Sample records for gene discovery project

  1. Peanut EST Project and Gene Discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The overall goal of this project is to develop functional tools and resources for the peanut research community to better understand the disease resistance and seed protein synthesis and diversity in order to advance towards improving host resistance to diseases and mitigating food safety issues suc...

  2. 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.

  3. Project Discovery II. FIPSE Project.

    ERIC Educational Resources Information Center

    Ciaccio, Leonard A.; Sanders, James W.

    Project Discovery II was based on a previous highly successful Fund for the Improvement of Postsecondary Education (FIPSE) project called Project Discovery. Teams of high school teachers and college faculty in the project planned and implemented an integrated, discovery based curriculum with groups of block-programmed students in New York City…

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

    PubMed

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

    2014-06-01

    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

  5. 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…

  6. DOE “Discovery Across Texas” Project 

    E-print Network

    Holloway, M.

    2011-01-01

    Milton Holloway, Ph.D. CATEE 2011 Conference Dallas, Texas 8-9 November 2011 Discovery Across Texas A CCET Smart Grid Demonstration Project Providing Technology Solutions for Wind Integration in ERCOT Center for the Commercialization... of Electric Technologies DOE Smart Grid Demonstration Project ? Award Date: 4 January 2010 ? Award Number: DE-OE-0000194 ? Title: Discovery Across Texas: Technology Solutions for Wind Integration in ERCOT ? Value: $27 million total; $13.5 million...

  7. 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

  8. 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.

  9. Gene Specific Co-regulation Discovery: An Improved Approach

    E-print Network

    Xu, Kai "Kevin"

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

  10. Project Discovery: College Option Orientation Program. FIPSE Final Report.

    ERIC Educational Resources Information Center

    Total Action Against Poverty, Inc., Roanoke, VA.

    Project Discovery is a community-based educational intervention program for low income and minority students. It operates outside the traditional public education system. The following projects comprise the program: (1) Project Discovery for ninth to eleventh graders, which is a College Option Orientation program; and (2) Discovery Groups for…

  11. CARTaGENE Project

    Cancer.gov

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

  12. 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.

  13. Biomarker gene signature discovery integrating network knowledge.

    PubMed

    Cun, Yupeng; Fröhlich, Holger

    2012-01-01

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

  14. Biomarker Gene Signature Discovery Integrating Network Knowledge

    PubMed Central

    Cun, Yupeng; Fröhlich, Holger

    2012-01-01

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

  15. Cancer Proliferation Gene Discovery Through Functional Genomics

    PubMed Central

    Schlabach, Michael R.; Luo, Ji; Solimini, Nicole L.; Hu, Guang; Xu, Qikai; Li, Mamie Z.; Zhao, Zhenming; Smogorzewska, Agata; Sowa, Mathew E.; Ang, Xiaolu L.; Westbrook, Thomas F.; Liang, Anthony C.; Chang, Kenneth; Hackett, Jennifer A.; Harper, J. Wade; Hannon, Gregory J.; Elledge, Stephen J.

    2010-01-01

    Retroviral short hairpin RNA (shRNA)–mediated genetic screens in mammalian cells are powerful tools for discovering loss-of-function phenotypes. We describe a highly parallel multiplex methodology for screening large pools of shRNAs using half-hairpin barcodes for microarray deconvolution. We carried out dropout screens for shRNAs that affect cell proliferation and viability in cancer cells and normal cells. We identified many shRNAs to be antiproliferative that target core cellular processes, such as the cell cycle and protein translation, in all cells examined. Moreover, we identified genes that are selectively required for proliferation and survival in different cell lines. Our platform enables rapid and cost-effective genome-wide screens to identify cancer proliferation and survival genes for target discovery. Such efforts are complementary to the Cancer Genome Atlas and provide an alternative functional view of cancer cells. PMID:18239126

  16. Gene Discovery Methods from Large-Scale Gene Expression Data

    NASA Astrophysics Data System (ADS)

    Shimizu, Akifumi; Yano, Kentaro

    2010-01-01

    Microarrays provide genome-wide gene expression changes. In current analyses, the majority of genes on the array are frequently eliminated for further analysis just in order for computational effort to be affordable. This strategy risks failure to discover whole sets of genes related to a quantitative trait of interest, which is generally controlled by several loci that might be eliminated in current approaches. Here, we describe a high-throughput gene discovery method based on correspondence analysis with a new index for expression ratios [arctan (1/ratio)] and three artificial marker genes. This method allows us to quickly analyze the whole microarray dataset without elimination and discover up/down-regulated genes related to a trait of interest. We employed an example dataset to show the theoretical advantage of this method. We then used the method to identify 88 cancer-related genes from a published microarray data from patients with breast cancer. This method can be easily performed and the result is also visible in three-dimensional viewing software that we have developed. Our method is useful for revaluating the wealth of microarray data available from web-sites.

  17. Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.

    PubMed

    Verbist, Bie; Klambauer, Günter; Vervoort, Liesbet; Talloen, Willem; Shkedy, Ziv; Thas, Olivier; Bender, Andreas; Göhlmann, Hinrich W H; Hochreiter, Sepp

    2015-05-01

    The pharmaceutical industry is faced with steadily declining R&D efficiency which results in fewer drugs reaching the market despite increased investment. A major cause for this low efficiency is the failure of drug candidates in late-stage development owing to safety issues or previously undiscovered side-effects. We analyzed to what extent gene expression data can help to de-risk drug development in early phases by detecting the biological effects of compounds across disease areas, targets and scaffolds. For eight drug discovery projects within a global pharmaceutical company, gene expression data were informative and able to support go/no-go decisions. Our studies show that gene expression profiling can detect adverse effects of compounds, and is a valuable tool in early-stage drug discovery decision making. PMID:25582842

  18. Gene expression network discovery: a pattern based biclustering approach

    Microsoft Academic Search

    Debahuti Mishra; Kailash Shaw; Sashikala Mishra; Amiya Kumar Rath; Milu Acharya

    2011-01-01

    Discovering biologically significant information from gene expression data is now a days playing important role in gene function detection, gene regulation, drug discovery, detecting and predicting the diseases. Many traditional clustering algorithms are present to discover such gene regulations. Such discovered clusters are known as global clusters, which incurs more processing overhead. To overcome such problem, the biclustering approach, also

  19. A Gene-Coexpression Network for Global Discovery of

    E-print Network

    Kim, Stuart

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

  20. 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...

  1. Online Discovery and Refinement of Novel Genes Using GeneScope

    Microsoft Academic Search

    Hasan Jamil Jesmin; J. Jesmin

    2009-01-01

    We present a novel gene finding and validation tool, called GeneScope, which is capable of finding and validat- ing genes declaratively by autonomously integrating hetero- geneous online resources. GeneScope also supports user defined concepts to articulate gene structures, and refine ex- isting concepts toward the discovery of the intended genes. The system relies upon a new string query language called

  2. 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 ...

  3. Gene Discoveries Could Help Rheumatoid Arthritis Treatment

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy Recent Health News Related MedlinePlus Health Topics Genes and Gene Therapy Rheumatoid Arthritis About MedlinePlus Site Map FAQs Contact ...

  4. 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)

  5. A Discovery Lab for Studying Gene Regulation.

    ERIC Educational Resources Information Center

    Moss, Robert

    1997-01-01

    Presents a laboratory in which students are provided with cultures of three bacterial strains. Using the results, students will determine which of the strains corresponds to a mutant lacking a particular functional gene. (DDR)

  6. Discovery Park Impact International Breast Cancer & Nutrition (IBCN) Project

    E-print Network

    Holland, Jeffrey

    Discovery Park Impact International Breast Cancer & Nutrition (IBCN) Project NEED The development interdisciplinary projects and centers. One of the newest is the International Breast Cancer & Nutrition (IBCN effort to understand the link between breast cancer types, nutrition and the epigenome; (2) to foster

  7. 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...

  8. Cancer Gene Discovery in Hepatocellular Carcinoma

    PubMed Central

    Zender, Lars; Villanueva, Augusto; Tovar, Victoria; Sia, Daniela; Chiang, Derek Y.; Llovet, Josep M.

    2010-01-01

    Hepatocellular carcinoma (HCC) is a deadly cancer, whose incidence is increasing worldwide. Albeit the main risk factors for HCC development have been clearly identified, such as hepatitis B and C virus infection and alcohol abuse, there is still preliminary understanding of the key drivers of this malignancy. Recent data suggest that genomic analysis of cirrhotic tissue - the pre-neoplastic carcinogenic field - may provide a read-out to identify at risk populations for cancer development. Given this contextual complexity, it is of utmost importance to characterize the molecular pathogenesis of this disease, and pinpoint the dominant pathways/drivers by integrative oncogenomic approaches and/or sophisticated experimental models. Identification of the dominant proliferative signals and key aberrations will allow for a more personalized therapy. Pathway-based approaches and functional experimental studies have aided in identifying the activation of different signaling cascades in HCC (e.g. epidermal growth factor, insulin-like growth factor, RAS, MTOR, WNT-ßcatenin, etc.). However, the introduction of new high-throughput genomic technologies (e.g. microarrays, deep sequencing, etc.), and increased sophistication of computational biology (e.g. bioinfomatics, biomodeling, etc.), opens the field to new strategies in oncogene and tumor suppressor discovery. These oncogenomic approaches are framed within emerging new disciplines such as systems biology, which integrates multiple inputs to explain cancer onset and progression. In addition, the consolidation of sophisticated animal models, such as mosaic cancer mouse models or the use of transposons for mutagenesis screens, have been instrumental for the identification of novel tumor drivers. We herein review some classical as well as some recent fast track approaches for oncogene discovery in HCC, and provide a comprehensive landscape of the currently known spectrum of molecular aberrations involved in hepatocarcinogenesis. PMID:20385424

  9. A Discovery Laboratory Investigating Bacterial Gene Regulation

    NSDL National Science Digital Library

    Robert Moss (Wofford College; )

    1999-01-01

    This laboratory exercise introduces students to experimental design and gene regulation using different sugar ("food" sources) and an enzyme assay for beta-glalctosidase to identify different E. coli stains with respect to lac operon mutations, then designing their own experiments to study the various aspects of the lac operon.

  10. BIOINFORMATICS Biomarker Discovery in Microarray Gene

    E-print Network

    Ghahramani, Zoubin

    score for prostate cancer data. Our results demonstrate how multi-gene markers that may be initially are often ordinal in routine clinical practice, such as the TNM system for staging prostate cancer. The development of these technologies has also motivated interest in their use in clinical trials and diagnosis

  11. 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.

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

    PubMed Central

    Lin, Frank PY; Coiera, Enrico; Lan, Ruiting; Sintchenko, Vitali

    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 Using gene occurrence patterns in sample genomes, we developed two CGP methods (statistical and inductive CGP) to assist with the discovery of bacterial gene functions. Statistical CGP exploits the differences in gene frequency against phenotypic groups, while inductive CGP applies supervised machine learning to identify gene occurrence pattern across genomes. Three rediscovery experiments were designed to evaluate the CGP frameworks. The first experiment attempted to rediscover peptidoglycan genes with 417 published genome sequences. Both CGP methods achieved best areas under receiver operating characteristic curve (AUC) of 0.911 in Escherichia coli K-12 (EC-K12) and 0.978 Streptococcus agalactiae 2603 (SA-2603) genomes, with an average improvement in precision of >3.2-fold and a maximum of >27-fold using statistical CGP. A median AUC of >0.95 could still be achieved with as few as 10 genome examples in each group of genome examples in the rediscovery of the peptidoglycan metabolism genes. In the second experiment, a maximum of 109-fold improvement in precision was achieved in the rediscovery of anaerobic fermentation genes in EC-K12. The last experiment attempted to rediscover genes from 31 metabolic pathways in SA-2603, where 14 pathways achieved AUC >0.9 and 28 pathways achieved AUC >0.8 with the best inductive CGP algorithms. Conclusion Our results demonstrate that the two CGP methods can assist with the study of functionally uncategorised genomic regions and discovery of bacterial gene-function relationships. Our rediscovery experiments also provide a set of standard tasks against which future methods may be compared. PMID:19292914

  13. Genomic advances for gene discovery in hereditary hearing loss.

    PubMed

    Avraham, Karen B; Kanaan, Moien

    2012-01-01

    High-throughput sequencing is changing the face of genetic diagnosis and counseling. While in the past, it would take on average 1 to 5 years to identify a mutation leading to deafness, today, the genetic basis for deafness can be determined within months in a child or adult with inherited hearing loss. Obstacles and challenges still remain, but the field is changing at a dramatic rate, making gene discovery a much easier and more efficient task than in the past. PMID:22962211

  14. 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

  15. Gene discovery and product development for grain quality traits.

    PubMed

    Mazur, B; Krebbers, E; Tingey, S

    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 marker-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. PMID:10411493

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

    E-print Network

    Guy, Fred; Palmer, Joy Elizabeth

    2010-01-01

    Abstract – Purpose The paper describes the context and the progress with the Discovery to Delivery project. Approach Having set the scene for discovery to delivery, the paper describes how the project work was ...

  17. 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.

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

    PubMed

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

    2011-04-27

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

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  20. Sugarcane functional genomics: gene discovery for agronomic trait development.

