disability, epilepsy and schizophrenia provides strong evidence of the importance of de novo and gene-disruptive events. There are now several hundred new candidate genes and targeted resequencing technologies that allow screening of dozens of genes in tens of thousands of individuals with high specificity and sensitivity. The decision of which genes to pursue depends on many factors, including recurrence, previous evidence of overlap with pathogenic copy number variants, the position of the mutation in the protein, the mutational burden among healthy individuals and membership of the candidate gene in disease-implicated protein networks. We discuss these emerging criteria for gene prioritization and the potential impact on the field of neuroscience. PMID:24866042

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

    PubMed Central

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

    2015-01-01

    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

  16. Single Nucleotide Polymorphism Discovery in the Avian Tapasin Gene1

    Microsoft Academic Search

    L. Sironi; B. Lazzari; P. Ramelli; C. Gorni; P. Mariani

    Tapasin is a transmembrane glycoprotein located in the endoplasmic reticulum. Its function is to assist the assembly of major histocompatibility complex class I molecules. The chicken Tapasin gene includes 8 exons and is localized inside the major histocompatibility complex between the 2 class II? genes. The aim of the current study was the estimation of single nucleotide polymorphism frequency within

  17. A projection and density estimation method for knowledge discovery.

    PubMed

    Stanski, Adam; Hellwich, Olaf

    2012-01-01

    A key ingredient to modern data analysis is probability density estimation. However, it is well known that the curse of dimensionality prevents a proper estimation of densities in high dimensions. The problem is typically circumvented by using a fixed set of assumptions about the data, e.g., by assuming partial independence of features, data on a manifold or a customized kernel. These fixed assumptions limit the applicability of a method. In this paper we propose a framework that uses a flexible set of assumptions instead. It allows to tailor a model to various problems by means of 1d-decompositions. The approach achieves a fast runtime and is not limited by the curse of dimensionality as all estimations are performed in 1d-space. The wide range of applications is demonstrated at two very different real world examples. The first is a data mining software that allows the fully automatic discovery of patterns. The software is publicly available for evaluation. As a second example an image segmentation method is realized. It achieves state of the art performance on a benchmark dataset although it uses only a fraction of the training data and very simple features. PMID:23049675

  18. Literature Mining for the Discovery of Hidden Connections between Drugs, Genes and Diseases

    PubMed Central

    Frijters, Raoul; van Vugt, Marianne; Smeets, Ruben; van Schaik, René; de Vlieg, Jacob; Alkema, Wynand

    2010-01-01

    The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs. PMID:20885778

  19. Computational discovery of gene modules, regulatory networks and expression programs

    E-print Network

    Gerber, Georg Kurt, 1970-

    2007-01-01

    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 ...

  20. GENOME-ENABLED DISCOVERY OF CARBON SEQUESTRATION GENES IN POPLAR

    SciTech Connect

    DAVIS J M

    2007-10-11

    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.

  1. Discrimination discovery in scientific project evaluation: A case study$ Andrea Romei, Salvatore Ruggieri and Franco Turini

    E-print Network

    Ruggieri, Salvatore

    Discrimination discovery in scientific project evaluation: A case study$ Andrea Romei, Salvatore, experimentation with real data. This paper contributes by presenting a case study on gender discrimination in a dataset of scientific research proposals, and by distilling from the case study a general discrimination

  2. Gene discovery in the horned beetle Onthophagus taurus

    PubMed Central

    2010-01-01

    Background Horned beetles, in particular in the genus Onthophagus, are important models for studies on sexual selection, biological radiations, the origin of novel traits, developmental plasticity, biocontrol, conservation, and forensic biology. Despite their growing prominence as models for studying both basic and applied questions in biology, little genomic or transcriptomic data are available for this genus. We used massively parallel pyrosequencing (Roche 454-FLX platform) to produce a comprehensive EST dataset for the horned beetle Onthophagus taurus. To maximize sequence diversity, we pooled RNA extracted from a normalized library encompassing diverse developmental stages and both sexes. Results We used 454 pyrosequencing to sequence ESTs from all post-embryonic stages of O. taurus. Approximately 1.36 million reads assembled into 50,080 non-redundant sequences encompassing a total of 26.5 Mbp. The non-redundant sequences match over half of the genes in Tribolium castaneum, the most closely related species with a sequenced genome. Analyses of Gene Ontology annotations and biochemical pathways indicate that the O. taurus sequences reflect a wide and representative sampling of biological functions and biochemical processes. An analysis of sequence polymorphisms revealed that SNP frequency was negatively related to overall expression level and the number of tissue types in which a given gene is expressed. The most variable genes were enriched for a limited number of GO annotations whereas the least variable genes were enriched for a wide range of GO terms directly related to fitness. Conclusions This study provides the first large-scale EST database for horned beetles, a much-needed resource for advancing the study of these organisms. Furthermore, we identified instances of gene duplications and alternative splicing, useful for future study of gene regulation, and a large number of SNP markers that could be used in population-genetic studies of O. taurus and possibly other horned beetles. PMID:21156066

  3. Discovery of rare protein-coding genes in model methylotroph Methylobacterium extorquens AM1.

    PubMed

    Kumar, Dhirendra; Mondal, Anupam Kumar; Yadav, Amit Kumar; Dash, Debasis

    2014-12-01

    Proteogenomics involves the use of MS to refine annotation of protein-coding genes and discover genes in a genome. We carried out comprehensive proteogenomic analysis of Methylobacterium extorquens AM1 (ME-AM1) from publicly available proteomics data with a motive to improve annotation for methylotrophs; organisms capable of surviving in reduced carbon compounds such as methanol. Besides identifying 2482(50%) proteins, 29 new genes were discovered and 66 annotated gene models were revised in ME-AM1 genome. One such novel gene is identified with 75 peptides, lacks homolog in other methylobacteria but has glycosyl transferase and lipopolysaccharide biosynthesis protein domains, indicating its potential role in outer membrane synthesis. Many novel genes are present only in ME-AM1 among methylobacteria. Distant homologs of these genes in unrelated taxonomic classes and low GC-content of few genes suggest lateral gene transfer as a potential mode of their origin. Annotations of methylotrophy related genes were also improved by the discovery of a short gene in methylotrophy gene island and redefining a gene important for pyrroquinoline quinone synthesis, essential for methylotrophy. The combined use of proteogenomics and rigorous bioinformatics analysis greatly enhanced the annotation of protein-coding genes in model methylotroph ME-AM1 genome. PMID:25158906

  4. DISCOVERY OF GENES THAT AFFECT HUMAN BRAIN CONNECTIVITY: A GENOME-WIDE ANALYSIS OF THE CONNECTOME

    E-print Network

    Thompson, Paul

    DISCOVERY OF GENES THAT AFFECT HUMAN BRAIN CONNECTIVITY: A GENOME-WIDE ANALYSIS OF THE CONNECTOME, twin modeling, human connectome 1. INTRODUCTION The human brain is a complex network of structural, Australia ABSTRACT Human brain connectivity is disrupted in a wide range of disorders ­ from Alzheimer

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

    E-print Network

    Kellis, Manolis

    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

  6. Genome Medicine 2009, 1:108 Discovery of microvascular miRNAs using public gene expression

    E-print Network

    Paris-Sud XI, Université de

    Genome Medicine 2009, 1:108 Research Discovery of microvascular miRNAs using public gene expression to growth factor gradients in vitro. Published: 16 November 2009 Genome Medicine 2009, 1:108 (doi:10.1186/gm, Equipe Avenir Tour Lavoisier, 6e étage, 149 rue de Sčvres, 75015 Paris, France. #Department of Medicine

  7. Resequencing and comparative genomics of Stagonospora nodorum: Sectional gene absence and effector discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    S. 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...

  8. Gene Expression Data Knowledge Discovery using Global and Local Clustering

    E-print Network

    H, Swathi

    2010-01-01

    To understand complex biological systems, the research community has produced huge corpus of gene expression data. A large number of clustering approaches have been proposed for the analysis of gene expression data. However, extracting important biological knowledge is still harder. To address this task, clustering techniques are used. In this paper, hybrid Hierarchical k-Means algorithm is used for clustering and biclustering gene expression data is used. To discover both local and global clustering structure biclustering and clustering algorithms are utilized. A validation technique, Figure of Merit is used to determine the quality of clustering results. Appropriate knowledge is mined from the clusters by embedding a BLAST similarity search program into the clustering and biclustering process. To discover both local and global clustering structure biclustering and clustering algorithms are utilized. To determine the quality of clustering results, a validation technique, Figure of Merit is used. Appropriate ...

  9. Discovery of a new puroindole b gene in wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wilkinson and co-workers (2008) reported the existence of three new variant forms of puroindoline b. Termed simply variants 1, 2 and 3, these genes were purported to be encoded by the same Pinb-2 locus on chromosome 7A. In our research, we examined a total of 5 wheat cultivars, 38 ditelosomic line...

  10. Discovery of induced point mutations in maize genes by TILLING

    Microsoft Academic Search

    Bradley J Till; Steven H Reynolds; Clifford Weil; Nathan Springer; Chris Burtner; Kim Young; Elisabeth Bowers; Christine A Codomo; Linda C Enns; Anthony R Odden; Elizabeth A Greene; Luca Comai; Steven Henikoff

    2004-01-01

    BACKGROUND: Going from a gene sequence to its function in the context of a whole organism requires a strategy for targeting mutations, referred to as reverse genetics. Reverse genetics is highly desirable in the modern genomics era; however, the most powerful methods are generally restricted to a few model organisms. Previously, we introduced a reverse-genetic strategy with the potential for

  11. Discovery and Functional Characterization of Recurrent Gene Fusions from 4,932 Primary Tumor Transcriptomes Across 19 Human Cancers - Chai Bandlamudi, TCGA Scientific Symposium 2014

    Cancer.gov

    Home News and Events Multimedia Library Videos Discovery and Functional Characterization of Recurrent Gene Fusions from 4,932 Primary Tumor Transcr Discovery and Functional Characterization of Recurrent Gene Fusions from 4,932 Primary Tumor Transcriptomes

  12. 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...

  13. Cryptococcus neoformans Virulence Gene Discovery through Insertional Mutagenesis

    Microsoft Academic Search

    Alexander Idnurm; Jennifer L. Reedy; Jesse C. Nussbaum; Joseph Heitman

    2004-01-01

    Insertional mutagenesis was applied to Cryptococcus neoformans to identify genes associated with virulence attributes. Using biolistic transformation, we generated 4,300 nourseothricin (NAT)-resistant strains, of which 590 exhibited stable resistance. We focused on mutants with defects in established virulence factors and identified two with reduced growth at 37°C, four with reduced production of the antioxidant pigment melanin, and two with an

  14. Tissue Compartment Analysis for Biomarker Discovery by Gene Expression Profiling

    PubMed Central

    Disset, Antoine; Cheval, Lydie; Soutourina, Olga; Duong Van Huyen, Jean-Paul; Li, Guorong; Genin, Christian; Tostain, Jacques; Loupy, Alexandre

    2009-01-01

    Background Although high throughput technologies for gene profiling are reliable tools, sample/tissue heterogeneity limits their outcomes when applied to identify molecular markers. Indeed, inter-sample differences in cell composition contribute to scatter the data, preventing detection of small but relevant changes in gene expression level. To date, attempts to circumvent this difficulty were based on isolation of the different cell structures constituting biological samples. As an alternate approach, we developed a tissue compartment analysis (TCA) method to assess the cell composition of tissue samples, and applied it to standardize data and to identify biomarkers. Methodology/Principal Findings TCA is based on the comparison of mRNA expression levels of specific markers of the different constitutive structures in pure isolated structures, on the one hand, and in the whole sample on the other. TCA method was here developed with human kidney samples, as an example of highly heterogeneous organ. It was validated by comparison of the data with those obtained by histo-morphometry. TCA demonstrated the extreme variety of composition of kidney samples, with abundance of specific structures varying from 5 to 95% of the whole sample. TCA permitted to accurately standardize gene expression level amongst >100 kidney biopsies, and to identify otherwise imperceptible molecular disease markers. Conclusions/Significance Because TCA does not require specific preparation of sample, it can be applied to all existing tissue or cDNA libraries or to published data sets, inasmuch specific operational compartments markers are available. In human, where the small size of tissue samples collected in clinical practice accounts for high structural diversity, TCA is well suited for the identification of molecular markers of diseases, and the follow up of identified markers in single patients for diagnosis/prognosis and evaluation of therapy efficiency. In laboratory animals, TCA will interestingly be applied to central nervous system where tissue heterogeneity is a limiting factor. PMID:19901995

  15. GEM-TREND: a web tool for gene expression data mining toward relevant network discovery

    PubMed Central

    Feng, Chunlai; Araki, Michihiro; Kunimoto, Ryo; Tamon, Akiko; Makiguchi, Hiroki; Niijima, Satoshi; Tsujimoto, Gozoh; Okuno, Yasushi

    2009-01-01

    Background DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database. Results GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories. Conclusion GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at . PMID:19728865

  16. Scientific Discovery with the Blue Gene/L

    SciTech Connect

    Negele, John W.

    2011-12-09

    This project succeeded in developing key software optimization tools to bring fundamental QCD calculations of nucleon structure from the Terascale era through the Petascale era and prepare for the Exascale era. It also enabled fundamental QCD physics calculations and demonstrated the power of placing small versions of frontier emerging architectures at MIT to attract outstanding students to computational science. MIT also hosted a workshop September 19 2008 to brainstorm ways to promote computational science at top tier research universities and attract gifted students into the field, some of whom would provide the next generation of talent at our defense laboratories.

  17. Discovery of novel sodium channel inhibitors-A gene family-based approach.

    PubMed

    Clare, Jeff J

    2006-09-01

    Voltage-gated sodium (Na(V)) channel inhibitors are an important class of drugs that are used to treat a number of CNS indications including pain, local anaesthesia, epilepsy and bipolar disorder. These drugs all have their origins in traditional "empirical" pharmacology, and it was only some time after discovery that they were found to inhibit Na(V) channels. The basis for therapeutic selectivity of these drugs within different disease indications is currently unknown. However, the subsequent discovery of a multi-gene family of Na(V) channels suggests a possible mechanism and has opened the way for more targeted approaches to finding improved therapeutic inhibitors. This article describes some ongoing approaches to systematically clone, express and characterise the entire family of Na(V) subtypes in order to better understand their properties and define their individual physiological and pathophysiological roles. As well as providing specific disease validation for individual subtypes, this also provides a panel of reagents for comprehensively exploring the efficacy, selectivity and potency relationships of existing Na(V)-blocking drugs. In this way, a gene family-based approach to Na(V) channels has enabled a "drug-to-target" approach, reversing the more usual "gene-to-target-to-drug" paradigm. Together with recent advances in assay technology, gene family-based approaches are increasing the tractability of these targets and are re-invigorating Na(V) drug discovery within the pharmaceutical industry. PMID:20483263

  18. Cohesin gene mutations in tumorigenesis: from discovery to clinical significance

    PubMed Central

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

    2014-01-01

    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

  19. Chemical discovery and global gene expression analysis in zebrafish.

    PubMed

    Pichler, Franz B; Laurenson, Sophie; Williams, Liam C; Dodd, Andrew; Copp, Brent R; Love, Donald R

    2003-08-01

    The zebrafish (Danio rerio) provides an excellent model for studying vertebrate development and human disease because of its ex utero, optically transparent embryogenesis and amenability to in vivo manipulation. The rapid embryonic developmental cycle, large clutch sizes and ease of maintenance at large numbers also add to the appeal of this species. Considerable genomic data has recently become publicly available that is aiding the construction of zebrafish microarrays, thus permitting global gene expression analysis. The zebrafish is also suitable for chemical genomics, in part as a result of the permeability of its embryos to small molecules and consequent avoidance of external confounding maternal effects. Finally, there is increasing characterization and analysis of zebrafish models of human disease. Thus, the zebrafish offers a high-quality, high-throughput bioassay tool for determining the biological effect of small molecules as well as for dissecting biological pathways. PMID:12894204

  20. Emerging voices in a university pen?pal project: Layers of discovery in action research

    Microsoft Academic Search

    Maria A. Ceprano; Elaine M. Garan

    1998-01-01

    Describes how a semester?long pen?pal project enabled the 18 participating university language arts students, a class of first graders and their teacher, and the university instructors to become co?learners in meaningful, action research. The weekly letters the university students exchanged with a class of first?graders became the springboard for discussion, discovery and genuine research questions. Insights about writing as derived

  1. The Alveolate Perkinsus marinus: Biological Insights from EST Gene Discovery

    PubMed Central

    2010-01-01

    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

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

    PubMed

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

    2015-01-28

    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

  3. Discovery and characterization of medaka miRNA genes by next generation sequencing platform

    Microsoft Academic Search

    Sung-Chou Li; Wen-Ching Chan; Meng-Ru Ho; Kuo-Wang Tsai; Ling-Yueh Hu; Chun-Hung Lai; Chun-Nan Hsu; Pung-Pung Hwang; Wen-chang Lin

    2010-01-01

    BACKGROUND: MicroRNAs (miRNAs) are endogenous non-protein-coding RNA genes which exist in a wide variety of organisms, including animals, plants, virus and even unicellular organisms. Medaka (Oryzias latipes) is a useful model organism among vertebrate animals. However, no medaka miRNAs have been investigated systematically. It is beneficial to conduct a genome-wide miRNA discovery study using the next generation sequencing (NGS) technology,

  4. The discovery that mutations in single genes can modulate aging was not only fascinating but it provided

    E-print Network

    de Magalhăes, Joăo Pedro

    The discovery that mutations in single genes can modulate aging was not only in 68 genes have been shown to affect lifespan in mice. Among mouse genes in which mutations extend-releasing factor for Ras, exhibit a significant increase (~20%) in average and maximum lifespan. This increase

  5. ExpertDiscovery and UGENE integrated system for intelligent analysis of regulatory regions of genes.

    PubMed

    Vaskin, Y Y; Khomicheva, I V; Ignatieva, E V; Vityaev, E E

    The task of automatic extraction of the hierarchical structure of eukaryotic gene regulatory regions is in the junction of the fields of biology, mathematics and information technologies. A solution of the problem involves understanding of sophisticated mechanisms of eukaryotic gene regulation and applying advanced data mining technologies. In the paper the integrated system, implementing a powerful relation mining of biological data method, is discussed. The system allows taking into account prior information about the gene regulatory regions that is known by the biologist, performing the analysis on each hierarchical level, searching for a solution from a simple hypothesis to a complex one. The integration of ExpertDiscovery system into UGENE toolkit provides a convenient environment for conducting complex research and automating the work of a biologist. For demonstration, the system has been applied for recognition of SF1, SREBP, HNF4 vertebrate binding sites and for the analysis the human gene regulatory regions that promote liver-specific transcription. PMID:22935964

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

    PubMed Central

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

    2014-01-01

    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

  7. Ontological Discovery Environment: a system for integrating gene-phenotype associations.

    PubMed

    Baker, Erich J; Jay, Jeremy J; Philip, Vivek M; Zhang, Yun; Li, Zuopan; Kirova, Roumyana; Langston, Michael A; Chesler, Elissa J

    2009-12-01

    The wealth of genomic technologies has enabled biologists to rapidly ascribe phenotypic characters to biological substrates. Central to effective biological investigation is the operational definition of the process under investigation. We propose an elucidation of categories of biological characters, including disease relevant traits, based on natural endogenous processes and experimentally observed biological networks, pathways and systems rather than on externally manifested constructs and current semantics such as disease names and processes. The Ontological Discovery Environment (ODE) is an Internet accessible resource for the storage, sharing, retrieval and analysis of phenotype-centered genomic data sets across species and experimental model systems. Any type of data set representing gene-phenotype relationships, such quantitative trait loci (QTL) positional candidates, literature reviews, microarray experiments, ontological or even meta-data, may serve as inputs. To demonstrate a use case leveraging the homology capabilities of ODE and its ability to synthesize diverse data sets, we conducted an analysis of genomic studies related to alcoholism. The core of ODE's gene set similarity, distance and hierarchical analysis is the creation of a bipartite network of gene-phenotype relations, a unique discrete graph approach to analysis that enables set-set matching of non-referential data. Gene sets are annotated with several levels of metadata, including community ontologies, while gene set translations compare models across species. Computationally derived gene sets are integrated into hierarchical trees based on gene-derived phenotype interdependencies. Automated set identifications are augmented by statistical tools which enable users to interpret the confidence of modeled results. This approach allows data integration and hypothesis discovery across multiple experimental contexts, regardless of the face similarity and semantic annotation of the experimental systems or species domain. PMID:19733230

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

    PubMed

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

    2010-11-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

    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.

  10. Designing and Developing a NASA Research Projects Knowledge Base and Implementing Knowledge Management and Discovery Techniques

    NASA Astrophysics Data System (ADS)

    Dabiru, L.; O'Hara, C. G.; Shaw, D.; Katragadda, S.; Anderson, D.; Kim, S.; Shrestha, B.; Aanstoos, J.; Frisbie, T.; Policelli, F.; Keblawi, N.

    2006-12-01

    The Research Project Knowledge Base (RPKB) is currently being designed and will be implemented in a manner that is fully compatible and interoperable with enterprise architecture tools developed to support NASA's Applied Sciences Program. Through user needs assessment, collaboration with Stennis Space Center, Goddard Space Flight Center, and NASA's DEVELOP Staff personnel insight to information needs for the RPKB were gathered from across NASA scientific communities of practice. To enable efficient, consistent, standard, structured, and managed data entry and research results compilation a prototype RPKB has been designed and fully integrated with the existing NASA Earth Science Systems Components database. The RPKB will compile research project and keyword information of relevance to the six major science focus areas, 12 national applications, and the Global Change Master Directory (GCMD). The RPKB will include information about projects awarded from NASA research solicitations, project investigator information, research publications, NASA data products employed, and model or decision support tools used or developed as well as new data product information. The RPKB will be developed in a multi-tier architecture that will include a SQL Server relational database backend, middleware, and front end client interfaces for data entry. The purpose of this project is to intelligently harvest the results of research sponsored by the NASA Applied Sciences Program and related research program results. We present various approaches for a wide spectrum of knowledge discovery of research results, publications, projects, etc. from the NASA Systems Components database and global information systems and show how this is implemented in SQL Server database. The application of knowledge discovery is useful for intelligent query answering and multiple-layered database construction. Using advanced EA tools such as the Earth Science Architecture Tool (ESAT), RPKB will enable NASA and partner agencies to efficiently identify the significant results for new experiment directions and principle investigators to formulate experiment directions for new proposals.

  11. Gene Discovery of Modular Diterpene Metabolism in Nonmodel Systems1[W][OA

    PubMed Central

    Zerbe, Philipp; Hamberger, Björn; Yuen, Macaire M.S.; Chiang, Angela; Sandhu, Harpreet K.; Madilao, Lina L.; Nguyen, Anh; Hamberger, Britta; Bach, Sřren Spanner; Bohlmann, Jörg

    2013-01-01

    Plants produce over 10,000 different diterpenes of specialized (secondary) metabolism, and fewer diterpenes of general (primary) metabolism. Specialized diterpenes may have functions in ecological interactions of plants with other organisms and also benefit humanity as pharmaceuticals, fragrances, resins, and other industrial bioproducts. Examples of high-value diterpenes are taxol and forskolin pharmaceuticals or ambroxide fragrances. Yields and purity of diterpenes obtained from natural sources or by chemical synthesis are often insufficient for large-volume or high-end applications. Improvement of agricultural or biotechnological diterpene production requires knowledge of biosynthetic genes and enzymes. However, specialized diterpene pathways are extremely diverse across the plant kingdom, and most specialized diterpenes are taxonomically restricted to a few plant species, genera, or families. Consequently, there is no single reference system to guide gene discovery and rapid annotation of specialized diterpene pathways. Functional diversification of genes and plasticity of enzyme functions of these pathways further complicate correct annotation. To address this challenge, we used a set of 10 different plant species to develop a general strategy for diterpene gene discovery in nonmodel systems. The approach combines metabolite-guided transcriptome resources, custom diterpene synthase (diTPS) and cytochrome P450 reference gene databases, phylogenies, and, as shown for select diTPSs, single and coupled enzyme assays using microbial and plant expression systems. In the 10 species, we identified 46 new diTPS candidates and over 400 putatively terpenoid-related P450s in a resource of nearly 1 million predicted transcripts of diterpene-accumulating tissues. Phylogenetic patterns of lineage-specific blooms of genes guided functional characterization. PMID:23613273

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

    PubMed Central

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

    2012-01-01

    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

  13. High-throughput platform for the discovery of elicitors of silent bacterial gene clusters

    PubMed Central

    Seyedsayamdost, Mohammad R.

    2014-01-01

    Over the past decade, bacterial genome sequences have revealed an immense reservoir of biosynthetic gene clusters, sets of contiguous genes that have the potential to produce drugs or drug-like molecules. However, the majority of these gene clusters appear to be inactive for unknown reasons prompting terms such as “cryptic” or “silent” to describe them. Because natural products have been a major source of therapeutic molecules, methods that rationally activate these silent clusters would have a profound impact on drug discovery. Herein, a new strategy is outlined for awakening silent gene clusters using small molecule elicitors. In this method, a genetic reporter construct affords a facile read-out for activation of the silent cluster of interest, while high-throughput screening of small molecule libraries provides potential inducers. This approach was applied to two cryptic gene clusters in the pathogenic model Burkholderia thailandensis. The results not only demonstrate a prominent activation of these two clusters, but also reveal that the majority of elicitors are themselves antibiotics, most in common clinical use. Antibiotics, which kill B. thailandensis at high concentrations, act as inducers of secondary metabolism at low concentrations. One of these antibiotics, trimethoprim, served as a global activator of secondary metabolism by inducing at least five biosynthetic pathways. Further application of this strategy promises to uncover the regulatory networks that activate silent gene clusters while at the same time providing access to the vast array of cryptic molecules found in bacteria. PMID:24808135

  14. RNA-Seq Analysis and Gene Discovery of Andrias davidianus Using Illumina Short Read Sequencing

    PubMed Central

    Li, Fenggang; Wang, Lixin; Lan, Qingjing; Yang, Hui; Li, Yang; Liu, Xiaolin; Yang, Zhaoxia

    2015-01-01

    The Chinese giant salamander, Andrias davidianus, is an important species in the course of evolution; however, there is insufficient genomic data in public databases for understanding its immunologic mechanisms. High-throughput transcriptome sequencing is necessary to generate an enormous number of transcript sequences from A. davidianus for gene discovery. In this study, we generated more than 40 million reads from samples of spleen and skin tissue using the Illumina paired-end sequencing technology. De novo assembly yielded 87,297 transcripts with a mean length of 734 base pairs (bp). Based on the sequence similarities, searching with known proteins, 38,916 genes were identified. Gene enrichment analysis determined that 981 transcripts were assigned to the immune system. Tissue-specific expression analysis indicated that 443 of transcripts were specifically expressed in the spleen and skin. Among these transcripts, 147 transcripts were found to be involved in immune responses and inflammatory reactions, such as fucolectin, ?-defensins and lymphotoxin beta. Eight tissue-specific genes were selected for validation using real time reverse transcription quantitative PCR (qRT-PCR). The results showed that these genes were significantly more expressed in spleen and skin than in other tissues, suggesting that these genes have vital roles in the immune response. This work provides a comprehensive genomic sequence resource for A. davidianus and lays the foundation for future research on the immunologic and disease resistance mechanisms of A. davidianus and other amphibians. PMID:25874626

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

    PubMed Central

    2013-01-01

    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

  16. A Genomics Based Discovery of Secondary Metabolite Biosynthetic Gene Clusters in Aspergillus ustus

    PubMed Central

    Pi, Borui; Yu, Dongliang; Dai, Fangwei; Song, Xiaoming; Zhu, Congyi; Li, Hongye; Yu, Yunsong

    2015-01-01

    Secondary metabolites (SMs) produced by Aspergillus have been extensively studied for their crucial roles in human health, medicine and industrial production. However, the resulting information is almost exclusively derived from a few model organisms, including A. nidulans and A. fumigatus, but little is known about rare pathogens. In this study, we performed a genomics based discovery of SM biosynthetic gene clusters in Aspergillus ustus, a rare human pathogen. A total of 52 gene clusters were identified in the draft genome of A. ustus 3.3904, such as the sterigmatocystin biosynthesis pathway that was commonly found in Aspergillus species. In addition, several SM biosynthetic gene clusters were firstly identified in Aspergillus that were possibly acquired by horizontal gene transfer, including the vrt cluster that is responsible for viridicatumtoxin production. Comparative genomics revealed that A. ustus shared the largest number of SM biosynthetic gene clusters with A. nidulans, but much fewer with other Aspergilli like A. niger and A. oryzae. These findings would help to understand the diversity and evolution of SM biosynthesis pathways in genus Aspergillus, and we hope they will also promote the development of fungal identification methodology in clinic. PMID:25706180

  17. SPARCoC: A New Framework for Molecular Pattern Discovery and Cancer Gene Identification.

    PubMed

    Ma, Shiqian; Johnson, Daniel; Ashby, Cody; Xiong, Donghai; Cramer, Carole L; Moore, Jason H; Zhang, Shuzhong; Huang, Xiuzhen

    2015-01-01

    It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust), which is based on a novel Common-background and Sparse-foreground Decomposition (CSD) model and the Maximum Block Improvement (MBI) co-clustering technique. SPARCoC has clear advantages compared with widely-used alternative approaches: hierarchical clustering (Hclust) and nonnegative matrix factorization (NMF). We apply SPARCoC to the study of lung adenocarcinoma (ADCA), an extremely heterogeneous histological type, and a significant challenge for molecular subtyping. For testing and verification, we use high quality gene expression profiling data of lung ADCA patients, and identify prognostic gene signatures which could cluster patients into subgroups that are significantly different in their overall survival (with p-values < 0.05). Our results are only based on gene expression profiling data analysis, without incorporating any other feature selection or clinical information; we are able to replicate our findings with completely independent datasets. SPARCoC is broadly applicable to large-scale genomic data to empower pattern discovery and cancer gene identification. PMID:25768286

  18. SPARCoC: A New Framework for Molecular Pattern Discovery and Cancer Gene Identification

    PubMed Central

    Ma, Shiqian; Johnson, Daniel; Ashby, Cody; Xiong, Donghai; Cramer, Carole L.; Moore, Jason H.; Zhang, Shuzhong; Huang, Xiuzhen

    2015-01-01

    It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust), which is based on a novel Common-background and Sparse-foreground Decomposition (CSD) model and the Maximum Block Improvement (MBI) co-clustering technique. SPARCoC has clear advantages compared with widely-used alternative approaches: hierarchical clustering (Hclust) and nonnegative matrix factorization (NMF). We apply SPARCoC to the study of lung adenocarcinoma (ADCA), an extremely heterogeneous histological type, and a significant challenge for molecular subtyping. For testing and verification, we use high quality gene expression profiling data of lung ADCA patients, and identify prognostic gene signatures which could cluster patients into subgroups that are significantly different in their overall survival (with p-values < 0.05). Our results are only based on gene expression profiling data analysis, without incorporating any other feature selection or clinical information; we are able to replicate our findings with completely independent datasets. SPARCoC is broadly applicable to large-scale genomic data to empower pattern discovery and cancer gene identification. PMID:25768286

  19. A Genomics Based Discovery of Secondary Metabolite Biosynthetic Gene Clusters in Aspergillus ustus.

    PubMed

    Pi, Borui; Yu, Dongliang; Dai, Fangwei; Song, Xiaoming; Zhu, Congyi; Li, Hongye; Yu, Yunsong

    2015-01-01

    Secondary metabolites (SMs) produced by Aspergillus have been extensively studied for their crucial roles in human health, medicine and industrial production. However, the resulting information is almost exclusively derived from a few model organisms, including A. nidulans and A. fumigatus, but little is known about rare pathogens. In this study, we performed a genomics based discovery of SM biosynthetic gene clusters in Aspergillus ustus, a rare human pathogen. A total of 52 gene clusters were identified in the draft genome of A. ustus 3.3904, such as the sterigmatocystin biosynthesis pathway that was commonly found in Aspergillus species. In addition, several SM biosynthetic gene clusters were firstly identified in Aspergillus that were possibly acquired by horizontal gene transfer, including the vrt cluster that is responsible for viridicatumtoxin production. Comparative genomics revealed that A. ustus shared the largest number of SM biosynthetic gene clusters with A. nidulans, but much fewer with other Aspergilli like A. niger and A. oryzae. These findings would help to understand the diversity and evolution of SM biosynthesis pathways in genus Aspergillus, and we hope they will also promote the development of fungal identification methodology in clinic. PMID:25706180

  20. Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

    PubMed Central

    Li, Xia; Rao, Shaoqi; Jiang, Wei; Li, Chuanxing; Xiao, Yun; Guo, Zheng; Zhang, Qingpu; Wang, Lihong; Du, Lei; Li, Jing; Li, Li; Zhang, Tianwen; Wang, Qing K

    2006-01-01

    Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to the development, aging and progressive pathogenesis of a complex disease where potential dependences between different experiment units might occurs. PMID:16420705

  1. Effector Genomics Accelerates Discovery and Functional Profiling of Potato Disease Resistance and Phytophthora Infestans Avirulence Genes

    PubMed Central

    Vleeshouwers, Vivianne G. A. A.; Rietman, Hendrik; Krenek, Pavel; Champouret, Nicolas; Young, Carolyn; Oh, Sang-Keun; Wang, Miqia; Bouwmeester, Klaas; Vosman, Ben; Visser, Richard G. F.; Jacobsen, Evert; Govers, Francine; Kamoun, Sophien; Van der Vossen, Edwin A. G.

    2008-01-01

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity) on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR) in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties. PMID:18682852

  2. Effector genomics accelerates discovery and functional profiling of potato disease resistance and phytophthora infestans avirulence genes.

    PubMed

    Vleeshouwers, Vivianne G A A; Rietman, Hendrik; Krenek, Pavel; Champouret, Nicolas; Young, Carolyn; Oh, Sang-Keun; Wang, Miqia; Bouwmeester, Klaas; Vosman, Ben; Visser, Richard G F; Jacobsen, Evert; Govers, Francine; Kamoun, Sophien; Van der Vossen, Edwin A G

    2008-01-01

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity) on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR) in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties. PMID:18682852

  3. Discovery of genes related to formothion resistance in oriental fruit fly (Bactrocera dorsalis) by a constrained functional genomics analysis.

    PubMed

    Kuo, T C-Y; Hu, C-C; Chien, T-Y; Chen, M J M; Feng, H-T; Chen, L-F O; Chen, C-Y; Hsu, J-C

    2015-06-01

    Artificial selection can provide insights into how insecticide resistance mechanisms evolve in populations. The underlying basis of such phenomena can involve complex interactions of multiple genes, and the resolution of this complexity first necessitates confirmation that specific genes are involved in resistance mechanisms. Here, we used a novel approach invoking a constrained RNA sequencing analysis to refine the discovery of specific genes involved in insecticide resistance. Specifically, for gene discovery, an additional constraint was added to the traditional comparisons of susceptible vs. resistant flies by the incorporation of a line in which insecticide susceptibility was 'recovered' within a resistant line by the removal of insecticide stress. In our analysis, the criterion for the classification of any gene as related to insecticide resistance was based on evidence for differential expression in the resistant line as compared with both the susceptible and recovered lines. The incorporation of this additional constraint reduced the number of differentially expressed genes putatively involved in resistance to 464, compared with more than 1000 that had been identified previously using this same species. In addition, our analysis identified several key genes involved in metabolic detoxification processes that showed up-regulated expression. Furthermore, the involvement of acetylcholinesterase, a known target for modification in insecticide resistance, was associated with three key nonsynonymous amino acid substitutions within our data. In conclusion, the incorporation of an additional constraint using a 'recovered' line for gene discovery provides a higher degree of confidence in genes identified to be involved in insecticide resistance phenomena. PMID:25702834

  4. Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory

    ERIC Educational Resources Information Center

    Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

    2010-01-01

    A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…

  5. Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis.

    PubMed

    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

    2014-10-01

    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

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

    PubMed Central

    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

    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

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

    PubMed Central

    Giles, Peter F.; Soanes, Darren M.