    PubMed

    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

  1. Integrative Biomarker Discovery for Breast Cancer Metastasis from Gene Expression and Protein Interaction Data Using Error-tolerant Pattern Mining

    E-print Network

    Kumar, Vipin

    Integrative Biomarker Discovery for Breast Cancer Metastasis from Gene Expression and Protein, University of Minnesota - Twin Cities, Minneapolis, MN 55455 Abstract Biomarker discovery for complex source is used to discover biomarkers. These factors account for the discovery of inconsistent biomark

  2. Leaf ESTs from Stevia rebaudiana : a resource for gene discovery in diterpene synthesis

    Microsoft Academic Search

    J. E. Brandle; A. Richman; A. K. Swanson; B. P. Chapman

    2002-01-01

    Expressed sequence tags (ESTs) are providing a new approach to gene discovery in plant secondary metabolism. Steviarebaudiana Bert. leaves produce high concentrations of diterpene steviol glycosides and should be a rich source of transcripts involved in diterpene synthesis. In order to create a resource for gene discovery and increase our understanding of steviol glycoside biosynthesis, we sequenced 5548 ESTs from

  3. In silico analysis of the exome for gene discovery.

    PubMed

    Hinchcliffe, Marcus; Webster, Paul

    2011-01-01

    Here we describe a bioinformatic strategy for extracting and analyzing the list of variants revealed from an exome sequencing project to identify potential disease genes. This in silico method filters out the majority of common SNPs and extracts a list of potential candidate protein-coding and non-coding RNA (ncRNA) genes. The workflow employs Galaxy, a publically available Web-based software, to filter and sort sequence variants identified by capture-based target enrichment and sequencing from exomes including selected ncRNAs. PMID:21779993

  4. 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

  5. Rice genome sequence accelerates the discovery of commercially important genes and polymorphisms

    Microsoft Academic Search

    Daniel LE Waters; Louis MT Bradbury; Russell F Reinke; Melissa A Fitzgerald; Qingsheng Jin; Robert J Henry

    2006-01-01

    Traditionally, identification of genes which control important traits has been labour intensive and time consuming. We have demonstrated the annotated rice genome sequence used in combination with re-sequencing by PCR greatly facilitates the discovery of both genes and polymorphisms within genes, which control commercially important traits. Identification of the gene which controls fragrance was achieved using a relatively small mapping

  6. 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

  7. 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

  8. Pattern discovery in gene regulation; designing an analysis environment.

    PubMed

    Veretnik, S; Schatz, B

    1993-01-01

    Interactions that determine cellular fate are exceedingly complex, can take place at different levels of gene regulation and involve a large number of components (such as genes, proteins). 'Wet lab' biology has an inherent difficulty in considering multiple components within one experimental set-up. Thus, the individual experimental results may reflect the behavior of a sub-system and be missing some important information concerning interactions with other components. Computational tools can help in simultaneously analyzing many different pieces of biological knowledge from different data sources. Such tools will aid in comprehending the whole system (cell, organism) as a function of all of its components; this, in turn, will facilitate discovery of the global patterns in genetic regulation. The Worm Community System (WCS) which contains extensive knowledge from many different sources regarding model organism C. elegans, presents a suitable environment for development of the integrated analysis tools. Here we describe a working version of WCS and the strategies employed for the development of the global analysis tools within the System. The present paper deals with the construction of a highly interconnected information space (in the context of the problem) by introducing more sophisticated data objects representing knowledge about genetic regulation. We describe construction of the in-depth objects, development of the analysis tools and discuss the type of analysis feasible within such interconnected space. The analysis tools will serve as an ideal environment for 'dry biology' experimentation and provide a context for 'wet' experiments. PMID:7584365

  9. Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia

    PubMed Central

    Potkin, SG; Turner, JA; Fallon, JA; Lakatos, A; Keator, DB; Guffanti, G; Macciardi, F

    2012-01-01

    We have discovered two genes, RSRC1 and ARHGAP18, associated with schizophrenia and in an independent study provided additional support for this association. We have both discovered and verified the association of two genes, RSRC1 and ARHGAP18, with schizophrenia. We combined a genome-wide screening strategy with neuroimaging measures as the quantitative phenotype and identified the single nucleotide polymorphisms (SNPs) related to these genes as consistently associated with the phenotypic variation. To control for the risk of false positives, the empirical P-value for association significance was calculated using permutation testing. The quantitative phenotype was Blood-Oxygen-Level Dependent (BOLD) Contrast activation in the left dorsal lateral prefrontal cortex measured during a working memory task. The differential distribution of SNPs associated with these two genes in cases and controls was then corroborated in a larger, independent sample of patients with schizophrenia (n = 82) and healthy controls (n = 91), thus suggesting a putative etiological function for both genes in schizophrenia. Up until now these genes have not been linked to any neuropsychiatric illness, although both genes have a function in prenatal brain development. We introduce the use of functional magnetic resonance imaging activation as a quantitative phenotype in conjunction with genome-wide association as a gene discovery tool. PMID:19065146

  10. Gene Discovery by EST Sequencing in Toxoplasma gondii Reveals Sequences Restricted to the Apicomplexa

    Microsoft Academic Search

    James W. Ajioka; John C. Boothroyd; Brian P. Brunk; Adrian Hehl; Ledeana Hillier; Ian D. Manger; Marco Marra; G. Christian Overton; David S. Roos; Kiew-Lian Wan; Robert Waterston; L. David Sibley

    1998-01-01

    To accelerate gene discovery and facilitate genetic mapping in the protozoan parasite Toxoplasma gondii, we have generated >7000 new ESTs from the 58 ends of randomly selected tachyzoite cDNAs. Comparison of the ESTs with the existing gene databases identified possible functions for more than 500 new T. gondii genes by virtue of sequence motifs shared with conserved protein families, including

  11. Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

    PubMed Central

    Laha, Thewarach; Pinlaor, Porntip; Mulvenna, Jason; Sripa, Banchob; Sripa, Manop; Smout, Michael J; Gasser, Robin B; Brindley, Paul J; Loukas, Alex

    2007-01-01

    Background Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum) than to free-living (Schmidtea mediterranea) flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA. Conclusion This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions, drugs and vaccines, to control O. viverrini and related flukes. PMID:17587442

  12. Discovery and New Frontiers Project Budget Analysis Tool

    NASA Technical Reports Server (NTRS)

    Newhouse, Marilyn E.

    2011-01-01

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

  13. 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.

  14. Gene discovery and microarray analysis of cacao ( Theobroma cacao L.) varieties

    Microsoft Academic Search

    Paul G. Jones; David Allaway; Martin D. Gilmour; Chris Harris; Debbie Rankin; Ernest R. Retzel; Chris A. Jones

    2002-01-01

    The cacao bean harvest from the relatively under developed tropical tree cacao (Theobroma cacao L.) is subject to high losses in potential production due to pests and diseases. To discover and understand the stability of putative natural resistance mechanisms in this commodity crop, essential for chocolate production, we undertook a gene-discovery program and demonstrated its use in gene-expression arrays. Sequencing

  15. New Discoveries From The Archean Biosphere Drilling Project (ABDP)

    NASA Astrophysics Data System (ADS)

    Nedachi, M.

    2004-12-01

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

  16. Host genes associated with HIV/AIDS: advances in gene discovery.

    PubMed

    An, Ping; Winkler, Cheryl A

    2010-03-01

    Twenty-five years after the discovery of HIV as the cause of AIDS there is still no effective vaccine and no cure for this disease. HIV susceptibility shows a substantial degree of individual heterogeneity, much of which can be conferred by host genetic variation. In an effort to discover host factors required for HIV replication, identify crucial pathogenic pathways, and reveal the full armament of host defenses, there has been a shift from candidate-gene studies to unbiased genome-wide genetic and functional studies. However, the number of securely identified host factors involved in HIV disease remains small, explaining only approximately 15-20% of the observed heterogeneity - most of which is attributable to human lymphocyte antigen (HLA) variants. Multidisciplinary approaches integrating genetic epidemiology to systems biology will be required to fully understand virus-host interactions to effectively combat HIV/AIDS. PMID:20149939

  17. 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

  18. 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

  19. Discovery of gene-regulation pathways using local causal search.

    PubMed Central

    Yoo, Changwon; Cooper, Gregory F.

    2002-01-01

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

  20. 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

  1. Discovery.

    ERIC Educational Resources Information Center

    Smithsonian Institution, Washington, DC. National Air And Space Museum.

    This material presents the historical perspectives of flight and student activities for grades K-3 prepared by the National Air and Space Museum (NASM) and National Aeronautics and Space Administration (NASA). Sections included are: (1) "Historical Perspective of Flight"; (2) "Discovery Vocabulary" (listing the terms found in the first section);…

  2. Terrorism Knowledge Discovery Project: A Knowledge Discovery Approach to Addressing the Threats of Terrorism

    Microsoft Academic Search

    Edna Reid; Jialun Qin; Wingyan Chung; Jennifer Jie Xu; Yilu Zhou; Robert P. Schumaker; Marc Sageman; Hsinchun Chen

    2004-01-01

    Ever since the 9-11 incident, the multidisciplinary field of terrorism has experienced tremendous growth. As the domain has benefited greatly from recent advances in information technologies, more complex and challeng- ing new issues have emerged from numerous counter-terrorism-related research communities as well as governments of all levels. In this paper, we describe an advanced knowledge discovery approach to addressing terrorism

  3. Network-based gene prediction for Plasmodium falciparum malaria towards genetics-based drug discovery

    PubMed Central

    2015-01-01

    Background Malaria is the most deadly parasitic infectious disease. Existing drug treatments have limited efficacy in malaria elimination, and the complex pathogenesis of the disease is not fully understood. Detecting novel malaria-associated genes not only contributes in revealing the disease pathogenesis, but also facilitates discovering new targets for anti-malaria drugs. Methods In this study, we developed a network-based approach to predict malaria-associated genes. We constructed a cross-species network to integrate human-human, parasite-parasite and human-parasite protein interactions. Then we extended the random walk algorithm on this network, and used known malaria genes as the seeds to find novel candidate genes for malaria. Results We validated our algorithms using 77 known malaria genes: 14 human genes and 63 parasite genes were ranked averagely within top 2% and top 4%, respectively among human and parasite genomes. We also evaluated our method for predicting novel malaria genes using a set of 27 genes with literature supporting evidence. Our approach ranked 12 genes within top 1% and 24 genes within top 5%. In addition, we demonstrated that top-ranked candied genes were enriched for drug targets, and identified commonalities underlying top-ranked malaria genes through pathway analysis. In summary, the candidate malaria-associated genes predicted by our data-driven approach have the potential to guide genetics-based anti-malaria drug discovery. PMID:26099491

  4. Discovery of a widely distributed toxin biosynthetic gene cluster

    E-print Network

    Nizet, Victor

    - cently identified through transposon and targeted mutagenesis coupled with heterologous expression (2, 5­7). The sag locus consists of nine genes (A­I), and allelic exchange mutagenesis has shown sag

  5. 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 ...

  6. 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.

  7. 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

  8. Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1

    E-print Network

    Sheridan, Jennifer

    Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 (received for review March 1, 2007) Eukaryotic parasites are a leading cause of morbidity and mortality genetic screen to study pathogenesis in the protozoan parasite Toxoplasma gondii. By using modified

  9. 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

  10. Transient transformation meets gene function discovery: the strawberry fruit case

    PubMed Central

    Guidarelli, Michela; Baraldi, Elena

    2015-01-01

    Beside the well known nutritional and health benefits, strawberry (Fragaria X ananassa) crop draws increasing attention as plant model system for the Rosaceae family, due to the short generation time, the rapid in vitro regeneration, and to the availability of the genome sequence of F. X ananassa and F. vesca species. In the last years, the use of high-throughput sequence technologies provided large amounts of molecular information on the genes possibly related to several biological processes of this crop. Nevertheless, the function of most genes or gene products is still poorly understood and needs investigation. Transient transformation technology provides a powerful tool to study gene function in vivo, avoiding difficult drawbacks that typically affect the stable transformation protocols, such as transformation efficiency, transformants selection, and regeneration. In this review we provide an overview of the use of transient expression in the investigation of the function of genes important for strawberry fruit development, defense and nutritional properties. The technical aspects related to an efficient use of this technique are described, and the possible impact and application in strawberry crop improvement are discussed. PMID:26124771

  11. Analysis of gene expression in pathophysiological states: balancing false discovery and false negative rates.

    PubMed

    Norris, Andrew W; Kahn, C Ronald

    2006-01-17

    Nucleotide-microarray technology, which allows the simultaneous measurement of the expression of tens of thousands of genes, has become an important tool in the study of disease. In disorders such as malignancy, gene expression often undergoes broad changes of sizable magnitude, whereas in many common multifactorial diseases, such as diabetes, obesity, and atherosclerosis, the changes in gene expression are modest. In the latter circumstance, it is therefore challenging to distinguish the truly changing from non-changing genes, especially because statistical significance must be considered in the context of multiple hypothesis testing. Here, we present a balanced probability analysis (BPA), which provides the biologist with an approach to interpret results in the context of the total number of genes truly differentially expressed and false discovery and false negative rates for the list of genes reaching any significance threshold. In situations where the changes are of modest magnitude, sole consideration of the false discovery rate can result in poor power to detect genes truly differentially expressed. Concomitant analysis of the rate of truly differentially expressed genes not identified, i.e., the false negative rate, allows balancing of the two error rates and a more thorough insight into the data. To this end, we have developed a unique, model-based procedure for the estimation of false negative rates, which allows application of BPA to real data in which changes are modest. PMID:16407153

  12. Sleeping Beauty mutagenesis: exploiting forward genetic screens for cancer gene discovery.

    PubMed

    Mann, Michael B; Jenkins, Nancy A; Copeland, Neal G; Mann, Karen M

    2014-02-01

    Sleeping Beauty (SB) is a powerful insertional mutagen used in somatic forward genetic screens to identify novel candidate cancer genes. In the past two years, SB has become widely adopted to model human pancreatic, hepatocellular, colorectal and neurological cancers to identify loci that participate in tumor initiation, progression and metastasis. Oncogenomic approaches have directly linked hundreds of genes identified by SB with human cancers, many with prognostic implications. These SB candidate cancer genes are aiding to prioritize punitive human cancer genes for follow-up studies and as possible biomarkers or therapeutic targets. This review highlights recent advances in SB cancer gene discovery, approaches to validate candidate cancer genes, and efforts to integrate SB data across all tumor types to prioritize drug development and tumor specificity. PMID:24657532

  13. The National Laboratory Gene Library Project

    SciTech Connect

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

    1988-01-01

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

  14. 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

  15. Activation tagging in plants: a tool for gene discovery

    Microsoft Academic Search

    Helen Tani; Xinwei Chen; Pedro Nurmberg; John J. Grant; Marjorie SantaMaria; Andrea Chini; Eleanor Gilroy; Paul R. J. Birch; Gary J. Loake

    2004-01-01

    A significant limitation of classical loss-of-function screens designed to dissect genetic pathways is that they rarely uncover genes that function redundantly, are compensated by alternative metabolic or regulatory circuits, or which have an additional role in early embryo or gametophyte development. Activation T-DNA tagging is one approach that has emerged in plants to help circumvent these potential problems. This technique

  16. Literature-based discovery of IFN-gamma and vaccine-mediated gene interaction networks.

    PubMed

    Ozgür, Arzucan; Xiang, Zuoshuang; Radev, Dragomir R; He, Yongqun

    2010-01-01

    Interferon-gamma (IFN-gamma) regulates various immune responses that are often critical for vaccine-induced protection. In order to annotate the IFN-gamma-related gene interaction network from a large amount of IFN-gamma research reported in the literature, a literature-based discovery approach was applied with a combination of natural language processing (NLP) and network centrality analysis. The interaction network of human IFN-gamma (Gene symbol: IFNG) and its vaccine-specific subnetwork were automatically extracted using abstracts from all articles in PubMed. Four network centrality metrics were further calculated to rank the genes in the constructed networks. The resulting generic IFNG network contains 1060 genes and 26313 interactions among these genes. The vaccine-specific subnetwork contains 102 genes and 154 interactions. Fifty six genes such as TNF, NFKB1, IL2, IL6, and MAPK8 were ranked among the top 25 by at least one of the centrality methods in one or both networks. Gene enrichment analysis indicated that these genes were classified in various immune mechanisms such as response to extracellular stimulus, lymphocyte activation, and regulation of apoptosis. Literature evidence was manually curated for the IFN-gamma relatedness of 56 genes and vaccine development relatedness for 52 genes. This study also generated many new hypotheses worth further experimental studies. PMID:20625487

  17. 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

  18. Gene expression monitoring for gene discovery in models of peripheral and central nervous system differentiation, regeneration, and trauma.

    PubMed

    Farlow, D N; Vansant, G; Cameron, A A; Chang, J; Khoh-Reiter, S; Pham, N L; Wu, W; Sagara, Y; Nicholls, J G; Carlo, D J; Ill, C R

    2000-10-20

    Gene expression monitoring using gene expression microarrays represents an extremely powerful technology for gene discovery in a variety of systems. We describe the results of seven experiments using Incyte GEM technology to compile a proprietary portfolio of data concerning differential gene expression in six different models of neuronal differentiation and regeneration, and recovery from injury or disease. Our first two experiments cataloged genes significantly up- or down-regulated during two phases of the retinoic acid-induced differentiation of the embryonal carcinoma line Ntera-2. To identify genes involved in neuronal regeneration we performed three GEM experiments, which included changes in gene expression in rat dorsal root ganglia during the healing of experimentally injured sciatic nerve, in regenerating neonatal opossum spinal cord, and during lipopolysaccharide stimulation of primary cultures of rat Schwann cells. Finally we have monitored genes involved in the recovery phase of the inflammatory disease of the rat spinal cord, experimental allergic encephalomyelitis, as well as those responsible for protection from oxidative stress in a glutamate-resistant rat hippocampal cell line. Analysis of the results of the approximately 70,000 data points collected is presented. PMID:11074584

  19. 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.

  20. 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...

  1. 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

  2. A Projection and Density Estimation Method for Knowledge Discovery

    PubMed Central

    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

  3. 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

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

    PubMed Central

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

    2015-01-01

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

  5. Discovery of new candidate genes related to brain development using protein interaction information.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Tsai, Yu-Shuen; Lin, Chin-Teng; Tseng, George C; Chung, I-Fang; Pal, Nikhil Ranjan

    2008-01-01

    Background The Signal-to-Noise-Ratio (SNR) is often used for identification of biomarkers for two-class problems and no formal and useful generalization of SNR is available for multiclass problems. We propose innovative generalizations of SNR for multiclass cancer discrimination through introduction of two indices, Gene Dominant Index and Gene Dormant Index (GDIs). These two indices lead to the concepts of dominant and dormant genes with biological significance. We use these indices to develop methodologies for discovery of dominant and dormant biomarkers with interesting biological significance. The dominancy and dormancy of the identified biomarkers and their excellent discriminating power are also demonstrated pictorially using the scatterplot of individual gene and 2-D Sammon's projection of the selected set of genes. Using information from the literature we have shown that the GDI based method can identify dominant and dormant genes that play significant roles in cancer biology. These biomarkers are also used to design diagnostic prediction systems. Results and discussion To evaluate the effectiveness of the GDIs, we have used four multiclass cancer data sets (Small Round Blue Cell Tumors, Leukemia, Central Nervous System Tumors, and Lung Cancer). For each data set we demonstrate that the new indices can find biologically meaningful genes that can act as biomarkers. We then use six machine learning tools, Nearest Neighbor Classifier (NNC), Nearest Mean Classifier (NMC), Support Vector Machine (SVM) classifier with linear kernel, and SVM classifier with Gaussian kernel, where both SVMs are used in conjunction with one-vs-all (OVA) and one-vs-one (OVO) strategies. We found GDIs to be very effective in identifying biomarkers with strong class specific signatures. With all six tools and for all data sets we could achieve better or comparable prediction accuracies usually with fewer marker genes than results reported in the literature using the same computational protocols. The dominant genes are usually easy to find while good dormant genes may not always be available as dormant genes require stronger constraints to be satisfied; but when they are available, they can be used for authentication of diagnosis. Conclusion Since GDI based schemes can find a small set of dominant/dormant biomarkers that is adequate to design diagnostic prediction systems, it opens up the possibility of using real-time qPCR assays or antibody based methods such as ELISA for an easy and low cost diagnosis of diseases. The dominant and dormant genes found by GDIs can be used in different ways to design more reliable diagnostic prediction systems. PMID:18842155

  7. Gene discovery and microarray analysis of cacao (Theobroma cacao L.) varieties.

    PubMed

    Jones, Paul G; Allaway, David; Gilmour, D Martin; Harris, Chris; Rankin, Debbie; Retzel, Ernest R; Jones, Chris A

    2002-12-01

    The cacao bean harvest from the relatively under developed tropical tree cacao (Theobroma cacao L.) is subject to high losses in potential production due to pests and diseases. To discover and understand the stability of putative natural resistance mechanisms in this commodity crop, essential for chocolate production, we undertook a gene-discovery program and demonstrated its use in gene-expression arrays. Sequencing and assembling bean and leaf cDNA library inserts produced a unique contig set of 1,380 members. High-quality annotation of this gene set using Blast and MetaFam produced annotation for 75% of the contigs and allowed us to identify the types of gene expressed in cacao beans and leaves. Microarrays were constructed using amplified inserts of the uni-gene set and challenged with bean and leaf RNA from five cacao varieties. The microarray performed well across the five randomly chosen cacao genotypes and did not show a bias towards either leaf or bean tissues. This demonstrates that the gene sequences are useful for microarray analysis across cacao genotypes and tissue types. The array results, when compared with real-time PCR results for selected genes, showed a correlation with differential gene-expression patterns. We intend that the resultant DNA sequences and molecular microarray platform will help the cacao community to understand the basis, likely stability and pathotype resistance range of candidate cacao plants. PMID:12447539

  8. The Salinas Airshower Learning And Discovery Project (SALAD)

    NASA Astrophysics Data System (ADS)

    Hernandez, Victor; Niduaza, Rommel; Ruiz Castruita, Daniel; Knox, Adrian; Ramos, Daniel; Fan, Sewan; Fatuzzo, Laura

    2015-04-01

    The SALAD project partners community college and high school STEM students in order to develop and investigate cosmic ray detector telescopes and the physical concepts, using a new light sensor technology based on silicon photomultiplier (SiPM) detectors. Replacing the conventional photomultiplier with the SiPM, offers notable advantages in cost and facilitates more in depth, hands-on learning laboratory activities. The students in the SALAD project design, construct and extensively evaluate the SiPM detector modules. These SiPM modules, can be completed in a short time utilizing cost effective components. We describe our research to implement SiPM as read out light detectors for plastic scintillators in a cosmic ray detector telescope for use in high schools. In particular, we describe our work in the design, evaluation and the assembly of (1) a fast preamplifier, (2) a simple coincidence circuit using fast comparators, to discriminate the SiPM noise signal pulses, and (3) a monovibrator circuit to shape the singles plus the AND logic pulses for subsequent processing. To store the singles and coincidence counts data, an Arduino micro-controller with program sketches can be implemented. Results and findings from our work would be described and presented. US Department of Education Title V Grant Award PO31S090007

  9. Evolving connectionist systems for knowledge discovery from gene expression data of cancer tissue.

    PubMed

    Futschik, Matthias E; Reeve, Anthony; Kasabov, Nikola

    2003-06-01

    Microarray techniques have made it possible to observe the expression of thousands of genes simultaneously. They have recently been applied to study gene expression patterns in tissue samples. This may lead to highly desirable improvements in the diagnosis and treatment of human diseases. Statistical and machine learning methods have recently been used to classify cancer tissue based on gene expression data. Although some of these methods have achieved a high degree of accuracy, they generally lack transparency in their classification process. This, however, is crucial for the application in the medical field. In order to overcome this obstacle, we used knowledge-based neurocomputing (KBN), since KBN seeks to gain knowledge that is comprehensible to humans. In particular, we applied evolving fuzzy neural networks (EFuNNs) to classify cancer tissue, which is illustrated on the case studies of leukaemia and colon cancer. EFuNNs belong to the evolving connectionist system paradigm (ECOS) that has been recently introduced. They are well suited for adaptive learning and knowledge discovery. Fuzzy logic rules can be extracted from the trained networks and offer knowledge about the classification process in an easily accessible form. These rules point to genes that are strongly associated with specific types of cancer and may be used for the development of new tests and treatment discoveries. PMID:12893118

  10. 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

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

    PubMed Central

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

    2013-01-01

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

  12. 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, Søren 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

  13. Discovery of novel genes derived from transposable elements using integrative genomic analysis.

    PubMed

    Hoen, Douglas R; Bureau, Thomas E

    2015-06-01

    Complex eukaryotes contain millions of transposable elements (TEs), comprising large fractions of their nuclear genomes. TEs consist of structural, regulatory, and coding sequences that are ordinarily associated with transposition, but that occasionally confer on the organism a selective advantage and may thereby become exapted. Exapted transposable element genes (ETEs) are known to play critical roles in diverse systems, from vertebrate adaptive immunity to plant development. Yet despite their evident importance, most ETEs have been identified fortuitously and few systematic searches have been conducted, suggesting that additional ETEs may await discovery. To explore this possibility, we develop a comprehensive systematic approach to searching for ETEs. We use TE-specific conserved domains to identify with high precision genes derived from TEs and screen them for signatures of exaptation based on their similarities to reference sets of known ETEs, conventional (non-TE) genes, and TE genes across diverse genetic attributes including repetitiveness, conservation of genomic location and sequence, and levels of expression and repressive small RNAs. Applying this approach in the model plant Arabidopsis thaliana, we discover a surprisingly large number of novel high confidence ETEs. Intriguingly, unlike known plant ETEs, several of the novel ETE families form tandemly arrayed gene clusters, whereas others are relatively young. Our results not only identify novel TE-derived genes that may have practical applications but also challenge the notion that TE exaptation is merely a relic of ancient life, instead suggesting that it may continue to fundamentally drive evolution. PMID:25713212

  14. Inherited retinal diseases in dogs: advances in gene/mutation discovery

    PubMed Central

    Miyadera, Keiko

    2015-01-01

    1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed.

  15. PhenomeNET: a whole-phenome approach to disease gene discovery

    PubMed Central

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2011-01-01

    Phenotypes are investigated in model organisms to understand and reveal the molecular mechanisms underlying disease. Phenotype ontologies were developed to capture and compare phenotypes within the context of a single species. Recently, these ontologies were augmented with formal class definitions that may be utilized to integrate phenotypic data and enable the direct comparison of phenotypes between different species. We have developed a method to transform phenotype ontologies into a formal representation, combine phenotype ontologies with anatomy ontologies, and apply a measure of semantic similarity to construct the PhenomeNET cross-species phenotype network. We demonstrate that PhenomeNET can identify orthologous genes, genes involved in the same pathway and gene–disease associations through the comparison of mutant phenotypes. We provide evidence that the Adam19 and Fgf15 genes in mice are involved in the tetralogy of Fallot, and, using zebrafish phenotypes, propose the hypothesis that the mammalian homologs of Cx36.7 and Nkx2.5 lie in a pathway controlling cardiac morphogenesis and electrical conductivity which, when defective, cause the tetralogy of Fallot phenotype. Our method implements a whole-phenome approach toward disease gene discovery and can be applied to prioritize genes for rare and orphan diseases for which the molecular basis is unknown. PMID:21737429

  16. RNA-Seq analysis and gene discovery of Andrias davidianus using Illumina short read sequencing.

    PubMed

    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

  17. The Berkeley Drosophila Genome Project Gene Disruption Project: Single P-Element Insertions Mutating 25% of Vital Drosophila Genes

    Microsoft Academic Search

    Allan C. Spradling; Dianne Stern; Amy Beaton; E. Jay Rhem; Todd Laverty; Nicole Mozden; Sima Misra; Gerald M. Rubin

    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

  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. Efficient generalized matrix approximations for biomarker discovery and visualization in gene expression data.

    PubMed

    Li, Wenyuan; Peng, Yanxiong; Huang, Hung-Chung; Liu, Ying

    2006-01-01

    In most real-life gene expression data sets, there are often multiple sample classes with ordinals, which are categorized into the normal or diseased type. The traditional feature or attribute selection methods consider multiple classes equally without paying attention to the up/down regulation across the normal and diseased types of classes, while the specific gene selection methods particularly consider the differential expressions across the normal and diseased, but ignore the existence of multiple classes. In this paper, for improving the biomarker discovery, we propose to make the best use of these two aspects: the differential expressions (that can be viewed as the domain knowledge of gene expression data) and the multiple classes (that can be viewed as a kind of data set characteristic). Therefore, we simultaneously take into account these two aspects by employing the 1-rank generalized matrix approximations (GMA). Our results show that the consideration of both aspects can not only improve the accuracy of classifying the samples, but also provide a visualization method to effectively analyze the gene expression data on both genes and samples. Based on the GMA mechanism, we further propose an algorithm for obtaining the compact biomarker by reducing the redundancy. PMID:17369632

  20. 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

  1. PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice.

    PubMed

    Rad, Roland; Rad, Lena; Wang, Wei; Cadinanos, Juan; Vassiliou, George; Rice, Stephen; Campos, Lia S; Yusa, Kosuke; Banerjee, Ruby; Li, Meng Amy; de la Rosa, Jorge; Strong, Alexander; Lu, Dong; Ellis, Peter; Conte, Nathalie; Yang, Fang Tang; Liu, Pentao; Bradley, Allan

    2010-11-19

    Transposons are mobile DNA segments that can disrupt gene function by inserting in or near genes. Here, we show that insertional mutagenesis by the PiggyBac transposon can be used for cancer gene discovery in mice. PiggyBac transposition in genetically engineered transposon-transposase mice induced cancers whose type (hematopoietic versus solid) and latency were dependent on the regulatory elements introduced into transposons. Analysis of 63 hematopoietic tumors revealed that PiggyBac is capable of genome-wide mutagenesis. The PiggyBac screen uncovered many cancer genes not identified in previous retroviral or Sleeping Beauty transposon screens, including Spic, which encodes a PU.1-related transcription factor, and Hdac7, a histone deacetylase gene. PiggyBac and Sleeping Beauty have different integration preferences. To maximize the utility of the tool, we engineered 21 mouse lines to be compatible with both transposon systems in constitutive, tissue- or temporal-specific mutagenesis. Mice with different transposon types, copy numbers, and chromosomal locations support wide applicability. PMID:20947725

  2. Gene discovery through imaging genetics: identification of two novel genes associated with schizophrenia

    Microsoft Academic Search

    S G Potkin; J A Turner; J A Fallon; A Lakatos; D B Keator; G Guffanti; F Macciardi