    2003-01-01

    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

  8. Discovery and validation of gene classifiers for endocrine-disrupting chemicals in zebrafish (danio rerio)

    PubMed Central

    2012-01-01

    Background Development and application of transcriptomics-based gene classifiers for ecotoxicological applications lag far behind those of biomedical sciences. Many such classifiers discovered thus far lack vigorous statistical and experimental validations. A combination of genetic algorithm/support vector machines and genetic algorithm/K nearest neighbors was used in this study to search for classifiers of endocrine-disrupting chemicals (EDCs) in zebrafish. Searches were conducted on both tissue-specific and tissue-combined datasets, either across the entire transcriptome or within individual transcription factor (TF) networks previously linked to EDC effects. Candidate classifiers were evaluated by gene set enrichment analysis (GSEA) on both the original training data and a dedicated validation dataset. Results Multi-tissue dataset yielded no classifiers. Among the 19 chemical-tissue conditions evaluated, the transcriptome-wide searches yielded classifiers for six of them, each having approximately 20 to 30 gene features unique to a condition. Searches within individual TF networks produced classifiers for 15 chemical-tissue conditions, each containing 100 or fewer top-ranked gene features pooled from those of multiple TF networks and also unique to each condition. For the training dataset, 10 out of 11 classifiers successfully identified the gene expression profiles (GEPs) of their targeted chemical-tissue conditions by GSEA. For the validation dataset, classifiers for prochloraz-ovary and flutamide-ovary also correctly identified the GEPs of corresponding conditions while no classifier could predict the GEP from prochloraz-brain. Conclusions The discrepancies in the performance of these classifiers were attributed in part to varying data complexity among the conditions, as measured to some degree by Fisher’s discriminant ratio statistic. This variation in data complexity could likely be compensated by adjusting sample size for individual chemical-tissue conditions, thus suggesting a need for a preliminary survey of transcriptomic responses before launching a full scale classifier discovery effort. Classifier discovery based on individual TF networks could yield more mechanistically-oriented biomarkers. GSEA proved to be a flexible and effective tool for application of gene classifiers but a similar and more refined algorithm, connectivity mapping, should also be explored. The distribution characteristics of classifiers across tissues, chemicals, and TF networks suggested a differential biological impact among the EDCs on zebrafish transcriptome involving some basic cellular functions. PMID:22849515

  9. Resequencing and comparative genomics of Stagonospora nodorum: sectional gene absence and effector discovery.

    PubMed

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

    2013-06-01

    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

  10. Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis.

    PubMed

    Nilsson, Roland; Schultz, Iman J; Pierce, Eric L; Soltis, Kathleen A; Naranuntarat, Amornrat; Ward, Diane M; Baughman, Joshua M; Paradkar, Prasad N; Kingsley, Paul D; Culotta, Valeria C; Kaplan, Jerry; Palis, James; Paw, Barry H; Mootha, Vamsi K

    2009-08-01

    Heme biosynthesis consists of a series of eight enzymatic reactions that originate in mitochondria and continue in the cytosol before returning to mitochondria. Although these core enzymes are well studied, additional mitochondrial transporters and regulatory factors are predicted to be required. To discover such unknown components, we utilized a large-scale computational screen to identify mitochondrial proteins whose transcripts consistently coexpress with the core machinery of heme biosynthesis. We identified SLC25A39, SLC22A4, and TMEM14C, which are putative mitochondrial transporters, as well as C1orf69 and ISCA1, which are iron-sulfur cluster proteins. Targeted knockdowns of all five genes in zebrafish resulted in profound anemia without impacting erythroid lineage specification. Moreover, silencing of Slc25a39 in murine erythroleukemia cells impaired iron incorporation into protoporphyrin IX, and vertebrate Slc25a39 complemented an iron homeostasis defect in the orthologous yeast mtm1Delta deletion mutant. Our results advance the molecular understanding of heme biosynthesis and offer promising candidate genes for inherited anemias. PMID:19656490

  11. 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

  12. Discovery of genes related to diabetic nephropathy in various animal models by current techniques.

    PubMed

    Wada, Jun; Sun, Lin; Kanwar, Yashpal S

    2011-01-01

    One of the major problems facing clinical nephrology currently throughout the world is an exponential increase in patients with end-stage renal disease (ESRD), which is largely related to a high incidence of diabetic nephropathy. The latter is characterized by a multitude of metabolic and signaling events following excessive channeling of glucose, which leads to an increased synthesis of extracellular matrix (ECM) glycoproteins resulting in glomerulosclerosis, interstitial fibrosis and ultimately ESRD. With the incidence of nephropathy at pandemic levels and a high rate of ESRD, physicians around the world must treat a disproportionately large number of diabetic patients with upto-date innovative measures. In this regard, identification of genes that are crucially involved in the progression of diabetic nephropathy would enhance the discovery of new biomarkers and could also promote the development of novel therapeutic strategies. Over the last decade, we focused on the recent methodologies of high-throughput and genome-wide screening for identification of relevant genes in various animal models, which included the following: (1) single nucleotide polymorphism-based genome- wide screening; (2) the transcriptome approach, such as differential display reverse transcription polymerase chain reaction (DDRT-PCR), representational difference analysis of cDNA (cDNA-RDA)/suppressive subtractive hybridization, SAGE (serial analysis of gene expression) and DNA Microarray; and (3) the proteomic approach and 2- dimensional polyacrylamide gel electrophoresis (2D- PAGE) coupled with mass spectroscopic analysis. Several genes, such as Tim44 (translocase of inner mitochondrial membrane- 44), RSOR/MIOX (renal specific oxidoreductase/myo-inositol oxygenase), UbA52, Rap1b (Ras-related GTPase), gremlin, osteopontin, hydroxysteroid dehydrogenase- 3? isotype 4 and those of the Wnt signaling pathway, were identified as differentially expressed genes in kidneys of diabetic rodents. Functional analysis of these genes and the subsequent translational research in the clinical settings would be very valuable in the prevention and treatment of diabetic nephropathy. Future trends for identification of the biomarkers and therapeutic target genes should also include genome scale DNA/histonemethylation profiling, metabolomic approaches (e.g. metabolic phenotyping by 1H spectroscopy) and lectin microarray for glycan profiling along with the development of robust data-mining strategies. PMID:21252517

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

    PubMed

    Pehkonen, Petri; Wong, Garry; Törönen, Petri

    2010-01-01

    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

  14. Gene discovery using mutagen-induced polymorphisms and deep sequencing: application to plant disease resistance.

    PubMed

    Zhu, Ying; Mang, Hyung-gon; Sun, Qi; Qian, Jun; Hipps, Ashley; Hua, Jian

    2012-09-01

    Next-generation sequencing technologies are accelerating gene discovery by combining multiple steps of mapping and cloning used in the traditional map-based approach into one step using DNA sequence polymorphisms existing between two different accessions/strains/backgrounds of the same species. The existing next-generation sequencing method, like the traditional one, requires the use of a segregating population from a cross of a mutant organism in one accession with a wild-type (WT) organism in a different accession. It therefore could potentially be limited by modification of mutant phenotypes in different accessions and/or by the lengthy process required to construct a particular mapping parent in a second accession. Here we present mapping and cloning of an enhancer mutation with next-generation sequencing on bulked segregants in the same accession using sequence polymorphisms induced by a chemical mutagen. This method complements the conventional cloning approach and makes forward genetics more feasible and powerful in molecularly dissecting biological processes in any organisms. The pipeline developed in this study can be used to clone causal genes in background of single mutants or higher order of mutants and in species with or without sequence information on multiple accessions. PMID:22714407

  15. Gene Discovery Using Mutagen-Induced Polymorphisms and Deep Sequencing: Application to Plant Disease Resistance

    PubMed Central

    Zhu, Ying; Mang, Hyung-gon; Sun, Qi; Qian, Jun; Hipps, Ashley; Hua, Jian

    2012-01-01

    Next-generation sequencing technologies are accelerating gene discovery by combining multiple steps of mapping and cloning used in the traditional map-based approach into one step using DNA sequence polymorphisms existing between two different accessions/strains/backgrounds of the same species. The existing next-generation sequencing method, like the traditional one, requires the use of a segregating population from a cross of a mutant organism in one accession with a wild-type (WT) organism in a different accession. It therefore could potentially be limited by modification of mutant phenotypes in different accessions and/or by the lengthy process required to construct a particular mapping parent in a second accession. Here we present mapping and cloning of an enhancer mutation with next-generation sequencing on bulked segregants in the same accession using sequence polymorphisms induced by a chemical mutagen. This method complements the conventional cloning approach and makes forward genetics more feasible and powerful in molecularly dissecting biological processes in any organisms. The pipeline developed in this study can be used to clone causal genes in background of single mutants or higher order of mutants and in species with or without sequence information on multiple accessions. PMID:22714407

  16. Improved RNA-seq of blood-derived RNA increases gene discovery and coverage

    E-print Network

    Cai, Long

    -derived RNA can aid discovery of the cause of disease, as well as preclinical research. However, the high variants and isoforms is particularly important to discovery, preclinical and clinical research, for which

  17. Target discovery

    Microsoft Academic Search

    Mark A. Lindsay

    2003-01-01

    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

  18. A genome-wide cis-regulatory element discovery method based on promoter sequences and gene co-expression networks

    PubMed Central

    2013-01-01

    Background Deciphering cis-regulatory networks has become an attractive yet challenging task. This paper presents a simple method for cis-regulatory network discovery which aims to avoid some of the common problems of previous approaches. Results Using promoter sequences and gene expression profiles as input, rather than clustering the genes by the expression data, our method utilizes co-expression neighborhood information for each individual gene, thereby overcoming the disadvantages of current clustering based models which may miss specific information for individual genes. In addition, rather than using a motif database as an input, it implements a simple motif count table for each enumerated k-mer for each gene promoter sequence. Thus, it can be used for species where previous knowledge of cis-regulatory motifs is unknown and has the potential to discover new transcription factor binding sites. Applications on Saccharomyces cerevisiae and Arabidopsis have shown that our method has a good prediction accuracy and outperforms a phylogenetic footprinting approach. Furthermore, the top ranked gene-motif regulatory clusters are evidently functionally co-regulated, and the regulatory relationships between the motifs and the enriched biological functions can often be confirmed by literature. Conclusions Since this method is simple and gene-specific, it can be readily utilized for insufficiently studied species or flexibly used as an additional step or data source for previous transcription regulatory networks discovery models. PMID:23368633

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

    PubMed Central

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

    1999-01-01

    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

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

    PubMed Central

    2014-01-01

    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

  1. Display technologies: application for the discovery of drug and gene delivery agents

    PubMed Central

    Sergeeva, Anna; Kolonin, Mikhail G.; Molldrem, Jeffrey J.; Pasqualini, Renata; Arap, Wadih

    2007-01-01

    Recognition of molecular diversity of cell surface proteomes in disease is essential for the development of targeted therapies. Progress in targeted therapeutics requires establishing effective approaches for high-throughput identification of agents specific for clinically relevant cell surface markers. Over the past decade, a number of platform strategies have been developed to screen polypeptide libraries for ligands targeting receptors selectively expressed in the context of various cell surface proteomes. Streamlined procedures for identification of ligand-receptor pairs that could serve as targets in disease diagnosis, profiling, imaging and therapy have relied on the display technologies, in which polypeptides with desired binding profiles can be serially selected, in a process called biopanning, based on their physical linkage with the encoding nucleic acid. These technologies include virus/phage display, cell display, ribosomal display, mRNA display and covalent DNA display (CDT), with phage display being by far the most utilized. The scope of this review is the recent advancements in the display technologies with a particular emphasis on molecular mapping of cell surface proteomes with peptide phage display. Prospective applications of targeted compounds derived from display libraries in the discovery of targeted drugs and gene therapy vectors are discussed. PMID:17123658

  2. Expressed sequence tags from the zhikong scallop (Chlamys farreri): discovery and annotation of host-defense genes.

    PubMed

    Wang, Lingling; Song, Linsheng; Zhao, Jianmin; Qiu, Limei; Zhang, Huan; Xu, Wei; Li, Honglei; Li, Chenhua; Wu, Longtao; Guo, Ximing

    2009-05-01

    A high-quality cDNA library was constructed from whole body tissues of the zhikong scallop, Chlamys farreri, challenged by Listonella anguillarum. A total of 5720 clones were sequenced, yielding 5123 expressed sequence tags (ESTs). Among the 3326 unique genes identified, 2289 (69%) genes had no significant (E-value < 1e-5) matches to known sequences in public databases and 194 (6%) matched proteins of unknown functions. The remaining 843 (25%) genes that exhibited homology with genes of known functions, showed broad involvement in metabolic processes (31%), cell structure and motility (20%), gene and protein expression (12%), cell signaling and cell communication (8%), cell division (4%), and notably, 25% of those genes were related to immune function. They included stress response genes, complement-like genes, proteinase and proteinase inhibitors, immune recognition receptors and immune effectors. The EST collection obtained in this study provides a useful resource for gene discovery and especially for the identification of host-defense genes and systems in scallops and other molluscs. PMID:19328855

  3. Gene-based single nucleotide polymorphism discovery in bovine muscle using next-generation transcriptomic sequencing

    PubMed Central

    2013-01-01

    Background Genetic information based on molecular markers has increasingly being used in cattle breeding improvement programmes, as a mean to improve conventionally phenotypic selection. Advances in molecular genetics have led to the identification of several genetic markers associated with genes affecting economic traits. Until recently, the identification of the causative genetic variants involved in the phenotypes of interest has remained a difficult task. The advent of novel sequencing technologies now offers a new opportunity for the identification of such variants. Despite sequencing costs plummeting, sequencing whole-genomes or large targeted regions is still too expensive for most laboratories. A transcriptomic-based sequencing approach offers a cheaper alternative to identify a large number of polymorphisms and possibly to discover causative variants. In the present study, we performed a gene-based single nucleotide polymorphism (SNP) discovery analysis in bovine Longissimus thoraci, using RNA-Seq. To our knowledge, this represents the first study done in bovine muscle. Results Messenger RNAs from Longissimus thoraci from three Limousin bull calves were subjected to high-throughput sequencing. Approximately 36–46 million paired-end reads were obtained per library. A total of 19,752 transcripts were identified and 34,376 different SNPs were detected. Fifty-five percent of the SNPs were found in coding regions and ~22% resulted in an amino acid change. Applying a very stringent SNP quality threshold, we detected 8,407 different high-confidence SNPs, 18% of which are non synonymous coding SNPs. To analyse the accuracy of RNA-Seq technology for SNP detection, 48 SNPs were selected for validation by genotyping. No discrepancies were observed when using the highest SNP probability threshold. To test the usefulness of the identified SNPs, the 48 selected SNPs were assessed by genotyping 93 bovine samples, representing mostly the nine major breeds used in France. Principal component analysis indicates a clear separation between the nine populations. Conclusions The RNA-Seq data and the collection of newly discovered coding SNPs improve the genomic resources available for cattle, especially for beef breeds. The large amount of variation present in genes expressed in Limousin Longissimus thoracis, especially the large number of non synonymous coding SNPs, may prove useful to study the mechanisms underlying the genetic variability of meat quality traits. PMID:23651547

  4. De Novo Transcriptomic Analysis of Peripheral Blood Lymphocytes from the Chinese Goose: Gene Discovery and Immune System Pathway Description

    PubMed Central

    Tariq, Mansoor; Chen, Rong; Yuan, Hongyu; Liu, Yanjie; Wu, Yanan; Wang, Junya; Xia, Chun

    2015-01-01

    Background The Chinese goose is one of the most economically important poultry birds and is a natural reservoir for many avian viruses. However, the nature and regulation of the innate and adaptive immune systems of this waterfowl species are not completely understood due to limited information on the goose genome. Recently, transcriptome sequencing technology was applied in the genomic studies focused on novel gene discovery. Thus, this study described the transcriptome of the goose peripheral blood lymphocytes to identify immunity relevant genes. Principal Findings De novo transcriptome assembly of the goose peripheral blood lymphocytes was sequenced by Illumina-Solexa technology. In total, 211,198 unigenes were assembled from the 69.36 million cleaned reads. The average length, N50 size and the maximum length of the assembled unigenes were 687 bp, 1,298 bp and 18,992 bp, respectively. A total of 36,854 unigenes showed similarity by BLAST search against the NCBI non-redundant (Nr) protein database. For functional classification, 163,161 unigenes were comprised of three Gene Ontology (Go) categories and 67 subcategories. A total of 15,334 unigenes were annotated into 25 eukaryotic orthologous groups (KOGs) categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) database annotated 39,585 unigenes into six biological functional groups and 308 pathways. Among the 2,757 unigenes that participated in the 15 immune system KEGG pathways, 125 of the most important immune relevant genes were summarized and analyzed by STRING analysis to identify gene interactions and relationships. Moreover, 10 genes were confirmed by PCR and analyzed. Of these 125 unigenes, 109 unigenes, approximately 87%, were not previously identified in the goose. Conclusion This de novo transcriptome analysis could provide important Chinese goose sequence information and highlights the value of new gene discovery, pathways investigation and immune system gene identification, and comparison with other avian species as useful tools to understand the goose immune system. PMID:25816068

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

    SciTech Connect

    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

    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.

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

    ScienceCinema

    Muchero, Wellington [Oak Ridge National Laboratory

    2013-01-22

    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.

  7. elemental discoveries

    NSDL National Science Digital Library

    Experienced science journalist David Bradley serves up this resource on current chemical happenings. Tracking some of the discoveries and controversies at the forefront of chemistry, each issue of elemental discoveries summarizes a range of newsworthy topics, from gene control and tubular sensors to singing fish. In addition to the current issue, readers may browse past issues beginning December 1997. Two additional sections, Elemental Reviews and Book Sale, provide brief commentary on or descriptions (with UK prices) of related resources.

  8. Abstract--We present new results from Computational Neurogenetic Modeling to aid discoveries of complex gene

    E-print Network

    Benuskova, Luba

    of complex gene interactions underlying oscillations in neural systems. Interactions of genes in neurons gene/protein expression values and neuronal parameters, particular target states of the neural network, 5] has the following components: · neuronal genes and their expression levels; · protein expression

  9. drug discovery drug discovery

    E-print Network

    drug discovery at Purdue #12;drug discovery 2 #12;drug discovery 3 Introduction The drug discovery and innovative drug candidates to treat chronic and acute illnesses. Our researchers also continue to be invested in various approaches to drug discovery, which include understanding of drug targets for future drug

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

    PubMed Central

    2010-01-01

    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

  11. SSHscreen and SSHdb, generic software for microarray based gene discovery: application to the stress response in cowpea

    PubMed Central

    2010-01-01

    Background Suppression subtractive hybridization is a popular technique for gene discovery from non-model organisms without an annotated genome sequence, such as cowpea (Vigna unguiculata (L.) Walp). We aimed to use this method to enrich for genes expressed during drought stress in a drought tolerant cowpea line. However, current methods were inefficient in screening libraries and management of the sequence data, and thus there was a need to develop software tools to facilitate the process. Results Forward and reverse cDNA libraries enriched for cowpea drought response genes were screened on microarrays, and the R software package SSHscreen 2.0.1 was developed (i) to normalize the data effectively using spike-in control spot normalization, and (ii) to select clones for sequencing based on the calculation of enrichment ratios with associated statistics. Enrichment ratio 3 values for each clone showed that 62% of the forward library and 34% of the reverse library clones were significantly differentially expressed by drought stress (adjusted p value < 0.05). Enrichment ratio 2 calculations showed that > 88% of the clones in both libraries were derived from rare transcripts in the original tester samples, thus supporting the notion that suppression subtractive hybridization enriches for rare transcripts. A set of 118 clones were chosen for sequencing, and drought-induced cowpea genes were identified, the most interesting encoding a late embryogenesis abundant Lea5 protein, a glutathione S-transferase, a thaumatin, a universal stress protein, and a wound induced protein. A lipid transfer protein and several components of photosynthesis were down-regulated by the drought stress. Reverse transcriptase quantitative PCR confirmed the enrichment ratio values for the selected cowpea genes. SSHdb, a web-accessible database, was developed to manage the clone sequences and combine the SSHscreen data with sequence annotations derived from BLAST and Blast2GO. The self-BLAST function within SSHdb grouped redundant clones together and illustrated that the SSHscreen plots are a useful tool for choosing anonymous clones for sequencing, since redundant clones cluster together on the enrichment ratio plots. Conclusions We developed the SSHscreen-SSHdb software pipeline, which greatly facilitates gene discovery using suppression subtractive hybridization by improving the selection of clones for sequencing after screening the library on a small number of microarrays. Annotation of the sequence information and collaboration was further enhanced through a web-based SSHdb database, and we illustrated this through identification of drought responsive genes from cowpea, which can now be investigated in gene function studies. SSH is a popular and powerful gene discovery tool, and therefore this pipeline will have application for gene discovery in any biological system, particularly non-model organisms. SSHscreen 2.0.1 and a link to SSHdb are available from http://microarray.up.ac.za/SSHscreen. PMID:20359330

  12. Large-scale gene discovery in the septoria tritici blotch fungus Mycosphaerella graminicola with a focus on in planta expression.

    PubMed

    Kema, Gert H J; van der Lee, Theo A J; Mendes, Odette; Verstappen, Els C P; Lankhorst, René Klein; Sandbrink, Hans; van der Burgt, Ate; Zwiers, Lute-Harm; Csukai, Michael; Waalwijk, Cees

    2008-09-01

    The foliar disease septoria tritici blotch, caused by the fungus Mycosphaerella graminicola, is currently the most important wheat disease in Europe. Gene expression was examined under highly different conditions, using 10 expressed sequence tag libraries generated from M. graminicola isolate IPO323 using seven in vitro and three in planta growth conditions. To identify fungal clones in the interaction libraries, we developed a selection method based on hybridization with the entire genomic DNA of M. graminicola, to selectively enrich these libraries for fungal genes. Assembly of the 27,007 expressed sequence tags resulted in 9,190 unigenes, representing 5.2 Mb of the estimated 39-Mb genome size of M. graminicola. All libraries contributed significantly to the number of unigenes, especially the in planta libraries representing different stages of pathogenesis, which covered 15% of the library-specific unigenes. Even under presymptomatic conditions (5 days postinoculation), when fungal biomass is less than 5%, this method enabled us to efficiently capture fungal genes expressed during pathogenesis. Many of these genes were uniquely expressed in planta, indicating that in planta gene expression significantly differed from in vitro expression. Examples of gene discovery included a number of cell wall-degrading enzymes, a broad set of genes involved in signal transduction (n=11) and a range of ATP-binding cassette (n=20) and major facilitator superfamily transporter genes (n=12) potentially involved in protection against antifungal compounds or the secretion of pathogenicity factors. In addition, evidence is provided for a mycovirus in M. graminicola that is highly expressed under various stress conditions, in particular, under nitrogen starvation. Our analyses provide a unique window on in vitro and in planta gene expression of M. graminicola. PMID:18700829

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

    PubMed

    Kongchum, Pawapol; Palti, Yniv; Hallerman, Eric M; Hulata, Gideon; David, Lior

    2010-08-01

    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 develop molecular tools for breeding CyHV-3-resistant carp, we have amplified and sequenced 11 candidate genes for viral disease resistance including TLR2, TLR3, TLR4ba, TLR7, TLR9, TLR21, TLR22, MyD88, TRAF6, type I IFN and IL-1beta. For each gene, we initially cloned and sequenced PCR amplicons from 8 to 12 fish (2-3 fish per strain) from the SNP discovery panel. We then identified and evaluated putative SNPs for their polymorphisms in the SNP discovery panel and validated their usefulness for linkage analysis in a full-sib family using the SNaPshot method. Our sequencing results and phylogenetic analyses suggested that TLR3, TLR7 and MyD88 genes are duplicated in the common carp genome. We, therefore, developed locus-specific PCR primers and SNP genotyping assays for the duplicated loci. A total of 48 SNP markers were developed from PCR fragments of the 13 loci (7 single-locus and 3 duplicated genes). Thirty-nine markers were polymorphic with estimated minor allele frequencies of more than 0.1. The utility of the SNP markers was evaluated in one full-sib family and revealed that 20 markers from 9 loci segregated in a disomic and Mendelian pattern and would be useful for linkage analysis. PMID:20420915

  14. 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.

  15. Mapping our genes: The genome projects: How big, how fast

    SciTech Connect

    none,

    1988-04-01

    For the past 2 years, scientific and technical journals in biology and medicine 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 of the public agenda. The debate involves science, technology, and politics. Congress is responsible for /open quotes/writing the rules/close quotes/ of what various federal agencies do and for funding their work. This report surveys the points made so far in the debate, focusing on those that most directly influence the policy options facing the US Congress. Congressional interest focused on how to assess the rationales for conducting human genome projects, how to fund human genome projects (at what level and through which mechanisms), how to coordinate the scientific and technical programs of the several federal agencies and private interests already supporting various genome projects, and how to strike a balance regarding the impact of genome projects on international scientific cooperation and international economic competition in biotechnology. OTA prepared this report with the assistance of several hundred experts throughout the world. 342 refs., 26 figs., 11 tabs.

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

    E-print Network

    Paria, Nandina

    2012-02-14

    The genetic component of mammalian male fertility is complex and involves thousands of genes. The majority of these genes are distributed on autosomes and the X chromosome, while a small number are located on the Y chromosome. Human and mouse...

  17. Gene discovery in the tropical scallop Nodipecten nodosus: construction and sequencing of a normalized cDNA library.

    PubMed

    Americo, Juliana Alves; Dondero, Francesco; Moraes, Milton Ozório; Allodi, Silvana; de Freitas Rebelo, Mauro

    2013-10-01

    We report the construction and characterization of a normalized cDNA library from the digestive gland of the marine bivalve Nodipecten nodosus, a commercially valuable tropical scallop. A total of 288 clones were sequenced, and 250 unique sequences were obtained. The cDNA library showed a small sequence redundancy (2.3%) and high numbers of recombinant (99.9%) and independent clones (2.0 × 10(6) cfu), indicating that the cDNA library generated in this study is a profitable resource for efficient gene discovery for N. nodosus. EST functional annotation by Gene Ontology term assignment revealed the identification of sequences potentially involved in aquaculture and ecotoxicology relevant processes such as apoptosis, growth, lipid metabolism, reproduction, development, response to stress and immunity. PMID:23669241

  18. Discovery and analysis of hepatocellular carcinoma genes using cDNA microarrays

    Microsoft Academic Search

    Yao Li; Yali Li; Rong Tang; Hong Xu; Minyan Qiu; Qin Chen; Juxiang Chen; Zhiren Fu; Kang Ying; Yi Xie; Yumin Mao

    2002-01-01

    Purpose. Microarray analysis on a genomic scale was used to profile changes in gene expression accompanying hepatocellular carcinoma. Methods. Gene expression profiles of liver tissues from twelve hepatocellular carcinoma samples relative to the gene expression profile of the normal liver tissue were analyzed using 4096 chips and 12800 chips. The results of microarray experiments were verified by the Northern blot

  19. Discovery and genetic mapping of single nucleotide polymorphisms in candidate genes for pathogen defence response in perennial ryegrass ( Lolium perenne L.)

    Microsoft Academic Search

    P. M. Dracatos; N. O. I. Cogan; M. P. Dobrowolski; T. I. Sawbridge; G. C. Spangenberg; K. F. Smith; J. W. Forster

    2008-01-01

    Susceptibility to foliar pathogens commonly causes significant reductions in productivity of the important temperate forage\\u000a perennial ryegrass. Breeding for durable disease resistance involves not only the deployment of major genes but also the additive\\u000a effects of minor genes. An approach based on in vitro single nucleotide polymorphism (SNP) discovery in candidate defence\\u000a response (DR) genes has been used to develop

  20. A Hybrid Computational Method for the Discovery of Novel Reproduction-Related Genes

    PubMed Central

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

    2015-01-01

    Uncovering the molecular mechanisms underlying reproduction is of great importance to infertility treatment and to the generation of healthy offspring. In this study, we discovered novel reproduction-related genes with a hybrid computational method, integrating three different types of method, which offered new clues for further reproduction research. This method was first executed on a weighted graph, constructed based on known protein-protein interactions, to search the shortest paths connecting any two known reproduction-related genes. Genes occurring in these paths were deemed to have a special relationship with reproduction. These newly discovered genes were filtered with a randomization test. Then, the remaining genes were further selected according to their associations with known reproduction-related genes measured by protein-protein interaction score and alignment score obtained by BLAST. The in-depth analysis of the high confidence novel reproduction genes revealed hidden mechanisms of reproduction and provided guidelines for further experimental validations. PMID:25768094

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

    E-print Network

    Alberto De Gregorio

    2005-06-06

    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.

  2. Discovery of core biotic stress responsive genes in Arabidopsis by weighted gene co-expression network analysis.

    PubMed

    Amrine, Katherine C H; Blanco-Ulate, Barbara; Cantu, Dario

    2015-01-01

    Intricate signal networks and transcriptional regulators translate the recognition of pathogens into defense responses. In this study, we carried out a gene co-expression analysis of all currently publicly available microarray data, which were generated in experiments that studied the interaction of the model plant Arabidopsis thaliana with microbial pathogens. This work was conducted to identify (i) modules of functionally related co-expressed genes that are differentially expressed in response to multiple biotic stresses, and (ii) hub genes that may function as core regulators of disease responses. Using Weighted Gene Co-expression Network Analysis (WGCNA) we constructed an undirected network leveraging a rich curated expression dataset comprising 272 microarrays that involved microbial infections of Arabidopsis plants with a wide array of fungal and bacterial pathogens with biotrophic, hemibiotrophic, and necrotrophic lifestyles. WGCNA produced a network with scale-free and small-world properties composed of 205 distinct clusters of co-expressed genes. Modules of functionally related co-expressed genes that are differentially regulated in response to multiple pathogens were identified by integrating differential gene expression testing with functional enrichment analyses of gene ontology terms, known disease associated genes, transcriptional regulators, and cis-regulatory elements. The significance of functional enrichments was validated by comparisons with randomly generated networks. Network topology was then analyzed to identify intra- and inter-modular gene hubs. Based on high connectivity, and centrality in meta-modules that are clearly enriched in defense responses, we propose a list of 66 target genes for reverse genetic experiments to further dissect the Arabidopsis immune system. Our results show that statistical-based data trimming prior to network analysis allows the integration of expression datasets generated by different groups, under different experimental conditions and biological systems, into a functionally meaningful co-expression network. PMID:25730421

  3. Discovery of Core Biotic Stress Responsive Genes in Arabidopsis by Weighted Gene Co-Expression Network Analysis

    PubMed Central

    Amrine, Katherine C. H.; Blanco-Ulate, Barbara; Cantu, Dario

    2015-01-01

    Intricate signal networks and transcriptional regulators translate the recognition of pathogens into defense responses. In this study, we carried out a gene co-expression analysis of all currently publicly available microarray data, which were generated in experiments that studied the interaction of the model plant Arabidopsis thaliana with microbial pathogens. This work was conducted to identify (i) modules of functionally related co-expressed genes that are differentially expressed in response to multiple biotic stresses, and (ii) hub genes that may function as core regulators of disease responses. Using Weighted Gene Co-expression Network Analysis (WGCNA) we constructed an undirected network leveraging a rich curated expression dataset comprising 272 microarrays that involved microbial infections of Arabidopsis plants with a wide array of fungal and bacterial pathogens with biotrophic, hemibiotrophic, and necrotrophic lifestyles. WGCNA produced a network with scale-free and small-world properties composed of 205 distinct clusters of co-expressed genes. Modules of functionally related co-expressed genes that are differentially regulated in response to multiple pathogens were identified by integrating differential gene expression testing with functional enrichment analyses of gene ontology terms, known disease associated genes, transcriptional regulators, and cis-regulatory elements. The significance of functional enrichments was validated by comparisons with randomly generated networks. Network topology was then analyzed to identify intra- and inter-modular gene hubs. Based on high connectivity, and centrality in meta-modules that are clearly enriched in defense responses, we propose a list of 66 target genes for reverse genetic experiments to further dissect the Arabidopsis immune system. Our results show that statistical-based data trimming prior to network analysis allows the integration of expression datasets generated by different groups, under different experimental conditions and biological systems, into a functionally meaningful co-expression network. PMID:25730421

  4. Discovery and analysis of pancreatic adenocarcinoma genes using cDNA microarrays

    PubMed Central

    Jin, Gang; Hu, Xian-Gui; Ying, Kang; Tang, Yan; Liu, Rui; Zhang, Yi-Jie; Jing, Zai-Ping; Xie, Yi; Mao, Yu-Min

    2005-01-01

    AIM: To study the pathogenetic processes and the role of gene expression by microarray analyses in expediting our understanding of the molecular pathophysiology of pancreatic adenocarcinoma, and to identify the novel cancer-associated genes. METHODS: Nine histologically defined pancreatic head adenocarcinoma specimens associated with clinical data were studied. Total RNA and mRNA were isolated and labeled by reverse transcription reaction with Cy5 and Cy3 for cDNA probe. The cDNA microarrays that represent a set of 4 096 human genes were hybridized with labeled cDNA probe and screened for molecular profiling analyses. RESULTS: Using this methodology, 184 genes were screened out for differences in gene expression level after nine couples of hybridizations. Of the 184 genes, 87 were upregulated and 97 downregulated, including 11 novel human genes. In pancreatic adenocarcinoma tissue, several invasion and metastasis related genes showed their high expression levels, suggesting that poor prognosis of pancreatic adenocarcinoma might have a solid molecular biological basis. CONCLUSION: The application of cDNA microarray technique for analysis of gene expression patterns is a powerful strategy to identify novel cancer-associated genes, and to rapidly explore their role in clinical pancreatic adenocarcinoma. Microarray profiles provide us new insights into the carcinogenesis and invasive process of pancreatic adenocarcinoma. Our results suggest that a highly organized and structured process of tumor invasion exists in the pancreas. PMID:16425432

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

    PubMed Central

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

    2012-01-01

    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

  6. Using the power of developmental biology for drug discovery

    Microsoft Academic Search

    Simon J Rhodes; Rosamund C Smith

    1998-01-01

    With the rapid advancement of the human genome project, the race is on to identify the relatively few useful target genes for drug discovery. The power of developmental biology in this effort has recently begun to be recognized. In addition to the use of model developmental organisms for functional studies, certain pluripotent cell populations and gene products that are present

  7. Discovery and saturation analysis of cancer genes across 21 tumor types

    PubMed Central

    Lawrence, Michael S.; Stojanov, Petar; Mermel, Craig H.; Garraway, Levi A.; Golub, Todd R.; Meyerson, Matthew; Gabriel, Stacey B.; Lander, Eric S.; Getz, Gad

    2014-01-01

    Summary While a few cancer genes are mutated in a high proportion of tumors of a given type (>20%), most are mutated at intermediate frequencies (2–20%). To explore the feasibility of creating a comprehensive catalog of cancer genes, we analyzed somatic point mutations in exome sequence from 4,742 tumor-normal pairs across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumor types. Our analysis also identified 33 genes not previously known to be significantly mutated, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes, mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600–5000 samples per tumor type, depending on background mutation rate. The results help guide the next stage of cancer genomics. PMID:24390350

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

    Microsoft Academic Search

    Aaron Klug

    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

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

    Microsoft Academic Search

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

    2010-01-01

    Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food\\u000a for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative\\u000a propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method\\u000a for the discovery and characterization of nucleotide

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

    PubMed Central

    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

    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

  11. 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.

  12. Shotgun proteomics aids discovery of novel protein-coding genes, alternative splicing, and “resurrected” pseudogenes in the mouse genome

    PubMed Central

    Brosch, Markus; Saunders, Gary I.; Frankish, Adam; Collins, Mark O.; Yu, Lu; Wright, James; Verstraten, Ruth; Adams, David J.; Harrow, Jennifer; Choudhary, Jyoti S.; Hubbard, Tim

    2011-01-01

    Recent advances in proteomic mass spectrometry (MS) offer the chance to marry high-throughput peptide sequencing to transcript models, allowing the validation, refinement, and identification of new protein-coding loci. We present a novel pipeline that integrates highly sensitive and statistically robust peptide spectrum matching with genome-wide protein-coding predictions to perform large-scale gene validation and discovery in the mouse genome for the first time. In searching an excess of 10 million spectra, we have been able to validate 32%, 17%, and 7% of all protein-coding genes, exons, and splice boundaries, respectively. Moreover, we present strong evidence for the identification of multiple alternatively spliced translations from 53 genes and have uncovered 10 entirely novel protein-coding genes, which are not covered in any mouse annotation data sources. One such novel protein-coding gene is a fusion protein that spans the Ins2 and Igf2 loci to produce a transcript encoding the insulin II and the insulin-like growth factor 2–derived peptides. We also report nine processed pseudogenes that have unique peptide hits, demonstrating, for the first time, that they are not just transcribed but are translated and are therefore resurrected into new coding loci. This work not only highlights an important utility for MS data in genome annotation but also provides unique insights into the gene structure and propagation in the mouse genome. All these data have been subsequently used to improve the publicly available mouse annotation available in both the Vega and Ensembl genome browsers (http://vega.sanger.ac.uk). PMID:21460061

  13. The AEROPATH project targeting Pseudomonas aeruginosa: crystallographic studies for assessment of potential targets in early-stage drug discovery

    PubMed Central

    Moynie, Lucille; Schnell, Robert; McMahon, Stephen A.; Sandalova, Tatyana; Boulkerou, Wassila Abdelli; Schmidberger, Jason W.; Alphey, Magnus; Cukier, Cyprian; Duthie, Fraser; Kopec, Jolanta; Liu, Huanting; Jacewicz, Agata; Hunter, William N.; Naismith, James H.; Schneider, Gunter

    2013-01-01

    Bacterial infections are increasingly difficult to treat owing to the spread of antibiotic resistance. A major concern is Gram-negative bacteria, for which the discovery of new antimicrobial drugs has been particularly scarce. In an effort to accelerate early steps in drug discovery, the EU-funded AEROPATH project aims to identify novel targets in the opportunistic pathogen Pseudomonas aeruginosa by applying a multidisciplinary approach encompassing target validation, structural characterization, assay development and hit identification from small-molecule libraries. Here, the strategies used for target selection are described and progress in protein production and structure analysis is reported. Of the 102 selected targets, 84 could be produced in soluble form and the de novo structures of 39 proteins have been determined. The crystal structures of eight of these targets, ranging from hypothetical unknown proteins to metabolic enzymes from different functional classes (PA1645, PA1648, PA2169, PA3770, PA4098, PA4485, PA4992 and PA5259), are reported here. The structural information is expected to provide a firm basis for the improvement of hit compounds identified from fragment-based and high-throughput screening campaigns. PMID:23295481

  14. Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.