    2009-01-01

    We have discovered two genes, RSRC1 and ARHGAP18, associated with schizophrenia and in an independent study provided additional support for this association. We have both discovered and verified the association of two genes, RSRC1 and ARHGAP18, with schizophrenia. We combined a genome-wide screening strategy with neuroimaging measures as the quantitative phenotype and identified the single nucleotide polymorphisms (SNPs) related to

  3. Analysis of Brassica rapa ESTs: gene discovery and expression patterns of AP2\\/ERF family genes

    Microsoft Academic Search

    Jing Zhuang; Ai-Sheng Xiong; Ri-He Peng; Feng Gao; Bo Zhu; Jian Zhang; Xiao-Yan Fu; Xiao-Feng Jin; Jian-Min Chen; Zhen Zhang; Yu-Shan Qiao; Quan-Hong Yao

    2010-01-01

    Chinese cabbage (Brassica rapa subsp. pekinensis) is among the most important vegetables and is widely cultivated in world. Genes in the AP2\\/ERF family encode transcriptional\\u000a regulators that serve a variety of functions in the plants. Expressed sequence tags (ESTs) are created by partially sequencing\\u000a randomly isolated gene transcripts and have proved valuable in molecular biology. Starting from the database with

  4. TargetMine, an Integrated Data Warehouse for Candidate Gene Prioritisation and Target Discovery

    PubMed Central

    Mizuguchi, Kenji

    2011-01-01

    Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/. PMID:21408081

  5. iCOSSY: An Online Tool for Context-Specific Subnetwork Discovery from Gene Expression Data

    PubMed Central

    Saha, Ashis; Jeon, Minji; Tan, Aik Choon; Kang, Jaewoo

    2015-01-01

    Pathway analyses help reveal underlying molecular mechanisms of complex biological phenotypes. Biologists tend to perform multiple pathway analyses on the same dataset, as there is no single answer. It is often inefficient for them to implement and/or install all the algorithms by themselves. Online tools can help the community in this regard. Here we present an online gene expression analytical tool called iCOSSY which implements a novel pathway-based COntext-specific Subnetwork discoverY (COSSY) algorithm. iCOSSY also includes a few modifications of COSSY to increase its reliability and interpretability. Users can upload their gene expression datasets, and discover important subnetworks of closely interacting molecules to differentiate between two phenotypes (context). They can also interactively visualize the resulting subnetworks. iCOSSY is a web server that finds subnetworks that are differentially expressed in two phenotypes. Users can visualize the subnetworks to understand the biology of the difference. PMID:26147457

  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. 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

  8. An Update on Soybean Functional Genomics and Microarray Resources for Gene Discovery and Crop Improvement

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA microarrays are powerful tools to analyze the expression patterns of thousands of genes simultaneously. We review recent soybean genomics projects that have produced public-sector resources for this important legume crop. As part of the NSF-sponsored “Soybean Functional Genomics Program”, we hav...

  9. Gene discovery and expression analysis of immune-relevant genes from Biomphalaria glabrata hemocytes

    Microsoft Academic Search

    G. Mitta; R. Galinier; P. Tisseyre; J.-F. Allienne; Y. Girerd-Chambaz; F. Guillou; A. Bouchut; C. Coustau

    2005-01-01

    The immune effector cells (hemocytes) of the snail host Biomphalaria glabrata are known to play a key role in recognition and elimination of larval helminths such as the human blood fluke Schistosoma mansoni. To identify novel immune-relevant genes, we undertook an expressed sequence tag program. A hemocyte cDNA library was constructed using snails that were not exposed to a particular

  10. Discovery of MicroRNA169 Gene Copies in Genomes of Flowering Plants through Positional Information

    PubMed Central

    Calviño, Martín; Messing, Joachim

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

    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

  12. De novo assembly of chickpea transcriptome using short reads for gene discovery and marker identification.

    PubMed

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

    2011-02-01

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

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

    Microsoft Academic Search

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

    2004-01-01

    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

  15. Adeno-associated virus at 50: a golden anniversary of discovery, research, and gene therapy success-a personal perspective.

    PubMed

    Hastie, Eric; Samulski, R Jude

    2015-05-01

    Fifty years after the discovery of adeno-associated virus (AAV) and more than 30 years after the first gene transfer experiment was conducted, dozens of gene therapy clinical trials are in progress, one vector is approved for use in Europe, and breakthroughs in virus modification and disease modeling are paving the way for a revolution in the treatment of rare diseases, cancer, as well as HIV. This review will provide a historical perspective on the progression of AAV for gene therapy from discovery to the clinic, focusing on contributions from the Samulski lab regarding basic science and cloning of AAV, optimized large-scale production of vectors, preclinical large animal studies and safety data, vector modifications for improved efficacy, and successful clinical applications. PMID:25807962

  16. Paradigm of Tunable Clustering Using Binarization of Consensus Partition Matrices (Bi-CoPaM) for Gene Discovery

    PubMed Central

    Abu-Jamous, Basel; Fa, Rui; Roberts, David J.; Nandi, Asoke K.

    2013-01-01

    Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies. PMID:23409186

  17. Applying knowledge-anchored hypothesis discovery methods to advance clinical and translational research: the OAMiner project

    PubMed Central

    Jackson, Rebecca D; Best, Thomas M; Borlawsky, Tara B; Lai, Albert M; James, Stephen; Gurcan, Metin N

    2012-01-01

    The conduct of clinical and translational research regularly involves the use of a variety of heterogeneous and large-scale data resources. Scalable methods for the integrative analysis of such resources, particularly when attempting to leverage computable domain knowledge in order to generate actionable hypotheses in a high-throughput manner, remain an open area of research. In this report, we describe both a generalizable design pattern for such integrative knowledge-anchored hypothesis discovery operations and our experience in applying that design pattern in the experimental context of a set of driving research questions related to the publicly available Osteoarthritis Initiative data repository. We believe that this ‘test bed’ project and the lessons learned during its execution are both generalizable and representative of common clinical and translational research paradigms. PMID:22647689

  18. Applying knowledge-anchored hypothesis discovery methods to advance clinical and translational research: the OAMiner project.

    PubMed

    Payne, Philip R O; Jackson, Rebecca D; Best, Thomas M; Borlawsky, Tara B; Lai, Albert M; James, Stephen; Gurcan, Metin N

    2012-01-01

    The conduct of clinical and translational research regularly involves the use of a variety of heterogeneous and large-scale data resources. Scalable methods for the integrative analysis of such resources, particularly when attempting to leverage computable domain knowledge in order to generate actionable hypotheses in a high-throughput manner, remain an open area of research. In this report, we describe both a generalizable design pattern for such integrative knowledge-anchored hypothesis discovery operations and our experience in applying that design pattern in the experimental context of a set of driving research questions related to the publicly available Osteoarthritis Initiative data repository. We believe that this 'test bed' project and the lessons learned during its execution are both generalizable and representative of common clinical and translational research paradigms. PMID:22647689

  19. 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

  20. Gene invasion in distant eukaryotic lineages: discovery of mutually exclusive genetic elements reveals marine biodiversity

    PubMed Central

    Monier, Adam; Sudek, Sebastian; Fast, Naomi M; Worden, Alexandra Z

    2013-01-01

    Inteins are rare, translated genetic parasites mainly found in bacteria and archaea, while spliceosomal introns are distinctly eukaryotic features abundant in most nuclear genomes. Using targeted metagenomics, we discovered an intein in an Atlantic population of the photosynthetic eukaryote, Bathycoccus, harbored by the essential spliceosomal protein PRP8 (processing factor 8 protein). Although previously thought exclusive to fungi, we also identified PRP8 inteins in parasitic (Capsaspora) and predatory (Salpingoeca) protists. Most new PRP8 inteins were at novel insertion sites that, surprisingly, were not in the most conserved regions of the gene. Evolutionarily, Dikarya fungal inteins at PRP8 insertion site a appeared more related to the Bathycoccus intein at a unique insertion site, than to other fungal and opisthokont inteins. Strikingly, independent analyses of Pacific and Atlantic samples revealed an intron at the same codon as the Bathycoccus PRP8 intein. The two elements are mutually exclusive and neither was found in cultured Bathycoccus or other picoprasinophyte genomes. Thus, wild Bathycoccus contain one of few non-fungal eukaryotic inteins known and a rare polymorphic intron. Our data indicate at least two Bathycoccus ecotypes exist, associated respectively with oceanic or mesotrophic environments. We hypothesize that intein propagation is facilitated by marine viruses; and, while intron gain is still poorly understood, presence of a spliceosomal intron where a locus lacks an intein raises the possibility of new, intein-primed mechanisms for intron gain. The discovery of nucleus-encoded inteins and associated sequence polymorphisms in uncultivated marine eukaryotes highlights their diversity and reveals potential sexual boundaries between populations indistinguishable by common marker genes. PMID:23635865

  1. Gene invasion in distant eukaryotic lineages: discovery of mutually exclusive genetic elements reveals marine biodiversity.

    PubMed

    Monier, Adam; Sudek, Sebastian; Fast, Naomi M; Worden, Alexandra Z

    2013-09-01

    Inteins are rare, translated genetic parasites mainly found in bacteria and archaea, while spliceosomal introns are distinctly eukaryotic features abundant in most nuclear genomes. Using targeted metagenomics, we discovered an intein in an Atlantic population of the photosynthetic eukaryote, Bathycoccus, harbored by the essential spliceosomal protein PRP8 (processing factor 8 protein). Although previously thought exclusive to fungi, we also identified PRP8 inteins in parasitic (Capsaspora) and predatory (Salpingoeca) protists. Most new PRP8 inteins were at novel insertion sites that, surprisingly, were not in the most conserved regions of the gene. Evolutionarily, Dikarya fungal inteins at PRP8 insertion site a appeared more related to the Bathycoccus intein at a unique insertion site, than to other fungal and opisthokont inteins. Strikingly, independent analyses of Pacific and Atlantic samples revealed an intron at the same codon as the Bathycoccus PRP8 intein. The two elements are mutually exclusive and neither was found in cultured Bathycoccus or other picoprasinophyte genomes. Thus, wild Bathycoccus contain one of few non-fungal eukaryotic inteins known and a rare polymorphic intron. Our data indicate at least two Bathycoccus ecotypes exist, associated respectively with oceanic or mesotrophic environments. We hypothesize that intein propagation is facilitated by marine viruses; and, while intron gain is still poorly understood, presence of a spliceosomal intron where a locus lacks an intein raises the possibility of new, intein-primed mechanisms for intron gain. The discovery of nucleus-encoded inteins and associated sequence polymorphisms in uncultivated marine eukaryotes highlights their diversity and reveals potential sexual boundaries between populations indistinguishable by common marker genes. PMID:23635865

  2. 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

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

    PubMed Central

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

    2015-01-01

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

  4. A control study to evaluate a computer-based microarray experiment design recommendation system for gene-regulation pathways discovery.

    PubMed

    Yoo, Changwon; Cooper, Gregory F; Schmidt, Martin

    2006-04-01

    The main topic of this paper is evaluating a system that uses the expected value of experimentation for discovering causal pathways in gene expression data. By experimentation we mean both interventions (e.g., a gene knock-out experiment) and observations (e.g., passively observing the expression level of a "wild-type" gene). We introduce a system called GEEVE (causal discovery in Gene Expression data using Expected Value of Experimentation), which implements expected value of experimentation in discovering causal pathways using gene expression data. GEEVE provides the following assistance, which is intended to help biologists in their quest to discover gene-regulation pathways: Recommending which experiments to perform (with a focus on "knock-out" experiments) using an expected value of experimentation (EVE) method. Recommending the number of measurements (observational and experimental) to include in the experimental design, again using an EVE method. Providing a Bayesian analysis that combines prior knowledge with the results of recent microarray experimental results to derive posterior probabilities of gene regulation relationships. In recommending which experiments to perform (and how many times to repeat them) the EVE approach considers the biologist's preferences for which genes to focus the discovery process. Also, since exact EVE calculations are exponential in time, GEEVE incorporates approximation methods. GEEVE is able to combine data from knock-out experiments with data from wild-type experiments to suggest additional experiments to perform and then to analyze the results of those microarray experimental results. It models the possibility that unmeasured (latent) variables may be responsible for some of the statistical associations among the expression levels of the genes under study. To evaluate the GEEVE system, we used a gene expression simulator to generate data from specified models of gene regulation. Using the simulator, we evaluated the GEEVE system using a randomized control study that involved 10 biologists, some of whom used GEEVE and some of whom did not. The results show that biologists who used GEEVE reached correct causal assessments about gene regulation more often than did those biologists who did not use GEEVE. The GEEVE users also reached their assessments in a more cost-effective manner. PMID:16203178

  5. 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.

  6. 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

  7. Gene discovery using massively parallel pyrosequencing to develop ESTs for the flesh fly Sarcophaga crassipalpis

    PubMed Central

    Hahn, Daniel A; Ragland, Gregory J; Shoemaker, D DeWayne; Denlinger, David L

    2009-01-01

    Background Flesh flies in the genus Sarcophaga are important models for investigating endocrinology, diapause, cold hardiness, reproduction, and immunity. Despite the prominence of Sarcophaga flesh flies as models for insect physiology and biochemistry, and in forensic studies, little genomic or transcriptomic data are available for members of this genus. We used massively parallel pyrosequencing on the Roche 454-FLX platform to produce a substantial EST dataset for the flesh fly Sarcophaga crassipalpis. To maximize sequence diversity, we pooled RNA extracted from whole bodies of all life stages and normalized the cDNA pool after reverse transcription. Results We obtained 207,110 ESTs with an average read length of 241 bp. These reads assembled into 20,995 contigs and 31,056 singletons. Using BLAST searches of the NR and NT databases we were able to identify 11,757 unique gene elements (E<0.0001) representing approximately 9,000 independent transcripts. Comparison of the distribution of S. crassipalpis unigenes among GO Biological Process functional groups with that of the Drosophila melanogaster transcriptome suggests that our ESTs are broadly representative of the flesh fly transcriptome. Insertion and deletion errors in 454 sequencing present a serious hurdle to comparative transcriptome analysis. Aided by a new approach to correcting for these errors, we performed a comparative analysis of genetic divergence across GO categories among S. crassipalpis, D. melanogaster, and Anopheles gambiae. The results suggest that non-synonymous substitutions occur at similar rates across categories, although genes related to response to stimuli may evolve slightly faster. In addition, we identified over 500 potential microsatellite loci and more than 12,000 SNPs among our ESTs. Conclusion Our data provides the first large-scale EST-project for flesh flies, a much-needed resource for exploring this model species. In addition, we identified a large number of potential microsatellite and SNP markers that could be used in population and systematic studies of S. crassipalpis and other flesh flies. PMID:19454017

  8. Improving data discovery and usability through commentary and user feedback: the CHARMe project

    NASA Astrophysics Data System (ADS)

    Alegre, R.; Blower, J. D.

    2014-12-01

    Earth science datasets are highly diverse. Users of these datasets are similarly varied, ranging from research scientists through industrial users to government decision- and policy-makers. It is very important for these users to understand the applicability of any dataset to their particular problem so that they can select the most appropriate data sources for their needs. Although data providers often provide rich supporting information in the form of metadata, typically this information does not include community usage information that can help other users judge fitness-for-purpose.The CHARMe project (http://www.charme.org.uk) is filling this gap by developing a system for sharing "commentary metadata". These are annotations that are generated and shared by the user community and include: Links between publications and datasets. The CHARMe system can record information about why a particular dataset was used (e.g. the paper may describe the dataset, it may use the dataset as a source, or it may be publishing results of a dataset assessment). These publications may appear in the peer-reviewed literature, or may be technical reports, websites or blog posts. Free-text comments supplied by the user. Provenance information, including links between datasets and descriptions of processing algorithms and sensors. External events that may affect data quality (e.g. large volcanic eruptions or El Niño events); we call these "significant events". Data quality information, e.g. system maturity indices. Commentary information can be linked to anything that can be uniquely identified (e.g. a dataset with a DOI or a persistent web address). It is also possible to associate commentary with particular subsets of datasets, for example to highlight an issue that is confined to a particular geographic region. We will demonstrate tools that show these capabilities in action, showing how users can apply commentary information during data discovery, visualization and analysis. The CHARMe project has implemented a set of open-source tools to create, store and explore commentary information, using open Web standards. In this presentation we will describe the application of the CHARMe system to the particular case of the climate data community; however the techniques and technologies are generic and can be applied in many fields.

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

    PubMed Central

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

    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 mouse genome sequence databases can be used as part of a high-throughput pipeline for the in silico discovery of gene-coding variations within murine QTLs. As a test of this approach we focused on two QTLs on mouse chromosomes 1 and 13 that are involved in physical dependence on alcohol. Results Interstrain alignment of sequences derived from the relevant mouse strain genome sequence databases for 199 QTL-localized genes spanning 210,020 base-pairs of coding sequence identified 21 genes with different coding sequences for the progenitor strains. Several of these genes, including four that exhibit strong phenotypic links to chronic alcohol withdrawal, are promising candidates to underlie these QTLs. Conclusions This approach has wide general utility, and should be applicable to any of the several hundred mouse QTLs, encompassing over 60 different complex traits, that have been identified using strains for which relatively complete genome sequences are available. PMID:12537567

  10. 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

  11. Rapid and accurate large-scale genotyping of duplicated genes and discovery of novel sites of interlocus gene conversion

    PubMed Central

    Nuttle, Xander; Huddleston, John; O'Roak, Brian J.; Antonacci, Francesca; Fichera, Marco; Romano, Corrado; Shendure, Jay; Eichler, Evan E.

    2013-01-01

    Over 900 genes have been annotated within duplicated regions of the human genome, yet their functions and potential roles in disease remain largely unknown. One major obstacle has been our inability to accurately and comprehensively assay genetic variation for these genes in a high-throughput manner. We developed a sequencing-based method for rapid and high-throughput genotyping of duplicated genes using molecular inversion probes designed to unique paralogous sequence variants. We apply this method to genotype all members of two gene families, SRGAP2 and RH, among a diversity panel of 1,056 humans. The approach can accurately distinguish copy number in paralogs having up to ?99.6% sequence identity, identify small gene-disruptive deletions, detect single nucleotide variants, define breakpoints of unequal crossover, and discover regions of interlocus gene conversion. Our analysis of SRGAP2 suggests that nonreciprocal genetic exchange akin to interlocus gene conversion can occur over long distances (> 80 Mbp) between paralogs. The ability to rapidly and accurately genotype multiple gene families in thousands of individuals at low cost enables the development of genome-wide gene conversion maps and unlocks many duplicated genes for association with human traits. PMID:23892896

  12. 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

  13. 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

  14. Graph-based consensus clustering for class discovery from gene expression data

    Microsoft Academic Search

    Zhiwen Yu; Hau-san Wong; Hongqiang Wang

    2007-01-01

    Motivation: Consensus clustering, also known as cluster ensemble, is one of the important techniques for microarray data analysis, and is particularly useful for class discovery from microarray data. Compared with traditional clustering algorithms, consensus cluster- ing approaches have the ability to integrate multiple partitions from different cluster solutions to improve the robustness, stability, scalability and parallelization of the clustering algorithms.

  15. The NEIBank project for ocular genomics: data-mining gene expression in human and rodent eye tissues.

    PubMed

    Wistow, Graeme

    2006-01-01

    NEIBank is a project to gather and organize genomic resources for eye research. The first phase of this project covers the construction and sequence analysis of cDNA libraries from human and animal model eye tissues to develop an overview of the repertoire of genes expressed in the eye and a resource of cDNA clones for further studies. The sequence data are grouped and identified using the tools of bioinformatics and the results are displayed through a web site where they can be interrogated by keyword search, chromosome location, by Blast (sequence comparison) or by alignment on completed genomes. Many novel proteins and novel splice forms of known genes have already emerged from analysis of the accumulating data. This review provides an overview of the current state of the database for human eye tissues, with specific comparisons to some parallel data from mouse and rat, and with illustrative examples of the kinds of insights and discoveries these data can produce. One of the major themes that emerges is that at the molecular level human eye tissues have significant differences from those of rodents, encompassing species specific genes, alternative splice forms and great variation in levels of gene expression. These point to specific adaptations and mechanisms in the human eye and emphasize that care needs to be taken in the application of appropriate animal model systems. PMID:16005676

  16. 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

  17. 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

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

    PubMed

    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

    2011-05-01

    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

  19. Comparative Toxicogenomics Database: a knowledgebase and discovery tool for chemical-gene-disease networks

    Microsoft Academic Search

    Allan Peter Davis; Cynthia G. Murphy; Cynthia A. Saraceni-richards; Michael C. Rosenstein; Thomas C. Wiegers; Carolyn J. Mattingly

    2009-01-01

    The Comparative Toxicogenomics Database (CTD) is a curated database that promotes understanding about the effects of environmental chemicals on human health. Biocurators at CTD manually curate chemical-gene interactions, chemical-disease rela- tionships and gene-disease relationships from the literature. This strategy allows data to be integrated to construct chemical-gene-disease networks. CTD is unique in numerous respects: curation focuses on environmental chemicals; interactions

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

    PubMed Central

    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

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

    Microsoft Academic Search

    Alberto De Gregorio

    2005-01-01

    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

  2. Snpdat: Easy and rapid annotation of results from de novo snp discovery projects for model and non-model organisms

    PubMed Central

    2013-01-01

    Background Single nucleotide polymorphisms (SNPs) are the most abundant genetic variant found in vertebrates and invertebrates. SNP discovery has become a highly automated, robust and relatively inexpensive process allowing the identification of many thousands of mutations for model and non-model organisms. Annotating large numbers of SNPs can be a difficult and complex process. Many tools available are optimised for use with organisms densely sampled for SNPs, such as humans. There are currently few tools available that are species non-specific or support non-model organism data. Results Here we present SNPdat, a high throughput analysis tool that can provide a comprehensive annotation of both novel and known SNPs for any organism with a draft sequence and annotation. Using a dataset of 4,566 SNPs identified in cattle using high-throughput DNA sequencing we demonstrate the annotations performed and the statistics that can be generated by SNPdat. Conclusions SNPdat provides users with a simple tool for annotation of genomes that are either not supported by other tools or have a small number of annotated SNPs available. SNPdat can also be used to analyse datasets from organisms which are densely sampled for SNPs. As a command line tool it can easily be incorporated into existing SNP discovery pipelines and fills a niche for analyses involving non-model organisms that are not supported by many available SNP annotation tools. SNPdat will be of great interest to scientists involved in SNP discovery and analysis projects, particularly those with limited bioinformatics experience. PMID:23390980

  3. 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

  4. Induction of comprehensible models for gene expression datasets by subgroup discovery methodology

    Microsoft Academic Search

    Dragan Gambergera; Nada Lavracb; Filip Zeleznyd; Jakub Tolarf

    Finding disease markers (classifiers) from gene expression data by machine learning algorithms is characterized by a high risk of overfitting the data due the abundance of attributes (simultaneously measured gene expression values) and shortage of available examples (observations). To avoid this pitfall and achieve predictor robustness, state-of-the-art approaches construct complex clas- sifiers that combine relatively weak contributions of up to

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

    PubMed

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

    2014-09-01

    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

  6. Gene Discovery Using Computational and Microarray Analysis of Transcription in the Drosophila melanogaster Testis

    PubMed Central

    Andrews, Justen; Bouffard, Gerard G.; Cheadle, Chris; Lü, Jining; Becker, Kevin G.; Oliver, Brian

    2000-01-01

    Identification and annotation of all the genes in the sequenced Drosophila genome is a work in progress. Wild-type testis function requires many genes and is thus of potentially high value for the identification of transcription units. We therefore undertook a survey of the repertoire of genes expressed in the Drosophila testis by computational and microarray analysis. We generated 3141 high-quality testis expressed sequence tags (ESTs). Testis ESTs computationally collapsed into 1560 cDNA set used for further analysis. Of those, 11% correspond to named genes, and 33% provide biological evidence for a predicted gene. A surprising 47% fail to align with existing ESTs and 16% with predicted genes in the current genome release. EST frequency and microarray expression profiles indicate that the testis mRNA population is highly complex and shows an extended range of transcript abundance. Furthermore, >80% of the genes expressed in the testis showed onefold overexpression relative to ovaries, or gonadectomized flies. Additionally, >3% showed more than threefold overexpression at p <0.05. Surprisingly, 22% of the genes most highly overexpressed in testis match Drosophila genomic sequence, but not predicted genes. These data strongly support the idea that sequencing additional cDNA libraries from defined tissues, such as testis, will be important tools for refined annotation of the Drosophila genome. Additionally, these data suggest that the number of genes in Drosophila will significantly exceed the conservative estimate of 13,601. [The sequence data described in this paper have been submitted to the dbEST data library under accession nos. AI944400–AI947263 and BE661985–BE662262.] [The microarray data described in this paper have been submitted to the GEO data library under accession nos. GPLS, GSM3–GSM10.] PMID:11116097

  7. 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

  8. 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

  9. 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

  10. Discovery, characterization and expression of a novel zebrafish gene, znfr, important for notochord formation.

    PubMed

    Xu, Yan; Zou, Peng; Liu, Yao; Deng, Fengjiao

    2010-06-01

    Genes specifically expressed in the notochord may be crucial for proper notochord development. Using the digital differential display program offered by the National Center for Biotechnology Information, we identified a novel EST sequence from a zebrafish ovary library (No. XM_701450). The full-length cDNA of this transcript was cloned by performing 3' and 5'-RACE and was further confirmed by PCR and sequencing. The resulting 614 bp gene was found to encode a novel 94 amino acid protein that did not share significant homology with any other known protein. Characterization of the genomic sequence revealed that the gene spanned 4.9 kb and was composed of four exons and three introns. RT-PCR gene expression analysis revealed that our gene of interest was expressed in ovary, kidney, brain, mature oocytes and during the early stages of embryogenesis. During embryonic development, znfr mRNA was found to be expressed in the embryonic shield, chordamesoderm and the vacuolated notochord cells by in situ hybridization. Based on this information, we hypothesize that this novel gene is an important maternal factor required for zebrafish notochord formation during early embryonic development. We have thus named this gene znfr (zebrafish notochord formation related). PMID:19688271

  11. A multi-gene transcriptional profiling approach to the discovery of cell signature markers

    PubMed Central

    Wada, Youichiro; Li, Dan; Merley, Anne; Zukauskas, Andrew; Aird, William C.; Dvorak, Harold F.

    2010-01-01

    A profile of transcript abundances from multiple genes constitutes a molecular signature if the expression pattern is unique to one cell type. Here we measure mRNA copy numbers per cell by normalizing per million copies of 18S rRNA and identify 6 genes (TIE1, KDR, CDH5, TIE2, EFNA1 and MYO5C) out of 79 genes tested as excellent molecular signature markers for endothelial cells (ECs) in vitro. The selected genes are uniformly expressed in ECs of 4 different origins but weakly or not expressed in 4 non-EC cell lines. A multi-gene transcriptional profile of these 6 genes clearly distinguishes ECs from non-ECs in vitro. We conclude that (i) a profile of mRNA copy numbers per cell from a well-chosen multi-gene panel can act as a sensitive and accurate cell type signature marker, and (ii) the method described here can be applied to in vivo cell fingerprinting and molecular diagnosis. PMID:20972619

  12. Gene discovery for the bark beetle-vectored fungal tree pathogen Grosmannia clavigera

    PubMed Central

    2010-01-01

    Background Grosmannia clavigera is a bark beetle-vectored fungal pathogen of pines that causes wood discoloration and may kill trees by disrupting nutrient and water transport. Trees respond to attacks from beetles and associated fungi by releasing terpenoid and phenolic defense compounds. It is unclear which genes are important for G. clavigera's ability to overcome antifungal pine terpenoids and phenolics. Results We constructed seven cDNA libraries from eight G. clavigera isolates grown under various culture conditions, and Sanger sequenced the 5' and 3' ends of 25,000 cDNA clones, resulting in 44,288 high quality ESTs. The assembled dataset of unique transcripts (unigenes) consists of 6,265 contigs and 2,459 singletons that mapped to 6,467 locations on the G. clavigera reference genome, representing ~70% of the predicted G. clavigera genes. Although only 54% of the unigenes matched characterized proteins at the NCBI database, this dataset extensively covers major metabolic pathways, cellular processes, and genes necessary for response to environmental stimuli and genetic information processing. Furthermore, we identified genes expressed in spores prior to germination, and genes involved in response to treatment with lodgepole pine phloem extract (LPPE). Conclusions We provide a comprehensively annotated EST dataset for G. clavigera that represents a rich resource for gene characterization in this and other ophiostomatoid fungi. Genes expressed in response to LPPE treatment are indicative of fungal oxidative stress response. We identified two clusters of potentially functionally related genes responsive to LPPE treatment. Furthermore, we report a simple method for identifying contig misassemblies in de novo assembled EST collections caused by gene overlap on the genome. PMID:20920358