    PubMed

    Kohannim, Omid; Hibar, Derrek P; Stein, Jason L; Jahanshad, Neda; Hua, Xue; Rajagopalan, Priya; Toga, Arthur W; Jack, Clifford R; Weiner, Michael W; de Zubicaray, Greig I; McMahon, Katie L; Hansell, Narelle K; Martin, Nicholas G; Wright, Margaret J; Thompson, Paul M

    2012-01-01

    We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8?±?2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain. PMID:22888310

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

    Microsoft Academic Search

    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

    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

  16. Assessment of discretization techniques for relevant pattern discovery from gene expression data

    E-print Network

    Boulicaut, Jean-François

    function, or module, within the cell. A set of co-regulated genes and the set of biological situations boolean matrices that encode gene properties. To take the most from these approaches, a needed step expression data. The impact of this preprocessing step on both the quantity and the relevancy

  17. 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...

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

    PubMed Central

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

    2014-01-01

    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

  19. Effector Genomics Accelerates Discovery and Functional Profiling of Potato Disease Resistance and Phytophthora Infestans Avirulence Genes

    Microsoft Academic Search

    Vivianne G. A. A. Vleeshouwers; Hendrik Rietman; Pavel Krenek; Nicolas Champouret; Carolyn Young; Sang-Keun Oh; Miqia Wang; Klaas Bouwmeester; Ben Vosman; Richard G. F. Visser; Evert Jacobsen; Francine Govers; Sophien Kamoun; Edwin A. G. van der Vossen; Hany A. El-Shemy

    2008-01-01

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted

  20. Effector genomics accelerates discovery and functional profiling of potato disease resistance and Phytophthora infestans avirulence genes

    Microsoft Academic Search

    Vivianne G. A. A. Vleeshouwers; Hendrik Rietman; Pavel Krenek; Nicolas Champouret; Carolyn Young; Sang-Keun Oh; Miqia Wang; Klaas Bouwmeester; Ben Vosman; Richard G. F. Visser; Evert Jacobsen; Francine Govers; Sophien Kamoun; Vossen van der E. A. G

    2008-01-01

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted

  1. 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...

  2. The Venus Transit 2004 (VT-2004) Programme: The Exceptional Impact of a Unique Public Science Discovery Project

    NASA Astrophysics Data System (ADS)

    Boffin, H.; West, R.

    2005-12-01

    We report on a major pan-European educational activity: the Venus Transit 2004 Public Science Discovery Programme. The key objectives were to use the 2004 Transit as a vehicle for disseminating knowledge about the Solar System, for raising awareness of exoplanet research, to enable the public to re-enact the historical measurement of the Sun-Earth distance, to raise public appreciation of the scientific method and to collectively obtain a basic scientific result based on geographically distributed observations. This very successful pilot project encompassed the development of an extensive set of teaching materials for schools, an effective web-based information and reporting system, observational activities as well as a video contest and a thorough post-event evaluation during a final meeting.

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

    PubMed Central

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

    2013-01-01

    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

  4. De novo assembly of Auricularia polytricha transcriptome using Illumina sequencing for gene discovery and SSR marker identification.

    PubMed

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

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  6. De Novo Assembly of the Common Bean Transcriptome Using Short Reads for the Discovery of Drought-Responsive Genes

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2001-01-01

    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

  8. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes.

    PubMed

    Pińero, Janet; Queralt-Rosinach, Núria; Bravo, Ŕlex; Deu-Pons, Jordi; Bauer-Mehren, Anna; Baron, Martin; Sanz, Ferran; Furlong, Laura I

    2015-01-01

    DisGeNET is a comprehensive discovery platform designed to address a variety of questions concerning the genetic underpinning of human diseases. DisGeNET contains over 380?000 associations between >16 000 genes and 13?000 diseases, which makes it one of the largest repositories currently available of its kind. DisGeNET integrates expert-curated databases with text-mined data, covers information on Mendelian and complex diseases, and includes data from animal disease models. It features a score based on the supporting evidence to prioritize gene-disease associations. It is an open access resource available through a web interface, a Cytoscape plugin and as a Semantic Web resource. The web interface supports user-friendly data exploration and navigation. DisGeNET data can also be analysed via the DisGeNET Cytoscape plugin, and enriched with the annotations of other plugins of this popular network analysis software suite. Finally, the information contained in DisGeNET can be expanded and complemented using Semantic Web technologies and linked to a variety of resources already present in the Linked Data cloud. Hence, DisGeNET offers one of the most comprehensive collections of human gene-disease associations and a valuable set of tools for investigating the molecular mechanisms underlying diseases of genetic origin, designed to fulfill the needs of different user profiles, including bioinformaticians, biologists and health-care practitioners. Database URL: http://www.disgenet.org/. PMID:25877637

  9. DisGeNET: a discovery platform for the dynamical exploration of human diseases and their genes

    PubMed Central

    Pińero, Janet; Queralt-Rosinach, Núria; Bravo, Ŕlex; Deu-Pons, Jordi; Bauer-Mehren, Anna; Baron, Martin; Sanz, Ferran; Furlong, Laura I.

    2015-01-01

    DisGeNET is a comprehensive discovery platform designed to address a variety of questions concerning the genetic underpinning of human diseases. DisGeNET contains over 380?000 associations between >16 000 genes and 13?000 diseases, which makes it one of the largest repositories currently available of its kind. DisGeNET integrates expert-curated databases with text-mined data, covers information on Mendelian and complex diseases, and includes data from animal disease models. It features a score based on the supporting evidence to prioritize gene-disease associations. It is an open access resource available through a web interface, a Cytoscape plugin and as a Semantic Web resource. The web interface supports user-friendly data exploration and navigation. DisGeNET data can also be analysed via the DisGeNET Cytoscape plugin, and enriched with the annotations of other plugins of this popular network analysis software suite. Finally, the information contained in DisGeNET can be expanded and complemented using Semantic Web technologies and linked to a variety of resources already present in the Linked Data cloud. Hence, DisGeNET offers one of the most comprehensive collections of human gene-disease associations and a valuable set of tools for investigating the molecular mechanisms underlying diseases of genetic origin, designed to fulfill the needs of different user profiles, including bioinformaticians, biologists and health-care practitioners. Database URL: http://www.disgenet.org/ PMID:25877637

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

    SciTech Connect

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

    2014-01-15

    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.

  11. Discovery and validation of gene classifiers for endocrine-disrupting chemicals in zebrafish (Danio rerio)

    EPA Science Inventory

    Development and application of transcriptomics-based gene classifiers for ecotoxicological applications lag far behind those of human biomedical science. Many such classifiers discovered thus far lack vigorous statistical and experimental validations, with their stability and rel...

  12. Discovery and saturation analysis of cancer genes across 21 tumour types

    E-print Network

    Lawrence, Michael S.

    Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2–20%). To explore the feasibility of creating a comprehensive catalogue of ...

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

    PubMed

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

    2012-01-01

    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

  14. 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.

  15. Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis

    PubMed Central

    Ponsuksili, Siriluck; Murani, Eduard; Trakooljul, Nares; Schwerin, Manfred; Wimmers, Klaus

    2014-01-01

    Biochemical and biophysical processes that take place in muscle under relaxed and stressed conditions depend on the abundance and activity of gene products of metabolic and structural pathways. In livestock at post-mortem, these muscle properties determine aspects of meat quality and are measurable. The conversion of muscle to meat mimics pathological processes associated with muscle ischemia, injury or damage in humans and it is an economic factor in pork production. Linkage, association, and expression analyses independently contributed to the identification of trait-associated molecular pathways and genes. We aim at providing multiple evidences for the role of specific genes in meat quality by integrating a genome-wide association study (GWAS) for meat quality traits and the detection of eQTL based on trait-correlated expressed genes and trait-associated markers. The GWAS revealed 51 and 200 SNPs significantly associated with meat quality in a crossbred Pietrain×(German Landrace×Large White) (Pi×(GL×LW)) and a purebred German Landrace (GL) population, respectively. Most significant SNPs in Pi×(GL×LW) were located on chromosomes (SSC) 4 and 6. The data of 47,836 eQTLs at a significance level of p<10-5 were used to scale down the number candidate genes located in these regions. These SNPs on SSC4 showed association with expression levels of ZNF704, IMPA1, and OXSR1; SSC6 SNPs were associated with expression of SIGLEC10 and PIH1D1. Most significant SNPs in GL were located on SSC6 and associated with expression levels of PIH1D1, SIGLEC10, TBCB, LOC100518735, KIF1B, LOC100514845, and two unknown genes. The abundance of transcripts of these genes in muscle, in turn, is significantly correlated with meat quality traits. We identified several genes with evidence for their candidacy for meat quality arising from the integrative approach of a genome-wide association study and eQTL analysis. PMID:24643240

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

    PubMed Central

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

    2013-01-01

    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

  17. Discovery and characterization of two novel salt-tolerance genes in Puccinellia tenuiflora.

    PubMed

    Li, Ying; Takano, Tetsuo; Liu, Shenkui

    2014-01-01

    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

  18. BIOINFORMATIC RESOURCES FOR SNP AND INDEL DISCOVERY IN THE MAIZE MAPPING PROJECT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of our single nucleotide polymorphism (SNP) project is to anchor maize unigenes to the intermated B73 x Mo17 (IBM) genetic map. Starting with maize unigene sequences, primers were designed with Primer3 to give a polymerase chain reactor (PCR) products of ~300 bases. The PCR products ...

  19. Project Quest: A Journey of Discovery with Beginning Teachers in Urban Schools

    ERIC Educational Resources Information Center

    Alkins, Kimberley; Banks-Santilli, Linda; Elliott, Paula; Guttenberg, Nicole; Kamii, Mieko

    2006-01-01

    Seven higher education institutions in Massachusetts collaborated to develop and implement Project QUEST (Quality Urban Education and Support for Teachers), a support program for beginning urban teachers. Motivated by both the need to retain beginning teachers beyond the first few years of teaching and the desire to increase urban school…

  20. Project ARCHIMEDES: Applications, Reasoning and Concepts for High School Instructors: Making Educational Discoveries and Expanding Skills.

    ERIC Educational Resources Information Center

    Lea, Suzanne M.

    Project ARCHIMEDES was designed in cooperation with local teachers to enhance concept understanding of teachers of physics and physical sciences, to increase use of electronics and computers in the classroom, and to introduce research on students' misconceptions in physics, teaching methods for identifying and remediating misconceptions, and ways…

  1. The human genome project and the discovery of genetic determinants of cancer susceptibility

    Microsoft Academic Search

    R. Taramelli; F. Acquati

    2004-01-01

    The Human Genome Project has recently provided a great deal of information on the sequence that comprises the human genome. We are now in the process of structuring and deciphering the 3×109 base sequence in order to gain insights into its functional role. Several efforts are focusing on the search for DNA sequence variations underlying common\\/complex diseases that constitute a

  2. Integrating microRNA target predictions for the discovery of gene regulatory networks: a semi-supervised ensemble learning approach

    PubMed Central

    2014-01-01

    Background MicroRNAs (miRNAs) are small non-coding RNAs which play a key role in the post-transcriptional regulation of many genes. Elucidating miRNA-regulated gene networks is crucial for the understanding of mechanisms and functions of miRNAs in many biological processes, such as cell proliferation, development, differentiation and cell homeostasis, as well as in many types of human tumors. To this aim, we have recently presented the biclustering method HOCCLUS2, for the discovery of miRNA regulatory networks. Experiments on predicted interactions revealed that the statistical and biological consistency of the obtained networks is negatively affected by the poor reliability of the output of miRNA target prediction algorithms. Recently, some learning approaches have been proposed to learn to combine the outputs of distinct prediction algorithms and improve their accuracy. However, the application of classical supervised learning algorithms presents two challenges: i) the presence of only positive examples in datasets of experimentally verified interactions and ii) unbalanced number of labeled and unlabeled examples. Results We present a learning algorithm that learns to combine the score returned by several prediction algorithms, by exploiting information conveyed by (only positively labeled/) validated and unlabeled examples of interactions. To face the two related challenges, we resort to a semi-supervised ensemble learning setting. Results obtained using miRTarBase as the set of labeled (positive) interactions and mirDIP as the set of unlabeled interactions show a significant improvement, over competitive approaches, in the quality of the predictions. This solution also improves the effectiveness of HOCCLUS2 in discovering biologically realistic miRNA:mRNA regulatory networks from large-scale prediction data. Using the miR-17-92 gene cluster family as a reference system and comparing results with previous experiments, we find a large increase in the number of significantly enriched biclusters in pathways, consistent with miR-17-92 functions. Conclusion The proposed approach proves to be fundamental for the computational discovery of miRNA regulatory networks from large-scale predictions. This paves the way to the systematic application of HOCCLUS2 for a comprehensive reconstruction of all the possible multiple interactions established by miRNAs in regulating the expression of gene networks, which would be otherwise impossible to reconstruct by considering only experimentally validated interactions. PMID:24564296

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

    PubMed Central

    Johnston, Ian A.

    2010-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25566351

  5. The Extragalactic Distance Scale Key Project VIII. The Discovery of Cepheids and a New Distance to NGC 3621 Using the Hubble Space Telescope

    NASA Technical Reports Server (NTRS)

    Rawson, D. M.; Mould, J. R.; Macri, L. M.; Huchra, J. P.; Kennicutt, R. C.; Harding, P.; Freedman, W. L.; Hill, R. J.; Phelps, R. L.; Madore, B. F.; Silbermann, N. A.; Graham, J. A.; Ferrarese, L.; Ford, H. C.; Illingworth, G. D.; Hoessel, J. G.; Han, M.; Hughes, S. M.; Saha, A.; Stetson, P. B.

    1996-01-01

    We report on the discovery of Cepheids in the field spiral galaxy NGC3621, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope (HST). NGC 3621 is one of 18 galaxies observed as part of the HST Key Project on the Extragalctic Distance Scale, which aims to measure the Hubble Constant to 10 percent accuracy.

  6. Discovery of Inhibitors of Aberrant Gene Transcription from Libraries of DNA Binding Molecules: Inhibition of LEF-1 Mediated Gene Transcription and Oncogenic Transformation

    PubMed Central

    Stover, James S.; Shi, Jin; Jin, Wei; Vogt, Peter K.; Boger, Dale L.

    2009-01-01

    The screening of a >9000 compound library of synthetic DNA binding molecules for selective binding to the consensus sequence of the transcription factor LEF-1 followed by assessment of the candidate compounds in a series of assays that characterized functional activity (disruption of DNA–LEF-1 binding) at the intended target and site (inhibition of intracellular LEF-1 mediated gene transcription) resulting in a desired phenotypic cellular change (inhibit LEF-1 driven cell transformation) provided two lead compounds: lefmycin-1 and lefmycin-2. The sequence of screens defining the approach assures that activity in the final functional assay may be directly related to the inhibition of gene transcription and DNA binding properties of the identified molecules. Central to the implementation of this generalized approach to the discovery of DNA binding small molecule inhibitors of gene transcription was: (1) the use of a technically non-demanding fluorescent intercalator displacement (FID) assay for initial assessment of the DNA binding affinity and selectivity of a library of compounds for any sequence of interest, and (2) the technology used to prepare a sufficiently large library of DNA binding compounds. PMID:19216569

  7. Discovery of Phytophthora infestans Genes Expressed in Planta through Mining of cDNA Libraries

    PubMed Central

    Chaves, Diego; Pinzón, Andrés; Grajales, Alejandro; Rojas, Alejandro; Mutis, Gabriel; Cárdenas, Martha; Burbano, Daniel; Jiménez, Pedro; Bernal, Adriana; Restrepo, Silvia

    2010-01-01

    Background Phytophthora infestans (Mont.) de Bary causes late blight of potato and tomato, and has a broad host range within the Solanaceae family. Most studies of the Phytophthora – Solanum pathosystem have focused on gene expression in the host and have not analyzed pathogen gene expression in planta. Methodology/Principal Findings We describe in detail an in silico approach to mine ESTs from inoculated host plants deposited in a database in order to identify particular pathogen sequences associated with disease. We identified candidate effector genes through mining of 22,795 ESTs corresponding to P. infestans cDNA libraries in compatible and incompatible interactions with hosts from the Solanaceae family. Conclusions/Significance We annotated genes of P. infestans expressed in planta associated with late blight using different approaches and assigned putative functions to 373 out of the 501 sequences found in the P. infestans genome draft, including putative secreted proteins, domains associated with pathogenicity and poorly characterized proteins ideal for further experimental studies. Our study provides a methodology for analyzing cDNA libraries and provides an understanding of the plant – oomycete pathosystems that is independent of the host, condition, or type of sample by identifying genes of the pathogen expressed in planta. PMID:20352100

  8. A comprehensive resource of drought- and salinity- responsive ESTs for gene discovery and marker development in chickpea (Cicer arietinum L.)

    PubMed Central

    2009-01-01

    Background Chickpea (Cicer arietinum L.), an important grain legume crop of the world is seriously challenged by terminal drought and salinity stresses. However, very limited number of molecular markers and candidate genes are available for undertaking molecular breeding in chickpea to tackle these stresses. This study reports generation and analysis of comprehensive resource of drought- and salinity-responsive expressed sequence tags (ESTs) and gene-based markers. Results A total of 20,162 (18,435 high quality) drought- and salinity- responsive ESTs were generated from ten different root tissue cDNA libraries of chickpea. Sequence editing, clustering and assembly analysis resulted in 6,404 unigenes (1,590 contigs and 4,814 singletons). Functional annotation of unigenes based on BLASTX analysis showed that 46.3% (2,965) had significant similarity (?1E-05) to sequences in the non-redundant UniProt database. BLASTN analysis of unique sequences with ESTs of four legume species (Medicago, Lotus, soybean and groundnut) and three model plant species (rice, Arabidopsis and poplar) provided insights on conserved genes across legumes as well as novel transcripts for chickpea. Of 2,965 (46.3%) significant unigenes, only 2,071 (32.3%) unigenes could be functionally categorised according to Gene Ontology (GO) descriptions. A total of 2,029 sequences containing 3,728 simple sequence repeats (SSRs) were identified and 177 new EST-SSR markers were developed. Experimental validation of a set of 77 SSR markers on 24 genotypes revealed 230 alleles with an average of 4.6 alleles per marker and average polymorphism information content (PIC) value of 0.43. Besides SSR markers, 21,405 high confidence single nucleotide polymorphisms (SNPs) in 742 contigs (with ? 5 ESTs) were also identified. Recognition sites for restriction enzymes were identified for 7,884 SNPs in 240 contigs. Hierarchical clustering of 105 selected contigs provided clues about stress- responsive candidate genes and their expression profile showed predominance in specific stress-challenged libraries. Conclusion Generated set of chickpea ESTs serves as a resource of high quality transcripts for gene discovery and development of functional markers associated with abiotic stress tolerance that will be helpful to facilitate chickpea breeding. Mapping of gene-based markers in chickpea will also add more anchoring points to align genomes of chickpea and other legume species. PMID:19912666

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

    PubMed

    Finlay, William J J; Almagro, Juan C

    2012-01-01

    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

  10. Plant gravitropic signal transduction: A network analysis leads to gene discovery

    NASA Astrophysics Data System (ADS)

    Wyatt, Sarah

    Gravity plays a fundamental role in plant growth and development. Although a significant body of research has helped define the events of gravity perception, the role of the plant growth regulator auxin, and the mechanisms resulting in the gravity response, the events of signal transduction, those that link the biophysical action of perception to a biochemical signal that results in auxin redistribution, those that regulate the gravitropic effects on plant growth, remain, for the most part, a “black box.” Using a cold affect, dubbed the gravity persistent signal (GPS) response, we developed a mutant screen to specifically identify components of the signal transduction pathway. Cloning of the GPS genes have identified new proteins involved in gravitropic signaling. We have further exploited the GPS response using a multi-faceted approach including gene expression microarrays, proteomics analysis, and bioinformatics analysis and continued mutant analysis to identified additional genes, physiological and biochemical processes. Gene expression data provided the foundation of a regulatory network for gravitropic signaling. Based on these gene expression data and related data sets/information from the literature/repositories, we constructed a gravitropic signaling network for Arabidopsis inflorescence stems. To generate the network, both a dynamic Bayesian network approach and a time-lagged correlation coefficient approach were used. The dynamic Bayesian network added existing information of protein-protein interaction while the time-lagged correlation coefficient allowed incorporation of temporal regulation and thus could incorporate the time-course metric from the data set. Thus the methods complemented each other and provided us with a more comprehensive evaluation of connections. Each method generated a list of possible interactions associated with a statistical significance value. The two networks were then overlaid to generate a more rigorous, intersected network with shared genes and interactions. This network is flexible and can be updated with new data from the original research. The network allows identification of hubs/additional components and processes that are involved in gravitropic signal transduction to provide further hypotheses for testing. In essence, genes identified through experimental methods can be located and interactions that might connect them identified. Genes along these connections can then tested, much like stopping at towns along a driving route from one city to another.

  11. Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome

    Microsoft Academic Search

    Neda Jahanshad; Derrek P. Hibar; April Ryles; Arthur W. Toga; Katie L. McMahon; Greig I. de Zubicaray; Narelle K. Hansell; Grant W. Montgomery; Nicholas G. Martin; Margaret J. Wright; Paul M. Thompson

    2012-01-01

    Human brain connectivity is disrupted in a wide range of disorders — from Alzheimer's disease to autism — but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high

  12. Discovery and functional assessment of gene variants in the vascular endothelial growth factor pathway

    PubMed Central

    Paré-Brunet, Laia; Glubb, Dylan; Evans, Patrick; Berenguer-Llergo, Antoni; Etheridge, Amy S.; Skol, Andrew D.; Di Rienzo, Anna; Duan, Shiwei; Gamazon, Eric R.; Innocenti, Federico

    2014-01-01

    Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and YRI HapMap lymphoblastoid cell lines (LCLs) in 23 resequenced genes. Among 356 cis-eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis-eQTLs provided mechanistic evidence for two GWAS findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6, could predict 44, 37 and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role. PMID:24186849

  13. A Soybean Transcript Map: Discovery and Mapping of Single Nucleotide Polymorphisms in Soybean Genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) were discovered via the re-sequencing of sequence tagged sites (STS) developed from EST sequence. From an initial set of 9,459 primers sets designed to a diverse set of genes, 4,240 STS were amplified and sequenced in each of six diverse soybean genotypes. In...

  14. ESTs as a source for sequence polymorphism discovery in sugarcane: example of the Adh genes

    Microsoft Academic Search

    L. Grivet; J.-C. Glaszmann; M. Vincentz; F. da Silva; P. Arruda

    2003-01-01

    Expressed sequence tags (ESTs) have proven to be a valuable tool to discover single nucleotide polymorphism (SNP) in human genes but their use for this purpose is still limited in higher plants. Using a database of approximately 250,000 sugarcane ESTs we have recovered 219 sequences encoding alcohol dehydrogenases (Adh), which tagged 178 distinct cDNAs from 27 libraries, constructed from at

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

    PubMed

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

    2015-01-01

    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

  16. Discovery of two potential DAZL gene markers for sperm quality in boars by population association studies.

    PubMed

    Ma, Changping; Li, Jialian; Tao, Hu; Lei, Bin; Li, Yan; Tong, Keya; Zhang, Xuying; Guan, Kaifeng; Shi, Yufeng; Li, Fenge

    2013-12-01

    The Deleted in AZoospermia Like (DAZL) gene is a member of the DAZ (deleted in azoospermia) gene family which are critical for successful germ cell development in diverse animals. In previous research, we discovered two SNPs (DAZL c.570+385 A>G, DAZL c.735+150 C>A) associated with litter size traits in sows. Here we selected DAZL gene as a candidate gene for boar sperm quality traits based on its function on the formation of germ cells during spermatogenesis, and then analyzed the associations of the two SNPs with sperm quality traits in Duroc (n=185), Large White (n=87) and Landrace (n=49) pig populations. The results showed DAZL c.570+385 AG boars had significantly higher motility (MOT) than GG boars (P<0.05) in Large White and Landrace pigs; Duroc DAZL c.735+150 CA boars had significantly lower MOT and lower sperm concentration (SCON) than CC and AA boars (P<0.05), respectively; Large White DAZL c.735+150 CC boars produced lower abnormal sperm rate (ASR) than CA and AA boars (P<0.05), with favorable allelic C substitution effect -0.94% (P<0.05). Our research indicated that DAZL c.570+385 A>G and DAZL c.735+150 C>A locus were the potential molecular markers for improving the sperm quality traits in pigs. PMID:24183113

  17. Transcriptome Analysis of Catharanthus roseus for Gene Discovery and Expression Profiling

    PubMed Central

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

    2014-01-01

    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

  18. Human Transporter Database: Comprehensive Knowledge and Discovery Tools in the Human Transporter Genes

    PubMed Central

    Ye, Adam Y.; Liu, Qing-Rong; Li, Chuan-Yun; Zhao, Min; Qu, Hong

    2014-01-01

    Transporters are essential in homeostatic exchange of endogenous and exogenous substances at the systematic, organic, cellular, and subcellular levels. Gene mutations of transporters are often related to pharmacogenetics traits. Recent developments in high throughput technologies on genomics, transcriptomics and proteomics allow in depth studies of transporter genes in normal cellular processes and diverse disease conditions. The flood of high throughput data have resulted in urgent need for an updated knowledgebase with curated, organized, and annotated human transporters in an easily accessible way. Using a pipeline with the combination of automated keywords query, sequence similarity search and manual curation on transporters, we collected 1,555 human non-redundant transporter genes to develop the Human Transporter Database (HTD) (http://htd.cbi.pku.edu.cn). Based on the extensive annotations, global properties of the transporter genes were illustrated, such as expression patterns and polymorphisms in relationships with their ligands. We noted that the human transporters were enriched in many fundamental biological processes such as oxidative phosphorylation and cardiac muscle contraction, and significantly associated with Mendelian and complex diseases such as epilepsy and sudden infant death syndrome. Overall, HTD provides a well-organized interface to facilitate research communities to search detailed molecular and genetic information of transporters for development of personalized medicine. PMID:24558441

  19. 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.

  20. 108 PostErs EMBnet.journal 18.B Biomedical Text Mining for Disease Gene Discovery

    E-print Network

    as an input from the user (e.g., sleep disorders). Then, we use the E-utilities from PubMed to retrieve and tool to discover genes implicated in any given disease or disorder. In fact, our tool takes from

  1. USING NATURAL VARIATION FOR GENE DISCOVERY TO IMPROVE SEED IRON NUTRITIONAL VALUE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We and others are interested in developing crops biofortified with iron to improve their nutritional value for human consumption. One of the crucial tasks, therefore, is to identify relevant genes that can be targeted for transgenic or conventional breeding approaches to improve the Fe concentratio...

  2. Human transporter database: comprehensive knowledge and discovery tools in the human transporter genes.

    PubMed

    Ye, Adam Y; Liu, Qing-Rong; Li, Chuan-Yun; Zhao, Min; Qu, Hong

    2014-01-01

    Transporters are essential in homeostatic exchange of endogenous and exogenous substances at the systematic, organic, cellular, and subcellular levels. Gene mutations of transporters are often related to pharmacogenetics traits. Recent developments in high throughput technologies on genomics, transcriptomics and proteomics allow in depth studies of transporter genes in normal cellular processes and diverse disease conditions. The flood of high throughput data have resulted in urgent need for an updated knowledgebase with curated, organized, and annotated human transporters in an easily accessible way. Using a pipeline with the combination of automated keywords query, sequence similarity search and manual curation on transporters, we collected 1,555 human non-redundant transporter genes to develop the Human Transporter Database (HTD) (http://htd.cbi.pku.edu.cn). Based on the extensive annotations, global properties of the transporter genes were illustrated, such as expression patterns and polymorphisms in relationships with their ligands. We noted that the human transporters were enriched in many fundamental biological processes such as oxidative phosphorylation and cardiac muscle contraction, and significantly associated with Mendelian and complex diseases such as epilepsy and sudden infant death syndrome. Overall, HTD provides a well-organized interface to facilitate research communities to search detailed molecular and genetic information of transporters for development of personalized medicine. PMID:24558441

  3. The MY NASA DATA Project: Tools and a Collaboration Space for Knowledge Discovery

    NASA Astrophysics Data System (ADS)

    Chambers, L. H.; Alston, E. J.; Diones, D. D.; Moore, S. W.; Oots, P. C.; Phelps, C. S.

    2006-05-01

    The Atmospheric Science Data Center (ASDC) at NASA Langley Research Center is charged with serving a wide user community that is interested in its large data holdings in the areas of Aerosols, Clouds, Radiation Budget, and Tropospheric Chemistry. Most of the data holdings, however, are in large files with specialized data formats. The MY NASA DATA (mynasadata.larc.nasa.gov) project began in 2004, as part of the NASA Research, Education, and Applications Solutions Network (REASoN), in order to open this important resource to a broader community including K-12 education and citizen scientists. MY NASA DATA (short for Mentoring and inquirY using NASA Data on Atmospheric and earth science for Teachers and Amateurs) consists of a web space that collects tools, lesson plans, and specially developed documentation to help the target audience more easily use the vast collection of NASA data about the Earth System. The core piece of the MY NASA DATA project is the creation of microsets (both static and custom) that make data easily accessible. The installation of a Live Access Server (LAS) greatly enhanced the ability for teachers, students, and citizen scientists to create and explore custom microsets of Earth System Science data. The LAS, which is an open source software tool using emerging data standards, also allows the MY NASA DATA team to make available data on other aspects of the Earth System from collaborating data centers. We are currently working with the Physical Oceanography DAAC at the Jet Propulsion Laboratory to bring in several parameters describing the ocean. In addition, MY NASA DATA serves as a central space for the K-12 community to share resources. The site already includes a dozen User-contributed lesson plans. This year we will be focusing on the Citizen Science portion of the site, and will be welcoming user-contributed project ideas, as well as reports of completed projects. An e-mentor network has also been created to involve a wider community in answering questions on scientific and pedagogical aspects of data use. The MY NASA DATA website, and an initial collection of lesson plans, have passed the NASA Earth Science Education peer review process, and thus are also being cataloged in the Digital Library for Earth System Education (DLESE).

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

    PubMed Central

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

    2011-01-01

    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

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

    PubMed Central

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

    2009-01-01

    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 GS-FLX produced more than 47,000 sequencing reads. These reads represented 20,741 unique sequences that passed quality control (mean length = 186 bp). These were assembled into 1,831 contigs (mean contig depth = 4.1 sequences). Over 4,000 sequencing reads (~19%) were assigned gene ontologies, mostly to protein, RNA, and ion binding. A total of 877 candidate SNPs were identified from > 50 different genes. We employed an analytical approach from theoretical ecology (rarefaction) to evaluate depth of sequencing coverage relative to gene discovery. We also considered the relative merits of normalized versus native cDNA libraries when using next-generation sequencing platforms. Not surprisingly, fewer genes from the normalized libraries were rRNA subunits. Rarefaction suggests that normalization has little influence on the efficiency of gene discovery, at least when working with thousands of reads from a single tissue type. Conclusion Our data indicate that titration runs on 454 sequencers can characterize thousands of expressed sequence tags which can be used to identify SNPs, gene ontologies, and levels of gene expression in species of conservation concern. We anticipate that rarefaction will be useful in evaluations of gene discovery and that next-generation sequencing technologies hold great potential for the study of other non-model organisms. PMID:19402907

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

    PubMed Central

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

    2013-01-01

    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

  7. Gene Discovery through Transcriptome Sequencing for the Invasive Mussel Limnoperna fortunei

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

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

    2011-01-01

    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

  9. The CLN3 Gene is a Novel Molecular Target for Cancer Drug Discovery1

    Microsoft Academic Search

    Svetlana N. Rylova; Andrea Amalfitano; Dixie-Ann Persaud-Sawin; Wei-Xing Guo; Jerry Chang; Paul J. Jansen; Alan D. Proia; Rose-Mary Boustany

    2002-01-01

    Juvenile Batten disease is a neurodegenerative disease caused by accel- erated apoptotic death of photoreceptors and neurons attributable to defects in the CLN3 gene. CLN3 is antiapoptotic when overexpressed in NT2 neuronal precursor cells. CLN3 negatively modulates endogenous ceramide levels in NT2 cells and acts upstream of ceramide generation. Because defects in regulation of apoptosis are involved in the development

  10. SAM Thresholding and False Discovery Rates for Detecting Differential Gene Expression in DNA Microarrays

    Microsoft Academic Search

    John D. Storey; Robert Tibshirani

    SAM is a computer package for correlating gene expression with an outcome parameter such as treatment, survival time, or diagnostic class. It thresholds an appropriate test statistic and reports the q-value of each test based on a set of sample permutations. SAM works as a Microsoft Excel add-in and has additional features for fold-change thresholding and block permutations. Here, we

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

    PubMed Central

    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

    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

  12. Gene discovery and transcript analyses in the corn smut pathogen Ustilago maydis: expressed sequence tag and genome sequence comparison

    PubMed Central

    Ho, Eric CH; Cahill, Matt J; Saville, Barry J

    2007-01-01

    Background Ustilago maydis is the basidiomycete fungus responsible for common smut of corn and is a model organism for the study of fungal phytopathogenesis. To aid in the annotation of the genome sequence of this organism, several expressed sequence tag (EST) libraries were generated from a variety of U. maydis cell types. In addition to utility in the context of gene identification and structure annotation, the ESTs were analyzed to identify differentially abundant transcripts and to detect evidence of alternative splicing and anti-sense transcription. Results Four cDNA libraries were constructed using RNA isolated from U. maydis diploid teliospores (U. maydis strains 518 × 521) and haploid cells of strain 521 grown under nutrient rich, carbon starved, and nitrogen starved conditions. Using the genome sequence as a scaffold, the 15,901 ESTs were assembled into 6,101 contiguous expressed sequences (contigs); among these, 5,482 corresponded to predicted genes in the MUMDB (MIPS Ustilago maydis database), while 619 aligned to regions of the genome not yet designated as genes in MUMDB. A comparison of EST abundance identified numerous genes that may be regulated in a cell type or starvation-specific manner. The transcriptional response to nitrogen starvation was assessed using RT-qPCR. The results of this suggest that there may be cross-talk between the nitrogen and carbon signalling pathways in U. maydis. Bioinformatic analysis identified numerous examples of alternative splicing and anti-sense transcription. While intron retention was the predominant form of alternative splicing in U. maydis, other varieties were also evident (e.g. exon skipping). Selected instances of both alternative splicing and anti-sense transcription were independently confirmed using RT-PCR. Conclusion Through this work: 1) substantial sequence information has been provided for U. maydis genome annotation; 2) new genes were identified through the discovery of 619 contigs that had previously escaped annotation; 3) evidence is provided that suggests the regulation of nitrogen metabolism in U. maydis differs from that of other model fungi, and 4) Alternative splicing and anti-sense transcription were identified in U. maydis and, amid similar observations in other basidiomycetes, this suggests these phenomena may be widespread in this group of fungi. These advances emphasize the importance of EST analysis in genome annotation. PMID:17892571

  13. Human Genome Project discoveries: Dialectics and rhetoric in the science of genetics

    NASA Astrophysics Data System (ADS)

    Robidoux, Charlotte A.