  13. Essential Gene Discovery in the Basidiomycete Cryptococcus neoformans for Antifungal Drug Target Prioritization

    PubMed Central

    Ianiri, Giuseppe

    2015-01-01

    ABSTRACT Fungal diseases represent a major burden to health care globally. As with other pathogenic microbes, there is a limited number of agents suitable for use in treating fungal diseases, and resistance to these agents can develop rapidly. Cryptococcus neoformans is a basidiomycete fungus that causes cryptococcosis worldwide in both immunocompromised and healthy individuals. As a basidiomycete, it diverged from other common pathogenic or model ascomycete fungi more than 500 million years ago. Here, we report C. neoformans genes that are essential for viability as identified through forward and reverse genetic approaches, using an engineered diploid strain and genetic segregation after meiosis. The forward genetic approach generated random insertional mutants in the diploid strain, the induction of meiosis and sporulation, and selection for haploid cells with counterselection of the insertion event. More than 2,500 mutants were analyzed, and transfer DNA (T-DNA) insertions in several genes required for viability were identified. The genes include those encoding the thioredoxin reductase (Trr1), a ribosome assembly factor (Rsa4), an mRNA-capping component (Cet1), and others. For targeted gene replacement, the C. neoformans homologs of 35 genes required for viability in ascomycete fungi were disrupted, meiosis and sporulation were induced, and haploid progeny were evaluated for their ability to grow on selective media. Twenty-one (60%) were found to be required for viability in C. neoformans. These genes are involved in mitochondrial translation, ergosterol biosynthesis, and RNA-related functions. The heterozygous diploid mutants were evaluated for haploinsufficiency on a number of perturbing agents and drugs, revealing phenotypes due to the loss of one copy of an essential gene in C. neoformans. This study expands the knowledge of the essential genes in fungi using a basidiomycete as a model organism. Genes that have no mammalian homologs and are essential in both Cryptococcus and ascomycete human pathogens would be ideal for the development of antifungal drugs with broad-spectrum activity. PMID:25827419

  14. Informatics-guided procurement of patient samples for biomarker discovery projects in cancer research.

    PubMed

    Suh, K Stephen; Remache, Yvonne K; Patel, Jalpa S; Chen, Steve H; Haystrand, Russell; Ford, Peggy; Shaikh, Anadil M; Wang, Jian; Goy, Andre H

    2009-02-01

    Modern cancer research for biomarker discovery program requires solving several tasks that are directly involved with patient sample procurement. One requirement is to construct a highly efficient workflow on the clinical side for the procurement to generate a consistent supply of high quality samples for research. This undertaking needs a network of interdepartmental collaborations and participations at various levels, including physical human interactions, information technology implementations and a bioinformatics tool that is highly effective and user-friendly to busy clinicians and researchers associated with the sample procurement. Collegial participation that is sequential but continual from one department to another demands dedicated bioinformatics software coordinating between the institutional clinic and the tissue repository facility. Participants in the process include admissions, consenting process, phlebotomy, surgery center and pathology. During this multiple step procedures, clinical data are collected for detailed analytical endpoints to supplement logistics of defining and validating the discovery of biomarkers. PMID:19016349

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

    PubMed Central

    2011-01-01

    Background DNA transposons have emerged as indispensible tools for manipulating vertebrate genomes with applications ranging from insertional 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 to evaluate their advantages and disadvantages for use in gene therapy and gene discovery. Results We have observed that (1) the Tol2 transposase (but not piggyBac) is highly sensitive to molecular engineering; (2) the piggyBac donor with only the 40 bp 3'-and 67 bp 5'-terminal repeat domain is sufficient for effective transposition; and (3) a small amount of piggyBac transposases results in robust transposition suggesting the piggyBac transpospase is highly active. Performing genome-wide target profiling on data sets obtained by retrieving chromosomal targeting sequences from individual clones, we have identified several piggyBac and Tol2 hotspots and observed that (4) piggyBac and Tol2 display a clear difference in targeting preferences in the human genome. Finally, we have observed that (5) only sites with a particular sequence context can be targeted by either piggyBac or Tol2. Conclusions The non-overlapping targeting preference of piggyBac and Tol2 makes them complementary research tools for manipulating mammalian genomes. PiggyBac is the most promising transposon-based vector system for achieving site-specific targeting of therapeutic genes due to the flexibility of its transposase for being molecularly engineered. Insights from this study will provide a basis for engineering piggyBac transposases to achieve site-specific therapeutic gene targeting. PMID:21447194

  16. 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...

  17. 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 ...

  18. Drug discovery of the future: the implications of the human genome project

    Microsoft Academic Search

    Thomas Reiss

    2001-01-01

    The elucidation of the 3.2-gigabase human genome will have various impacts on drug discovery. The number of drug targets will increase by at least one order of magnitude and target validation will become a high-throughput process. To benefit from these opportunities, a theory-based integration of the vast amount of new biological data into models of biological systems is called for.

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

    Microsoft Academic Search

    Alberto De Gregorio

    2005-01-01

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

  20. G-SESAME: web tools for GO-term-based gene similarity analysis and knowledge discovery

    PubMed Central

    Du, Zhidian; Li, Lin; Chen, Chin-Fu; Yu, Philip S.; Wang, James Z.

    2009-01-01

    We have developed a set of online tools for measuring the semantic similarities of Gene Ontology (GO) terms and the functional similarities of gene products, and for further discovering biomedical knowledge from the GO database. The tools have been used for about 6.9 million times by 417 institutions from 43 countries since October 2006. The online tools are available at: http://bioinformatics.clemson.edu/G-SESAME. PMID:19491312

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

    Microsoft Academic Search

    Bertrand R. Huber; Martha L. Bulyk

    2006-01-01

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

  2. 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

  3. Induction of comprehensible models for gene expression datasets by subgroup discovery methodology

    Microsoft Academic Search

    Dragan Gamberger; Nada Lavrac; Filip Zelezný; Jakub Tolar

    2004-01-01

    Finding disease markers (classifiers) from gene expression data by machine learning algorithms is characterized by a high risk of overfitting the data due the abundance of attributes (simultaneously measured gene expression values) and shortage of available examples (observations). To avoid this pitfall and achieve predictor robustness, state-of-the-art approaches construct complex clas-sifiers that combine relatively weak contributions of up to thousands

  4. Discovery and expression profile analysis of AP2\\/ERF family genes from Triticum aestivum

    Microsoft Academic Search

    Jing Zhuang; Jian-Min Chen; Quan-Hong Yao; Fei Xiong; Chao-Cai Sun; Xi-Rong Zhou; Jian Zhang; Ai-Sheng Xiong

    2011-01-01

    Throughout its development, common wheat, Triticum aestivum responds to different kinds of adverse abiotic and biotic stress by expressing specific genes that allow it to adapt to these\\u000a stresses. In this process, genes in the AP2\\/ERF family encode transcriptional regulators involved in diverse developmental\\u000a and physiological processes play critical roles. Here, we established an extensive picture of the AP2\\/ERF family

  5. Discovery of mitochondrial chimeric-gene associated with cytoplasmic male sterility of HL-rice

    Microsoft Academic Search

    Ping Yi; Li Wang; Qingping Sun; Yingguo Zhu

    2002-01-01

    The mitochondrial genome libraries of HL-type sterile line (A) and maintainer line(B) have been constructed. Mitochondrial\\u000a gene, atp6, was used to screen libraries, due to the different Southern and Northern blot results between sterile and maintainer line.\\u000a Sequencing analysis of positive clones proved that there were two copies of atp6 gene in sterile line and only one in maintainer line.

  6. 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

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

    PubMed Central

    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

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

    PubMed Central

    Ficklin, Stephen P.; Feltus, Frank Alex

    2013-01-01

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

  9. The discovery that RNA interference (RNAi) and related small-RNA-mediated pathways have central roles in the silencing of gene expression

    E-print Network

    Cai, Long

    The discovery that RNA interference (RNAi) and related small-RNA- mediated pathways have central and mice, mutations in the genetic regions encoding the protein and/or RNA components of RNAi result these mechanisms enable gene expression to be precisely tuned in response to internal and external stimuli. RNAi

  10. 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

  11. Discovery of microarray-identified genes associated with ovarian cancer progression.

    PubMed

    Liu, Xia; Gao, Yutao; Zhao, Bingbing; Li, Xiaofeng; Lu, Yi; Zhang, Jian; Li, Danrong; Li, Li; Yin, Fuqiang

    2015-06-01

    Ovarian cancer is the most lethal cancer of female reproductive system. There is a consistent and urgent need to better understand its mechanism. In this study, we retrieved 186 genes that were dysregulated by at least 4-fold in 594 ovarian serous cystadenocarcinomas in comparison with eight normal ovaries, according to The Cancer Genome Atlas Ovarian Statistics data deposited in Oncomine database. DAVID analysis of these genes enriched two biological processes indicating that the cell cycle and microtubules might play critical roles in ovarian cancer progression. Among these 186 genes, 46 were dysregulated by at least 10-fold and their expression was further confirmed by the Bonome Ovarian Statistics data deposited in Oncomine, which covered 185 cases of ovarian carcinomas and 10 cases of normal ovarian surface epithelium. Six genes, including aldehyde dehydrogenase 1 family, member A2 (ALDH1A2), alcohol dehydrogenase 1B (class I), ? polypeptide (ADH1B), NEL-like 2 (chicken) (NELL2), hemoglobin, ? (HBB), ATP-binding cassette, sub-family A (ABC1), member 8 (ABCA8) and hemoglobin, ?1 (HBA1) were identified to be downregulated by at least 10-fold in 779 ovarian cancers compared with 18 normal controls. Using mRNA expression profiles retrieved from microarrays deposited in the Gene Expression Omnibus Profiles database, RT-qPCR measurement and bioinformatics analysis, we further indicated that high expression of HBB might predict a poorer 5-year survival, high expression of ALDH1A2 and ABCA8 might predict a poor outcome; while ALDH1A2, ADH1B, HBB and ABCA8, in particular the former two genes, might be associated with drug resistance, and ALDH1A2 and NELL2 might contribute to invasiveness and metastasis in ovarian cancer. This study thus contributes to our understanding of the mechanism of ovarian cancer progression and development, and the six identified genes may be potential therapeutic targets and biomarkers for diagnosis and prognosis. PMID:25891226

  12. Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma

    PubMed Central

    Gu, De-Leung; Chen, Yen-Hsieh; Shih, Jou-Ho; Lin, Chi-Hung; Jou, Yuh-Shan; Chen, Chian-Feng

    2013-01-01

    High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/?-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients. PMID:24379610

  13. 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

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

    PubMed

    Bower, Neil I; Johnston, Ian A

    2010-10-01

    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

  15. Serious limitations of the QTL/Microarray approach for QTL gene discovery

    PubMed Central

    2010-01-01

    Background It has been proposed that the use of gene expression microarrays in nonrecombinant parental or congenic strains can accelerate the process of isolating individual genes underlying quantitative trait loci (QTL). However, the effectiveness of this approach has not been assessed. Results Thirty-seven studies that have implemented the QTL/microarray approach in rodents were reviewed. About 30% of studies showed enrichment for QTL candidates, mostly in comparisons between congenic and background strains. Three studies led to the identification of an underlying QTL gene. To complement the literature results, a microarray experiment was performed using three mouse congenic strains isolating the effects of at least 25 biometric QTL. Results show that genes in the congenic donor regions were preferentially selected. However, within donor regions, the distribution of differentially expressed genes was homogeneous once gene density was accounted for. Genes within identical-by-descent (IBD) regions were less likely to be differentially expressed in chromosome 2, but not in chromosomes 11 and 17. Furthermore, expression of QTL regulated in cis (cis eQTL) showed higher expression in the background genotype, which was partially explained by the presence of single nucleotide polymorphisms (SNP). Conclusions The literature shows limited successes from the QTL/microarray approach to identify QTL genes. Our own results from microarray profiling of three congenic strains revealed a strong tendency to select cis-eQTL over trans-eQTL. IBD regions had little effect on rate of differential expression, and we provide several reasons why IBD should not be used to discard eQTL candidates. In addition, mismatch probes produced false cis-eQTL that could not be completely removed with the current strains genotypes and low probe density microarrays. The reviewed studies did not account for lack of coverage from the platforms used and therefore removed genes that were not tested. Together, our results explain the tendency to report QTL candidates as differentially expressed and indicate that the utility of the QTL/microarray as currently implemented is limited. Alternatives are proposed that make use of microarray data from multiple experiments to overcome the outlined limitations. PMID:20624276

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

    Microsoft Academic Search

    A. C. Spradling; D. M. Stern; I. Kiss

    1995-01-01

    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

  17. 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.

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

    PubMed Central

    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

  19. Discovery of Antibiotics-derived Polymers for Gene Delivery using Combinatorial Synthesis and Cheminformatics Modeling

    PubMed Central

    Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D.; Ramos, James; Breneman, Curt M.; Rege, Kaushal

    2014-01-01

    We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and ‘building block’ polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. PMID:24331709

  20. 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

  1. 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...

  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. 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

  4. Integration of genetic, physical, and expression mapping resources for gene discovery and beet improvement

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Expressed Sequence Tags (ESTs) provide an entry into the analyses of ‘gene space’ at the molecular level. As expression markers, they indicate particular biochemical process that operate in various organ tissues, and can help discover developmental or response-to-environment pathways that might not ...