    The Human Genome Project (HGP), a $437 million effort that began in 1990 to chart the chemical sequence of our three billion base pairs of DNA, was completed in 2003, marking the 50th anniversary that proved the definitive structure of the molecule. This study considered how dialectical and rhetorical arguments functioned in the science, political, and public forums over a 20-year period, from 1980 to 2000, to advance human genome research and to establish the official project. I argue that Aristotle's continuum of knowledge--which ranges from the probable on one end to certified or demonstrated knowledge on the other--provides useful distinctions for analyzing scientific reasoning. While contemporary scientific research seeks to discover certified knowledge, investigators generally employ the hypothetico-deductive or scientific method, which often yields probable rather than certain findings, making these dialectical in nature. Analysis of the discourse describing human genome research revealed the use of numerous rhetorical figures and topics. Persuasive and probable reasoning were necessary for scientists to characterize unknown genetic phenomena, to secure interest in and funding for large-scale human genome research, to solve scientific problems, to issue probable findings, to convince colleagues and government officials that the findings were sound and to disseminate information to the public. Both government and private venture scientists drew on these tools of reasoning to promote their methods of mapping and sequencing the genome. The debate over how to carry out sequencing was rooted in conflicting values. Scientists representing the academic tradition valued a more conservative method that would establish high quality results, and those supporting private industry valued an unconventional approach that would yield products and profits more quickly. Values in turn influenced political and public forum arguments. Agency representatives and investors sided with the approach that reflected values they supported. Fascinated with this controversy and the convincing comparisons, the media often endorsed Celera's work for its efficiency. The analysis of discourse from the science, political, and public forums revealed that value systems influenced the accuracy and quality of the arguments more than the type or number of figures used to describe the research to various audiences.

  14. Transcriptome analysis of head kidney in grass carp and discovery of immune-related genes

    PubMed Central

    2012-01-01

    Background Grass carp (Ctenopharyngodon idella) is one of the most economically important freshwater fish, but its production is often affected by diseases that cause serious economic losses. To date, no good breeding varieties have been obtained using the oriented cultivation technique. The ability to identify disease resistance genes in grass carp is important to cultivate disease-resistant varieties of grass carp. Results In this study, we constructed a non-normalized cDNA library of head kidney in grass carp, and, after clustering and assembly, we obtained 3,027 high-quality unigenes. Solexa sequencing was used to generate sequence tags from the transcriptomes of the head kidney in grass carp before and after grass carp reovirus (GCRV) infection. After processing, we obtained 22,144 tags that were differentially expressed by more than 2-fold between the uninfected and infected groups. 679 of the differentially expressed tags (3.1%) mapped to 483 of the unigenes (16.0%). The up-regulated and down-regulated unigenes were annotated using gene ontology terms; 16 were annotated as immune-related and 42 were of unknown function having no matches to any of the sequences in the databases that were used in the similarity searches. Semi-quantitative RT-PCR revealed four unknown unigenes that showed significant responses to the viral infection. Based on domain structure predictions, one of these sequences was found to encode a protein that contained two transmembrane domains and, therefore, may be a transmembrane protein. Here, we proposed that this novel unigene may encode a virus receptor or a protein that mediates the immune signalling pathway at the cell surface. Conclusion This study enriches the molecular basis data of grass carp and further confirms that, based on fish tissue-specific EST databases, transcriptome analysis is an effective route to discover novel functional genes. PMID:22776770

  15. Functional Analysis and Discovery of Microbial Genes Transforming Metallic and Organic Pollutants: Database and Experimental Tools

    SciTech Connect

    Lawrence P. Wackett; Lynda B.M. Ellis

    2004-12-09

    Microbial functional genomics is faced with a burgeoning list of genes which are denoted as unknown or hypothetical for lack of any knowledge about their function. The majority of microbial genes encode enzymes. Enzymes are the catalysts of metabolism; catabolism, anabolism, stress responses, and many other cell functions. A major problem facing microbial functional genomics is proposed here to derive from the breadth of microbial metabolism, much of which remains undiscovered. The breadth of microbial metabolism has been surveyed by the PIs and represented according to reaction types on the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD): http://umbbd.ahc.umn.edu/search/FuncGrps.html The database depicts metabolism of 49 chemical functional groups, representing most of current knowledge. Twice that number of chemical groups are proposed here to be metabolized by microbes. Thus, at least 50% of the unique biochemical reactions catalyzed by microbes remain undiscovered. This further suggests that many unknown and hypothetical genes encode functions yet undiscovered. This gap will be partly filled by the current proposal. The UM-BBD will be greatly expanded as a resource for microbial functional genomics. Computational methods will be developed to predict microbial metabolism which is not yet discovered. Moreover, a concentrated effort to discover new microbial metabolism will be conducted. The research will focus on metabolism of direct interest to DOE, dealing with the transformation of metals, metalloids, organometallics and toxic organics. This is precisely the type of metabolism which has been characterized most poorly to date. Moreover, these studies will directly impact functional genomic analysis of DOE-relevant genomes.

  16. A Proposed Essential Gene Discovery Pipeline: A Campylobacter jejuni Case Study.

    PubMed

    Reuter, Mark; Gaskin, Duncan J H; Metris, Aline

    2015-01-01

    Genes required for an organism's growth and survival are termed essential and represent potential intervention targets. Following in the footsteps of the genomics era, the "next-gen" genomic era provides vast amounts of genetic information. Sequencing of a representative bacterial pathogen genome has been superseded by sequencing of whole strain collections, whether from environmental or clinical sources (Harris et al., Science 327:469-474, 2010; Lewis et al., J Hosp Infect 75:37-41, 2010; Beres et al., Proc Natl Acad Sci U S A 107:4371-4376, 2010; Qi et al., PLoS Pathog 5:e1000580, 2009; He et al., Proc Natl Acad Sci U S A 107:7527-7532, 2010; Barrick et al., Nature 461:1243-1247, 2009; Sheppard et al., Mol Ecol 22:1051-1064, 2013). However, the challenge of using this information to gain biological insight remains. Nonetheless, this information, in combination with experimental data from the literature, can serve as the framework for gaining a better understanding of an organism's biology. Generic metabolic pathways have long been known, and a number of websites (e.g., KEGG and BioCyc) attempt to map information from genome annotation to metabolic pathways (Kanehisa et al., Nucleic Acids Res 40:D109-D114, 2010; Karp et al., Nucleic Acids Res 33:6083-6089, 2005). Extending this analysis to incorporate metabolic flux models further allows in silico prediction of potential essential genes. Such efforts are of value, either to highlight novel generic antimicrobials or to seek novel treatments for non-paradigm organisms. Such in silico approaches are attractive as they can highlight pathways and genes that would otherwise only be identified by costly and time-consuming laboratory methods. PMID:25636619

  17. Robust Target Gene Discovery through Transcriptome Perturbations and Genome-Wide Enhancer Predictions in Drosophila Uncovers a Regulatory Basis for Sensory Specification

    PubMed Central

    Aerts, Stein; Quan, Xiao-Jiang; Claeys, Annelies; Naval Sanchez, Marina; Tate, Phillip; Yan, Jiekun; Hassan, Bassem A.

    2010-01-01

    A comprehensive systems-level understanding of developmental programs requires the mapping of the underlying gene regulatory networks. While significant progress has been made in mapping a few such networks, almost all gene regulatory networks underlying cell-fate specification remain unknown and their discovery is significantly hampered by the paucity of generalized, in vivo validated tools of target gene and functional enhancer discovery. We combined genetic transcriptome perturbations and comprehensive computational analyses to identify a large cohort of target genes of the proneural and tumor suppressor factor Atonal, which specifies the switch from undifferentiated pluripotent cells to R8 photoreceptor neurons during larval development. Extensive in vivo validations of the predicted targets for the proneural factor Atonal demonstrate a 50% success rate of bona fide targets. Furthermore we show that these enhancers are functionally conserved by cloning orthologous enhancers from Drosophila ananassae and D. virilis in D. melanogaster. Finally, to investigate cis-regulatory cross-talk between Ato and other retinal differentiation transcription factors (TFs), we performed motif analyses and independent target predictions for Eyeless, Senseless, Suppressor of Hairless, Rough, and Glass. Our analyses show that cisTargetX identifies the correct motif from a set of coexpressed genes and accurately predicts target genes of individual TFs. The validated set of novel Ato targets exhibit functional enrichment of signaling molecules and a subset is predicted to be coregulated by other TFs within the retinal gene regulatory network. PMID:20668662

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

    SciTech Connect

    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

    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.

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

    PubMed

    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

    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

  20. Detection, Distribution, and Organohalogen Compound Discovery Implications of the Reduced Flavin Adenine Dinucleotide-Dependent Halogenase Gene in Major Filamentous Actinomycete Taxonomic Groups? †

    PubMed Central

    Gao, Peng; Huang, Ying

    2009-01-01

    Halogenases have been shown to play a significant role in biosynthesis and introducing the bioactivity of many halogenated secondary metabolites. In this study, 54 reduced flavin adenine dinucleotide (FADH2)-dependent halogenase gene-positive strains were identified after the PCR screening of a large collection of 228 reference strains encompassing all major families and genera of filamentous actinomycetes. The wide distribution of this gene was observed to extend to some rare lineages with higher occurrences and large sequence diversity. Subsequent phylogenetic analyses revealed that strains containing highly homologous halogenases tended to produce halometabolites with similar structures, and halogenase genes are likely to propagate by horizontal gene transfer as well as vertical inheritance within actinomycetes. Higher percentages of halogenase gene-positive strains than those of halogenase gene-negative ones contained polyketide synthase genes and/or nonribosomal peptide synthetase genes or displayed antimicrobial activities in the tests applied, indicating their genetic and physiological potentials for producing secondary metabolites. The robustness of this halogenase gene screening strategy for the discovery of particular biosynthetic gene clusters in rare actinomycetes besides streptomycetes was further supported by genome-walking analysis. The described distribution and phylogenetic implications of the FADH2-dependent halogenase gene present a guide for strain selection in the search for novel organohalogen compounds from actinomycetes. PMID:19447951

  1. Large-scale gene discovery in the pea aphid Acyrthosiphon pisum (Hemiptera)

    PubMed Central

    Sabater-Muńoz, Beatriz; Legeai, Fabrice; Rispe, Claude; Bonhomme, Joël; Dearden, Peter; Dossat, Carole; Duclert, Aymeric; Gauthier, Jean-Pierre; Ducray, Daničle Giblot; Hunter, Wayne; Dang, Phat; Kambhampati, Srini; Martinez-Torres, David; Cortes, Teresa; Moya, Andrčs; Nakabachi, Atsushi; Philippe, Cathy; Prunier-Leterme, Nathalie; Rahbé, Yvan; Simon, Jean-Christophe; Stern, David L; Wincker, Patrick; Tagu, Denis

    2006-01-01

    Aphids are the leading pests in agricultural crops. A large-scale sequencing of 40,904 ESTs from the pea aphid Acyrthosiphon pisum was carried out to define a catalog of 12,082 unique transcripts. A strong AT bias was found, indicating a compositional shift between Drosophila melanogaster and A. pisum. An in silico profiling analysis characterized 135 transcripts specific to pea-aphid tissues (relating to bacteriocytes and parthenogenetic embryos). This project is the first to address the genetics of the Hemiptera and of a hemimetabolous insect. PMID:16542494

  2. MixMir: microRNA motif discovery from gene expression data using mixed linear models.

    PubMed

    Diao, Liyang; Marcais, Antoine; Norton, Scott; Chen, Kevin C

    2014-01-01

    microRNAs (miRNAs) are a class of ?22nt non-coding RNAs that potentially regulate over 60% of human protein-coding genes. miRNA activity is highly specific, differing between cell types, developmental stages and environmental conditions, so the identification of active miRNAs in a given sample is of great interest. Here we present a novel computational approach for analyzing both mRNA sequence and gene expression data, called MixMir. Our method corrects for 3' UTR background sequence similarity between transcripts, which is known to correlate with mRNA transcript abundance. We demonstrate that after accounting for kmer sequence similarities in 3' UTRs, a statistical linear model based on motif presence/absence can effectively discover active miRNAs in a sample. MixMir utilizes fast software implementations for solving mixed linear models, which are widely used in genome-wide association studies (GWASs). Essentially we use 3' UTR sequence similarity in place of population cryptic relatedness in the GWAS problem. Compared to similar methods such as miReduce, Sylamer and cWords, we found that MixMir performed better at discovering true miRNA motifs in three mouse Dicer-knockout experiments from different tissues, two of which were collected by our group. We confirmed these results on protein and mRNA expression data obtained from miRNA transfection experiments in human cell lines. MixMir can be freely downloaded from https://github.com/ldiao/MixMir. PMID:25081207

  3. MixMir: microRNA motif discovery from gene expression data using mixed linear models

    PubMed Central

    Diao, Liyang; Marcais, Antoine; Norton, Scott; Chen, Kevin C.

    2014-01-01

    microRNAs (miRNAs) are a class of ?22nt non-coding RNAs that potentially regulate over 60% of human protein-coding genes. miRNA activity is highly specific, differing between cell types, developmental stages and environmental conditions, so the identification of active miRNAs in a given sample is of great interest. Here we present a novel computational approach for analyzing both mRNA sequence and gene expression data, called MixMir. Our method corrects for 3’ UTR background sequence similarity between transcripts, which is known to correlate with mRNA transcript abundance. We demonstrate that after accounting for kmer sequence similarities in 3’ UTRs, a statistical linear model based on motif presence/absence can effectively discover active miRNAs in a sample. MixMir utilizes fast software implementations for solving mixed linear models, which are widely used in genome-wide association studies (GWASs). Essentially we use 3’ UTR sequence similarity in place of population cryptic relatedness in the GWAS problem. Compared to similar methods such as miReduce, Sylamer and cWords, we found that MixMir performed better at discovering true miRNA motifs in three mouse Dicer-knockout experiments from different tissues, two of which were collected by our group. We confirmed these results on protein and mRNA expression data obtained from miRNA transfection experiments in human cell lines. MixMir can be freely downloaded from https://github.com/ldiao/MixMir. PMID:25081207

  4. [De novotranscriptomic analysis of Chlorella sorokiniana: Pathway description and gene discovery for lipid production ].

    PubMed

    Li, Lin; Wang, Qinhong; Yang, Hailin; Wang, Wu

    2014-09-01

    [ OBJECTIVE] The paucity of genomic information limits the metabolic engineering of non-model microalgae Chlorella sorokiniana. Our study aimed to elucidate the fatty acid, triacylglycerol and starch biosynthetic pathways in the microalgae C. sorokiniana based on de novo transcriptomic analysis. [METHODS] We cultured C. sorokiniana with different nitrogen concentrations (KNO3: 8g/L and 2g/L) , then sequenced the transcriptomeusing Illumina Hiseq2000 platform. We used Trinity to de novo assemble the reads so as to obtain transcripts, aligned all the transcripts with Nr database, UniProtKB/Swiss-Prot database and COG database to annotate the function and classify using BLASTx algorithm, and assigned the transcript with metabolic pathway by aligning with KEGG database. Then we used RSEM to calculate FPKM value, and used it for preliminary analysis of different gene expression in the related pathways. [RESULTS] Over 49M high quality raw reads were produced with the length of 100bp, We used Trinity to assembled these reads into 49885 transcripts with an N50 of 1941bp, ranging from 300bp to 14100bp. 26479 transcripts were annotated through BLASTx similarity search, 2357 transcripts were assigned with EC number, and 207 metabolic pathways were assigned in total. Based on these analyses, we reconstructed the fatty acids, triacylglycerol and starch biosynthetic pathways in C. sorokiniana. We also identified preliminarily different geneexpression in the pathways. [CONCLUSION] Using RNA-seq technology, we reconstructed the metabolic pathways involving in the fatty acid, triacylglycerol and starch biosynthesis in non-model microalgae C. sorokiniana without genomic data, which is consistent with those in model microalgae Chlamydomonas reinhardtii, and compared the gene expression level under different conditions. These information is very useful for the metabolic engineering of C. sorokiniana and other microalgae to enhance the production of lipids. PMID:25522590

  5. Pattern discovery and cancer gene identification in integrated cancer genomic data

    PubMed Central

    Mo, Qianxing; Wang, Sijian; Seshan, Venkatraman E.; Olshen, Adam B.; Schultz, Nikolaus; Sander, Chris; Powers, R. Scott; Ladanyi, Marc; Shen, Ronglai

    2013-01-01

    Large-scale integrated cancer genome characterization efforts including the cancer genome atlas and the cancer cell line encyclopedia have created unprecedented opportunities to study cancer biology in the context of knowing the entire catalog of genetic alterations. A clinically important challenge is to discover cancer subtypes and their molecular drivers in a comprehensive genetic context. Curtis et al. [Nature (2012) 486(7403):346–352] has recently shown that integrative clustering of copy number and gene expression in 2,000 breast tumors reveals novel subgroups beyond the classic expression subtypes that show distinct clinical outcomes. To extend the scope of integrative analysis for the inclusion of somatic mutation data by massively parallel sequencing, we propose a framework for joint modeling of discrete and continuous variables that arise from integrated genomic, epigenomic, and transcriptomic profiling. The core idea is motivated by the hypothesis that diverse molecular phenotypes can be predicted by a set of orthogonal latent variables that represent distinct molecular drivers, and thus can reveal tumor subgroups of biological and clinical importance. Using the cancer cell line encyclopedia dataset, we demonstrate our method can accurately group cell lines by their cell-of-origin for several cancer types, and precisely pinpoint their known and potential cancer driver genes. Our integrative analysis also demonstrates the power for revealing subgroups that are not lineage-dependent, but consist of different cancer types driven by a common genetic alteration. Application of the cancer genome atlas colorectal cancer data reveals distinct integrated tumor subtypes, suggesting different genetic pathways in colon cancer progression. PMID:23431203

  6. EST-SNP discovery and dense genetic mapping in lentil (Lens culinaris Medik.) enable candidate gene selection for boron tolerance.

    PubMed

    Kaur, Sukhjiwan; Cogan, Noel O I; Stephens, Amber; Noy, Dianne; Butsch, Mirella; Forster, John W; Materne, Michael

    2014-03-01

    Large-scale SNP discovery and dense genetic mapping in a lentil intraspecific cross permitted identification of a single chromosomal region controlling tolerance to boron toxicity, an important breeding objective. Lentil (Lens culinaris Medik.) is a highly nutritious food legume crop that is cultivated world-wide. Until recently, lentil has been considered a genomic 'orphan' crop, limiting the feasibility of marker-assisted selection strategies in breeding programs. The present study reports on the identification of single-nucleotide polymorphisms (SNPs) from transcriptome sequencing data, utilisation of expressed sequence tag (EST)-derived simple sequence repeat (SSR) and SNP markers for construction of a gene-based genetic linkage map, and identification of markers in close linkage to major QTLs for tolerance to boron (B) toxicity. A total of 2,956 high-quality SNP markers were identified from a lentil EST database. Sub-sets of 546 SSRs and 768 SNPs were further used for genetic mapping of an intraspecific mapping population (Cassab × ILL2024) that exhibits segregation for B tolerance. Comparative analysis of the lentil linkage map with the sequenced genomes of Medicago truncatula Gaertn., soybean (Glycine max [L.] Merr.) and Lotus japonicus L. indicated blocks of conserved macrosynteny, as well as a number of rearrangements. A single genomic region was found to be associated with variation for B tolerance in lentil, based on evaluation performed over 2 years. Comparison of flanking markers to genome sequences of model species (M. truncatula, soybean and Arabidopsis thaliana) identified candidate genes that are functionally associated with B tolerance, and could potentially be used for diagnostic marker development in lentil. PMID:24370962

  7. Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo.

    PubMed

    Grgic, Ivica; Hofmeister, Andreas F; Genovese, Giulio; Bernhardy, Andrea J; Sun, Hua; Maarouf, Omar H; Bijol, Vanesa; Pollak, Martin R; Humphreys, Benjamin D

    2014-12-01

    Identifying new biomarkers and therapeutic targets for podocytopathies such as focal segmental glomerulosclerosis (FSGS) requires a detailed analysis of transcriptional changes in podocytes over the course of disease. Here we used translating ribosome affinity purification (TRAP) to isolate and profile podocyte-specific mRNA in two different models of FSGS. We expressed enhanced green fluorescent protein-tagged to ribosomal protein L10a in podocytes under the control of the collagen-1?1 promoter, enabling one-step podocyte-specific mRNA isolation over the course of disease. This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed Col1?1-eGFP-L10a mice with the Actn4(-/-) and Actn4(+/K256E) models of FSGS and analyzed podocyte transcriptional profiles at 2, 6, and 44 weeks of age. Two upregulated podocyte genes in murine FSGS (CXCL1 and DMPK) were found to be upregulated at the protein level in biopsies from patients with FSGS, validating this approach. There was no dilution of podocyte-specific transcripts during disease. These are the first podocyte-specific RNA expression data sets during aging and in two models of FSGS. This approach identified new podocyte proteins that are upregulated in FSGS and defines novel biomarkers and therapeutic targets for human glomerular disease. PMID:24940801

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

    PubMed

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

    2014-10-24

    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

  9. Discovery, taxonomic distribution, and phenotypic characterization of a gene required for 3-methylhopanoid production

    PubMed Central

    Welander, Paula V.; Summons, Roger E.

    2012-01-01

    Hopanoids methylated at the C-3 position are a subset of bacterial triterpenoids that are readily preserved in modern and ancient sediments and in petroleum. The production of 3-methylhopanoids by extant aerobic methanotrophs and their common occurrence in modern and fossil methane seep communities, in conjunction with carbon isotope analysis, has led to their use as biomarker proxies for aerobic methanotrophy. In addition, these lipids are also produced by aerobic acetic acid bacteria and, lacking carbon isotope analysis, are more generally used as indicators for aerobiosis in ancient ecosystems. However, recent genetic studies have brought into question our current understanding of the taxonomic diversity of methylhopanoid-producing bacteria and have highlighted that a proper interpretation of methylhopanes in the rock record requires a deeper understanding of their cellular function. In this study, we identified and deleted a gene, hpnR, required for methylation of hopanoids at the C-3 position in the obligate methanotroph Methylococcus capsulatus strain Bath. Bioinformatics analysis revealed that the taxonomic distribution of HpnR extends beyond methanotrophic and acetic acid bacteria. Phenotypic analysis of the M. capsulatus hpnR deletion mutant demonstrated a potential physiological role for 3-methylhopanoids; they appear to be required for the maintenance of intracytoplasmic membranes and cell survival in late stationary phase. Therefore, 3-methylhopanoids may prove more useful as proxies for specific environmental conditions encountered during stationary phase rather than a particular bacterial group. PMID:22826256

  10. Analysis of Gene Expression Profiles in Leaf Tissues of Cultivated Peanuts and Development of EST-SSR Markers and Gene Discovery

    PubMed Central

    Guo, Baozhu; Chen, Xiaoping; Hong, Yanbin; Liang, Xuanqiang; Dang, Phat; Brenneman, Tim; Holbrook, Corley; Culbreath, Albert

    2009-01-01

    Peanut is vulnerable to a range of foliar diseases such as spotted wilt caused by Tomato spotted wilt virus (TSWV), early (Cercospora arachidicola) and late (Cercosporidium personatum) leaf spots, southern stem rot (Sclerotium rolfsii), and sclerotinia blight (Sclerotinia minor). In this study, we report the generation of 17,376 peanut expressed sequence tags (ESTs) from leaf tissues of a peanut cultivar (Tifrunner, resistant to TSWV and leaf spots) and a breeding line (GT-C20, susceptible to TSWV and leaf spots). After trimming vector and discarding low quality sequences, a total of 14,432 high-quality ESTs were selected for further analysis and deposition to GenBank. Sequence clustering resulted in 6,888 unique ESTs composed of 1,703 tentative consensus (TCs) sequences and 5185 singletons. A large number of ESTs (5717) representing genes of unknown functions were also identified. Among the unique sequences, there were 856 EST-SSRs identified. A total of 290 new EST-based SSR markers were developed and examined for amplification and polymorphism in cultivated peanut and wild species. Resequencing information of selected amplified alleles revealed that allelic diversity could be attributed mainly to differences in repeat type and length in the SSR regions. In addition, a few additional INDEL mutations and substitutions were observed in the regions flanking the microsatellite regions. In addition, some defense-related transcripts were also identified, such as putative oxalate oxidase (EU024476) and NBS-LRR domains. EST data in this study have provided a new source of information for gene discovery and development of SSR markers in cultivated peanut. A total of 16931 ESTs have been deposited to the NCBI GenBank database with accession numbers ES751523 to ES768453. PMID:19584933

  11. Analysis of Gene Expression Profiles in Leaf Tissues of Cultivated Peanuts and Development of EST-SSR Markers and Gene Discovery.

    PubMed

    Guo, Baozhu; Chen, Xiaoping; Hong, Yanbin; Liang, Xuanqiang; Dang, Phat; Brenneman, Tim; Holbrook, Corley; Culbreath, Albert

    2009-01-01

    Peanut is vulnerable to a range of foliar diseases such as spotted wilt caused by Tomato spotted wilt virus (TSWV), early (Cercospora arachidicola) and late (Cercosporidium personatum) leaf spots, southern stem rot (Sclerotium rolfsii), and sclerotinia blight (Sclerotinia minor). In this study, we report the generation of 17,376 peanut expressed sequence tags (ESTs) from leaf tissues of a peanut cultivar (Tifrunner, resistant to TSWV and leaf spots) and a breeding line (GT-C20, susceptible to TSWV and leaf spots). After trimming vector and discarding low quality sequences, a total of 14,432 high-quality ESTs were selected for further analysis and deposition to GenBank. Sequence clustering resulted in 6,888 unique ESTs composed of 1,703 tentative consensus (TCs) sequences and 5185 singletons. A large number of ESTs (5717) representing genes of unknown functions were also identified. Among the unique sequences, there were 856 EST-SSRs identified. A total of 290 new EST-based SSR markers were developed and examined for amplification and polymorphism in cultivated peanut and wild species. Resequencing information of selected amplified alleles revealed that allelic diversity could be attributed mainly to differences in repeat type and length in the SSR regions. In addition, a few additional INDEL mutations and substitutions were observed in the regions flanking the microsatellite regions. In addition, some defense-related transcripts were also identified, such as putative oxalate oxidase (EU024476) and NBS-LRR domains. EST data in this study have provided a new source of information for gene discovery and development of SSR markers in cultivated peanut. A total of 16931 ESTs have been deposited to the NCBI GenBank database with accession numbers ES751523 to ES768453. PMID:19584933

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

    PubMed Central

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

    2008-01-01

    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

  13. Bioinformatics Approaches to Biomarker Discovery BIOC 218/ BMI 231

    E-print Network

    Verma seemav@stanford.edu #12;1. Introduction The availability of the complete human genome has paved there are about 30,000 genes in the human genome (http://www.ncbi.nlm.nih.gov/genome/guide/human/), the protein1 Bioinformatics Approaches to Biomarker Discovery BIOC 218/ BMI 231 FINAL PROJECT March 2007 Seema

  14. Cell Discoveries

    NSDL National Science Digital Library

    Shelly Peretz (Thornridge High School REV)

    1994-07-30

    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.

  15. Discovery and genetic mapping of single nucleotide polymorphisms in candidate genes for pathogen defence response in perennial ryegrass (Lolium perenne L.).

    PubMed

    Dracatos, P M; Cogan, N O I; Dobrowolski, M P; Sawbridge, T I; Spangenberg, G C; Smith, K F; Forster, J W

    2008-07-01

    Susceptibility to foliar pathogens commonly causes significant reductions in productivity of the important temperate forage perennial ryegrass. Breeding for durable disease resistance involves not only the deployment of major genes but also the additive effects of minor genes. An approach based on in vitro single nucleotide polymorphism (SNP) discovery in candidate defence response (DR) genes has been used to develop potential diagnostic genetic markers. SNPs were predicted, validated and mapped for representatives of the pathogenesis-related (PR) protein-encoding and reactive oxygen species (ROS)-generating gene classes. The F(1)(NA(6) x AU(6)) two-way pseudo-test cross population was used for SNP genetic mapping and detection of quantitative trait loci (QTLs) in response to a crown rust field infection. Novel resistance QTLs were coincident with mapped DR gene SNPs. QTLs on LG3 and LG7 also coincided with both herbage quality QTLs and candidate genes for lignin biosynthesis. Multiple DR gene SNP loci additionally co-located with QTLs for grey leaf spot, bacterial wilt and crown rust resistance from other published studies. Further functional validation of DR gene SNP loci using methods such as fine-mapping and association genetics will improve the efficiency of parental selection based on superior allele content. PMID:18446316

  16. The Drosophila Gene Disruption Project: Progress Using Transposons With Distinctive Site Specificities

    PubMed Central

    Bellen, Hugo J.; Levis, Robert W.; He, Yuchun; Carlson, Joseph W.; Evans-Holm, Martha; Bae, Eunkyung; Kim, Jaeseob; Metaxakis, Athanasios; Savakis, Charalambos; Schulze, Karen L.; Hoskins, Roger A.; Spradling, Allan C.

    2011-01-01

    The Drosophila Gene Disruption Project (GDP) has created a public collection of mutant strains containing single transposon insertions associated with different genes. These strains often disrupt gene function directly, allow production of new alleles, and have many other applications for analyzing gene function. Here we describe the addition of ?7600 new strains, which were selected from >140,000 additional P or piggyBac element integrations and 12,500 newly generated insertions of the Minos transposon. These additions nearly double the size of the collection and increase the number of tagged genes to at least 9440, approximately two-thirds of all annotated protein-coding genes. We also compare the site specificity of the three major transposons used in the project. All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of “transposon-free regions” (TFRs) in metazoan genomes. Within other genomic regions, Minos transposes essentially at random, whereas P or piggyBac elements display distinctive hotspots and coldspots. P elements, as previously shown, have a strong preference for promoters. In contrast, piggyBac site selectivity suggests that it has evolved to reduce deleterious and increase adaptive changes in host gene expression. The propensity of Minos to integrate broadly makes possible a hybrid finishing strategy for the project that will bring >95% of Drosophila genes under experimental control within their native genomic contexts. PMID:21515576

  17. Gene disruptions using P transposable elements: An integral component of the Drosophila genome project

    SciTech Connect

    Spradling, A.C.; Stern, D.M. [Howard Hughes Medical Institute Research Labs., Baltimore, MD (United States); Kiss, I. [Institute of Genetics, Szeged (Hungary)] [and others

    1995-11-21

    Biologists require genetic as well as molecular tools to decipher genomic information and ultimately to understand gene function. The Berkeley Drosophila Genome Project is addressing these needs with a massive gene disruption project that uses individual, genetically engineered P transposable elements to target open reading frames throughout the Drosophila genome DNA flanking the insertions is sequenced thereby placing and extensive series of genetic markers on the physical genomic map and associating insertions with specific open reading frames and genes. Insertions from the collection now lie within or near most Drosophila genes, greatly reducing the time required to identify new mutations and analyze gene functions. Information revealed from these studies about P element site specificity is being used to target the remaining open reading frames. 38 refs., 5 figs., 1 tab.

  18. NCI DTP Discovery Services

    Cancer.gov

    What's New Home Discovery Development Pathways Grants/Contracts Books/Publications Site Search Data Search What's New New NCI60 data release MicroXeno Project data now available NCI-60 characterization NCI Experimental Therapeutics Program (NExT)

  19. A novel approach to the discovery of survival biomarkers in glioblastoma using a joint analysis of DNA methylation and gene expression.

    PubMed

    Smith, Ashley A; Huang, Yen-Tsung; Eliot, Melissa; Houseman, E Andres; Marsit, Carmen J; Wiencke, John K; Kelsey, Karl T

    2014-06-01

    Glioblastoma multiforme (GBM) is the most aggressive of all brain tumors, with a median survival of less than 1.5 years. Recently, epigenetic alterations were found to play key roles in both glioma genesis and clinical outcome, demonstrating the need to integrate genetic and epigenetic data in predictive models. To enhance current models through discovery of novel predictive biomarkers, we employed a genome-wide, agnostic strategy to specifically capture both methylation-directed changes in gene expression and alternative associations of DNA methylation with disease survival in glioma. Human GBM-associated DNA methylation, gene expression, IDH1 mutation status, and survival data were obtained from The Cancer Genome Atlas. DNA methylation loci and expression probes were paired by gene, and their subsequent association with survival was determined by applying an accelerated failure time model to previously published alternative and expression-based association equations. Significant associations were seen in 27 unique methylation/expression pairs with expression-based, alternative, and combinatorial associations observed (10, 13, and 4 pairs, respectively). The majority of the predictive DNA methylation loci were located within CpG islands, and all but three of the locus pairs were negatively correlated with survival. This finding suggests that for most loci, methylation/expression pairs are inversely related, consistent with methylation-associated gene regulatory action. Our results indicate that changes in DNA methylation are associated with altered survival outcome through both coordinated changes in gene expression and alternative mechanisms. Furthermore, our approach offers an alternative method of biomarker discovery using a priori gene pairing and precise targeting to identify novel sites for locus-specific therapeutic intervention. PMID:24670968

  20. 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

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

    2008-11-01

    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 involving 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

  1. Discovery of a 29-Gene Panel in Peripheral Blood Mononuclear Cells for the Detection of Colorectal Cancer and Adenomas Using High Throughput Real-Time PCR

    PubMed Central

    Ciarloni, Laura; Hosseinian, Sahar; Monnier-Benoit, Sylvain; Imaizumi, Natsuko; Dorta, Gian; Ruegg, Curzio

    2015-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in developed countries. Early detection of CRC leads to decreased CRC mortality. A blood-based CRC screening test is highly desirable due to limited invasiveness and high acceptance rate among patients compared to currently used fecal occult blood testing and colonoscopy. Here we describe the discovery and validation of a 29-gene panel in peripheral blood mononuclear cells (PBMC) for the detection of CRC and adenomatous polyps (AP). Blood samples were prospectively collected from a multicenter, case-control clinical study. First, we profiled 93 samples with 667 candidate and 3 reference genes by high throughput real-time PCR (OpenArray system). After analysis, 160 genes were retained and tested again on 51 additional samples. Low expressed and unstable genes were discarded resulting in a final dataset of 144 samples profiled with 140 genes. To define which genes, alone or in combinations had the highest potential to discriminate AP and/or CRC from controls, data were analyzed by a combination of univariate and multivariate methods. A list of 29 potentially discriminant genes was compiled and evaluated for its predictive accuracy by penalized logistic regression and bootstrap. This method discriminated AP >1cm and CRC from controls with a sensitivity of 59% and 75%, respectively, with 91% specificity. The behavior of the 29-gene panel was validated with a LightCycler 480 real-time PCR platform, commonly adopted by clinical laboratories. In this work we identified a 29-gene panel expressed in PBMC that can be used for developing a novel minimally-invasive test for accurate detection of AP and CRC using a standard real-time PCR platform. PMID:25876024

  2. High-Throughput SNP Discovery and the Search for Candidate Genes for Long-Term SIVmac Nonprogression in Chinese Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Trask, J Satkoski; Garnica, WT; Malhi, RS; Kanthaswamy, S; Smith, DG

    2011-01-01

    Genetic differences between Indian and Chinese rhesus macaques contribute to the phenotypic variance of clinical trials, including experimental infection with SIVmac. The completion of the rhesus genome has facilitated the discovery of several thousand markers. Although the marker density necessary for whole genome association mapping of phenotypes has not yet been achieved, a SNP map will help researchers investigate variation in candidate genes. We developed a genome-wide SNP map for rhesus macaques containing 3,869 validated markers with an average distance of 0.88 megabases. We used the program VarLD to identify genomic areas with significant differences in linkage disequilibrium (LD) between Indian-derived and Chinese rhesus macaques, assuming that these areas provide the greatest potential for differential selection in these regional populations. These genomic areas provide entry to more detailed study of gene function. This method is also applicable to the study of differences in biomarkers between regional populations of other species. PMID:21781130

  3. Susceptibility Genes and Neurological Disorders: Learning the Right Lessons From the Human Genome Project

    Microsoft Academic Search

    Michael A. Grodin; Graeme T. Laurie

    2000-01-01

    urrent estimates suggest that the Human Genome Project (HGP) will be completed in 2003, by which time a comprehensive physical map of the 80000 to 100000 genes that constitute the entire human genome will be actualized. Few deny that this knowl- edge holds great promise. This advance will undoubtedly represent the beginning of a better understanding of the genetic basis

  4. The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery

    ERIC Educational Resources Information Center

    Grados, Marco A.

    2010-01-01

    Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

  5. The use of genetic modification technologies in the discovery of genes affecting production traits and disease resistance in animals

    Microsoft Academic Search

    AM Crawford

    2003-01-01

    Genetic modification technologies, developed initially in laboratory strains of selected bacteria and viruses, are essential tools for understanding the genomes of livestock. These tools allow researchers to: isolate, sequence and characterise any livestock gene; locate genes on chromosomes; follow the inheritance of any gene and\\/or chromosomal region in any pedigree; detect phenotypic variation due to, or associated with, variation in

  6. Field of genes: the politics of science and identity in the Estonian Genome Project.

    PubMed

    Fletcher, Amy L

    2004-04-01

    This case study of the Estonian Genome Project (EGP) analyses the Estonian policy decision to construct a national human gene bank. Drawing upon qualitative data from newspaper articles and public policy documents, it focuses on how proponents use discourse to link the EGP to the broader political goal of securing Estonia's position within the Western/European scientific and cultural space. This dominant narrative is then situated within the analytical notion of the "brand state", which raises potentially negative political consequences for this type of market-driven genomic research. Considered against the increasing number of countries engaging in gene bank and/or gene database projects, this analysis of Estonia elucidates issues that cross national boundaries, while also illuminating factors specific to this small, post-Soviet state as it enters the global biocybernetic economy. PMID:15468507

  7. 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...

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

    SciTech Connect

    Torok, Tamas

    2013-02-04

    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.

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

    SciTech Connect

    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

    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.

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

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

    2013-01-01

    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

  12. Weeder Web: discovery of transcription factor binding sites in a set of sequences from co-regulated genes

    Microsoft Academic Search

    Giulio Pavesi; Paolo Mereghetti; Giancarlo Mauri; Graziano Pesole

    2004-01-01

    Oneofthegreatestchallengesthatmodernmolecular biology is facing is the understanding of the complex mechanisms regulating gene expression. A funda- mental step in this process requires the characteriza- tion of regulatory motifs playing key roles in the regulation of gene expression at transcriptional and post-transcriptionallevels.Inparticular,transcription is modulated by the interaction of transcription fac- tors with their corresponding binding sites. Weeder Web isaweb interface to

  13. Discovery of genes expressed in response to Perkinsus marinus challenge in Eastern (Crassostrea virginica) and Pacific (C. gigas) oysters.

    PubMed

    Tanguy, Arnaud; Guo, Ximing; Ford, Susan E

    2004-08-18

    The protozoan pathogen Perkinsus marinus is the causative agent of Dermo, a lethal disease of the eastern oyster Crassostrea virginica, but not the Pacific oyster Crassostrea gigas. To understand the response of these two oysters to parasite exposure, a suppression subtractive hybridization (SSH) method was employed to characterize genes up-regulated during parasite challenge in both hemocytes and gills. The number of differentially expressed gene sequences obtained was 107 for C. virginica and 69 for C. gigas, including 46 and 37 sequences, respectively, that matched known genes in GenBank. Most of the sequences have not been characterized in other molluscs. Nineteen genes involved in immune system and cell communication, protein regulation and transcription, cell cycle, respiratory chain and cytoskeleton were selected for expression analysis by semi-quantitative PCR. Although varying in magnitude and timing post exposure, all genes screened showed over-expression in challenged oysters in both species, validating the SSH method. Results of this study highlighted some differences in gene expression between the two oysters in response to P. marinus infection, providing candidate genes and pathways for further analysis. PMID:15302413

  14. Design of the DISCovery project: tailored work-oriented interventions to improve employee health, well-being, and performance-related outcomes in hospital care

    PubMed Central

    2013-01-01

    Background It is well-known that health care workers in today’s general hospitals have to deal with high levels of job demands, which could have negative effects on their health, well-being, and job performance. A way to reduce job-related stress reactions and to optimize positive work-related outcomes is to raise the level of specific job resources and opportunities to recover from work. However, the question remains how to translate the optimization of the balance between job demands, job resources, and recovery opportunities into effective workplace interventions. The aim of the DISCovery project is to develop and implement tailored work-oriented interventions to improve health, well-being, and performance of health care personnel. Methods/Design A quasi-experimental field study with a non-equivalent control group pretest-posttest design will be conducted in a top general hospital. Four existing organizational departments will provide both an intervention and a comparison group. Two types of research methods are used: (1) a longitudinal web-based survey study, and (2) a longitudinal daily diary study. After base-line measures of both methods, existing and yet to be developed interventions will be implemented within the experimental groups. Follow-up measurements will be taken one and two years after the base-line measures to analyze short-term and long-term effects of the interventions. Additionally, a process evaluation and a cost-effectiveness analysis will be carried out. Discussion The DISCovery project fulfills a strong need for theory-driven and scientifically well-performed research on job stress and performance interventions. It will provide insight into (1) how a balance between job demands, job resources, and recovery from work can be optimized, (2) the short-term and long-term effects of tailored work-oriented effects, and (3) indicators for successful or unsuccessful implementation of interventions. PMID:23421647

  15. Pigmentation in sand pear (Pyrus pyrifolia) fruit: biochemical characterization, gene discovery and expression analysis with exocarp pigmentation mutant.

    PubMed

    Wang, Yue-zhi; Zhang, Shujun; Dai, Mei-song; Shi, Ze-bin

    2014-05-01

    Exocarp color of sand pear is an important trait for the fruit production and has caused our concern for a long time. Our previous study explored the different expression genes between the two genotypes contrasting for exocarp color, which indicated the different suberin, cutin, wax and lignin biosynthesis between the russet- and green-exocarp. In this study, we carried out microscopic observation and Fourier transform infrared spectroscopy analysis to detect the differences of tissue structure and biochemical composition between the russet- and green-exocarp of sand pear. The green exocarp was covered with epidermis and cuticle which was replaced by a cork layer on the surface of russet exocarp, and the chemicals of the russet exocarp were characterized by lignin, cellulose and hemicellulose. We explored differential gene expression between the russet exocarp of 'Niitaka' and its green exocarp mutant cv. 'Suisho' using Illumina RNA-sequencing. A total of 559 unigenes showed different expression between the two types of exocarp, and 123 of them were common to the previous study. The quantitative real time-PCR analysis supports the RNA-seq-derived gene with different expression between the two types of exocarp and revealed the preferential expression of these genes in exocarp than in mesocarp and fruit core. Gene ontology enrichment analysis revealed divorced expression of lipid metabolic process genes, transport genes, stress responsive genes and other biological process genes in the two types of exocarp. Expression changes in lignin metabolism-related genes were consistent with the different pigmentation of russet and green exocarp. Increased transcripts of putative genes involved the suberin, cutin and wax biosynthesis in 'Suisho' exocarp could facilitate deposition of the chemicals and take a role in the mutant trait responsible for the green exocarp. In addition, the divorced expression of ATP-binding cassette transporters involved in the trans-membrane transport of lignin, cutin, and suberin precursors suggests that the transport process could also affect the composition of exocarp and take a role in the regulation of exocarp pigmentation. Results from this study provide a base for the analysis of the molecular mechanism underlying sand pear russet/green exocarp mutation, and presents a comprehensive list of candidate genes that could be used to further investigate the trait mutation at the molecular level. PMID:24445590

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

    PubMed

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

    2014-09-01

    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

  17. Gene Expression Profiling for the Purposes of Biomarker Discovery in Oral Potentially Malignant Lesions: A Systematic Review

    PubMed Central

    AbdulMajeed, Ahmad A.; Farah, Camile S.

    2013-01-01

    Early and accurate diagnosis of oral potentially malignant lesions (OPML) is of critical importance in preventing malignant transformation. Although histopathological interpretation of the degree of epithelial dysplasia is considered the gold standard for diagnosis, this method is subjective and lacks sensitivity. Therefore, many attempts have been made to identify objective molecular biomarkers to improve diagnosis. Microarray technology has the advantage of screening the expression of the whole genome making it one of the best tools for searching for novel biomarkers. However, microarray studies of OPMLs are limited, and no review has been published to highlight and compare their findings. In this paper, we systematically review all studies that have incorporated microarray analyses in the investigation of gene profile alterations in OPMLs and suggest a set of commonly dysregulated genes across multiple gene expression profile studies. This list of common genes may help focus selection of markers for further analysis regarding their importance in the diagnosis and prognosis of OPMLs. PMID:24250244

  18. Gene expression profiling for the purposes of biomarker discovery in oral potentially malignant lesions: a systematic review.

    PubMed

    Abdulmajeed, Ahmad A; Farah, Camile S

    2013-01-01

    Early and accurate diagnosis of oral potentially malignant lesions (OPML) is of critical importance in preventing malignant transformation. Although histopathological interpretation of the degree of epithelial dysplasia is considered the gold standard for diagnosis, this method is subjective and lacks sensitivity. Therefore, many attempts have been made to identify objective molecular biomarkers to improve diagnosis. Microarray technology has the advantage of screening the expression of the whole genome making it one of the best tools for searching for novel biomarkers. However, microarray studies of OPMLs are limited, and no review has been published to highlight and compare their findings. In this paper, we systematically review all studies that have incorporated microarray analyses in the investigation of gene profile alterations in OPMLs and suggest a set of commonly dysregulated genes across multiple gene expression profile studies. This list of common genes may help focus selection of markers for further analysis regarding their importance in the diagnosis and prognosis of OPMLs. PMID:24250244

  19. Gene discovery and transcript analyses in the corn smut pathogen Ustilago maydis: expressed sequence tag and genome sequence comparison

    E-print Network

    Ho, Eric C H; Cahill, Matt J; Saville, Barry J

    2007-09-24

    expressed sequence tag (EST) libraries were generated from a variety of U. maydis cell types. In addition to utility in the context of gene identification and structure annotation, the ESTs were analyzed to identify differentially abundant transcripts...

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed Central

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

    2012-01-01

    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

  2. De novo assembly and discovery of genes that are involved in drought tolerance in Tibetan Sophora moorcroftiana.

    PubMed

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

    2015-01-01

    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

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

    PubMed

    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

    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

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

    PubMed Central

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

    2013-01-01

    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

  5. TLR and IMD signaling pathways from Caligus rogercresseyi (Crustacea: Copepoda): in silico gene expression and SNPs discovery.

    PubMed

    Valenzuela-Muńoz, V; Gallardo-Escárate, C

    2014-02-01

    The Toll and IMD signaling pathways represent one of the first lines of innate immune defense in invertebrates like Drosophila. However, for crustaceans like Caligus rogercresseyi, there is very little genomic information and, consequently, understanding of immune mechanisms. Massive sequencing data obtained for three developmental stages of C. rogercresseyi were used to evaluate in silico the expression patterns and presence of SNPs variants in genes involved in the Toll and IMD pathways. Through RNA-seq analysis, which used 20 contigs corresponding to relevant genes of the Toll and IMD pathways, an overexpression of genes linked to the Toll pathway, such as toll3 and Dorsal, were observed in the copepod stage. For the chalimus and adult stages, overexpression of genes in both pathways, such as Akirin and Tollip and IAP and Toll9, respectively, were observed. On the other hand, PCA statistical analysis inferred that in the chalimus and adult stages, the immune response mechanism was more developed, as evidenced by a relation between these two stages and the genes of both pathways. Moreover, 136 SNPs were identified for 20 contigs in genes of the Toll and IMD pathways. This study provides transcriptomic information about the immune response mechanisms of Caligus, thus providing a foundation for the development of new control strategies through blocking the innate immune response. PMID:24389530

  6. Discovery of sex-related genes through high-throughput transcriptome sequencing from the salmon louse Caligus rogercresseyi.

    PubMed

    Farlora, Rodolfo; Araya-Garay, José; Gallardo-Escárate, Cristian

    2014-06-01

    Understanding the molecular underpinnings involved in the reproduction of the salmon louse is critical for designing novel strategies of pest management for this ectoparasite. However, genomic information on sex-related genes is still limited. In the present work, sex-specific gene transcription was revealed in the salmon louse Caligus rogercresseyi using high-throughput Illumina sequencing. A total of 30,191,914 and 32,292,250 high quality reads were generated for females and males, and these were de novo assembled into 32,173 and 38,177 contigs, respectively. Gene ontology analysis showed a pattern of higher expression in the female as compared to the male transcriptome. Based on our sequence analysis and known sex-related proteins, several genes putatively involved in sex differentiation, including Dmrt3, FOXL2, VASA, and FEM1, and other potentially significant candidate genes in C. rogercresseyi, were identified for the first time. In addition, the occurrence of SNPs in several differentially expressed contigs annotating for sex-related genes was found. This transcriptome dataset provides a useful resource for future functional analyses, opening new opportunities for sea lice pest control. PMID:24642131

  7. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.

    PubMed

    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

    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

  8. Toxins and drug discovery.

    PubMed

    Harvey, Alan L

    2014-12-15

    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

  9. TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway.

    PubMed

    Rajamannan, Nalini M; Subramaniam, Malayannan; Abraham, Theodore P; Vasile, Vlad C; Ackerman, Michael J; Monroe, David G; Chew, Teng-Leong; Spelsberg, Thomas C

    2007-02-01

    Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGFbeta inducible early gene (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG(-/-) knock-out mouse was studied. Male mice age 4-16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The TIEG(-/-) knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG(-/-), and an increase in wall thickness in TIEG(-/-) mice of (1.85 +/- 0.21 mm), compared to the control (1.13 +/- 0.15 mm, P < 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG(-/-) heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG(-/-) mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse. PMID:16888812

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

    PubMed Central

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

    2014-01-01

    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

  11. An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits

    PubMed Central

    Demissie, Serkalem; Soranzo, Nicole; Bianchi, Estelle N.; Grundberg, Elin; Liang, Liming; Richards, J. Brent; Estrada, Karol; Zhou, Yanhua; van Nas, Atila; Moffatt, Miriam F.; Zhai, Guangju; Hofman, Albert; van Meurs, Joyce B.; Pols, Huibert A. P.; Price, Roger I.; Nilsson, Olle; Pastinen, Tomi; Cupples, L. Adrienne; Lusis, Aldons J.; Schadt, Eric E.; Ferrari, Serge; Uitterlinden, André G.

    2010-01-01

    Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons. Genome-wide association studies (GWAS) have become an unbiased approach to identify variations in the genome that potentially affect health. However, the genetic variants identified so far only explain a small proportion of the heritability for complex traits. Due to the modest genetic effect size and inadequate power, true association signals may not be revealed based on a stringent genome-wide significance threshold. Here, we take advantage of SNP and transcript arrays and integrate GWAS and expression signature profiling relevant to the skeletal system in cellular and animal models to prioritize the discovery of novel candidate genes for osteoporosis-related traits, including bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), as well as geometric indices of the hip (femoral neck-shaft angle, NSA; femoral neck length, NL; and narrow-neck width, NW). A two-stage meta-analysis of GWAS from 7,633 Caucasian women and 3,657 men, revealed three novel loci associated with osteoporosis-related traits, including chromosome 1p13.2 (RAP1A, p?=?3.6×10?8), 2q11.2 (TBC1D8), and 18q11.2 (OSBPL1A), and confirmed a previously reported region near TNFRSF11B/OPG gene. We also prioritized 16 suggestive genome-wide significant candidate genes based on their potential involvement in skeletal metabolism. Among them, 3 candidate genes were associated with BMD in women. Notably, 2 out of these 3 genes (GPR177, p?=?2.6×10?13; SOX6, p?=?6.4×10?10) associated with BMD in women have been successfully replicated in a large-scale meta-analysis of BMD, but none of the non-prioritized candidates (associated with BMD) did. Our results support the concept of our prioritization strategy. In the absence of direct biological support for identified genes, we highlighted the efficiency of subsequent functional characterization using publicly available expression profiling relevant to the skeletal system in cellular or whole animal models to prioritize candidate genes for further functional validation. PMID:20548944

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

    PubMed Central

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

    2014-01-01

    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

  13. Gene expression profiling of coelomic cells and discovery of immune-related genes in the earthworm, Eisenia andrei, using expressed sequence tags.

    PubMed

    Tak, Eun Sik; Cho, Sung-Jin; Park, Soon Cheol

    2015-03-01

    The coelomic cells of the earthworm consist of leukocytes, chlorogocytes, and coelomocytes, which play an important role in innate immunity reactions. To gain insight into the expression profiles of coelomic cells of the earthworm, Eisenia andrei, we analyzed 1151 expressed sequence tags (ESTs) derived from the cDNA library of the coelomic cells. Among the 1151 ESTs analyzed, 493 ESTs (42.8%) showed a significant similarity to known genes and represented 164 unique genes, of which 93 ESTs were singletons and 71 ESTs manifested as two or more ESTs. From the 164 unique genes sequenced, we found 24 immune-related and cell defense genes. Furthermore, real-time PCR analysis showed that levels of lysenin-related proteins mRNA in coelomic cells of E. andrei were upregulated after the injection of Bacillus subtilis bacteria. This EST data-set would provide a valuable resource for future researches of earthworm immune system. PMID:25496401

  14. Discovery of a Linear Peptide for Improving Tumor Targeting of Gene Products and Treatment of Distal Tumors by IL12 Gene Therapy

    Microsoft Academic Search

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

    2011-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    1997-03-01

    In the paper ``The Extragalactic Distance Scale Key Project. III. The Discovery of Cepheids and a New Distance to M101 Using the Hubble Space Telescope'' by 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, and John Huchra (ApJ, 463, 26 [1996]), two of the tables are in error. The magnitudes in Tables B1 and B2, in Appendix B, are ordered incorrectly. As a result, the Julian dates are not associated with their correct Cepheid magnitudes. We have now corrected these data, and updated versions of the tables are available on the World Wide Web. The tables are available in ASCII format at our Key Project site (http://www.ipac.caltech.edu/H0kp/) and will appear in volume 7 of the AAS CDROM. PostScript and paper copies are also available from the first author (http://www.ucolick.org/~kelson/H0/home.html or kelson@ucolick.org).

  16. Discovery Farms Dazey Waterway Site

    USGS Multimedia Gallery

    North Dakota Discovery Farms Dazey waterway site 1 located southeast of Dazey, North Dakota. In 2008, the Dazey Farm became the second farm in the North Dakota Discovery Farms project. Farm is owned and operated by Kim and Denise Amann and their family since 1955....

  17. Discovery of the rpl10 Gene in Diverse Plant Mitochondrial Genomes and Its Probable Replacement by the Nuclear Gene for Chloroplast RPL10 in Two Lineages of Angiosperms

    PubMed Central

    Kubo, Nakao; Arimura, Shin-ichi

    2010-01-01

    Mitochondrial genomes of plants are much larger than those of mammals and often contain conserved open reading frames (ORFs) of unknown function. Here, we show that one of these conserved ORFs is actually the gene for ribosomal protein L10 (rpl10) in plant. No rpl10 gene has heretofore been reported in any mitochondrial genome other than the exceptionally gene-rich genome of the protist Reclinomonas americana. Conserved ORFs corresponding to rpl10 are present in a wide diversity of land plant and green algal mitochondrial genomes. The mitochondrial rpl10 genes are transcribed in all nine land plants examined, with five seed plant genes subject to RNA editing. In addition, mitochondrial-rpl10-like cDNAs were identified in EST libraries from numerous land plants. In three lineages of angiosperms, rpl10 is either lost from the mitochondrial genome or a pseudogene. In two of them (Brassicaceae and monocots), no nuclear copy of mitochondrial rpl10 is identifiably present, and instead a second copy of nuclear-encoded chloroplast rpl10 is present. Transient assays using green fluorescent protein indicate that this duplicate gene is dual targeted to mitochondria and chloroplasts. We infer that mitochondrial rpl10 has been functionally replaced by duplicated chloroplast counterparts in Brassicaceae and monocots. PMID:19934175

  18. Transcriptome Analysis of the White Body of the Squid Euprymna tasmanica with Emphasis on Immune and Hematopoietic Gene Discovery

    PubMed Central

    Salazar, Karla A.; Joffe, Nina R.; Dinguirard, Nathalie; Houde, Peter; Castillo, Maria G.

    2015-01-01

    In the mutualistic relationship between the squid Euprymna tasmanica and the bioluminescent bacterium Vibrio fischeri, several host factors, including immune-related proteins, are known to interact and respond specifically and exclusively to the presence of the symbiont. In squid and octopus, the white body is considered to be an immune organ mainly due to the fact that blood cells, or hemocytes, are known to be present in high numbers and in different developmental stages. Hence, the white body has been described as the site of hematopoiesis in cephalopods. However, to our knowledge, there are no studies showing any molecular evidence of such functions. In this study, we performed a transcriptomic analysis of white body tissue of the Southern dumpling squid, E. tasmanica. Our primary goal was to gain insights into the functions of this tissue and to test for the presence of gene transcripts associated with hematopoietic and immune processes. Several hematopoiesis genes including CPSF1, GATA 2, TFIID, and FGFR2 were found to be expressed in the white body. In addition, transcripts associated with immune-related signal transduction pathways, such as the toll-like receptor/NF-??, and MAPK pathways were also found, as well as other immune genes previously identified in E. tasmanica’s sister species, E. scolopes. This study is the first to analyze an immune organ within cephalopods, and to provide gene expression data supporting the white body as a hematopoietic tissue. PMID:25775132

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 geno...

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

    PubMed

    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

    2015-02-01

    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. In order to 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

  1. 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...

  2. In silico discovery of gene-coding variants in murine quantitative trait loci using strain-specific genome sequence databases

    Microsoft Academic Search

    Kriste E Marshall; Elizabeth L Godden; Fan Yang; Sonya Burgers; Kari J Buck; James M Sikela

    2002-01-01

    BACKGROUND: The identification of genes underlying complex traits has been aided by quantitative trait locus (QTL) mapping approaches, which in turn have benefited from advances in mammalian genome research. Most recently, whole-genome draft sequences and assemblies have been generated for mouse strains that have been used for a large fraction of QTL mapping studies. Here we show how such strain-specific

  3. Transcriptome Analysis of the White Body of the Squid Euprymna tasmanica with Emphasis on Immune and Hematopoietic Gene Discovery.

    PubMed

    Salazar, Karla A; Joffe, Nina R; Dinguirard, Nathalie; Houde, Peter; Castillo, Maria G

    2015-01-01

    In the mutualistic relationship between the squid Euprymna tasmanica and the bioluminescent bacterium Vibrio fischeri, several host factors, including immune-related proteins, are known to interact and respond specifically and exclusively to the presence of the symbiont. In squid and octopus, the white body is considered to be an immune organ mainly due to the fact that blood cells, or hemocytes, are known to be present in high numbers and in different developmental stages. Hence, the white body has been described as the site of hematopoiesis in cephalopods. However, to our knowledge, there are no studies showing any molecular evidence of such functions. In this study, we performed a transcriptomic analysis of white body tissue of the Southern dumpling squid, E. tasmanica. Our primary goal was to gain insights into the functions of this tissue and to test for the presence of gene transcripts associated with hematopoietic and immune processes. Several hematopoiesis genes including CPSF1, GATA 2, TFIID, and FGFR2 were found to be expressed in the white body. In addition, transcripts associated with immune-related signal transduction pathways, such as the toll-like receptor/NF-??, and MAPK pathways were also found, as well as other immune genes previously identified in E. tasmanica's sister species, E. scolopes. This study is the first to analyze an immune organ within cephalopods, and to provide gene expression data supporting the white body as a hematopoietic tissue. PMID:25775132

  4. An application of bioinformatics and text mining to the discovery of novel genes related to bone biology

    Microsoft Academic Search

    Varun K. Gajendran; Jia-Ren Lin; David P. Fyhrie

    2007-01-01

    The treatment and management of complex genetic diseases such as osteoporosis can greatly benefit from the integration of relevant research across many different disciplines. We created a text mining tool that analyzes the PubMed literature database and integrates the available genomic information to provide a detailed mapping of the genes and their interrelationships within a particular network such as osteoporosis.

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

    NASA Technical Reports Server (NTRS)

    Freedman, Wendy L.; Hughes, Shaun M.; Madore, Barry F.; Mould, Jeremy R.; Lee, Myung Gyoon; Stetson, Peter; Kennicutt, Robert C.; Turner, Anne; Ferrarese, Laura; Ford, Holland

    1994-01-01

    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 and I magnitude system using a ground-based calibration. Apparent period-luminosity relations at V and I were constructed, from which apparent distance moduli were measured with respect to assumed values of mu(sub 0) = 18.50 mag and E(B - V) = 0.10 mag for the Large Magellanic Cloud. The difference in the apparent V and I moduli yields a measure of the difference in the total mean extinction between the M81 and the LMC Cepheid samples. A low total mean extinction to the M81 sample of E(B - V) = 0.03 +/- 0.05 mag is obtained. The true distance modulus to M81 is determined to be 27.80 +/- 0.20 mag, corresponding to a distance of 3.63 +/- 0.34 Mpc. These data illustrate that with an optimal (power-law) sampling strategy, the HST provides a powerful tool for the discovery of extragalactic Cepheids and their application to the distance scale. M81 is the first calibrating galaxy in the target sample of the HST Key Project on the Extragalactic Distance Scale, the ultimate aim of which is to provide a value of the Hubble constant to 10% accuracy.

  6. Scientific Discovery for All

    ERIC Educational Resources Information Center

    Zaikowski, Lori; Lichtman, Paul; Quarless, Duncan

    2007-01-01

    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…

  7. Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus.

    PubMed

    Woo, Patrick C Y; Lau, Susanna K P; Lam, Carol S F; Lau, Candy C Y; Tsang, Alan K L; Lau, John H N; Bai, Ru; Teng, Jade L L; Tsang, Chris C C; Wang, Ming; Zheng, Bo-Jian; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2012-04-01

    Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination. PMID:22278237

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

    PubMed

    Gaur, Rashmi; Bhatia, Sabhyata; Gupta, Meetu

    2014-07-01

    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

  9. The human genome project and the future of medical practice

    Microsoft Academic Search

    Bennett C. Nwanguma

    2003-01-01

    Contrary to the scepticism that characterised the planning stages of the human genome project, the technology and sequence data resulting from the project are set to revolutionise medical practice for good. The expected benefits include: enhanced discovery of disease genes, which will lead to improved knowledge on the genetic basis of diseases; availability of DNA-based diagnostic methods, which will find

  10. De Novo Transcriptomic Analysis of an Oleaginous Microalga: Pathway Description and Gene Discovery for Production of Next-Generation Biofuels

    Microsoft Academic Search

    LingLin Wan; Juan Han; Min Sang; AiFen Li; Hong Wu; ShunJi Yin; ChengWu Zhang

    2012-01-01

    BackgroundEustigmatos cf. polyphem is a yellow-green unicellular soil microalga belonging to the eustimatophyte with high biomass and considerable production of triacylglycerols (TAGs) for biofuels, which is thus referred to as an oleaginous microalga. The paucity of microalgae genome sequences, however, limits development of gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for a

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

    PubMed Central

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

    2008-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  13. Annotation of Genes Involved in Glycerolipid Biosynthesis in Chlamydomonas reinhardtii: Discovery of the Betaine Lipid Synthase BTA1Cr

    PubMed Central

    Riekhof, Wayne R.; Sears, Barbara B.; Benning, Christoph

    2005-01-01

    Lipid metabolism in flowering plants has been intensely studied, and knowledge regarding the identities of genes encoding components of the major fatty acid and membrane lipid biosynthetic pathways is very extensive. We now present an in silico analysis of fatty acid and glycerolipid metabolism in an algal model, enabled by the recent availability of expressed sequence tag and genomic sequences of Chlamydomonas reinhardtii. Genes encoding proteins involved in membrane biogenesis were predicted on the basis of similarity to proteins with confirmed functions and were organized so as to reconstruct the major pathways of glycerolipid synthesis in Chlamydomonas. This analysis accounts for the majority of genes predicted to encode enzymes involved in anabolic reactions of membrane lipid biosynthesis and compares and contrasts these pathways in Chlamydomonas and flowering plants. As an important result of the bioinformatics analysis, we identified and isolated the C. reinhardtii BTA1 (BTA1Cr) gene and analyzed the bifunctional protein that it encodes; we predicted this protein to be sufficient for the synthesis of the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS), a major membrane component in Chlamydomonas. Heterologous expression of BTA1Cr led to DGTS accumulation in Escherichia coli, which normally lacks this lipid, and allowed in vitro analysis of the enzymatic properties of BTA1Cr. In contrast, in the bacterium Rhodobacter sphaeroides, two separate proteins, BtaARs and BtaBRs, are required for the biosynthesis of DGTS. Site-directed mutagenesis of the active sites of the two domains of BTA1Cr allowed us to study their activities separately, demonstrating directly their functional homology to the bacterial orthologs BtaARs and BtaBRs. PMID:15701786

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

    PubMed

    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

    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

  15. Discovery of the Pion Anton Kapliy

    E-print Network

    1 Discovery of the Pion Anton Kapliy April 30, 2008 #12;2 Cecil Frank Powell 1903 - 1969 Wilson atomic project ­ Starts experiments with photoemulsions #12;5 Photographic emulsions Grains of silver years since discovery of the pion D. Perkins, The Discovery of the Pion in Bristol in 1947 http

  16. The TIGR Gene Indices: clustering and assembling EST and known genes and integration with eukaryotic genomes

    Microsoft Academic Search

    Yuandan Lee; Jennifer Tsai; S. Sunkara; Svetlana Karamycheva; Geo Pertea; Razvan Sultana; Valentin Antonescu; Agnes P. Chan; Foo Cheung; John Quackenbush

    2005-01-01

    Although the list of completed genome sequencing projects has expanded rapidly, sequencing and ana- lysis of expressed sequence tags (ESTs) remain a primary tool for discovery of novel genes in many eukaryotes and a key element in genome annotation. The TIGR Gene Indices (http:\\/\\/www.tigr.org\\/tdb\\/tgi) are a collection of 77 species-specific databases that use a highly refined protocol to analyze gene

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

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

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

    2014-08-01

    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

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed Central

    2010-01-01

    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

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

    PubMed

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

    2013-12-01

    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

  2. Automated Discovery of Tissue-Targeting Enhancers and Transcription Factors from Binding Motif and Gene Function Data

    PubMed Central

    Tuteja, Geetu; Moreira, Karen Betancourt; Chung, Tisha; Chen, Jenny; Wenger, Aaron M.; Bejerano, Gill

    2014-01-01

    Identifying enhancers regulating gene expression remains an important and challenging task. While recent sequencing-based methods provide epigenomic characteristics that correlate well with enhancer activity, it remains onerous to comprehensively identify all enhancers across development. Here we introduce a computational framework to identify tissue-specific enhancers evolving under purifying selection. First, we incorporate high-confidence binding site predictions with target gene functional enrichment analysis to identify transcription factors (TFs) likely functioning in a particular context. We then search the genome for clusters of binding sites for these TFs, overcoming previous constraints associated with biased manual curation of TFs or enhancers. Applying our method to the placenta, we find 33 known and implicate 17 novel TFs in placental function, and discover 2,216 putative placenta enhancers. Using luciferase reporter assays, 31/36 (86%) tested candidates drive activity in placental cells. Our predictions agree well with recent epigenomic data in human and mouse, yet over half our loci, including 7/8 (87%) tested regions, are novel. Finally, we establish that our method is generalizable by applying it to 5 additional tissues: heart, pancreas, blood vessel, bone marrow, and liver. PMID:24499934

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

    PubMed Central

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

    2013-01-01

    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

  4. Automated conserved non-coding sequence (CNS) discovery reveals differences in gene content and promoter evolution among grasses

    PubMed Central

    Turco, Gina; Schnable, James C.; Pedersen, Brent; Freeling, Michael

    2013-01-01

    Conserved non-coding sequences (CNS) are islands of non-coding sequence that, like protein coding exons, show less divergence in sequence between related species than functionless DNA. Several CNSs have been demonstrated experimentally to function as cis-regulatory regions. However, the specific functions of most CNSs remain unknown. Previous searches for CNS in plants have either anchored on exons and only identified nearby sequences or required years of painstaking manual annotation. Here we present an open source tool that can accurately identify CNSs between any two related species with sequenced genomes, including both those immediately adjacent to exons and distal sequences separated by >12 kb of non-coding sequence. We have used this tool to characterize new motifs, associate CNSs with additional functions, and identify previously undetected genes encoding RNA and protein in the genomes of five grass species. We provide a list of 15,363 orthologous CNSs conserved across all grasses tested. We were also able to identify regulatory sequences present in the common ancestor of grasses that have been lost in one or more extant grass lineages. Lists of orthologous gene pairs and associated CNSs are provided for reference inbred lines of arabidopsis, Japonica rice, foxtail millet, sorghum, brachypodium, and maize. PMID:23874343

  5. De novo characterization of the Dialeurodes citri transcriptome: mining genes involved in stress resistance and simple sequence repeats (SSRs) discovery.

    PubMed

    Chen, E-H; Wei, D-D; Shen, G-M; Yuan, G-R; Bai, P-P; Wang, J-J

    2014-02-01

    The citrus whitefly, Dialeurodes citri (Ashmead), is one of the three economically important whitefly species that infest citrus plants around the world; however, limited genetic research has been focused on D. citri, partly because of lack of genomic resources. In this study, we performed de novo assembly of a transcriptome using Illumina paired-end sequencing technology (Illumina Inc., San Diego, CA, USA). In total, 36,766 unigenes with a mean length of 497 bp were identified. Of these unigenes, we identified 17,788 matched known proteins in the National Center for Biotechnology Information database, as determined by Blast search, with 5731, 4850 and 14,441 unigenes assigned to clusters of orthologous groups (COG), gene ontology (GO), and SwissProt, respectively. In total, 7507 unigenes were assigned to 308 known pathways. In-depth analysis of the data showed that 117 unigenes were identified as potentially involved in the detoxification of xenobiotics and 67 heat shock protein (Hsp) genes were associated with environmental stress. In addition, these enzymes were searched against the GO and COG database, and the results showed that the three major detoxification enzymes and Hsps were classified into 18 and 3, 6, and 8 annotations, respectively. In addition, 149 simple sequence repeats were detected. The results facilitate the investigation of molecular resistance mechanisms to insecticides and environmental stress, and contribute to molecular marker development. The findings greatly improve our genetic understanding of D. citri, and lay the foundation for future functional genomics studies on this species. PMID:24164346

  6. High-throughput discovery of mutations in tef semi-dwarfing genes by next-generation sequencing analysis.

    PubMed

    Zhu, Qihui; Smith, Shavannor M; Ayele, Mulu; Yang, Lixing; Jogi, Ansuya; Chaluvadi, Srinivasa R; Bennetzen, Jeffrey L

    2012-11-01

    Tef (Eragrostis tef) is a major cereal crop in Ethiopia. Lodging is the primary constraint to increasing productivity in this allotetraploid species, accounting for losses of ?15-45% in yield each year. As a first step toward identifying semi-dwarf varieties that might have improved lodging resistance, an ?6× fosmid library was constructed and used to identify both homeologues of the dw3 semi-dwarfing gene of Sorghum bicolor. An EMS mutagenized population, consisting of ?21,210 tef plants, was planted and leaf materials were collected into 23 superpools. Two dwarfing candidate genes, homeologues of dw3 of sorghum and rht1 of wheat, were sequenced directly from each superpool with 454 technology, and 120 candidate mutations were identified. Out of 10 candidates tested, six independent mutations were validated by Sanger sequencing, including two predicted detrimental mutations in both dw3 homeologues with a potential to improve lodging resistance in tef through further breeding. This study demonstrates that high-throughput sequencing can identify potentially valuable mutations in under-studied plant species like tef and has provided mutant lines that can now be combined and tested in breeding programs for improved lodging resistance. PMID:22904035

  7. Genome-wide target profiling of piggyBac and Tol2 in HEK 293: pros and cons for gene discovery and gene therapy

    Microsoft Academic Search

    Yaa-Jyuhn J Meir; Matthew T Weirauch; Herng-Shing Yang; Pei-Cheng Chung; Robert K Yu; Sareina C-Y Wu

    2011-01-01

    Background  DNA transposons have emerged as indispensible tools for manipulating vertebrate genomes with applications ranging from insertional\\u000a mutagenesis and transgenesis to gene therapy. To fully explore the potential of two highly active DNA transposons, piggyBac and Tol2, as mammalian genetic tools, we have conducted a side-by-side comparison of the two transposon systems in the same setting\\u000a to evaluate their advantages and

  8. 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

    SciTech Connect

    Chen, X.N.; Gonsky, R.; Korenberg, J.R. [UCLA School of Medicine, Los Angeles, CA (United States). Cedars-Sinai Research Inst.] [UCLA School of Medicine, Los Angeles, CA (United States). Cedars-Sinai Research Inst.; Knauf, J.A.; Fagin, J.A. [Univ. of Cincinnati, OH (United States). Div. of Endocrinology/Metabolism] [Univ. of Cincinnati, OH (United States). Div. of Endocrinology/Metabolism; Wang, M.; Lai, E.H. [Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Pharmacology] [Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Pharmacology; Chissoe, S. [Washington Univ. School of Medicine, St. Louis, MO (United States). Genome Sequencing] [Washington Univ. School of Medicine, St. Louis, MO (United States). Genome Sequencing

    1998-08-01

    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. The authors 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. They 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 (PKC{epsilon}), 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 PKC{epsilon} as a previously unmapped candidate gene involved in thyroid tumorigenesis.

  9. Discovery Bottles

    NSDL National Science Digital Library

    Sandy Watson

    2008-07-01

    Discover discovery bottles! These wide-mouth plastic containers of any size filled with objects of different kinds can be terrific tools for science explorations and a great way to cultivate science minds in a K--2 science classroom. In addition, the author has found them to be a useful, inexpensive, and engaging way to help students develop skills in making predictions, observations, and comparisons. Here she shares a few of her favorite physical science lesson ideas using discovery bottles.