  5. Human embryonic stem cells as a model for cardiac gene discovery : from chip to chap

    Microsoft Academic Search

    A. Beqqali

    2008-01-01

    Here we described the use of human embryonic stem cells (hESCs) as a model to obtain insights into commitment to the mesoderm and endoderm lineages and the early steps in human cardiac cell differentiation by means of whole-genome temporal expression profiling. Furthermore, we used it as an approach to identify new genes that may be associated with (abnormal) human heart

  6. Discovery and assessment of conserved Pax6 target genes and enhancers

    PubMed Central

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

    2011-01-01

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

  7. Discovery of Chemosensory Genes in the Oriental Fruit Fly, Bactrocera dorsalis

    PubMed Central

    Wu, Zhongzhen; Zhang, He; Wang, Zhengbing; Bin, Shuying; He, Hualiang; Lin, Jintian

    2015-01-01

    The oriental fruit fly, Bactrocera dorsalis, is a devastating fruit fly pest in tropical and sub-tropical countries. Like other insects, this fly uses its chemosensory system to efficiently interact with its environment. However, our understanding of the molecular components comprising B. dorsalis chemosensory system is limited. Using next generation sequencing technologies, we sequenced the transcriptome of four B. dorsalis developmental stages: egg, larva, pupa and adult chemosensory tissues. A total of 31 candidate odorant binding proteins (OBPs), 4 candidate chemosensory proteins (CSPs), 23 candidate odorant receptors (ORs), 11 candidate ionotropic receptors (IRs), 6 candidate gustatory receptors (GRs) and 3 candidate sensory neuron membrane proteins (SNMPs) were identified. The tissue distributions of the OBP and CSP transcripts were determined by RT-PCR and a subset of nine genes were further characterized. The predicted proteins from these genes shared high sequence similarity to Drosophila melanogaster pheromone binding protein related proteins (PBPRPs). Interestingly, one OBP (BdorOBP19c) was exclusively expressed in the sex pheromone glands of mature females. RT-PCR was also used to compare the expression of the candidate genes in the antennae of male and female B. dorsalis adults. These antennae-enriched OBPs, CSPs, ORs, IRs and SNMPs could play a role in the detection of pheromones and general odorants and thus could be useful target genes for the integrated pest management of B. dorsalis and other agricultural pests. PMID:26070069

  8. 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

  9. Discovery of Chemosensory Genes in the Oriental Fruit Fly, Bactrocera dorsalis.

    PubMed

    Wu, Zhongzhen; Zhang, He; Wang, Zhengbing; Bin, Shuying; He, Hualiang; Lin, Jintian

    2015-01-01

    The oriental fruit fly, Bactrocera dorsalis, is a devastating fruit fly pest in tropical and sub-tropical countries. Like other insects, this fly uses its chemosensory system to efficiently interact with its environment. However, our understanding of the molecular components comprising B. dorsalis chemosensory system is limited. Using next generation sequencing technologies, we sequenced the transcriptome of four B. dorsalis developmental stages: egg, larva, pupa and adult chemosensory tissues. A total of 31 candidate odorant binding proteins (OBPs), 4 candidate chemosensory proteins (CSPs), 23 candidate odorant receptors (ORs), 11 candidate ionotropic receptors (IRs), 6 candidate gustatory receptors (GRs) and 3 candidate sensory neuron membrane proteins (SNMPs) were identified. The tissue distributions of the OBP and CSP transcripts were determined by RT-PCR and a subset of nine genes were further characterized. The predicted proteins from these genes shared high sequence similarity to Drosophila melanogaster pheromone binding protein related proteins (PBPRPs). Interestingly, one OBP (BdorOBP19c) was exclusively expressed in the sex pheromone glands of mature females. RT-PCR was also used to compare the expression of the candidate genes in the antennae of male and female B. dorsalis adults. These antennae-enriched OBPs, CSPs, ORs, IRs and SNMPs could play a role in the detection of pheromones and general odorants and thus could be useful target genes for the integrated pest management of B. dorsalis and other agricultural pests. PMID:26070069

  10. Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

    PubMed

    Perry, Antoinette S; O'Hurley, Gillian; Raheem, Omer A; Brennan, Kevin; Wong, Simon; O'Grady, Anthony; Kennedy, Anne-Marie; Marignol, Laure; Murphy, Therese M; Sullivan, Linda; Barrett, Ciara; Loftus, Barbara; Thornhill, John; Hewitt, Stephen M; Lawler, Mark; Kay, Elaine; Lynch, Thomas; Hollywood, Donal

    2013-04-15

    Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (? 7) and low (? 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (? 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer. PMID:22915211

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

    E-print Network

    California at Davis, University of

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

  12. 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

  13. Case-only exome sequencing and complex disease susceptibility gene discovery: study design considerations.

    PubMed

    Wu, Lang; Schaid, Daniel J; Sicotte, Hugues; Wieben, Eric D; Li, Hu; Petersen, Gloria M

    2015-01-01

    Whole exome sequencing (WES) provides an unprecedented opportunity to identify the potential aetiological role of rare functional variants in human complex diseases. Large-scale collaborations have generated germline WES data on patients with a number of diseases, especially cancer, but less often on healthy controls under the same sequencing procedures. These data can be a valuable resource for identifying new disease susceptibility loci if study designs are appropriately applied. This review describes suggested strategies and technical considerations when focusing on case-only study designs that use WES data in complex disease scenarios. These include variant filtering based on frequency and functionality, gene prioritisation, interrogation of different data types and targeted sequencing validation. We propose that if case-only WES designs were applied in an appropriate manner, new susceptibility genes containing rare variants for human complex diseases can be detected. PMID:25371537

  14. 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

  15. The use of gene-specific IgY antibodies for drug target discovery

    Microsoft Academic Search

    Wei-Wei Zhang

    2003-01-01

    Genomics and gene expression data require interpretation at the protein level to validate the biological or pathological findings. To match with the efficiency and capacity of DNA microarray application, methods and approaches of protein analysis in multiplex and high-throughput manner are required for effectively discovering disease-related proteins. Two-dimensional gel and MS-based technologies provide researchers with such approaches, but neither of

  16. Ac/Ds-transposon activation tagging in poplar: a powerful tool for gene discovery

    PubMed Central

    2012-01-01

    Background Rapid improvements in the development of new sequencing technologies have led to the availability of genome sequences of more than 300 organisms today. Thanks to bioinformatic analyses, prediction of gene models and protein-coding transcripts has become feasible. Various reverse and forward genetics strategies have been followed to determine the functions of these gene models and regulatory sequences. Using T-DNA or transposons as tags, significant progress has been made by using "Knock-in" approaches ("gain-of-function" or "activation tagging") in different plant species but not in perennial plants species, e.g. long-lived trees. Here, large scale gene tagging resources are still lacking. Results We describe the first application of an inducible transposon-based activation tagging system for a perennial plant species, as example a poplar hybrid (P. tremula L. × P. tremuloides Michx.). Four activation-tagged populations comprising a total of 12,083 individuals derived from 23 independent "Activation Tagging Ds" (ATDs) transgenic lines were produced and phenotyped. To date, 29 putative variants have been isolated and new ATDs genomic positions were successfully determined for 24 of those. Sequences obtained were blasted against the publicly available genome sequence of P. trichocarpa v2.0 (Phytozome v7.0; http://www.phytozome.net/poplar) revealing possible transcripts for 17 variants. In a second approach, 300 randomly selected individuals without any obvious phenotypic alterations were screened for ATDs excision. For one third of those transposition of ATDs was confirmed and in about 5% of these cases genes were tagged. Conclusions The novel strategy of first genotyping and then phenotyping a tagging population as proposed here is, in particular, applicable for long-lived, difficult to transform plant species. We could demonstrate the power of the ATDs transposon approach and the simplicity to induce ATDs transposition in vitro. Since a transposon is able to pass chromosomal boundaries, only very few primary transposon-carrying transgenic lines are required for the establishment of large transposon tagging populations. In contrast to T-DNA-based activation tagging, which is plagued by a lack of transformation efficiency and its time consuming nature, this for the first time, makes it feasible one day to tag (similarly to Arabidopsis) every gene within a perennial plant genome. PMID:22309468

  17. Pattern discovery Finding combinations of genes that are involved in some

    E-print Network

    Cabrera, Javier

    EWS.C9 1 3.203 1.655 3.278 1.006 2.710 2.059 1.848 2.714 2.356 1.929 3.616 2.151 2.312 1.069 0.919 0 Analysis: Group the genes (or samples) into k distinct natural groups. Hierarchical clustering: Build of points · Ward: R^2 change. Build a hierarchical tree: 1. Start with a cluster at each sample point 2

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

    PubMed Central

    2010-01-01

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

  19. Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: discovery of MK-2918.

    PubMed

    Paone, Daniel V; Nguyen, Diem N; Shaw, Anthony W; Burgey, Christopher S; Potteiger, Craig M; Deng, James Z; Mosser, Scott D; Salvatore, Christopher A; Yu, Sean; Roller, Shane; Kane, Stefanie A; Selnick, Harold G; Vacca, Joseph P; Williams, Theresa M

    2011-05-01

    In our ongoing efforts to develop CGRP receptor antagonists for the treatment of migraine, we aimed to improve upon telecagepant by targeting a compound with a lower projected clinical dose. Imidazoazepanes were identified as potent caprolactam replacements and SAR of the imidazole yielded the tertiary methyl ether as an optimal substituent for potency and hERG selectivity. Combination with the azabenzoxazinone spiropiperidine ultimately led to preclinical candidate 30 (MK-2918). PMID:21251825

  20. Discovery and preclinical validation of drug indications using compendia of public gene expression data

    PubMed Central

    Sirota, Marina; Dudley, Joel T.; Kim, Jeewon; Chiang, Annie P.; Morgan, Alex A.; Sweet-Cordero, Alejandro; Sage, Julien; Butte, Atul J.

    2012-01-01

    The application of established drug compounds to novel therapeutic indications, known as drug repositioning, offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval. Recent approaches to drug repositioning employ high-throughput experimental approaches to assess a compound’s potential therapeutic qualities. Here we present a systematic computational approach to predict novel therapeutic indications based on comprehensive testing of molecular signatures in drug-disease pairs. We integrated gene expression measurements from 100 diseases and gene expression measurements on 164 drug compounds yielding predicted therapeutic potentials for these drugs. We demonstrate the ability to recover many known drug and disease relationships using computationally derived therapeutic potentials, and also predict many new indications for these drugs. We experimentally validated a prediction for the anti-ulcer drug cimetidine as a candidate therapeutic in the treatment of lung adenocarcinoma, and demonstrate both in vitro and in vivo using mouse xenograft models. This novel computational method provides a novel and systematic approach to reposition established drugs to treat a wide range of human diseases. PMID:21849665

  1. 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.

  2. 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.

  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. 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…

  5. 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

  6. Discovery: Guidelines for Establishing an Outdoor Education Program in Special Education, ESEA Title III Project.

    ERIC Educational Resources Information Center

    Bott, Kristine Ann; Bannasch, Donald Max

    Funded through the 1965 Elementary and Secondary Education Act (ESEA) Title III, the Project began serving youngsters handicapped either physically, mentally, or emotionally, who qualified for special education services in the fall of 1971. Among its objectives were to: (1) improve these youngsters' achievement in reqular school subjects, their…

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

    PubMed Central

    Sabater-Muñoz, Beatriz; Legeai, Fabrice; Rispe, Claude; Bonhomme, Joël; Dearden, Peter; Dossat, Carole; Duclert, Aymeric; Gauthier, Jean-Pierre; Ducray, Danièle Giblot; Hunter, Wayne; Dang, Phat; Kambhampati, Srini; Martinez-Torres, David; Cortes, Teresa; Moya, Andrès; 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

  8. De Novo Regulatory Motif Discovery Identifies Significant Motifs in Promoters of Five Classes of Plant Dehydrin Genes

    PubMed Central

    Zolotarov, Yevgen; Strömvik, Martina

    2015-01-01

    Plants accumulate dehydrins in response to osmotic stresses. Dehydrins are divided into five different classes, which are thought to be regulated in different manners. To better understand differences in transcriptional regulation of the five dehydrin classes, de novo motif discovery was performed on 350 dehydrin promoter sequences from a total of 51 plant genomes. Overrepresented motifs were identified in the promoters of five dehydrin classes. The Kn dehydrin promoters contain motifs linked with meristem specific expression, as well as motifs linked with cold/dehydration and abscisic acid response. KS dehydrin promoters contain a motif with a GATA core. SKn and YnSKn dehydrin promoters contain motifs that match elements connected with cold/dehydration, abscisic acid and light response. YnKn dehydrin promoters contain motifs that match abscisic acid and light response elements, but not cold/dehydration response elements. Conserved promoter motifs are present in the dehydrin classes and across different plant lineages, indicating that dehydrin gene regulation is likely also conserved. PMID:26114291

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

    PubMed

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

    2011-08-01

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

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

    PubMed Central

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

    2011-01-01

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

  11. Immune gene discovery by expressed sequence tag analysis of hemocytes and hepatopancreas in the Pacific White Shrimp, Litopenaeus vannamei, and the Atlantic White Shrimp, L. setiferus

    Microsoft Academic Search

    P. S. Gross; T. C. Bartlett; C. L. Browdy; R. W. Chapman; G. W. Warr

    2001-01-01

    A pilot program was undertaken in immune gene discovery in two sister species of litopenaeid shrimp, the Pacific white shrimp, Litopenaeus vannamei and the Atlantic white shrimp, L. setiferus. RNA from the hemocytes and hepatopancreas of single individuals from each species was recovered, 4 cDNA libraries (one from each tissue\\/species) were made by a PCR-based method and a total of

  12. Challenges in Projecting Clustering Results Across Gene Expression - Profiling Datasets

    Microsoft Academic Search

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

    2007-01-01

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

  13. 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

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

    E-print Network

    Levin, Judith G.

    NCBI Handout Series | RefSeqGene | Last Update August 19, 2013 Contact: info@ncbi.nlm.nih.gov The RefSeqGene Project A collection of sequences as foundation for gene-based coordinates http://www.ncbi.nlm.nih.gov regions. Modifications made to RefSeqGene sequences are versioned and a tool (www.ncbi.nlm.nih.gov

  15. Whose genes are they? The Human Genome Diversity Project.

    PubMed

    Lone Dog, L

    1999-01-01

    The Human Genome Diversity Project (HGDP) has targeted several hundred indigenous peoples worldwide as their source of genetic material. Proponents for this project claim that information derived by analyzing these materials may be used for a variety of purposes ranging from finding a cure for diabetes to resolving debates about human origins. However, the HGDP plan raises many issues for indigenous people. This paper describes the project as well as the possible ethical and policy implications for Native communities. PMID:10538186

  16. 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

  17. 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.

  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. 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

  20. Gene disruptions using P transposable elements: an integral component of the Drosophila genome project.

    PubMed

    Spradling, A C; Stern, D M; Kiss, I; Roote, J; Laverty, T; Rubin, G M

    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 an 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. PMID:7479892

  1. 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.

  2. Cell Discoveries

    NSDL National Science Digital Library

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

    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.

  3. 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)

  4. Manipulating gene expression in projection-specific neuronal populations using combinatorial viral approaches

    PubMed Central

    Gore, Bryan B.; Soden, Marta E.; Zweifel, Larry S.

    2013-01-01

    The mammalian brain contains tremendous structural and genetic complexity that is vital for its function. The elucidation of gene expression profiles in the brain, coupled with the development of large-scale connectivity maps and emerging viral vector-based approaches for target-selective gene manipulation, now allow for detailed dissection of gene-circuit interfaces. This protocol details how to perform combinatorial viral injections to manipulate gene expression in subsets of neurons interconnecting two brain regions. This method utilizes stereotaxic injection of a retrograde transducing CAV2-Cre virus into one brain region, combined with injection of a locally transducing Cre-dependent AAV virus into another brain region. This technique is widely applicable to the genetic dissection of neural circuitry, as it enables selective expression of candidate genes, dominant-negatives, fluorescent reporters, or genetic tools within heterogeneous populations of neurons based upon their projection targets. PMID:25429312

  5. Discovery of a second SALMFamide gene in the sea urchin Strongylocentrotus purpuratus reveals that L-type and F-type SALMFamide neuropeptides coexist in an echinoderm species.