  10. A PKS I gene-based screening approach for the discovery of a new polyketide from Penicillium citrinum Salicorn 46.

    PubMed

    Wang, Xiaomin; Wang, Hui; Liu, Tianxing; Xin, Zhihong

    2014-06-01

    Salicorn 46, an endophytic fungus isolated from Salicornia herbacea Torr., was identified as Penicillium citrinum based on its internal transcribed spacer and ribosomal large-subunit DNA sequences using a type I polyketide synthase (PKS I) gene screening approach. A new polyketide, penicitriketo (1), and seven known compounds, including ergone (2), (3?,5?,8?,22E)-5,8-epidioxyergosta-6,9,22-trien-3-ol (3), (3?,5?,8?,22E)-5,8-epidioxyergosta-6,22-dien-3-ol (4), stigmasta-7,22-diene-3?,5?,6?-triol (5), 3?,5?-dihydroxy-(22E,24R)-ergosta-7,22-dien-6?-yl oleate (6), N b-acetyltryptamine (7), and 2-(1-oxo-2-hydroxyethyl) furan (8), were isolated from the culture of Salicorn 46, and their chemical structures were elucidated by spectroscopic analysis. Antioxidant experiments revealed that compound 1 possessed moderate DPPH radical scavenging activity with an IC50 value of 85.33?±?1.61 ?M. Antimicrobial assays revealed that compound 2 exhibited broad-spectrum antimicrobial activity against Candida albicans, Clostridium perfringens, Mycobacterium smegmatis, and Mycobacterium phlei with minimal inhibitory concentration (MIC) values of 25.5, 25.5, 18.5, and 51.0 ?M, respectively. Compound 3 displayed potent antimicrobial activities against C. perfringens and Micrococcus tetragenus with a MIC value of 23.5 ?M. Compounds 5 and 6 showed high levels of selectivity toward Bacillus subtilis and M. phlei with MIC values of 22.5 and 14.4 ?M, respectively. The results of this study highlight the use of PCR-based techniques for the screening of new polyketides from endophytic fungi containing PKS I genes. PMID:24535256

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

    PubMed Central

    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

    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

  12. In Vitro Assessment of the Inflammatory Breast Cancer Cell Line SUM 149: Discovery of 2 Single Nucleotide Polymorphisms in the RNase L Gene

    PubMed Central

    Nokes, Brandon T.; Cunliffe, Heather E.; LaFleur, Bonnie; Mount, David W.; Livingston, Robert B.; Futscher, Bernard W.; Lang, Julie E.

    2013-01-01

    Background: Inflammatory breast cancer (IBC) is a rare, highly aggressive form of breast cancer. The mechanism of IBC carcinogenesis remains unknown. We sought to evaluate potential genetic risk factors for IBC and whether or not the IBC cell lines SUM149 and SUM190 demonstrated evidence of viral infection. Methods: We performed single nucleotide polymorphism (SNP) genotyping for 2 variants of the ribonuclease (RNase) L gene that have been correlated with the risk of prostate cancer due to a possible viral etiology. We evaluated dose-response to treatment with interferon-alpha (IFN-?); and assayed for evidence of the putative human mammary tumor virus (HMTV, which has been implicated in IBC) in SUM149 cells. A bioinformatic analysis was performed to evaluate expression of RNase L in IBC and non-IBC. Results: 2 of 2 IBC cell lines were homozygous for RNase L common missense variants 462 and 541; whereas 2 of 10 non-IBC cell lines were homozygous positive for the 462 variant (p= 0.09) and 0 of 10 non-IBC cell lines were homozygous positive for the 541 variant (p = 0.015). Our real-time polymerase chain reaction (RT-PCR) and Southern blot analysis for sequences of HMTV revealed no evidence of the putative viral genome. Conclusion: We discovered 2 SNPs in the RNase L gene that were homozygously present in IBC cell lines. The 462 variant was absent in non-IBC lines. Our discovery of these SNPs present in IBC cell lines suggests a possible biomarker for risk of IBC. We found no evidence of HMTV in SUM149 cells. A query of a panel of human IBC and non-IBC samples showed no difference in RNase L expression. Further studies of the RNase L 462 and 541 variants in IBC tissues are warranted to validate our in vitro findings. PMID:23386909

  13. The role of the laboratory mouse in the human genome project

    Microsoft Academic Search

    Meisler

    1996-01-01

    The long-term goal of the human genome project is to identify and establish the function of each of the estimated 100,000 genes in the genome. The gene-discovery phase of the project is proceeding rapidly, via large-scale sequencing of genomic and cDNA clones. Establishing the functional roles for these genes is the challenge for the future. New methods have improved the

  14. Cys-loop ligand-gated ion channel gene discovery in the Locusta migratoria manilensis through the neuron transcriptome.

    PubMed

    Wang, Xin; Meng, Xiangkun; Liu, Chuanjun; Gao, Hongli; Zhang, Yixi; Liu, Zewen

    2015-05-01

    As an ideal model, Locusta migratoria manilensis (Meyen) has been widely used in the study of endocrinological and neurobiological processes. Here we created a large transcriptome of the locust neurons, which enriched ion channels whose potential for functional genetic experiments is currently limited. With high-throughput Illumina sequencing technology, we obtained more than 50 million raw reads, which were assembled into 61,056 unique sequences with average size of 737bp. Among the unigenes, a total 24,884 sequences had significant similarities with proteins in the five public databases (NR, SwissProt, GO, COG and KEGG) with a cut-off E-value of 10(-5) using BLASTx. Moreover, the number of potential genes of the cys-loop ligand-gated ion channels (LGICs) was manually curated, including 39 putative nicotinic acetylcholine receptors (nAChRs), 6 putative ?-aminobutyric acid (GABA) gated anion channels, 21 putative glutamate-gated chloride channels (GluCls) and 1 histamine-gated chloride channels (HisCls). In addition, the full-length of 11 nAChRs subunits (9 alpha and 2 beta) were obtained by RACE technique that would be helpful to further studies on nAChR neurochemistry and pharmacological aspects. To our knowledge, this is the first study to characterize the locust neuron transcriptome, which will provide a useful resource especially for future studies on the neuro-function and behavior of the locust. PMID:25701599

  15. Asymmetric Transcript Discovery by RNA-seq in C. elegans Blastomeres Identifies neg-1, a Gene Important for Anterior Morphogenesis

    PubMed Central

    Osborne Nishimura, Erin; Zhang, Jay C.; Werts, Adam D.; Goldstein, Bob; Lieb, Jason D.

    2015-01-01

    After fertilization but prior to the onset of zygotic transcription, the C. elegans zygote cleaves asymmetrically to create the anterior AB and posterior P1 blastomeres, each of which goes on to generate distinct cell lineages. To understand how patterns of RNA inheritance and abundance arise after this first asymmetric cell division, we pooled hand-dissected AB and P1 blastomeres and performed RNA-seq. Our approach identified over 200 asymmetrically abundant mRNA transcripts. We confirmed symmetric or asymmetric abundance patterns for a subset of these transcripts using smFISH. smFISH also revealed heterogeneous subcellular patterning of the P1-enriched transcripts chs-1 and bpl-1. We screened transcripts enriched in a given blastomere for embryonic defects using RNAi. The gene neg-1 (F32D1.6) encoded an AB-enriched (anterior) transcript and was required for proper morphology of anterior tissues. In addition, analysis of the asymmetric transcripts yielded clues regarding the post-transcriptional mechanisms that control cellular mRNA abundance during asymmetric cell divisions, which are common in developing organisms. PMID:25875092

  16. A late 17?-hydroxylase deficiency diagnosis that leads to the discovery of a new CYP17 gene mutation.

    PubMed

    Guenego, Agathe; Morel, Yves; Ionesco, Oana; Mallet, Delphine; Priou-Guesdon, Melanie

    2015-02-01

    17?-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia. It leads to a reduced production of cortisol and sex steroids and thus an increase in adrenocorticotrophic hormone and gonadotrophins levels. High adrenocorticotrophic hormone levels result in an accumulation of 17-deoxysteroids, such as deoxycorticosterone and corticosterone. Deoxycorticosterone and corticosterone have an important mineralocorticoid activity. We report the case of a 66-year-old woman who presented with hypertension and symptomatic hypokalaemia. Primary hyperaldosteronism was suspected and a right adrenal mass was removed. After surgery, the patient was referred to the endocrinology department for persistant hypokalaemia. Actually, she presented some signs of hypogonadism (impuberism, primary amenorrhea, infertility). Cortisol and 17OH-progesterone serum levels were low. Deoxycorticosterone and corticosterone were markedly elevated. The hypothesis of 17?-hydroxylase deficiency was considered and confirmed by genetic exploration. A non-sense mutation c.938G>A (p.Trp313X) in exon 5 of the CYP17 gene was found that had never been reported so far to our knowledge. Moreover, the patient's karyotype found a mosaic Turner syndrome. This case is particularly interesting because of the delay of diagnosis. The 17?-hydroxylase deficiency diagnosis is to be considered when hypertension is associated with hypokalaemia and hypogonadism, even in adult patients. PMID:25613935

  17. Developmental Gene Discovery in a Hemimetabolous Insect: De Novo Assembly and Annotation of a Transcriptome for the Cricket Gryllus bimaculatus

    PubMed Central

    Zeng, Victor; Ewen-Campen, Ben; Horch, Hadley W.; Roth, Siegfried; Mito, Taro; Extavour, Cassandra G.

    2013-01-01

    Most genomic resources available for insects represent the Holometabola, which are insects that undergo complete metamorphosis like beetles and flies. In contrast, the Hemimetabola (direct developing insects), representing the basal branches of the insect tree, have very few genomic resources. We have therefore created a large and publicly available transcriptome for the hemimetabolous insect Gryllus bimaculatus (cricket), a well-developed laboratory model organism whose potential for functional genetic experiments is currently limited by the absence of genomic resources. cDNA was prepared using mRNA obtained from adult ovaries containing all stages of oogenesis, and from embryo samples on each day of embryogenesis. Using 454 Titanium pyrosequencing, we sequenced over four million raw reads, and assembled them into 21,512 isotigs (predicted transcripts) and 120,805 singletons with an average coverage per base pair of 51.3. We annotated the transcriptome manually for over 400 conserved genes involved in embryonic patterning, gametogenesis, and signaling pathways. BLAST comparison of the transcriptome against the NCBI non-redundant protein database (nr) identified significant similarity to nr sequences for 55.5% of transcriptome sequences, and suggested that the transcriptome may contain 19,874 unique transcripts. For predicted transcripts without significant similarity to known sequences, we assessed their similarity to other orthopteran sequences, and determined that these transcripts contain recognizable protein domains, largely of unknown function. We created a searchable, web-based database to allow public access to all raw, assembled and annotated data. This database is to our knowledge the largest de novo assembled and annotated transcriptome resource available for any hemimetabolous insect. We therefore anticipate that these data will contribute significantly to more effective and higher-throughput deployment of molecular analysis tools in Gryllus. PMID:23671567

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

    PubMed Central

    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

    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

  19. The Extragalactic Distance Scale Key Project VIII. The Discovery of Cepheids and a New Distance to NGC 3621 Using the Hubble Space Telescope

    E-print Network

    Daya M. Rawson; Lucas M. Macri; Jeremy R. Mould; John P. Huchra; Wendy L. Freedman; Robert C. Kennicutt; Laura Ferrarese; Holland C. Ford; John A. Graham; Paul Harding; Mingsheng Han; Robert J. Hill; John G. Hoessel; Shaun M. G. Hughes; Garth D. Illingworth; Barry F. Madore; Randy L. Phelps; Abhijit Saha; Shoko Sakai; Nancy A. Silbermann; Peter B. Stetson

    1997-05-30

    We report on the discovery of Cepheids in the field spiral galaxy NGC 3621, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope (HST). NGC 3621 is one of 18 galaxies observed as a part of The HST Key Project on the Extragalactic Distance Scale, which aims to measure the Hubble constant to 10% accuracy. Sixty-nine Cepheids with periods in the range 9--60 days were observed over 12 epochs using the F555W filter, and 4 epochs using the F814W filter. The HST F555W and F814W data were transformed to the Johnson V and Kron-Cousins I magnitude systems, respectively. Photometry was performed using two independent packages, DAOPHOT II/ALLFRAME and DoPHOT. Period-luminosity relations in the V and I bands were constructed using 36 fairly isolated Cepheids present in our set of 69 variables. Extinction-corrected distance moduli relative to the LMC of 10.63 +/- 0.07 mag and 10.56 +/- 0.10 mag were obtained using the ALLFRAME and DoPHOT data, respectively. True distance moduli of 29.13 +/- 0.18 mag and 29.06 +/- 0.18 mag, corresponding to distances of 6.3 Mpc and 6.1 Mpc, were obtained by assuming values of 18.50 +/- 0.10 mag for the distance modulus of the LMC and E(V-I) = 0.13 mag for the reddening of the LMC.

  20. Characterisation of the wheat (triticum aestivum L.) transcriptome by de novo assembly for the discovery of phosphate starvation-responsive genes: gene expression in Pi-stressed wheat

    PubMed Central

    2013-01-01

    Background Phosphorus (P) is an essential macronutrient for plant growth and development. To modulate their P homeostasis, plants must balance P uptake, mobilisation, and partitioning to various organs. Despite the worldwide importance of wheat as a cultivated food crop, molecular mechanisms associated with phosphate (Pi) starvation in wheat remain unclear. To elucidate these mechanisms, we used RNA-Seq methods to generate transcriptome profiles of the wheat variety ‘Chinese Spring’ responding to 10 days of Pi starvation. Results We carried out de novo assembly on 73.8 million high-quality reads generated from RNA-Seq libraries. We then constructed a transcript dataset containing 29,617 non-redundant wheat transcripts, comprising 15,047 contigs and 14,570 non-redundant full-length cDNAs from the TriFLDB database. When compared with barley full-length cDNAs, 10,656 of the 15,047 contigs were unalignable, suggesting that many might be distinct from barley transcripts. The average expression level of the contigs was lower than that of the known cDNAs, implying that these contigs included transcripts that were rarely represented in the full-length cDNA library. Within the non-redundant transcript set, we identified 892–2,833 responsive transcripts in roots and shoots, corresponding on average to 23.4% of the contigs not covered by cDNAs in TriFLDB under Pi starvation. The relative expression level of the wheat IPS1 (Induced by Phosphate Starvation 1) homologue, TaIPS1, was 341-fold higher in roots and 13-fold higher in shoots; this finding was further confirmed by qRT-PCR analysis. A comparative analysis of the wheat- and rice-responsive transcripts for orthologous genes under Pi-starvation revealed commonly upregulated transcripts, most of which appeared to be involved in a general response to Pi starvation, namely, an IPS1-mediated signalling cascade and its downstream functions such as Pi remobilisation, Pi uptake, and changes in Pi metabolism. Conclusions Our transcriptome profiles demonstrated the impact of Pi starvation on global gene expression in wheat. This study revealed that enhancement of the Pi-mediated signalling cascade using IPS1 is a potent adaptation mechanism to Pi starvation that is conserved in both wheat and rice and validated the effectiveness of using short-read next-generation sequencing data for wheat transcriptome analysis in the absence of reference genome information. PMID:23379779

  1. Is a gene-centric human proteome project the best way for proteomics to serve biology?

    PubMed

    Rabilloud, Thierry; Hochstrasser, Denis; Simpson, Richard J

    2010-09-01

    With the recent developments in proteomic technologies, a complete human proteome project (HPP) appears feasible for the first time. However, there is still debate as to how it should be designed and what it should encompass. In "proteomics speak", the debate revolves around the central question as to whether a gene-centric or a protein-centric proteomics approach is the most appropriate way forward. In this paper, we try to shed light on what these definitions mean, how large-scale proteomics such as a HPP can insert into the larger omics chorus, and what we can reasonably expect from a HPP in the way it has been proposed so far. PMID:20648483

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

    PubMed

    Katz, Ira K; Lamprecht, Raphael

    2015-02-01

    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 naďve 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. PMID:25352022

  3. DOE “Discovery Across Texas” Project

    E-print Network

    Holloway, M.

    2011-01-01

    Smart appliances --- --- --- Yes HEM system --- --- --- Yes Load control (PCT adjustment) --- Yes (1-way) Yes (2-way) Yes (2-way) Solar panels --- --- --- Yes Energy storage system --- --- --- Yes * PEV charging station and lease vehicle... technologies for wind integration leveraging smart grid deployments of a start-up synchrophasor network, AMS, SMT and a solar community ? Primary Components: ? Synchrophasors ? Smart Meter Texas Portal ? Smart Grid Community of the Future 3 Context...

  4. Effective Dimension Reduction Using Sequential Projection Pursuit On Gene Expression Data for Cancer Classification

    SciTech Connect

    Webb-Robertson, Bobbie-Jo M.; Havre, Susan L.

    2004-06-23

    Motiviation: Classification is a powerful tool for uncovering interesting phenomena, for example classes of cancer, in microarray data. Due to the small number of observations (n) in comparison to the number of variables (p), genes, classification on microarray data is challenging. Thus, multivariate dimension reduction techniques are commonly used as a precursor to classification of microarray data; typically this is principal component analysis (PCA) or singular value decomposition (SVD). Since PCA and SVD are concerned with explaining the variance-covariance structure of the data, they may not be the best choice when the between-cluster variance is smaller than the within-cluster variance. Recently an attractive alternative to PCA, sequential projection pursuit (SPP), has been introduced which is designed to elicit clustering tendencies in the data. Thus, in some cases SPP may be more appropriate when performing clustering or classification analysis. Results: We compare the performance of SPP to PCA on two cancer gene expression datasets related to leukemia and colon cancer. Using PCA and SPP to reduce the dimensionality of the data to m<

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

    PubMed Central

    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

    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

  6. Construction and evaluation of normalized cDNA libraries enriched with full-length sequences for rapid discovery of new genes from Sisal (Agave sisalana Perr.) different developmental stages.

    PubMed

    Zhou, Wen-Zhao; Zhang, Yan-Mei; Lu, Jun-Ying; Li, Jun-Feng

    2012-01-01

    To provide a resource of sisal-specific expressed sequence data and facilitate this powerful approach in new gene research, the preparation of normalized cDNA libraries enriched with full-length sequences is necessary. Four libraries were produced with RNA pooled from Agave sisalana multiple tissues to increase efficiency of normalization and maximize the number of independent genes by SMART™ method and the duplex-specific nuclease (DSN). This procedure kept the proportion of full-length cDNAs in the subtracted/normalized libraries and dramatically enhanced the discovery of new genes. Sequencing of 3875 cDNA clones of libraries revealed 3320 unigenes with an average insert length about 1.2 kb, indicating that the non-redundancy of libraries was about 85.7%. These unigene functions were predicted by comparing their sequences to functional domain databases and extensively annotated with Gene Ontology (GO) terms. Comparative analysis of sisal unigenes and other plant genomes revealed that four putative MADS-box genes and knotted-like homeobox (knox) gene were obtained from a total of 1162 full-length transcripts. Furthermore, real-time PCR showed that the characteristics of their transcripts mainly depended on the tight expression regulation of a number of genes during the leaf and flower development. Analysis of individual library sequence data indicated that the pooled-tissue approach was highly effective in discovering new genes and preparing libraries for efficient deep sequencing. PMID:23202944

  7. Construction and Evaluation of Normalized cDNA Libraries Enriched with Full-Length Sequences for Rapid Discovery of New Genes from Sisal (Agave sisalana Perr.) Different Developmental Stages

    PubMed Central

    Zhou, Wen-Zhao; Zhang, Yan-Mei; Lu, Jun-Ying; Li, Jun-Feng

    2012-01-01

    To provide a resource of sisal-specific expressed sequence data and facilitate this powerful approach in new gene research, the preparation of normalized cDNA libraries enriched with full-length sequences is necessary. Four libraries were produced with RNA pooled from Agave sisalana multiple tissues to increase efficiency of normalization and maximize the number of independent genes by SMART™ method and the duplex-specific nuclease (DSN). This procedure kept the proportion of full-length cDNAs in the subtracted/normalized libraries and dramatically enhanced the discovery of new genes. Sequencing of 3875 cDNA clones of libraries revealed 3320 unigenes with an average insert length about 1.2 kb, indicating that the non-redundancy of libraries was about 85.7%. These unigene functions were predicted by comparing their sequences to functional domain databases and extensively annotated with Gene Ontology (GO) terms. Comparative analysis of sisal unigenes and other plant genomes revealed that four putative MADS-box genes and knotted-like homeobox (knox) gene were obtained from a total of 1162 full-length transcripts. Furthermore, real-time PCR showed that the characteristics of their transcripts mainly depended on the tight expression regulation of a number of genes during the leaf and flower development. Analysis of individual library sequence data indicated that the pooled-tissue approach was highly effective in discovering new genes and preparing libraries for efficient deep sequencing. PMID:23202944

  8. Accidental Discoveries

    NSDL National Science Digital Library

    2010-01-01

    The students will understand that science theories change in the face of new evidence, but those changes can be slow in coming. To download the lesson plan as a pdf, see the document below. Students willResearch scientific discoveries that happened by accident in the past and learn how gamma-rays were discovered by 20th century scientists

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

    Microsoft Academic Search

    Leming Shi; Laura H Reid; Wendell D Jones; Richard Shippy; Janet A Warrington; Shawn C Baker; Patrick J Collins; Francoise de Longueville; Ernest S Kawasaki; Kathleen Y Lee; Yuling Luo; Yongming Andrew Sun; James C Willey; Robert A Setterquist; Gavin M Fischer; Weida Tong; Yvonne P Dragan; David J Dix; Felix W Frueh; Federico M Goodsaid; Damir Herman; Roderick V Jensen; Charles D Johnson; Edward K Lobenhofer; Raj K Puri; Uwe Scherf; Jean Thierry-Mieg; Charles Wang; Mike Wilson; Paul K Wolber; Lu Zhang; Shashi Amur; Wenjun Bao; Catalin C Barbacioru; Anne Bergstrom Lucas; Vincent Bertholet; Cecilie Boysen; Bud Bromley; Donna Brown; Alan Brunner; Roger Canales; Xiaoxi Megan Cao; Thomas A Cebula; James J Chen; Jing Cheng; Tzu-Ming Chu; Eugene Chudin; John Corson; J Christopher Corton; Lisa J Croner; Christopher Davies; Timothy S Davison; Glenda Delenstarr; Xutao Deng; David Dorris; Aron C Eklund; Xiao-hui Fan; Hong Fang; Stephanie Fulmer-Smentek; James C Fuscoe; Kathryn Gallagher; Weigong Ge; Lei Guo; Xu Guo; Janet Hager; Paul K Haje; Jing Han; Tao Han; Heather C Harbottle; Stephen C Harris; Eli Hatchwell; Craig A Hauser; Susan Hester; Huixiao Hong; Patrick Hurban; Scott A Jackson; Hanlee Ji; Charles R Knight; Winston P Kuo; J Eugene LeClerc; Shawn Levy; Quan-Zhen Li; Chunmei Liu; Michael J Lombardi; Yunqing Ma; Scott R Magnuson; Botoul Maqsodi; Tim McDaniel; Nan Mei; Ola Myklebost; Baitang Ning; Natalia Novoradovskaya; Michael S Orr; Terry W Osborn; Adam Papallo; Tucker A Patterson; Roger G Perkins; Elizabeth H Peters; Ron Peterson; Kenneth L Philips; P Scott Pine; Lajos Pusztai; Feng Qian; Hongzu Ren; Mitch Rosen; Barry A Rosenzweig; Raymond R Samaha; Mark Schena; Gary P Schroth; Svetlana Shchegrova; Dave D Smith; Frank Staedtler; Zhenqiang Su; Hongmei Sun; Zoltan Szallasi; Zivana Tezak; Danielle Thierry-Mieg; Karol L Thompson; Irina Tikhonova; Yaron Turpaz; Beena Vallanat; Christophe Van; Stephen J Walker; Sue Jane Wang; Yonghong Wang; Russ Wolfinger; Alex Wong; Jie Wu; Chunlin Xiao; Qian Xie; Jun Xu; Wen Yang; Liang Zhang; Sheng Zhong; Yaping Zong; William Slikker; Ying Liu

    2006-01-01

    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, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as

  10. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    PubMed

    Gerhard, Daniela S; Wagner, Lukas; Feingold, Elise A; Shenmen, Carolyn M; Grouse, Lynette H; Schuler, Greg; Klein, Steven L; Old, Susan; Rasooly, Rebekah; Good, Peter; Guyer, Mark; Peck, Allison M; Derge, Jeffery G; Lipman, David; Collins, Francis S; Jang, Wonhee; Sherry, Steven; Feolo, Mike; Misquitta, Leonie; Lee, Eduardo; Rotmistrovsky, Kirill; Greenhut, Susan F; Schaefer, Carl F; Buetow, Kenneth; Bonner, Tom I; Haussler, David; Kent, Jim; Kiekhaus, Mark; Furey, Terry; Brent, Michael; Prange, Christa; Schreiber, Kirsten; Shapiro, Nicole; Bhat, Narayan K; Hopkins, Ralph F; Hsie, Florence; Driscoll, Tom; Soares, M Bento; Casavant, Tom L; Scheetz, Todd E; Brown-stein, Michael J; Usdin, Ted B; Toshiyuki, Shiraki; Carninci, Piero; Piao, Yulan; Dudekula, Dawood B; Ko, Minoru S H; Kawakami, Koichi; Suzuki, Yutaka; Sugano, Sumio; Gruber, C E; Smith, M R; Simmons, Blake; Moore, Troy; Waterman, Richard; Johnson, Stephen L; Ruan, Yijun; Wei, Chia Lin; Mathavan, S; Gunaratne, Preethi H; Wu, Jiaqian; Garcia, Angela M; Hulyk, Stephen W; Fuh, Edwin; Yuan, Ye; Sneed, Anna; Kowis, Carla; Hodgson, Anne; Muzny, Donna M; McPherson, John; Gibbs, Richard A; Fahey, Jessica; Helton, Erin; Ketteman, Mark; Madan, Anuradha; Rodrigues, Stephanie; Sanchez, Amy; Whiting, Michelle; Madari, Anup; Young, Alice C; Wetherby, Keith D; Granite, Steven J; Kwong, Peggy N; Brinkley, Charles P; Pearson, Russell L; Bouffard, Gerard G; Blakesly, Robert W; Green, Eric D; Dickson, Mark C; Rodriguez, Alex C; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M; Butterfield, Yaron S N; Griffith, Malachi; Griffith, Obi L; Krzywinski, Martin I; Liao, Nancy; Morin, Ryan; Morrin, Ryan; Palmquist, Diana; Petrescu, Anca S; Skalska, Ursula; Smailus, Duane E; Stott, Jeff M; Schnerch, Angelique; Schein, Jacqueline E; Jones, Steven J M; Holt, Robert A; Baross, Agnes; Marra, Marco A; Clifton, Sandra; Makowski, Kathryn A; Bosak, Stephanie; Malek, Joel

    2004-10-01

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline. PMID:15489334

  11. Mathematics Discoveries

    NSDL National Science Digital Library

    2009-01-01

    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."

  12. The discovery of GW bodies.

    PubMed

    Fritzler, Marvin J; Chan, Edward K L

    2013-01-01

    Human autoantibodies were a key to the discovery of GW bodies and their integral protein, GW182. This publication marks the tenth anniversary of the discovery of GW182. As it turns out, the discovery of GW182 was quite timely because it coincided with the elucidation of the RNA interference (RNAi) pathway, which is now known to have a major role in post-transcriptional gene regulation. Following our publication of the essential features of GW182 in 2002, laboratories from around the world began investigations that led to the elucidation of the role of GW182 in RNAi and other pathways of mRNA processing and degradation. This chapter reviews the discovery of GW182 and the description of GWB and some of the observations that followed that still remain to be elucidated. PMID:23224962

  13. Glutamatergic gene expression is specifically reduced in thalamocortical projecting relay neurons in schizophrenia

    PubMed Central

    Sodhi, Monsheel S.; Simmons, Micah; McCullumsmith, Robert; Haroutunian, Vahram; Meador-Woodruff, James H.

    2011-01-01

    Background Impairment of glutamate neurons which relay sensory and cognitive information from the medial dorsal thalamus to the dorsolateral prefrontal cortex and other cortical regions may contribute to the pathophysiology of schizophrenia. In this study we have assessed the cell-specific expression of glutamatergic transcripts in the medial dorsal thalamus. Methods and Materials We used laser-capture microdissection to harvest two populations of medial dorsal thalamic cells, one enriched with glutamatergic relay neurons, and the other with GABAergic neurons and astroglia, from postmortem brains of subjects with schizophrenia (n=14) and a comparison group (n=20). Quantitative polymerase chain reaction (QPCR) of extracted RNA was used to assay gene expression in different cell populations. Results The transcripts encoding the ionotropic glutamate receptor subunits NR2D, GluR3, GluR6, GluR7, and the intracellular proteins GRIP1 and SynGAP1 were significantly decreased in relay neurons but not in the mixed glial and interneuron population in schizophrenia. Discussion Our data suggest that reduced ionotropic glutamatergic expression occurs selectively in neurons giving rise to the cortical projections of the medial dorsal thalamus in schizophrenia, rather than in thalamic cells which function locally. Our findings indicate that glutamatergic innervation is dysfunctional in the circuitry between the medial dorsal thalamus and cortex. PMID:21549355

  14. Mutation discovery in bacterial genomes

    E-print Network

    Cai, Long

    , a gastric pathogen implicated in peptic ulcer disease and gastric cancer4,5. H. pylori infections are oftenMutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori Thomas J it to study metronidazole resistance in H. pylori. CGS identified mutations in several genes, most likely

  15. Scientific Discovery for All

    NSDL National Science Digital Library

    Duncan Quarless

    2007-03-01

    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. Students develop projects from an original idea that interests them, design the methodology, implement it, present results in written and oral format competitions and conferences, and propose and conduct further studies. The Uniondale program advisor and external mentors guide young investigators in "doing science" by instructing them in techniques, research ethics, and scientific integrity (NAS 1995), and advising students while they prepare research papers and presentations. This article describes the components of this successful program: careful recruitment; research projects that are devised by students; and recognition by the school, community, and outside entities.

  16. Mathematical modelling in drug discovery

    E-print Network

    Wirosoetisno, Djoko

    Spectroscopy Measurements · No observable response in PIP2 when upstream kinases are inhibited. ·Project response? #12;Oncology: Phosphoinositide Signalling Liu et al. (2009) Nature Rev. Drug Discovery #12;PIP2 (PIP) species. P P P Cell membrane (Diagram by Vikki Flemington) #12;PIP Signalling cascade Bunney et

  17. Harry Stottlemier's Discovery [Revised Edition].

    ERIC Educational Resources Information Center

    Lipman, Matthew

    "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…

  18. Impact of the human genome project on medical practice

    Microsoft Academic Search

    Belinda J. F. Rossiter; C. Thomas Caskey

    1995-01-01

    Background: The Human Genome Project is a coordinated effort to define the human genetic blueprint. The goals include construction of a variety of maps of the human genome, including the identification and localization of all genes. The discovery of genes responsible for human diseases has had a significant impact on the practice of medicine.\\u000aMethods: Methods for defining the human

  19. 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

    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

    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),

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

    Microsoft Academic Search

    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

    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

  1. High throughput sequencing approaches to mutation discovery in the mouse

    PubMed Central

    Simon, Michelle M; Mallon, Ann-Marie; Howell, Gareth R.; Reinholdt, Laura G.

    2013-01-01

    Phenotype driven approaches in mice are powerful strategies for the discovery of genes, gene functions and for unravelling complex biological mechanisms. Traditional methods for mutation discovery are reliable and robust, but they can also be laborious and time consuming. Recently, high throughput sequencing (HTS) technologies have revolutionised the process of forward genetics in mice by paving the way to rapid mutation discovery. However, successful application of HTS for mutation discovery is relies heavily on the sequencing approach employed and strategies for data analysis. Here, we review current HTS applications and resources for mutation discovery and provide an overview of the practical considerations for HTS implementation and data analysis. PMID:22991087

  2. 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.â?ť 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.

  3. De novo assembly of the pepper transcriptome (Capsicum annuum): a benchmark for in silico discovery of SNPs, SSRs and candidate genes

    PubMed Central

    2012-01-01

    Background Molecular breeding of pepper (Capsicum spp.) can be accelerated by developing DNA markers associated with transcriptomes in breeding germplasm. Before the advent of next generation sequencing (NGS) technologies, the majority of sequencing data were generated by the Sanger sequencing method. By leveraging Sanger EST data, we have generated a wealth of genetic information for pepper including thousands of SNPs and Single Position Polymorphic (SPP) markers. To complement and enhance these resources, we applied NGS to three pepper genotypes: Maor, Early Jalapeńo and Criollo de Morelos-334 (CM334) to identify SNPs and SSRs in the assembly of these three genotypes. Results Two pepper transcriptome assemblies were developed with different purposes. The first reference sequence, assembled by CAP3 software, comprises 31,196 contigs from >125,000 Sanger-EST sequences that were mainly derived from a Korean F1-hybrid line, Bukang. Overlapping probes were designed for 30,815 unigenes to construct a pepper Affymetrix GeneChip® microarray for whole genome analyses. In addition, custom Python scripts were used to identify 4,236 SNPs in contigs of the assembly. A total of 2,489 simple sequence repeats (SSRs) were identified from the assembly, and primers were designed for the SSRs. Annotation of contigs using Blast2GO software resulted in information for 60% of the unigenes in the assembly. The second transcriptome assembly was constructed from more than 200 million Illumina Genome Analyzer II reads (80–120 nt) using a combination of Velvet, CLC workbench and CAP3 software packages. BWA, SAMtools and in-house Perl scripts were used to identify SNPs among three pepper genotypes. The SNPs were filtered to be at least 50 bp from any intron-exon junctions as well as flanking SNPs. More than 22,000 high-quality putative SNPs were identified. Using the MISA software, 10,398 SSR markers were also identified within the Illumina transcriptome assembly and primers were designed for the identified markers. The assembly was annotated by Blast2GO and 14,740 (12%) of annotated contigs were associated with functional proteins. Conclusions Before availability of pepper genome sequence, assembling transcriptomes of this economically important crop was required to generate thousands of high-quality molecular markers that could be used in breeding programs. In order to have a better understanding of the assembled sequences and to identify candidate genes underlying QTLs, we annotated the contigs of Sanger-EST and Illumina transcriptome assemblies. These and other information have been curated in a database that we have dedicated for pepper project. PMID:23110314

  4. Use of the site-specific retargeting jump-in platform cell line to support biologic drug discovery.

    PubMed

    Butler, Robin; Hornigold, David; Huang, Ling; Huntington, Catherine; London, Tim; Dillon, Janette; Tigue, Natalie J; Rossi, Alessandra; Naylor, Jacqueline; Wilkinson, Trevor

    2015-04-01

    Biologics represent a fast-growing class of therapeutics in the pharmaceutical sector. Discovery of therapeutic antibodies and characterization of peptides can necessitate high expression of the target gene requiring the generation of clonal stably transfected cell lines. Traditional challenges of stable cell line transfection include gene silencing and cell-to-cell variability. Our inability to control these can present challenges in lead isolation. Recent progress in site-specific targeting of transgene to specific genomic loci has transformed the ability to generate stably transfected mammalian cell lines. In this article, we describe how the use of the Jump-In platform (Life Technologies, Carlsbad, CA) has been applied to drug discovery projects. It can easily and rapidly generate homogeneous high-expressing cell pools with a high degree of reproducibility. Their use in cell-based screening to identify specific binders, identify binding to relevant species variants, or detect functionally relevant therapeutic antibodies is central in driving drug discovery. PMID:25534831

  5. The Discovery Channel Telescope

    NASA Astrophysics Data System (ADS)

    Millis, R. L.; Dunham, E. W.; Sebring, T. A.; Smith, B. W.; de Kock, M.; Wiecha, O.

    2004-11-01

    The Discovery Channel Telescope (DCT) is a 4.2-m telescope to be built at a new site near Happy Jack, Arizona. The DCT features a large prime focus mosaic CCD camera with a 2-degree-diameter field of view especially designed for surveys of KBOs, Centaurs, NEAs and other moving or time-variable targets. The telescope can be switched quickly to a Ritchey-Chretien configuration for optical/IR spectroscopy or near-IR imaging. This flexibility allows timely follow-up physical studies of high priority objects discovered in survey mode. The ULE (ultra-low-expansion) meniscus primary and secondary mirror blanks for the telescope are currently in fabrication by Corning Glass. Goodrich Aerospace, Vertex RSI, M3 Engineering and Technology Corp., and e2v Technologies have recently completed in-depth conceptual design studies of the optics, mount, enclosure, and mosaic focal plane, respectively. The results of these studies were subjected to a formal design review in July, 2004. Site testing at the 7760-ft altitude Happy Jack site began in 2001. Differential image motion observations from 117 nights since January 1, 2003 gave median seeing of 0.84 arcsec FWHM, and the average of the first quartile was 0.62 arcsec. The National Environmental Policy Act (NEPA) process for securing long-term access to this site on the Coconino National Forest is nearing completion and ground breaking is expected in the spring of 2005. The Discovery Channel Telescope is a project of the Lowell Observatory with major financial support from Discovery Communications, Inc. (DCI). DCI plans ongoing television programming featuring the construction of the telescope and the research ultimately undertaken with the DCT. An additional partner can be accommodated in the project. Interested parties should contact the lead author.

  6. Open PHACTS: semantic interoperability for drug discovery.

    PubMed

    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

    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

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

    PubMed Central

    Bürglin, Thomas R

    2008-01-01

    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

  8. One goal of genome projects is to systematically identify genes1

    E-print Network

    Eddy, Sean

    RNAs. A pioneering study by Roy Parker's group found a few new RNA genes and small open reading frames (ORFs of Medicine, Saint Louis, Missouri 63110, USA. e-mail: eddy@genetics.wustl.edu © 2001 Macmillan Magazines Ltd

  9. THE BIOCATALYTIC DESULFURIZATION PROJECT

    SciTech Connect

    Steven E. Bonde; David Nunn

    2003-01-01

    During the first quarter of the Biological Desulfurization project several activities were pursued. A project kickoff meeting was held at the Diversa facility in San Diego, CA. Activities that were in process before the meeting and begun afterwards by Diversa Corporation and Petro Star Inc. include: Technology transfer in the form of information generated by Enchira to Diversa, the purchase and installation of equipment by Diversa, development of synthetic methods and preparation of organo-sulfur substrates for use in determining enzyme activities, production of extract via Petro Star's CED process, detailed analysis of Petro Star Inc. diesel and CED extract, and several activities in molecular biology. Diversa Corporation, in the area of molecular biology, engaged in several activities in support of the task list of the contract. These included: construction of a genomic library; development and utilization of a sequence-based gene discovery effort; a parallel discovery approach based on functional expression of enzymes with the ability to oxidize organosulfur compounds. Biodesulfurization genes have already been identified and are being sequenced and subcloned for expression in heterologous biological hosts. Diversa has evaluated and adapted assays developed by Enchira used to assess the activities of DBT and DBTO{sub 2} monooxygenases. Finally, Diversa personnel have developed two novel selection/screen strategies for the improvement of biocatalyst strains by directed evolution.

  10. Genes

    NSDL National Science Digital Library

    BEGIN:VCARD VERSION:2.1 FN:Access Excellence N:Excellence; Access REV:2005-03-12 END:VCARD

    2005-03-12

    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.

  11. 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

    Eickelberg, Garrett J.; Fisher, Alison J.

    2013-01-01

    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…

  12. Code-Assisted Discovery of TAL Effector Targets in Bacterial Leaf Streak of Rice Reveals Contrast with Bacterial Blight and a Novel Susceptibility Gene

    PubMed Central

    Cernadas, Raul A.; Doyle, Erin L.; Nińo-Liu, David O.; Wilkins, Katherine E.; Bancroft, Timothy; Wang, Li; Schmidt, Clarice L.; Caldo, Rico; Yang, Bing; White, Frank F.; Nettleton, Dan; Wise, Roger P.; Bogdanove, Adam J.

    2014-01-01

    Bacterial leaf streak of rice, caused by Xanthomonas oryzae pv. oryzicola (Xoc) is an increasingly important yield constraint in this staple crop. A mesophyll colonizer, Xoc differs from X. oryzae pv. oryzae (Xoo), which invades xylem to cause bacterial blight of rice. Both produce multiple distinct TAL effectors, type III-delivered proteins that transactivate effector-specific host genes. A TAL effector finds its target(s) via a partially degenerate code whereby the modular effector amino acid sequence identifies nucleotide sequences to which the protein binds. Virulence contributions of some Xoo TAL effectors have been shown, and their relevant targets, susceptibility (S) genes, identified, but the role of TAL effectors in leaf streak is uncharacterized. We used host transcript profiling to compare leaf streak to blight and to probe functions of Xoc TAL effectors. We found that Xoc and Xoo induce almost completely different host transcriptional changes. Roughly one in three genes upregulated by the pathogens is preceded by a candidate TAL effector binding element. Experimental analysis of the 44 such genes predicted to be Xoc TAL effector targets verified nearly half, and identified most others as false predictions. None of the Xoc targets is a known bacterial blight S gene. Mutational analysis revealed that Tal2g, which activates two genes, contributes to lesion expansion and bacterial exudation. Use of designer TAL effectors discriminated a sulfate transporter gene as the S gene. Across all targets, basal expression tended to be higher than genome-average, and induction moderate. Finally, machine learning applied to real vs. falsely predicted targets yielded a classifier that recalled 92% of the real targets with 88% precision, providing a tool for better target prediction in the future. Our study expands the number of known TAL effector targets, identifies a new class of S gene, and improves our ability to predict functional targeting. PMID:24586171

  13. 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 Central

    Miyamoto, Kiyoko T.; Komatsu, Mamoru

    2014-01-01

    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

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

    PubMed Central

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

    2009-01-01

    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

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

    PubMed Central

    Silveira, Linda A.

    2009-01-01

    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

  16. From genes to proteins to behavior: a laboratory project that enhances student understanding in cell and molecular biology.

    PubMed

    Aronson, Benjamin D; Silveira, Linda A

    2009-01-01

    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

  17. Studying Human Disease Genes in Caenorhabditis elegans: A Molecular Genetics Laboratory Project

    PubMed Central

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

    2012-01-01

    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

  18. St. Jude gene sequencing project discovers common driver of a childhood brain tumor

    Cancer.gov

    St. Jude Children’s Research Hospital -Washington University Pediatric Cancer Genome Project identifies the most common genetic alteration yet in the brain tumor ependymoma; results offer clues for fighting other cancers.

  19. Discovery of the Genes in Response to White Spot Syndrome Virus (WSSV) Infection in Fenneropenaeus chinensis Through cDNA Microarray

    Microsoft Academic Search

    Bing Wang; Fuhua Li; Bo Dong; Xiaojun Zhang; Chengsong Zhang; Jianhai Xiang

    2006-01-01

    We used microarray technology to study differentially expressed genes in white spot syndrome virus (WSSV)-infected shrimp.\\u000a A total of 3136 cDNA targets, including 1578 unique genes from a cephalothorax cDNA library and 1536 cDNA clones from reverse\\u000a and forward suppression subtractive hybridization (SSH) libraries of Fenneropenaeus chinensis, plus 14 negative and 8 blank control clones, were spotted onto a 18

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2014-01-01

    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

  2. 454 pyrosequencing project identifying expressed genes from the horn fly, Haematobia irritans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We used an EST approach to initiate a study of the genome of the horn fly, Haematobia irritans and have used 454 pyrosequencing techniques to sequence 73,512, 100,603, 71,550, and 85,769 expressed genes from the egg, first instar larvae, adult male, and adult female lifestages of the horn fly. cD...

  3. Studying Human Disease Genes in "Caenorhabditis Elegans": A Molecular Genetics Laboratory Project

    ERIC Educational Resources Information Center

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

    2012-01-01

    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

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

    ERIC Educational Resources Information Center

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

    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…

  5. Resource Discovery Services for Grid Computing Training 

    E-print Network

    Low, Boon; Fergusson, David; MacColl, John

    2007-03-20

    discovery services developed as part of an initiative to pilot e-learning and a shared digital library infrastructure for Grid Computing training projects in Europe. The development is also related to a project funded by the UK Joint Information Systems...

  6. Discovery Mechanisms for the Sensor Web

    PubMed Central

    Jirka, Simon; Bröring, Arne; Stasch, Christoph

    2009-01-01

    This paper addresses the discovery of sensors within the OGC Sensor Web Enablement framework. Whereas services like the OGC Web Map Service or Web Coverage Service are already well supported through catalogue services, the field of sensor networks and the according discovery mechanisms is still a challenge. The focus within this article will be on the use of existing OGC Sensor Web components for realizing a discovery solution. After discussing the requirements for a Sensor Web discovery mechanism, an approach will be presented that was developed within the EU funded project “OSIRIS”. This solution offers mechanisms to search for sensors, exploit basic semantic relationships, harvest sensor metadata and integrate sensor discovery into already existing catalogues. PMID:22574038

  7. The K2-ESPRINT Project I: Discovery of the Disintegrating Rocky Planet with a Cometary Head and Tail EPIC 201637175b

    E-print Network

    Sanchis-Ojeda, R; Pallé, E; Delrez, L; DeVore, J; Gandolfi, D; Fukui, A; Ribas, I; Stassun, K G; Albrecht, S; Dai, F; Gaidos, E; Gillon, M; Hirano, T; Holman, M; Howard, A W; Isaacson, H; Jehin, E; Kuzuhara, M; Mann, A W; Marcy, G W; Miles-Páez, P A; Montańés-Rodríguez, P A; Murgas, F; Narita, N; Nowak, G; Onitsuka, M; Paegert, M; Van Eylen, V; Winn, J N; Yu, L

    2015-01-01

    We present the discovery of a transiting exoplanet candidate in the K2 Field-1 with an orbital period of 9.1457 hours: EPIC 201637175b. The highly variable transit depths, ranging from $\\sim$0\\% to 1.3\\%, are suggestive of a planet that is disintegrating via the emission of dusty effluents. We characterize the host star as an M-dwarf with $T_{\\rm eff} \\simeq 3800$. We have obtained ground-based transit measurements with several 1-m class telescopes and with the GTC. These observations (1) improve the transit ephemeris; (2) confirm the variable nature of the transit depths; (3) indicate variations in the transit shapes; and (4) demonstrate clearly that at least on one occasion the transit depths were significantly wavelength dependent. The latter three effects tend to indicate extinction of starlight by dust rather than by any combination of solid bodies. The K2 observations yield a folded light curve with lower time resolution but with substantially better statistical precision compared with the ground-based ...

  8. Whole-exome Sequencing and an iPSC-Derived Cardiomyocyte Model Provides a Powerful Platform for Gene Discovery in Left Ventricular Hypertrophy

    PubMed Central

    Zhi, D.; Irvin, M. R.; Gu, C. C.; Stoddard, A. J.; Lorier, R.; Matter, A.; Rao, D. C.; Srinivasasainagendra, V.; Tiwari, H. K.; Turner, A.; Broeckel, U.; Arnett, D. K.

    2012-01-01

    Rationale: Left ventricular hypertrophy (LVH) is a heritable predictor of cardiovascular disease, particularly in blacks. Objective: Determine the feasibility of combining evidence from two distinct but complementary experimental approaches to identify novel genetic predictors of increased LV mass. Methods: Whole-exome sequencing (WES) was conducted in seven African-American sibling trios ascertained on high average familial LV mass indexed to height (LVMHT) using Illumina HiSeq technology. Identified missense or nonsense (MS/NS) mutations were examined for association with LVMHT using linear mixed models adjusted for age, sex, body weight, and familial relationship. To functionally assess WES findings, human induced pluripotent stem cell-derived cardiomyocytes (induced pluripotent stem cell-CM) were stimulated to induce hypertrophy; mRNA sequencing (RNA-seq) was used to determine gene expression differences associated with hypertrophy onset. Statistically significant findings under both experimental approaches identified LVH candidate genes. Candidate genes were further prioritized by seven supportive criteria that included additional association tests (two criteria), regional linkage evidence in the larger HyperGEN cohort (one criterion), and publically available gene and variant based annotations (four criteria). Results: WES reads covered 91% of the target capture region (of size 37.2?MB) with an average coverage of 65×. WES identified 31,426 MS/NS mutations among the 21 individuals. A total of 295 MS/NS variants in 265 genes were associated with LVMHT with q-value <0.25. Of the 265 WES genes, 44 were differentially expressed (P?genes identified, 5, including HLA-B, HTT, MTSS1, SLC5A12, and THBS1, met 3 of 7 supporting criteria. THBS1 encodes an adhesive glycoprotein that promotes matrix preservation in pressure-overload LVH. THBS1 gene expression was 34% higher in hypertrophied cells (P?=?0.0003) and a predicted conserved and damaging NS variant in exon 13 (A2099G) was significantly associated with LVHMT (P?=?4?×?10?6). Conclusion: Combining evidence from cutting-edge genetic and cellular experiments can enable identification of novel LVH risk loci. PMID:22654895

  9. Projecting 2D gene expression data into 3D and 4D space.

    PubMed

    Gerth, Victor E; Katsuyama, Kaori; Snyder, Kevin A; Bowes, Jeff B; Kitayama, Atsushi; Ueno, Naoto; Vize, Peter D

    2007-04-01

    Video games typically generate virtual 3D objects by texture mapping an image onto a 3D polygonal frame. The feeling of movement is then achieved by mathematically simulating camera movement relative to the polygonal frame. We have built customized scripts that adapt video game authoring software to texture mapping images of gene expression data onto b-spline based embryo models. This approach, known as UV mapping, associates two-dimensional (U and V) coordinates within images to the three dimensions (X, Y, and Z) of a b-spline model. B-spline model frameworks were built either from confocal data or de novo extracted from 2D images, once again using video game authoring approaches. This system was then used to build 3D models of 182 genes expressed in developing Xenopus embryos and to implement these in a web-accessible database. Models can be viewed via simple Internet browsers and utilize openGL hardware acceleration via a Shockwave plugin. Not only does this database display static data in a dynamic and scalable manner, the UV mapping system also serves as a method to align different images to a common framework, an approach that may make high-throughput automated comparisons of gene expression patterns possible. Finally, video game systems also have elegant methods for handling movement, allowing biomechanical algorithms to drive the animation of models. With further development, these biomechanical techniques offer practical methods for generating virtual embryos that recapitulate morphogenesis. PMID:17366623

  10. Transcriptome sequencing and annotation of the microalgae Dunaliella tertiolecta: Pathway description and gene discovery for production of next-generation biofuels

    PubMed Central

    2011-01-01

    Background Biodiesel or ethanol derived from lipids or starch produced by microalgae may overcome many of the sustainability challenges previously ascribed to petroleum-based fuels and first generation plant-based biofuels. The paucity of microalgae genome sequences, however, limits gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for the non-model microalgae species, Dunaliella tertiolecta, and identify pathways and genes of importance related to biofuel production. Results Next generation DNA pyrosequencing technology applied to D. tertiolecta transcripts produced 1,363,336 high quality reads with an average length of 400 bases. Following quality and size trimming, ~ 45% of the high quality reads were assembled into 33,307 isotigs with a 31-fold coverage and 376,482 singletons. Assembled sequences and singletons were subjected to BLAST similarity searches and annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology (KO) identifiers. These analyses identified the majority of lipid and starch biosynthesis and catabolism pathways in D. tertiolecta. Conclusions The construction of metabolic pathways involved in the biosynthesis and catabolism of fatty acids, triacylglycrols, and starch in D. tertiolecta as well as the assembled transcriptome provide a foundation for the molecular genetics and functional genomics required to direct metabolic engineering efforts that seek to enhance the quantity and character of microalgae-based biofuel feedstock. PMID:21401935

  11. 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...

  12. 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

    Microsoft Academic Search

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

    2008-01-01

    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

  13. Allele discovery of ten candidate drought-response genes in Austrian oak using a systematically informatics approach based on 454 amplicon sequencing

    PubMed Central

    2012-01-01

    Background Rise of temperatures and shortening of available water as result of predicted climate change will impose significant pressure on long-lived forest tree species. Discovering allelic variation present in drought related genes of two Austrian oak species can be the key to understand mechanisms of natural selection and provide forestry with key tools to cope with future challenges. Results In the present study we have used Roche 454 sequencing and developed a bioinformatic pipeline to process multiplexed tagged amplicons in order to identify single nucleotide polymorphisms and allelic sequences of ten candidate genes related to drought/osmotic stress from sessile oak (Quercus robur) and sessile oak (Q. petraea) individuals. Out of these, eight genes of 336 oak individuals growing in Austria have been detected with a total number of 158 polymorphic sites. Allele numbers ranged from ten to 52 with observed heterozygosity ranging from 0.115 to 0.640. All loci deviated from Hardy-Weinberg equilibrium and linkage disequilibrium was found among six combinations of loci. Conclusions We have characterized 183 alleles of drought related genes from oak species and detected first evidences of natural selection. Beside the potential for marker development, we have created an expandable bioinformatic pipeline for the analysis of next generation sequencing data. PMID:22472016

  14. 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

  15. Discovery in chemistry

    SciTech Connect

    Holley, C.E. Jr.

    1982-12-01

    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.

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

    PubMed Central

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

    2008-01-01

    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

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

    PubMed Central

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

    2011-01-01

    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

  18. Using comparative genomics to drive new discoveries in microbiology.

    PubMed

    Haft, Daniel H

    2015-02-01

    Bioinformatics looks to many microbiologists like a service industry. In this view, annotation starts with what is known from experiments in the lab, makes reasonable inferences of which genes match other genes in function, builds databases to make all that we know accessible, but creates nothing truly new. Experiments lead, then biocuration and computational biology follow. But the astounding success of genome sequencing is changing the annotation paradigm. Every genome sequenced is an intercepted coded message from the microbial world, and as all cryptographers know, it is easier to decode a thousand messages than a single message. Some biology is best discovered not by phenomenology, but by decoding genome content, forming hypotheses, and doing the first few rounds of validation computationally. Through such reasoning, a role and function may be assigned to a protein with no sequence similarity to any protein yet studied. Experimentation can follow after the discovery to cement and to extend the findings. Unfortunately, this approach remains so unfamiliar to most bench scientists that lab work and comparative genomics typically segregate to different teams working on unconnected projects. This review will discuss several themes in comparative genomics as a discovery method, including highly derived data, use of patterns of design to reason by analogy, and in silico testing of computationally generated hypotheses. PMID:25617609

  19. Gene sequencing project finds family of drugs with promise for treating childhood tumor

    Cancer.gov

    Drugs that enhance a process called oxidative stress were found to kill rhabdomyosarcoma tumor cells growing in the laboratory and possibly bolstered the effectiveness of chemotherapy against this aggressive tumor of muscle and other soft tissue. The findings are the latest from the St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project and appear in the December 9 edition of the scientific journal Cancer Cell.

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

    PubMed Central

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

    2014-01-01

    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

  1. Insights into Hepatopancreatic Functions for Nutrition Metabolism and Ovarian Development in the Crab Portunus trituberculatus: Gene Discovery in the Comparative Transcriptome of Different Hepatopancreas Stages

    PubMed Central

    Liu, Zhijun; Zheng, Huajun; Cheng, Yongxu

    2014-01-01

    The crustacean hepatopancreas has different functions including absorption, storage of nutrients and vitellogenesis during growth, and ovarian development. However, genetic information on the biological functions of the crustacean hepatopancreas during such processes is limited. The swimming crab, Portunus trituberculatus, is a commercially important species for both aquaculture and fisheries in the Asia-Pacific region. This study compared the transcriptome in the hepatopancreas of female P. trituberculatus during the growth and ovarian maturation stages by 454 high-throughput pyrosequencing and bioinformatics. The goal was to discover genes in the hepatopancreas involved in food digestion, nutrition metabolism and ovarian development, and to identify patterns of gene expression during growth and ovarian maturation. Our transcriptome produced 303,450 reads with an average length of 351 bp, and the high quality reads were assembled into 21,635 contigs and 31,844 singlets. Based on BLASTP searches of the deduced protein sequences, there were 7,762 contigs and 4,098 singlets with functional annotation. Further analysis revealed 33,427 unigenes with ORFs, including 17,388 contigs and 16,039 singlets in the hepatopancreas, while only 7,954 unigenes (5,691 contigs and 2,263 singlets) with the predicted protein sequences were annotated with biological functions. The deduced protein sequences were assigned to 3,734 GO terms, 25 COG categories and 294 specific pathways. Furthermore, there were 14, 534, and 22 identified unigenes involved in food digestion, nutrition metabolism and ovarian development, respectively. 212 differentially expressed genes (DEGs) were found between the growth and endogenous stage of the hepatopancreas, while there were 382 DEGs between the endogenous and exogenous stage hepatopancreas. Our results not only enhance the understanding of crustacean hepatopancreatic functions during growth and ovarian development, but also represent a basis for further research on new genes and functional genomics of P. trituberculatus or closely related species. PMID:24454766

  2. Discovery of Western European R1b1a2 Y chromosome variants in 1000 genomes project data: an online community approach.

    PubMed

    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

    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

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

    PubMed Central

    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

    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

  4. Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751

    PubMed Central

    Innocenti, Federico; Ramírez, Jacqueline; Obel, Jennifer; Xiong, Julia; Mirkov, Snezana; Chiu, Yi-Lin; Katz, David A.; Carr, Robert A.; Zhang, Wei; Das, Soma; Adjei, Araba; Moyer, Ann M.; Chen, Pei Xian; Krivoshik, Andrew; Medina, Diane; Gordon, Gary B.; Ratain, Mark J.; Sahelijo, Leonardo; Weinshilboum, Richard M.; Fleming, Gini F.; Bhathena, Anahita

    2013-01-01

    Objective ABT-751, a novel orally available antitubulin agent, is mainly eliminated as inactive glucuronide (ABT-751G) and sulfate (ABT-751S) conjugates. We performed a pharmacogenetic investigation of ABT-751 pharmacokinetics using in-vitro data to guide the selection of genes for genotyping in a phase I trial of ABT-751. Methods UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes were screened for ABT-751 metabolite formation in vitro. Forty-seven cancer patients treated with ABT-751 were genotyped for 21 variants in these genes. Results UGT1A1, UGT1A4, UGT1A8, UGT2B7, and SULT1A1 were found to be involved in the formation of inactive ABT-751 glucuronide (ABT-751G) and sulfate (ABT-751S). SULT1A1 copy number (> 2) was associated with an average 34% increase in ABT-751 clearance (P= 0.044), an 18% reduction in ABT-751 AUC (P = 0.045), and a 50% increase in sulfation metabolic ratios (P=0.025). UGT1A8 rs6431558 was associated with a 28% increase in glucuronidation metabolic ratios (P =0.022), and UGT1A4*2 was associated with a 65% decrease in ABT-751 Ctrough (P = 0.009). Conclusion These results might represent the first example of a clinical pharmacokinetic effect of the SULT1A1 copy number variant on the clearance of a SULT1A1 substrate. A-priori selection of candidate genes guided by in-vitro metabolic screening enhanced our ability to identify genetic determinants of interpatient pharmacokinetic variability. PMID:23670235

  5. Gene expression profiling analysis of the inner ear.

    PubMed

    Hildebrand, Michael S; de Silva, Michelle G; Klockars, Tuomas; Campbell, Colleen A; Smith, Richard J H; Dahl, Hans-Henrik M

    2007-03-01

    Recent developments in molecular genetics, including progress in the human genome project, have allowed identification of genes at an unprecedented rate. To date gene expression profiling studies have focused on identifying transcripts that are specifically or preferentially enriched within the inner ear on the assumption that they are more likely to be important for auditory and vestibular function. It is now apparent that some genes preferentially expressed in the cochleo-vestibular system are not crucial for hearing or balance or their functions are compensated for by other genes. In addition, transcripts expressed at low abundance in the inner ear are generally under-represented in gene profiling studies. In this review, we highlight the limitations of current gene expression profiling strategies as a discovery tool for genes involved in cochleo-vestibular development and function. We argue that expression profiling based on hierarchical clustering of transcripts by gene ontology, combined with tissue enrichment data, is more effective for inner ear gene discovery. This approach also provides a framework to assist and direct the functional characterization of gene products. PMID:17300888

  6. Parallel discovery of Alzheimer's therapeutics.

    PubMed

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

    2014-06-18

    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

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

    PubMed

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

    2015-03-01

    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

  8. The ERGOTM genome analysis and discovery system

    Microsoft Academic Search

    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

    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

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

    PubMed Central

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

    2013-01-01

    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

  10. Metagenomic biomarker discovery and explanation

    PubMed Central

    2011-01-01

    This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/. PMID:21702898

  11. Project #02: Mark Borodovsky and Huaiqiu Zhu: New gene finding methods for shotgun DNA sequences of microbial communities coexisting with a human host

    E-print Network

    Weber, Rodney

    Project #02: Mark Borodovsky and Huaiqiu Zhu: New gene finding methods for shotgun DNA sequences of DNA sequence analysis has been a major focus of research conducted by Dr. Borodovsky (Georgia Tech of microbial communities coexisting with a human host The recent advent of shotgun metagenomic sequencing

  12. 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.

  13. Radiation Detection Material Discovery Initiative at PNNL

    NASA Astrophysics Data System (ADS)

    Milbrath, Brian

    2006-05-01

    Today's security threats are being met with 30-year old radiation technology. Discovery of new radiation detection materials is currently a slow and Edisonian process. With heightened concerns over nuclear proliferation, terrorism and unconventional warfare, an alternative strategy for identification and development of potential radiation detection materials must be adopted. Through the Radiation Detection Materials Discovery Initiative, PNNL focuses on the science-based discovery of next generation materials for radiation detection by addressing three ``grand challenges'': fundamental understanding of radiation detection, identification of new materials, and accelerating the discovery process. The new initiative has eight projects addressing these challenges, which will be described, including early work, paths forward and the opportunities for collaboration.

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

    PubMed

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

    2014-06-01

    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

  15. Gene Discovery and Tissue-Specific Transcriptome Analysis in Chickpea with Massively Parallel Pyrosequencing and Web Resource Development1[W][OA

    PubMed Central

    Garg, Rohini; Patel, Ravi K.; Jhanwar, Shalu; Priya, Pushp; Bhattacharjee, Annapurna; Yadav, Gitanjali; Bhatia, Sabhyata; Chattopadhyay, Debasis; Tyagi, Akhilesh K.; Jain, Mukesh

    2011-01-01

    Chickpea (Cicer arietinum) is an important food legume crop but lags in the availability of genomic resources. In this study, we have generated about 2 million high-quality sequences of average length of 372 bp using pyrosequencing technology. The optimization of de novo assembly clearly indicated that hybrid assembly of long-read and short-read primary assemblies gave better results. The hybrid assembly generated a set of 34,760 transcripts with an average length of 1,020 bp representing about 4.8% (35.5 Mb) of the total chickpea genome. We identified more than 4,000 simple sequence repeats, which can be developed as functional molecular markers in chickpea. Putative function and Gene Ontology terms were assigned to at least 73.2% and 71.0% of chickpea transcripts, respectively. We have also identified several chickpea transcripts that showed tissue-specific expression and validated the results using real-time polymerase chain reaction analysis. Based on sequence comparison with other species within the plant kingdom, we identified two sets of lineage-specific genes, including those conserved in the Fabaceae family (legume specific) and those lacking significant similarity with any non chickpea species (chickpea specific). Finally, we have developed a Web resource, Chickpea Transcriptome Database, which provides public access to the data and results reported in this study. The strategy for optimization of de novo assembly presented here may further facilitate the transcriptome sequencing and characterization in other organisms. Most importantly, the data and results reported in this study will help to accelerate research in various areas of genomics and implementing breeding programs in chickpea. PMID:21653784

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

    SciTech Connect

    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

    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.

  17. 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...

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

    PubMed Central

    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

    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

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

    PubMed

    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

    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

  20. Pattern Discovery in Time-Ordered Data

    SciTech Connect

    CONRAD, GREGORY N.; BRITANIK, JOHN M.; DELAND, SHARON M.; JENKIN, CHRISTINA L.

    2002-02-01

    This report describes the results of a Laboratory-Directed Research and Development project on techniques for pattern discovery in discrete event time series data. In this project, we explored two different aspects of the pattern matching/discovery problem. The first aspect studied was the use of Dynamic Time Warping for pattern matching in continuous data. In essence, DTW is a technique for aligning time series along the time axis to optimize the similarity measure. The second aspect studied was techniques for discovering patterns in discrete event data. We developed a pattern discovery tool based on adaptations of the A-priori and GSP (Generalized Sequential Pattern mining) algorithms. We then used the tool on three different application areas--unattended monitoring system data from a storage magazine, computer network intrusion detection, and analysis of robot training data.

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

    PubMed Central

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

    2014-01-01

    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

  2. The Path to Open-Angle Glaucoma Gene Discovery: Endophenotypic Status of Intraocular Pressure, Cup-to-Disc Ratio, and Central Corneal Thickness

    PubMed Central

    Charlesworth, Jac; Kramer, Patricia L.; Dyer, Tom; Diego, Victor; Samples, John R.; Craig, Jamie E.; Mackey, David A.; Hewitt, Alex W.; Blangero, John

    2010-01-01

    Purpose. Primary open-angle glaucoma (POAG) is a complex disease with a genetic architecture that can be simplified through the investigation of individual traits underlying disease risk. It has been well studied in twin models, and this study was undertaken to investigate the heritability of some of these key endophenotypes in extended pedigrees. Methods. These data are derived from a large, multicenter study of extended, Caucasian POAG families from Australia and the United States. The study included 1181 people from 22 extended pedigrees. Variance components modeling was used to determine the heritabilities of maximum intraocular pressure (IOP), maximum vertical cup-to-disc ratio (VCDR), and mean central corneal thickness (CCT). Bivariate quantitative genetic analysis between these eye-related phenotypes and POAG itself was performed to determine whether any of these traits represent true endophenotypes. Results. Heritability estimates for IOP, VCDR, and CCT (0.42, 0.66, and 0.72, respectively) were significant and show strong concordance with data in previous studies. Bivariate analysis revealed that both IOP (RhoG = 0.80; P = 9.6 × 10?6) and VCDR (RhoG = 0.76; P = 4.8 × 10?10) showed strong evidence of genetic correlation with POAG susceptibility. These two traits also correlated genetically with each other (RhoG = 0.45; P = 0.0012). Alternatively, CCT did not correlate genetically with risk of POAG. Conclusions. All the proposed POAG-related traits have genetic components. However, the significant genetic correlations observed between IOP, VCDR, and POAG itself suggest that they most likely represent true endophenotypes that could aid in the identification of genes underlying POAG susceptibility. CCT did not correlate genetically with disease and is unlikely to be a useful surrogate endophenotype for POAG. PMID:20237253

  3. "Eureka, Eureka!" Discoveries in Science

    ERIC Educational Resources Information Center

    Agarwal, Pankaj

    2011-01-01

    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…

  4. Service Discovery in Ubiquitous Feedback Control Loops

    E-print Network

    Paris-Sud XI, Université de

    Seinturier, and Pierre Carton INRIA Lille-Nord Europe, ADAM Project-team University of Lille 1, LIFL CNRS UMR their behavior. In general, these providers use diverse discovery and in- teraction protocols. Furthermore, they can join and leave the environ- ment at anytime, making difficult the utilization of services

  5. Topology Discovery Using Cisco Discovery Protocol

    E-print Network

    Rodriguez, Sergio R

    2009-01-01

    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.

  6. Accelerating scientific discovery : 2007 annual report.

    SciTech Connect

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

    2008-11-14

    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.

  7. Serendipity and Scientific Discovery.

    ERIC Educational Resources Information Center

    Rosenman, Martin F.

    1988-01-01

    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)

  8. Friends' Discovery Camp

    ERIC Educational Resources Information Center

    Seymour, Seth

    2008-01-01

    This article features Friends' Discovery Camp, a program that allows children with and without autism spectrum disorder to learn and play together. In Friends' Discovery Camp, campers take part in sensory-rich experiences, ranging from hands-on activities and performing arts to science experiments and stories teaching social skills. Now in its 7th…

  9. Exploration and Empire: Iconographic Evidence of Iberian Ships of Discovery

    E-print Network

    Bojakowski, Katie

    2011-08-08

    This dissertation research project focuses on maritime exploration during the Age of Discovery and the vessels that were the technological impetus for this dynamic era that ultimately led Christopher Columbus to the New World and Vasco da Gama...

  10. Recent and Projected Increases in Atmospheric CO2 Concentration Can Enhance Gene Flow between Wild and Genetically Altered Rice (Oryza sativa)

    PubMed Central

    Ziska, Lewis H.; Gealy, David R.; Tomecek, Martha B.; Jackson, Aaron K.; Black, Howard L.

    2012-01-01

    Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO2 from an early 20th century concentration (300 µmol mol?1) to current (400 µmol mol?1) and projected, mid-21st century (600 µmol mol?1) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol?1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems. PMID:22649533

  11. Where is the Discovery in Literature-Based Discovery?

    NASA Astrophysics Data System (ADS)

    Kostoff, R. N.

    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.

  12. Discovery Informatics: AI Opportunities in Scientific Discovery

    E-print Network

    Gil, Yolanda

    and that continues to expand so rapidly (e.g., [Science 2011]). The volume, variety, and velocity of the data already of Discovery Informatics for two important current topics in science: "big data" and "the long tail" of science high-end instruments, data management services, and support for virtual organizations

  13. PROJECT: DISCOVERY Research and the Undergrad

    E-print Network

    Pedersen, Tom

    technique (layering two slide trans- parencies) to produce the picture's fuzzy, dream-like effect Campus News and Culture Letter to Japan · Cold War slides · Helping Honduras · OceanGybe · LSQ at 25

  14. Validation of PhenX measures in the personalized medicine research project for use in gene/environment studies

    PubMed Central

    2014-01-01

    Background The purpose of this paper is to describe the data collection efforts and validation of PhenX measures in the Personalized Medicine Research Project (PMRP) cohort. Methods Thirty-six measures were chosen from the PhenX Toolkit within the following domains: demographics; anthropometrics; alcohol, tobacco and other substances; cardiovascular; environmental exposures; cancer; psychiatric; neurology; and physical activity and physical fitness. Eligibility criteria for the current study included: living PMRP subjects with known addresses who consented to future contact and were not currently living in a nursing home, available GWAS data from eMERGE I for subjects where age-related cataract, HDL, dementia and resistant hypertension were the primary phenotypes, thus biasing the sample to the older PMRP participants. The questionnaires were mailed twice. Data from the PhenX measures were compared with information from PMRP questionnaires and data from Marshfield Clinic electronic medical records. Results Completed PhenX questionnaires were returned by 2271 subjects for a final response rate of 70%. The mean age reported on the PhenX questionnaire (73.1 years) was greater than the PMRP questionnaire (64.8 years) because the data were collected at different time points. The mean self-reported weight, and subsequently calculated BMI, were less on the PhenX survey than the measured values at the time of enrollment into PMRP (PhenX means 173.5 pounds and BMI 28.2 kg/m2 versus PMRP 182.9 pounds and BMI 29.6 kg/m2). There was 95.3% agreement between the two questionnaires about having ever smoked at least 100 cigarettes. 139 (6.2%) of subjects indicated on the PhenX questionnaire that they had been told they had a stroke. Of them, only 15 (10.8%) had no electronic indication of a prior stroke or TIA. All of the age-and gender-specific 95% confidence limits around point estimates for major depressive episodes overlap and show that 31% of women aged 50–64 reported symptoms associated with a major depressive episode. Conclusions The approach employed resulted in a high response rate and valuable data for future gene/environment analyses. These results and high response rate highlight the utility of the PhenX Toolkit to collect valid phenotypic data that can be shared across groups to facilitate gene/environment studies. PMID:24423110

  15. Discovery Channel Telescope software key technologies

    NASA Astrophysics Data System (ADS)

    Lotz, Paul J.

    2010-07-01

    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.

  16. Viral surveillance and discovery

    PubMed Central

    Lipkin, Walter Ian; Firth, Cadhla

    2014-01-01

    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

  17. Spatially conserved regulatory elements identified within human and mouse Cd247 gene using high-throughput sequencing data from the ENCODE project.

    PubMed

    Pundhir, Sachin; Hannibal, Tine Dahlbćk; Bang-Berthelsen, Claus Heiner; Wegener, Anne-Marie Karin; Pociot, Flemming; Holmberg, Dan; Gorodkin, Jan

    2014-07-15

    The Cd247 gene encodes for a transmembrane protein important for the expression and assembly of TCR/CD3 complex on the surface of T lymphocytes. Down-regulation of CD247 has functional consequences in systemic autoimmunity and has been shown to be associated with Type 1 Diabetes in NOD mouse. In this study, we have utilized the wealth of high-throughput sequencing data produced during the Encyclopedia of DNA Elements (ENCODE) project to identify spatially conserved regulatory elements within the Cd247 gene from human and mouse. We show the presence of two transcription factor binding sites, supported by histone marks and ChIP-seq data, that specifically have features of an enhancer and a promoter, respectively. We also identified a putative long non-coding RNA from the characteristically long first intron of the Cd247 gene. The long non-coding RNA annotation is supported by manual annotations from the GENCODE project in human and our expression quantification analysis performed in NOD and B6 mice using qRT-PCR. Furthermore, 17 of the 23 SNPs already known to be implicated with T1D were observed within the long non-coding RNA region in mouse. The spatially conserved regulatory elements identified in this study have the potential to enrich our understanding of the role of Cd247 gene in autoimmune diabetes. PMID:24797614

  18. The Learning Discovery

    ERIC Educational Resources Information Center

    Prout, Joan

    1975-01-01

    The learning discovery of youngsters is a do-it-yourself teaching method for clerical, administrative, and accountant trainees at the Bankside House headquarters of the Central Electricity Generating Board's South Eastern Region, London. (Author)

  19. The Discovery of Noggin.

    ERIC Educational Resources Information Center

    Oppenheimer, Steven B.

    1995-01-01

    Discusses recently published work that appears to have many of the answers to the question of how the nervous system develops. Focuses on the discovery of what is believed to be neural inducer, a protein called noggin. (LZ)

  20. The requirements discovery process

    SciTech Connect

    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

    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.

  1. Discovery Collection: Marine Animals

    NSDL National Science Digital Library

    Lisa Breslof

    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.

  2. Discovery Collection: Oyster Shells

    NSDL National Science Digital Library

    Lisa Breslof

    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.

  3. History of Saturn Discoveries

    NSDL National Science Digital Library

    2012-08-03

    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.

  4. Gene discovery in the Acanthamoeba castellanii genome

    SciTech Connect

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

    2005-08-01

    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.

  5. Brachypodium and gene discovery in oat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The hexaploid nature of the oat (Avena sativa) genome, coupled with its large genome and high repetitive element content, presents an obstacle to genome research in this crop. We assessed the potential value of the model grass Brachypodium as a surrogate genome for oat genome research, through compa...

  6. Knowledge discovery by accuracy maximization

    PubMed Central

    Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

    2014-01-01

    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

  7. Knowledge discovery by accuracy maximization.

    PubMed

    Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

    2014-04-01

    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

  8. Analysis of 4,664 high-quality sequence-finished poplar full-length cDNA clones and their utility for the discovery of genes responding to insect feeding

    PubMed Central

    Ralph, Steven G; Chun, Hye Jung E; Cooper, Dawn; Kirkpatrick, Robert; Kolosova, Natalia; Gunter, Lee; Tuskan, Gerald A; Douglas, Carl J; Holt, Robert A; Jones, Steven JM; Marra, Marco A; Bohlmann, Jörg

    2008-01-01

    Background The genus Populus includes poplars, aspens and cottonwoods, which will be collectively referred to as poplars hereafter unless otherwise specified. Poplars are the dominant tree species in many forest ecosystems in the Northern Hemisphere and are of substantial economic value in plantation forestry. Poplar has been established as a model system for genomics studies of growth, development, and adaptation of woody perennial plants including secondary xylem formation, dormancy, adaptation to local environments, and biotic interactions. Results As part of the poplar genome sequencing project and the development of genomic resources for poplar, we have generated a full-length (FL)-cDNA collection using the biotinylated CAP trapper method. We constructed four FLcDNA libraries using RNA from xylem, phloem and cambium, and green shoot tips and leaves from the P. trichocarpa Nisqually-1 genotype, as well as insect-attacked leaves of the P. trichocarpa × P. deltoides hybrid. Following careful selection of candidate cDNA clones, we used a combined strategy of paired end reads and primer walking to generate a set of 4,664 high-accuracy, sequence-verified FLcDNAs, which clustered into 3,990 putative unique genes. Mapping FLcDNAs to the poplar genome sequence combined with BLAST comparisons to previously predicted protein coding sequences in the poplar genome identified 39 FLcDNAs that likely localize to gaps in the current genome sequence assembly. Another 173 FLcDNAs mapped to the genome sequence but were not included among the previously predicted genes in the poplar genome. Comparative sequence analysis against Arabidopsis thaliana and other species in the non-redundant database of GenBank revealed that 11.5% of the poplar FLcDNAs display no significant sequence similarity to other plant proteins. By mapping the poplar FLcDNAs against transcriptome data previously obtained with a 15.5 K cDNA microarray, we identified 153 FLcDNA clones for genes that were differentially expressed in poplar leaves attacked by forest tent caterpillars. Conclusion This study has generated a high-quality FLcDNA resource for poplar and the third largest FLcDNA collection published to date for any plant species. We successfully used the FLcDNA sequences to reassess gene prediction in the poplar genome sequence, perform comparative sequence annotation, and identify differentially expressed transcripts associated with defense against insects. The FLcDNA sequences will be essential to the ongoing curation and annotation of the poplar genome, in particular for targeting gaps in the current genome assembly and further improvement of gene predictions. The physical FLcDNA clones will serve as useful reagents for functional genomics research in areas such as analysis of gene functions in defense against insects and perennial growth. Sequences from this study have been deposited in NCBI GenBank under the accession numbers EF144175 to EF148838. PMID:18230180

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

    E-print Network

    Stuart, Josh

    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

  10. Gene and Enhancer Trap Tagging of Vascular-Expressed Genes in Poplar Trees

    E-print Network

    Gene and Enhancer Trap Tagging of Vascular-Expressed Genes in Poplar Trees Andrew Groover*, Joseph, New York 11724 (R.M.) We report a gene discovery system for poplar trees based on gene and enhancer traps. Gene and enhancer trap vectors carrying the b-glucuronidase (GUS) reporter gene were inserted

  11. NCBI Handout Series | RefSeqGene | Last Update August 19, 2013 Contact: info@ncbi.nlm.nih.gov The RefSeqGene Project

    E-print Network

    Levin, Judith G.

    Sequence Viewer. The "GTR" column (C) provides links to the NIH Genetic Testing Registry (GTR-specific information. Sequence Viewer display In the Sequence Viewer display (shown below), the complete gene locus View" option to display the annotated se- quences in a new text window (H) within the Sequence viewer

  12. Mining biological databases for candidate disease genes

    NASA Astrophysics Data System (ADS)

    Braun, Terry A.; Scheetz, Todd; Webster, Gregg L.; Casavant, Thomas L.

    2001-07-01

    The publicly-funded effort to sequence the complete nucleotide sequence of the human genome, the Human Genome Project (HGP), has currently produced more than 93% of the 3 billion nucleotides of the human genome into a preliminary `draft' format. In addition, several valuable sources of information have been developed as direct and indirect results of the HGP. These include the sequencing of model organisms (rat, mouse, fly, and others), gene discovery projects (ESTs and full-length), and new technologies such as expression analysis and resources (micro-arrays or gene chips). These resources are invaluable for the researchers identifying the functional genes of the genome that transcribe and translate into the transcriptome and proteome, both of which potentially contain orders of magnitude more complexity than the genome itself. Preliminary analyses of this data identified approximately 30,000 - 40,000 human `genes.' However, the bulk of the effort still remains -- to identify the functional and structural elements contained within the transcriptome and proteome, and to associate function in the transcriptome and proteome to genes. A fortuitous consequence of the HGP is the existence of hundreds of databases containing biological information that may contain relevant data pertaining to the identification of disease-causing genes. The task of mining these databases for information on candidate genes is a commercial application of enormous potential. We are developing a system to acquire and mine data from specific databases to aid our efforts to identify disease genes. A high speed cluster of Linux of workstations is used to analyze sequence and perform distributed sequence alignments as part of our data mining and processing. This system has been used to mine GeneMap99 sequences within specific genomic intervals to identify potential candidate disease genes associated with Bardet-Biedle Syndrome (BBS).

  13. 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.

  14. A Decade of Discovery

    SciTech Connect

    none,

    2008-01-01

    This book provides a fascinating account of some of the most significant scientific discoveries and technological innovations coming out of the U.S. Department of Energy’s National Laboratories. This remarkable book illustrates how the men and women of the National Laboratories are keeping us on the cutting edge. Though few Americans are familiar with the scope and scale of the work conducted at these National Laboratories, their research is literally changing our lives and bettering our planet. The book describes the scientific discoveries and technological advancements "in recognition of the men and women working in DOE's seventeen national laboratories across the country." Through highly vivid and accessible stories, this book details recent breakthroughs in three critical areas: 1) Energy and Environment, 2) National Security and 3) Life and Physical Science. The book illustrates how this government-funded research has resulted in more energy-efficient buildings; new, cleaner alternative fuels that reduce greenhouse gas emissions; safer, more efficient, nuclear power plants; improved responses to disease outbreaks; more secure and streamlined airport security; more effective treatments for cancer and other diseases; and astonishing discoveries that are altering our understanding of the universe and enabling scientific breakthroughs in fields such as nanotechnology and particle physics. Specifically, it contains 37 stories. A Decade of Discovery is truly a recent history of discovery - and a fascinating look at what the next decade holds.

  15. Application of antisense oligonucleotides for gene functionalization and target validation.

    PubMed

    Bennett, C F; Cowsert, L M

    1999-06-01

    The Human Genome Project (complete sequencing of the human genome) will be complete soon and the information made available to the biomedical community. Although the project is not yet complete, it has dramatically changed the practice of biomedical sciences. With enormous amounts of information available from sequencing efforts, increasing demands are being put on researchers to quickly determine the biochemical function of novel molecular targets and to validate them as appropriate for drug discovery endeavors. Antisense oligonucleotides are an ideal technology for gene functionalization and target validation. They are an efficient methodology for gene functionalization and target validation and are a proven technology. Antisense technology can answer questions with a high degree of precision and it is a versatile technology. In this review the use of antisense oligonucleotides as a research tool for gene functionalization and target validation is discussed. PMID:11713801

  16. Accelerating the Rate of Astronomical Discovery

    NASA Astrophysics Data System (ADS)

    Norris, Ray P. Ruggles, Clive L. N.

    2010-05-01

    Special Session 5 on Accelerating the Rate of Astronomical Discovery addressed a range of potential limits to progress - paradigmatic, technological, organisational, and political - examining each issue both from modern and historical perspectives, and drawing lessons to guide future progress. A number of issues were identified which potentially regulate the flow of discoveries, such as the balance between large strongly-focussed projects and instruments, designed to answer the most fundamental questions confronting us, and the need to maintain a creative environment with room for unorthodox thinkers and bold, high risk, projects. Also important is the need to maintain historical and cultural perspectives, and the need to engage the minds of the most brilliant young people on the planet, regardless of their background, ethnicity, gender, or geography.

  17. 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.

  18. Open source drug discovery - a limited tutorial.

    PubMed

    Robertson, Murray N; Ylioja, Paul M; Williamson, Alice E; Woelfle, Michael; Robins, Michael; Badiola, Katrina A; Willis, Paul; Olliaro, Piero; Wells, Timothy N C; Todd, Matthew H

    2014-01-01

    Open science is a new concept for the practice of experimental laboratory-based research, such as drug discovery. The authors have recently gained experience in how to run such projects and here describe some straightforward steps others may wish to take towards more openness in their own research programmes. Existing and inexpensive online tools can solve many challenges, while some psychological barriers to the free sharing of all data and ideas are more substantial. PMID:23985301

  19. 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, ...

  20. 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...

  1. The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes

    E-print Network

    Kellis, Manolis

    Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but ...

  2. 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.

  3. 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.

  4. Discovery of Companion Asteroids

    NSDL National Science Digital Library

    This site displays the first-ever images of a large, double asteroid once assumed to be a single asteroid called Antiope. The images were recently released by the Southwest Research Institute (SWRI). Each asteroid in the pair is approximately 50 miles across, separated by about 100 miles. This discovery was made using the W.M. Keck Observatory, Mauna Kea, Hawaii. Images of another discovery, that of a small moon orbiting the large asteroid Pulcova, is featured at this site. In addition to still images, movies show the motion of the asteroids.

  5. Development Status of the WetLab-2 Project: New Tools for On-orbit Real-time Quantitative Gene Expression.

    NASA Technical Reports Server (NTRS)

    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

    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.

  6. STS-114: Discovery Propulsion System Modification Briefing

    NASA Technical Reports Server (NTRS)

    2005-01-01

    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.

  7. D3.3.1 Data-driven Change Discovery

    Microsoft Academic Search

    Johanna V; Denny Vrande

    EU-IST Integrated Project (IP) IST-2003-506826 SEKT Deliverable D3.3.1 (WP3.3) In this deliverable we present work performed in the task 'T3.3 Data-driven Change Discovery'. Text2Onto is a framework for data-driven change discovery by incremental ontology learning. It uses natural language processing and text mining techniques in order to extract an ontology from text and provides support for the adaptation of the

  8. Missing genes in metabolic pathways: a comparative genomics approach

    Microsoft Academic Search

    Andrei Osterman; Ross Overbeek

    2003-01-01

    The new techniques of genome context analysis — chromosomal gene clustering, protein fusions, occurrence profiles and shared regulatory sites — infer functional coupling between genes. In combination with metabolic reconstructions, these techniques can dramatically accelerate the pace of gene discovery.

  9. Birds. Nature Discovery I.

    ERIC Educational Resources Information Center

    Stone, Sally F.

    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…

  10. Frequent Subgraph Discovery

    Microsoft Academic Search

    Michihiro Kuramochi; George Karypis

    2001-01-01

    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

  11. discoveries in drugs and

    E-print Network

    Glasser, Benjamin J.

    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

  12. SeaDiscovery.com

    NSDL National Science Digital Library

    SeaDiscovery.com is an online source for "underwater tech and ocean science news." The site presents not only news, but information about maritime technology employment which includes featured jobs and resumes. It also allows access to the Maritime Technology Reporter magazine and provides links to a number of important directories.

  13. The Discovery of Argon

    Microsoft Academic Search

    G. H. Darwin

    1904-01-01

    IN your translation of Prof. Mendeléeff's interesting paper on the chemical elements (November 17, p. 94) I see that he attributes the discovery of argon and its congeners to Ramsay. Am I not right in believing that it was Lord Rayleigh who discovered argon, and that it was he who gave that impulse to chemistry which Sir William Ramsay has

  14. Network discovery with DCM

    Microsoft Academic Search

    Karl J. Friston; Baojuan Li; Jean Daunizeau; Klaas E. Stephan

    2011-01-01

    This paper is about inferring or discovering the functional architecture of distributed systems using Dynamic Causal Modelling (DCM). We describe a scheme that recovers the (dynamic) Bayesian dependency graph (connections in a network) using observed network activity. This network discovery uses Bayesian model selection to identify the sparsity structure (absence of edges or connections) in a graph that best explains

  15. Political Discovery Resource Book.

    ERIC Educational Resources Information Center

    Political Discovery Education Collaborative for Greater Boston, MA.

    This resource book for secondary students describes various aspects of federal, state, and local political processes. Originally written for use in the magnet education program "Political Discovery" in Boston, Massachusetts, the book can easily be used or adapted by teachers in any state. The first part of the book deals with the federal…

  16. A Passport to Discovery

    ERIC Educational Resources Information Center

    Taylor, Ellen

    2004-01-01

    Have you ever had an experience too good to be true; one that you could not wait to share with your friends? In this article, the author describes such an experience that she had last summer when she was a part of the "Passport to Discovery" tour offered by CRIZMAC Art and Cultural Education Materials, Inc., and led by founder Stevie Mack and…

  17. The Discovery of America

    ERIC Educational Resources Information Center

    Martin, Paul S.

    1973-01-01

    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)

  18. Synthetic Biology of Antimicrobial Discovery

    E-print Network

    Zakeri, Bijan

    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 ...

  19. Gene expression patterns within cell lines are predictive of chemosensitivity

    PubMed Central

    Ring, Brian Z; Chang, Stella; Ring, L Winston; Seitz, Robert S; Ross, Douglas T

    2008-01-01

    Background The NCI has undertaken a twenty-year project to characterize compound sensitivity patterns in a selected set of sixty tumor derived cell lines. Previous studies have explored the relationship between compound sensitivity patterns to gene expression, protein expression, and DNA copy number for these same cell lines. A strong correlation between the pattern of expression of a biomarker and sensitivity to a compound could suggest a clinically interesting biological relationship between the two. Results We isolated RNA's and measured expression of 40000 genes using cDNA microarrays from the fifty-nine publicly available cell lines. Analysis of this data set in comparison with published gene expression data sets demonstrates a high degree of reproducibility in expression level measurements even using completely independent RNA preparations and array technologies. Using the fifty-nine cell lines for discovery and an additional seven cell lines for which extensive compound sensitivity data were available as a test set, we determined that gene-compound pairs with a correlation coefficient above 0.6 had a false discovery rate of approximately 5%. Large scale features of the gene expression and chemosensitivity data, such as tissue of origin and other physiological factors, did not seem to explain the majority of correlations between gene and compound patterns. Conclusion A comparison of gene expression and compound sensitivity in panels of cell lines was demonstrated to have a relatively high validation and low false discovery rate supporting the use of this approach and datasets for identifying candidate biomarkers and targeted biologically active compounds. PMID:18261237

  20. Recent Discoveries and Bible Translation.

    ERIC Educational Resources Information Center

    Harrelson, Walter

    1990-01-01

    Discusses recent discoveries for "Bible" translation with a focus on the "Dead Sea Scrolls." Examines recent discoveries that provide direct support for alternative reading of biblical passages and those discoveries that have contributed additional insight to knowledge of cultural practices, especially legal and religious practices. (DB)

  1. Gene regulation in physiological stress

    Microsoft Academic Search

    Kenneth B. Storey

    2004-01-01

    A range of new tools in molecular biology are now available to allow the comparative biochemist to explore animal responses to environmental stress at multiple levels. In particular, new techniques of gene discovery, such as cDNA array screening, allow broad assessment of the responses of thousands of genes to a stress. This approach frequently identifies genes (and their associated metabolic

  2. Gene therapy in the CNS

    Microsoft Academic Search

    L C Costantini; J C Bakowska; X O Breakefield; O Isacson

    2000-01-01

    Gene therapy for neurological disorder is currently an experimental concept. The goals for clinical utilization are the relief of symptoms, slowing of disease progression, and correction of genetic abnormalities. Experimental studies are realizing these goals in the development of gene therapies in animal models. Discoveries of the molecular basis of neurological disease and advances in gene transfer systems have allowed

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

    PubMed Central

    2011-01-01

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

  4. MAPT and PAICE: Tools for time series and single time point transcriptionist visualization and knowledge discovery

    PubMed Central

    Hosseini, Parsa; Tremblay, Arianne; Matthews, Benjamin F; Alkharouf, Nadim W

    2012-01-01

    With the advent of next-generation sequencing, -omics fields such as transcriptomics have experienced increases in data throughput on the order of magnitudes. In terms of analyzing and visually representing these huge datasets, an intuitive and computationally tractable approach is to map quantified transcript expression onto biochemical pathways while employing datamining and visualization principles to accelerate knowledge discovery. We present two cross-platform tools: MAPT (Mapping and Analysis of Pathways through Time) and PAICE (Pathway Analysis and Integrated Coloring of Experiments), an easy to use analysis suite to facilitate time series and single time point transcriptomics analysis. In unison, MAPT and PAICE serve as a visual workbench for transcriptomics knowledge discovery, data-mining and functional annotation. Both PAICE and MAPT are two distinct but yet inextricably linked tools. The former is specifically designed to map EC accessions onto KEGG pathways while handling multiple gene copies, detection-call analysis, as well as UN/annotated EC accessions lacking quantifiable expression. The latter tool integrates PAICE datasets to drive visualization, annotation, and data-mining. Availability The database is available for free at http://sourceforge.net/projects/paice/http://sourceforge.net/projects/mapt/ PMID:22493539

  5. 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

    Ignatieva, Elena V.; Levitsky, Victor G.; Yudin, Nikolay S.; Moshkin, Mikhail P.; Kolchanov, Nikolay A.

    2014-01-01

    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

  6. Challenges of Antibacterial Discovery

    PubMed Central

    Silver, Lynn L.

    2011-01-01

    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

  7. 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.

  8. Discovery management workshop

    NASA Technical Reports Server (NTRS)

    1993-01-01

    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.

  9. Planetary Science Resource Discoveries

    NSDL National Science Digital Library

    G. J. Taylor

    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.

  10. Discovery as a process

    SciTech Connect

    Loehle, C.

    1994-05-01

    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.

  11. The language of discovery.

    PubMed

    Souba, Wiley

    2011-01-01

    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

  12. The discovery of stapes.

    PubMed

    Dispenza, F; Cappello, F; Kulamarva, G; De Stefano, A

    2013-10-01

    Giovanni Filippo Ingrassia revisited and redefined some of Galeno's reports, and was recognized as one of the leading Italian Physicians of the 16th century. Ingrassia principally studied the skull, and gave very important contributions to otorhinolaryngology, including the discovery of the stapes. He also isolated the inferior nasal concha from the maxillary bone, described the frontal sinus, the pterygopalatine fossa and several foramina of the skull. Ingrassia firstly attributed a sensorial function to the middle ear bones, which he called fifth particular function. He also added some details to the description of the VIII cranial nerve, which introduces the concept of bone conducting sound. The most important discovery in Ingrassia's study about the hearing organ was the first description of the third bone of the ossicular chain that he called "stapes". Ingrassia should thus be reconsidered under a new light for his important discovery and for his intuitions about the stapes and its role in hearing. It is appropriate for a Sicilian physician to be placed at his rightful place side-by-side with Eustachio and Valsalva in the history of otology. PMID:24227905

  13. Zbtb20 defines a hippocampal neuronal identity through direct repression of genes that control projection neuron development in the isocortex.

    PubMed

    Nielsen, Jakob V; Thomassen, Mads; Mřllgĺrd, Kjeld; Noraberg, Jens; Jensen, Niels A

    2014-05-01

    Hippocampal pyramidal neurons are important for encoding and retrieval of spatial maps and episodic memories. While previous work has shown that Zbtb20 is a cell fate determinant for CA1 pyramidal neurons, the regulatory mechanisms governing this process are not known. In this study, we demonstrate that Zbtb20 binds to genes that control neuronal subtype specification in the developing isocortex, including Cux1, Cux2, Fezf2, Foxp2, Mef2c, Rorb, Satb2, Sox5, Tbr1, Tle4, and Zfpm2. We show that Zbtb20 represses these genes during ectopic CA1 pyramidal neuron development in transgenic mice. These data reveal a novel regulatory mechanism by which Zbtb20 suppresses the acquisition of an isocortical fate during archicortical neurogenesis to ensure commitment to a CA1 pyramidal neuron fate. We further show that the expression pattern of Zbtb20 is evolutionary conserved in the fetal human hippocampus, where it is complementary to the expression pattern of the Zbtb20 target gene Tbr1. Therefore, the disclosed Zbtb20-mediated transcriptional repressor mechanism may be involved in development of the human archicortex. PMID:23283686

  14. 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.

  15. STS-114: Discovery Post MMT Briefing

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Wayne Hale, Space Shuttle Deputy Program Manager and Steve Poulos, Manager Orbit Project Office at Johnson Space Center is seen during a post Mission Management Team (MMT) briefing. The purpose of this briefing is to talk about the status of the Space Shuttle Discovery Orbiter, the Thermal Protection System (TPS) and the External Tank. Hale presents pictures of the missing foam off of the Hydrogen Protuberance Air Load (PAL) ramp and trajectory debris particles. Poulos explains in detail diagrams of the reinforced carbon-carbon system, possible scuff on the wing panel, coating damage, protruding gap filler and damaged tile blanket. Poulos tells what concerns him the most in terms of tile damage to the Space Shuttle Discovery.

  16. Human genome project and mutation research: A mating that needs to happen

    SciTech Connect

    Carrano, A.V. [Lawrence Livermore National Lab., CA (United States)

    1994-12-31

    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.

  17. Retrotransposition of gene transcripts leads to structural variation in mammalian genomes

    PubMed Central

    2013-01-01

    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

  18. Important discoveries from analysing bacterial phenotypes

    PubMed Central

    Bochner, Barry R; Giovannetti, Luciana; Viti, Carlo

    2008-01-01

    The ability to test hundreds to thousands of cellular phenotypes in a single experiment has opened up new avenues of investigation and exploration and led to important discoveries in very diverse applications of microbiological research and development. The information provided by global phenotyping is complementary to, and often more easily interpretable than information provided by global molecular analytical methods such as gene chips and proteomics. This report summarizes advances presented by scientists brought together to share their experiences and knowledge gained with high-throughput phenotyping. PMID:18681942

  19. Drug discovery in jeopardy

    PubMed Central

    Cuatrecasas, Pedro

    2006-01-01

    Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested. PMID:17080187

  20. Live Cams: Discovery Channel

    NSDL National Science Digital Library

    With cameras operating in Alaska, Hudson Bay and other far-flung locales, the Discovery Channel's Live Cams page is a great resource for those who love nature in all of its manifestations. First-time visitors should check out the Alaska: The Last Frontier cams as they offer a rich look at this most fascinating state. The Shark Cam is a delight as well and features sharks in the National Aquarium, including black-tip sharks, zebra sharks, and more. The Penguin Cam is also quite fun and visitors can watch the behavior of rockhopper and African penguins at the Audubon Aquarium of the Americas.

  1. Discovery Channel: Earth News

    NSDL National Science Digital Library

    This Discovery Channel website features a large assortment of fascinating information about the physical environment of the earth. The website's live cam shows images of Mexico's Popocatepetl, one the most active volcanoes. Visitors can observe the big craters created on the earth by past meteors while students can create their own earthquake. And, users can find daily pictures and journal writings from a team of Mt. Everest climbers. With so many online earth adventures and activities, everyone should visit this fun and exciting website.

  2. Research Discoveries After Kubin

    PubMed Central

    Vensko, Nancy W.; Ferguson, Steven M.

    2010-01-01

    This paper will discuss commercializing discoveries made at research organizations, particularly with a view to the In re Kubin case, decided April 3, 2009, by the Federal Circuit. Here, the existence of a general method of isolating DNA molecules was held to be relevant to the question whether the DNA molecules themselves would have been obvious under § 103 of the patent act. How are DNA inventions patented anyway? What does it take for academic research to reach patients? How might the decision of In re Kubin effect research commercialization and technology transfer? PMID:20543971

  3. Towards Robot Scientists for autonomous scientific discovery

    PubMed Central

    2010-01-01

    We review the main components of autonomous scientific discovery, and how they lead to the concept of a Robot Scientist. This is a system which uses techniques from artificial intelligence to automate all aspects of the scientific discovery process: it generates hypotheses from a computer model of the domain, designs experiments to test these hypotheses, runs the physical experiments using robotic systems, analyses and interprets the resulting data, and repeats the cycle. We describe our two prototype Robot Scientists: Adam and Eve. Adam has recently proven the potential of such systems by identifying twelve genes responsible for catalysing specific reactions in the metabolic pathways of the yeast Saccharomyces cerevisiae. This work has been formally recorded in great detail using logic. We argue that the reporting of science needs to become fully formalised and that Robot Scientists can help achieve this. This will make scientific information more reproducible and reusable, and promote the integration of computers in scientific reasoning. We believe the greater automation of both the physical and intellectual aspects of scientific investigations to be essential to the future of science. Greater automation improves the accuracy and reliability of experiments, increases the pace of discovery and, in common with conventional laboratory automation, removes tedious and repetitive tasks from the human scientist. PMID:20119518

  4. Intel Education: Design and Discovery

    NSDL National Science Digital Library

    Design and Discovery is a free program that includes a complete, downloadable and reproducible curriculum as well as related resource materials and an implementation guide. Design and Discovery is an academic enrichment opportunity that engages students in hands-on engineering and design activities intended to foster knowledge, skill development, and problem solving in the areas of science and engineering. Design and Discovery is most appropriate for informal education settings with extended blocks of time.

  5. 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 ...

  6. Discovery Channel: Teaching Tools

    NSDL National Science Digital Library

    The Discovery Channel has compiled this collection of teaching tools to use in Arts, Math, Business/Careers, Science, English, Social Studies, Health, Technology, and Language instruction. For example, several worksheets on Algebra, Geometry and math vocabulary are posted online and include a link to a solution page. Teachers can take the worksheets posted as samples and use the online form to create a custom worksheet. Similarly, the puzzles and quizzes can also be custom designed to suit particular instructional goals. Those who complete the free online registration form can use the Discovery Channels Custom Classroom tool to save worksheets, quizzes or puzzles in a personal account. A Clip Art Gallery makes it easy and free to spice up classroom materials. Some sections, such as the discussion forum, require registration. The site notes that it is regularly reviewed by practicing classroom teachers in elementary school, middle school, and high school to ensure the material is relevant. Advertising on the website is minimal and its producers say they are working on adding more tools.

  7. STS-82 Discovery Launch

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The Space Shuttle Discovery cuts a bright swath through the early-morning darkness as it lifts off from Launch Pad 39A on a scheduled 10-day flight to service the Hubble Space Telescope (HST). Liftoff of Mission STS-82 occurred on-time at 3:55:17 a.m. EST, Feb. 11, 1997. Leading the veteran crew is Mission Commander Kenneth D. Bowersox. Scott J. 'Doc' Horowitz is the pilot. Mark C. Lee is the payload commander. Rounding out the seven-member crew are Mission Specialists Steven L. Smith, Gregory J. Harbaugh, Joseph R. 'Joe' Tanner and Steven A. Hawley. Four of the astronauts will be divided into two teams to perform the scheduled four back-to-back extravehicular activities (EVAs) or spacewalks. Lee and Smith will team up for EVAs 1 and 3 on flight days 4 and 6; Harbaugh and Tanner will perform EVAs 2 and 4 on flight days 5 and 7. Among the tasks will be to replace two outdated scientific instruments with two new instruments the Space Telescope Imaging Spectrograph (STIS) and the Near Infrared Camera and Multi-Object Spectrometer (NICMOS). This is the second servicing mission for HST, which was originally deployed in 1990 and designed to be serviced on-orbit about every three years. Hubble was first serviced in 1993. STS-82 is the second of eight planned flights in 1997. It is the 22nd flight of Discovery and the 82nd Shuttle mission.

  8. METHODOLOGY ARTICLE Open Access The ‘PUCE CAFE ’ Project: the First 15K Coffee Microarray, a New Tool for Discovering Candidate Genes correlated to Agronomic and Quality Traits

    E-print Network

    Isabelle Privat; Amélie Bardil; Aureliano Bombarely Gomez; Dany Severac; Christelle Dantec; Ivanna Fuentes; Lukas Mueller; Thierry Joët; David Pot; Séverine Foucrier; Stéphane Dussert; Thierry Leroy; Laurent Journot; Re De Kochko; Claudine Campa; Marie-christine Combes; Benoit Bertr

    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),

  9. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success

    PubMed Central

    Timmerman, Vincent; Strickland, Alleene V.; Züchner, Stephan

    2014-01-01

    Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs. PMID:24705285

  10. The role of the laboratory mouse in the human genome project

    SciTech Connect

    Meisler, M.H. [Univ. of Michigan School of Medicine, Ann Arbor, MI (United States)

    1996-10-01

    The long-term goal of the human genome project is to identify and establish the function of each of the estimated 100,000 genes in the genome. The gene-discovery phase of the project is proceeding rapidly, via large-scale sequencing of genomic and cDNA clones. Establishing the functional roles for these genes is the challenge for the future. New methods have improved the power of the laboratory mouse to address questions of gene function and have attracted many investigators to the field. There has been dramatic progress in the efficiency of positional cloning of mutant mouse genes, induction of new mutants by chemical mutagenesis, targeted mutation of cloned genes by homologous recombination, strategies for analysis of polygenic traits, and comparative mapping of the human and mouse chromosomes. The contents of recent issues of the journals Human Molecular Genetics, Nature Genetics, and Genomics demonstrate the striking extent to which mouse genes and mouse mutants now occupy the attention of human geneticists. This paper provides a brief survey of recent developments with particular relevance to human genetics and the analysis of gene function. 56 refs., 2 figs., 4 tabs.

  11. Integrated bacterial genomics for the discovery of novel antimicrobials

    Microsoft Academic Search

    Hannes Loferer; Alexander Jacobi; Anton Posch; Christine Gauss; Sebastian Meier-Ewert; Bernd Seizinger

    2000-01-01

    Sequencing of bacterial genomes has been progressing with breathtaking speed. Currently, the genomes of 23 bacterial species are sequenced, with approximately 40 more sequencing projects in progress. Industrial research is now facing the challenge of translating this information efficiently into drug discovery. This review will summarize the impact of bacterial genomics, bioinformatics and second-generation genomic technologies on target identification, assay

  12. A general approach to single-nucleotide polymorphism discovery

    Microsoft Academic Search

    Ian Korf; Mark D. Yandell; Raymond T. Yeh; Zhijie Gu; Hamideh Zakeri; Nathan O. Stitziel; LaDeana Hillier; Warren R. Gish; Gabor T. Marth; Pui-Yan Kwok

    1999-01-01

    Single-nucleotide polymorphisms (SNPs) are the most abundant form of human genetic variation and a resource for mapping complex genetic traits. The large volume of data produced by high-throughput sequencing projects is a rich and largely untapped source of SNPs (refs 2, 3, 4, 5). We present here a unified approach to the discovery of variations in genetic sequence data of

  13. DISCOVERY OF MUTATED SUBNETWORKS ASSOCIATED WITH CLINICAL DATA IN CANCER

    E-print Network

    Raphael, Ben J.

    DISCOVERY OF MUTATED SUBNETWORKS ASSOCIATED WITH CLINICAL DATA IN CANCER FABIO VANDIN, PATRICK CLAY,pclay,eli,braphael}@cs.brown.edu A major goal of cancer sequencing projects is to identify genetic alterations that determine clinical phenotypes, such as survival time or drug response. Somatic mutations in cancer are typically very diverse

  14. SPRUCE Discovery Manual, 169 Investigations Indoors and Outdoors.

    ERIC Educational Resources Information Center

    Busch, Phyllis S.

    Contained are instructional materials developed by the Science Project Related to Upgrading Conservation Education ("SPRUCE"). It is designed for use with the SPRUCE "Discovery Box" and contains twenty-one sets of investigations based on the twenty-one packets of specimens in the box; three sets are recommended for each of Grades K through 6. Each…

  15. Assessment of Materials for Engaging Students in Statistical Discovery

    ERIC Educational Resources Information Center

    Froelich, Amy G.; Duckworth, William M.

    2008-01-01

    As part of an NSF funded project we developed new course materials for a general introductory statistics course designed to engage students in statistical discovery. The materials were designed to actively involve students in the design and implementation of data collection and the analysis and interpretation of the resulting data. Our overall…

  16. Enhancing the GEON Cyberinfrastructure: Semantic Registration, Discovery, Mediation, and Workflows

    E-print Network

    California at Davis, University of

    Enhancing the GEON Cyberinfrastructure: Semantic Registration, Discovery, Mediation, and Workflows and some of the challenges these projects face: To answer a specific scientific question, many different mediation services rewriting integration ontology services reasoning classification O1 O2 A1 A2 data sources

  17. Drug discovery from medicinal plants

    Microsoft Academic Search

    Marcy J. Balunas; A. Douglas Kinghorn

    2005-01-01

    Current research in drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Medicinal plant drug discovery continues to provide new and important leads against various pharmacological targets including cancer, HIV\\/AIDS, Alzheimer's, malaria, and pain. Several natural product drugs of plant origin have either recently been introduced to the United States market, including arteether,

  18. Self Assessment and Discovery Learning

    ERIC Educational Resources Information Center

    McDonald, Betty

    2011-01-01

    Discovery learning in higher education has been reported to be effective in assisting learners to understand difficult concepts and retain long term information. This paper seeks to illustrate how one self assessment model may be used to demonstrate discovery learning in a collaborative atmosphere of students sharing and getting to know each…

  19. Discovery Science Center

    NSDL National Science Digital Library

    The Discovery Science Center is dedicated to educating young minds, assisting teachers, and increasing public understanding of science, math and technology through interactive exhibits and programs. With a large emphasis on Earth science and physics, the Center has a Boeing Delta III Rocket, an exhibits hall devoted to earthquake science, a Sun Zone, and Dynamic Earth, and an exhibit illustrating how and why the Earth physically changes over time. One can even take a virtual, 3D tour of the Museum online. Exhibits and programming are tailored to K-12 standards which can be viewed online for each exhibit and program. Science on the Go brings science programs to offsite venues, Field Trips include an activity booklet for students, and professional development includes First Monday, where teachers can come to the Center for free and get information on programming and tour the facility.

  20. Discovery of cosmic rays

    NASA Astrophysics Data System (ADS)

    Carlson, Per

    2013-02-01

    The mysterious invisible radiation that ionized air was studied a century ago by many scientists. Finally, on 7 August 1912, Victor Hess in his seventh balloon flight that year, reached an altitude of about 5000 m. With his electroscopes on board the hydrogen-filled balloon he observed that the ionization instead of decreasing with altitude increased significantly. Hess had discovered cosmic rays, a discovery that gave him the 1936 Nobel Prize in physics. When research resumed after World War I focus was on understanding the nature of the cosmic radiation. Particles or radiation? Positive or negative? Electrons, positrons or protons? Progress came using new instruments like the Geiger-Muller tube and around 1940 it was clear that cosmic rays were mostly protons.