    PubMed

    Rowe, Matthew L; Elphick, Maurice R

    2010-06-01

    The SALMFamides are a family of neuropeptides that act as muscle relaxants in the phylum Echinodermata. Two types of SALMFamides have been identified in echinoderms: firstly, the prototypical L-type SALMFamide peptides with the C-terminal sequence Leu-X-Phe-NH(2) (where X is variable), which have been identified in several starfish species and in the sea cucumber Holothuria glaberrima; secondly, F-type SALMFamide peptides with the C-terminal sequence Phe-X-Phe-NH(2), which have been identified in the sea cucumber Apostichopus japonicus. However, the genetic basis and functional significance of the occurrence of these two types of SALMFamides in echinoderms are unknown. Here we have obtained a new insight on this issue with the discovery that in the sea urchin Strongylocentrotus purpuratus there are two SALMFamide genes. In addition to a gene encoding seven putative F-type SALMFamide neuropeptides with the C-terminal sequence Phe-X-Phe-NH(2) (SpurS1-SpurS7), which has been reported previously (Elphick and Thorndyke, 2005; J. Exp. Biol., 208, 4273-4282), we have identified a gene that is expressed in the nervous system and that encodes a precursor of two putative L-type SALMFamide neuropeptides with the C-terminal sequences Ile-His-Phe-NH(2) (SpurS8) and Leu-Leu-Phe-NH(2) (SpurS9). Our discovery has revealed for the first time that L-type and F-type SALMFamide neuropeptides can coexist in an echinoderm species but are encoded by different genes. We speculate that this feature of S. purpuratus may apply to other echinoderms and further insights on this issue will be possible if genomic and/or neural cDNA sequence data are obtained for other echinoderm species. PMID:21798202

  6. 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

  7. 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

  8. 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…

  9. In Proceedings of the Ninth ACM SIGKDD International Conference on Knowledge Discovery and Data Mining (KDD '03), pages 655660 Mining Phenotypes and Informative Genes from Gene

    E-print Network

    Buffalo, State University of New York

    Mining (KDD '03), pages 655­660 Mining Phenotypes and Informative Genes from Gene Expression Data Chun of the previous studies focus on clustering either genes or samples, it is interesting to ask whether we can partition the complete set of samples into exclusive groups (called phenotypes) and find a set

  10. 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...

  11. The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project.

    PubMed

    de Marco, R; Accordini, S; Antonicelli, L; Bellia, V; Bettin, M D; Bombieri, C; Bonifazi, F; Bugiani, M; Carosso, A; Casali, L; Cazzoletti, L; Cerveri, I; Corsico, A G; Ferrari, M; Fois, A G; Lo Cascio, V; Marcon, A; Marinoni, A; Olivieri, M; Perbellini, L; Pignatti, P; Pirina, P; Poli, A; Rolla, G; Trabetti, E; Verlato, G; Villani, S; Zanolin, M E

    2010-01-01

    The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions. PMID:20150743

  12. Combining SNP discovery from next-generation sequencing data with bulked segregant analysis (BSA) to fine-map genes in polyploid wheat

    PubMed Central

    2012-01-01

    Background Next generation sequencing (NGS) technologies are providing new ways to accelerate fine-mapping and gene isolation in many species. To date, the majority of these efforts have focused on diploid organisms with readily available whole genome sequence information. In this study, as a proof of concept, we tested the use of NGS for SNP discovery in tetraploid wheat lines differing for the previously cloned grain protein content (GPC) gene GPC-B1. Bulked segregant analysis (BSA) was used to define a subset of putative SNPs within the candidate gene region, which were then used to fine-map GPC-B1. Results We used Illumina paired end technology to sequence mRNA (RNAseq) from near isogenic lines differing across a ~30-cM interval including the GPC-B1 locus. After discriminating for SNPs between the two homoeologous wheat genomes and additional quality filtering, we identified inter-varietal SNPs in wheat unigenes between the parental lines. The relative frequency of these SNPs was examined by RNAseq in two bulked samples made up of homozygous recombinant lines differing for their GPC phenotype. SNPs that were enriched at least 3-fold in the corresponding pool (6.5% of all SNPs) were further evaluated. Marker assays were designed for a subset of the enriched SNPs and mapped using DNA from individuals of each bulk. Thirty nine new SNP markers, corresponding to 67% of the validated SNPs, mapped across a 12.2-cM interval including GPC-B1. This translated to 1 SNP marker per 0.31 cM defining the GPC-B1 gene to within 13-18 genes in syntenic cereal genomes and to a 0.4 cM interval in wheat. Conclusions This study exemplifies the use of RNAseq for SNP discovery in polyploid species and supports the use of BSA as an effective way to target SNPs to specific genetic intervals to fine-map genes in unsequenced genomes. PMID:22280551

  13. Gene discovery within the planctomycete division of the domain Bacteria using sequence tags from genomic DNA libraries

    PubMed Central

    Jenkins, Cheryl; Kedar, Vishram; Fuerst, John A

    2002-01-01

    Background The planctomycetes comprise a distinct group of the domain Bacteria, forming a separate division by phylogenetic analysis. The organization of their cells into membrane-defined compartments including membrane-bounded nucleoids, their budding reproduction and complete absence of peptidoglycan distinguish them from most other Bacteria. A random sequencing approach was applied to the genomes of two planctomycete species, Gemmata obscuriglobus and Pirellula marina, to discover genes relevant to their cell biology and physiology. Results Genes with a wide variety of functions were identified in G. obscuriglobus and Pi. marina, including those of metabolism and biosynthesis, transport, regulation, translation and DNA replication, consistent with established phenotypic characters for these species. The genes sequenced were predominantly homologous to those in members of other divisions of the Bacteria, but there were also matches with nuclear genomic genes of the domain Eukarya, genes that may have appeared in the planctomycetes via horizontal gene transfer events. Significant among these matches are those with two genes atypical for Bacteria and with significant cell-biology implications - integrin alpha-V and inter-alpha-trypsin inhibitor protein - with homologs in G. obscuriglobus and Pi. marina respectively. Conclusions The random-sequence-tag approach applied here to G. obscuriglobus and Pi. marina is the first report of gene recovery and analysis from members of the planctomycetes using genome-based methods. Gene homologs identified were predominantly similar to genes of Bacteria, but some significant best matches to genes from Eukarya suggest that lateral gene transfer events between domains may have involved this division at some time during its evolution. PMID:12093378

  14. Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing

    PubMed Central

    Pflueger, Dorothee; Terry, Stéphane; Sboner, Andrea; Habegger, Lukas; Esgueva, Raquel; Lin, Pei-Chun; Svensson, Maria A.; Kitabayashi, Naoki; Moss, Benjamin J.; MacDonald, Theresa Y.; Cao, Xuhong; Barrette, Terrence; Tewari, Ashutosh K.; Chee, Mark S.; Chinnaiyan, Arul M.; Rickman, David S.; Demichelis, Francesca; Gerstein, Mark B.; Rubin, Mark A.

    2011-01-01

    Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date, little is known about the presence of non-ETS fusion events in prostate cancer. We used next-generation transcriptome sequencing (RNA-seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and four involving non-ETS genes such as CDKN1A (p21), CD9, and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency, but, interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2–ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement-prone phenotype. PMID:21036922

  15. Simultaneous structure discovery and parameter estimation in gene networks using a multi-objective GP-PSO hybrid approach.

    PubMed

    Cai, Xinye; Koduru, Praveen; Das, Sanjoy; Welch, Stephen M

    2009-01-01

    This paper presents a hybrid algorithm based on Genetic Programming (GP) and Particle Swarm Optimisation (PSO) for the automated recovery of gene network structure. It uses gene expression time series data as well as phenotypic data pertaining to plant flowering time as its input data. The algorithm then attempts to discover simple structures to approximate the plant gene regulatory networks that produce model gene expressions and flowering times that closely resemble the input data. To show the efficacy of the proposed approach, simulation results applied to flowering time control in Arabidopsis thaliana are demonstrated and discussed. PMID:19525199

  16. 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

  17. 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

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

    PubMed

    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

  19. 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

  20. Discovery of immune-related genes in Chinese mitten crab ( Eriocheir sinensis) by expressed sequence tag analysis of haemocytes

    Microsoft Academic Search

    Daxian Zhao; Shuhui Song; Qun Wang; Xiaowei Zhang; Songnian Hu; Liqiao Chen

    2009-01-01

    To identify distinctive genes associated with immunity in the Chinese mitten crab (Eriocheir sinensis), an expressed sequence tag (EST) library was constructed from haemocytes of this economically important species. 3118 clones were unidirectionally sequenced and analyzed by homology searches against sequences in the GenBank, KEGG and Uniprot. Significant homology (BLASTX, e-values <10?5) to known genes was found in 488 of

  1. 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

  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. Bayesian hierarchical model for transcriptional module discovery by jointly modeling gene expression and ChIP-chip data

    Microsoft Academic Search

    Xiangdong Liu; Walter J. Jessen; Siva Sivaganesan; Bruce J. Aronow; Mario Medvedovic

    2007-01-01

    BACKGROUND: Transcriptional modules (TM) consist of groups of co-regulated genes and transcription factors (TF) regulating their expression. Two high-throughput (HT) experimental technologies, gene expression microarrays and Chromatin Immuno-Precipitation on Chip (ChIP-chip), are capable of producing data informative about expression regulatory mechanism on a genome scale. The optimal approach to joint modeling of data generated by these two complementary biological assays,

  4. Validation of the Intact Zwittermicin A Biosynthetic Gene Cluster and Discovery of a Complementary Resistance Mechanism in Bacillus thuringiensis?†

    PubMed Central

    Luo, Yi; Ruan, Li-Fang; Zhao, Chang-Ming; Wang, Cheng-Xian; Peng, Dong-Hai; Sun, Ming

    2011-01-01

    Zwittermicin A (ZmA) is a hybrid polyketide-nonribosomal peptide produced by certain Bacillus cereus group strains. It displays broad-spectrum antimicrobial activity. Its biosynthetic pathway in B. cereus has been proposed through analysis of the nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules involved in ZmA biosynthesis. In this study, we constructed a bacterial artificial chromosome (BAC) library from Bacillus thuringiensis subsp. kurstaki strain YBT-1520 genomic DNA. The presence of known genes involved in the biosynthesis of ZmA in this BAC library was investigated by PCR techniques. Nine positive clones were identified, two of which (covering an approximately 60-kb region) could confer ZmA biosynthesis ability upon B. thuringiensis BMB171 after simultaneous transfer into this host by two compatible shuttle BAC vectors. Another previously unidentified gene cluster, named zmaWXY, was found to improve the yield of ZmA and was experimentally defined to function as a ZmA resistance transporter which expels ZmA from the cells. Putative transposase genes were detected on the flanking regions of the two gene clusters (the ZmA synthetic cluster and zmaWXY), which suggests a mobile nature of these two gene clusters. The intact ZmA gene cluster was validated, and a resistance mechanism complementary to that for zmaR (the previously identified ZmA self-resistance gene) was revealed. This study also provided a straightforward strategy to isolate and identify a huge gene cluster from Bacillus. PMID:21730118

  5. 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

  6. Guided Discoveries.

    ERIC Educational Resources Information Center

    Ehrlich, Amos

    1991-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. 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

  9. 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

  10. 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

  11. Diversity of human tRNA genes from the 1000-genomes project

    PubMed Central

    Parisien, Marc; Wang, Xiaoyun; Pan, Tao

    2013-01-01

    The sequence diversity of individual human genomes has been extensively analyzed for variations and phenotypic implications for mRNA, miRNA, and long non-coding RNA genes. TRNA (tRNA) also exhibits large sequence diversity in the human genome, but tRNA gene sequence variation and potential functional implications in individual human genomes have not been investigated. Here we capitalize on the sequencing data from the 1000-genomes project to examine the diversity of tRNA genes in the human population. Previous analysis of the reference human genome indicated an unexpected large number of diverse tRNA genes beyond the necessity of translation, suggesting that some tRNA transcripts may perform non-canonical functions. We found 24 new tRNA sequences in > 1% and 76 new tRNA sequences in > 0.2% of all individuals, indicating that tRNA genes are also subject to evolutionary changes in the human population. Unexpectedly, two abundant new tRNA genes contain base-pair mismatches in the anticodon stem. We experimentally determined that these two new tRNAs have altered structures in vitro; however, one new tRNA is not aminoacylated but extremely stable in HeLa cells, suggesting that this new tRNA can be used for non-canonical function. Our results show that at the scale of human population, tRNA genes are more diverse than conventionally understood, and some new tRNAs may perform non-canonical, extra-translational functions that may be linked to human health and disease. PMID:24448271

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

    PubMed Central

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

    2012-01-01

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

  13. 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

  14. 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 580 bp and the EST cluster and assembly analyses produced 2796 unigenes, including 2487 singletons and 309 contigs. Of the known genes, 55 genes were sel ected 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

  15. Analysis of Brassica napus ESTs: gene discovery and expression patterns of AP2/ERF-family transcription factors.

    PubMed

    Zhuang, Jing; Zhu, Bo

    2014-01-01

    Starting from expressed sequence tag sequences and using the conserved amino acid sequence of the Arabidopsis thaliana AP2/ERF domain as a probe, we used in silico cloning to identify 87 genes that encode putative AP2/ERF transcription factors (TFs) from the Brassica napus. Almost all of the putative AP2/ERF factors from B. napus were similar to genes previously defined as AP2/ERF genes from A. thaliana. Based on the number of AP2-domains and the function of the genes, the AP2/ERF TFs from B. napus were classified into four subfamilies, named the AP2, DREB, ERF, and RAV subfamilies. We then predicted and analyzed cDNA sequences and amino acid sequences, amino acid compositions, physical and chemical characteristics, phylogenetic trees, conserved domain sequences, functional domains, molecular models, and folding states of the proteins they are predicted to encode. Expression analysis showed that four factors, which belonged to the ERF and DREB subfamilies, were induced by abiotic stresses, as well as by hormone treatment. This suggests that those AP2/ERF factors may be involved in signaling pathways responsive to abiotic and biotic stresses. The results from this study, reported herein, form a basis for future functional analyses of B. napus TFs that belong to the AP2/ERF family. PMID:24186851

  16. Gene Discovery in the Wood-Forming Tissues of Poplar: Analysis of 5,692 Expressed Sequence Tags

    Microsoft Academic Search

    Fredrik Sterky; Sharon Regan; Jan Karlsson; Magnus Hertzberg; Antje Rohde; Anders Holmberg; Bahram Amini; Rupali Bhalerao; Magnus Larsson; Raimundo Villarroel; Marc van Montagu; Goran Sandberg; Olof Olsson; Tuula T. Teeri; Wout Boerjan; Petter Gustafsson; Mathias Uhlen; Bjorn Sundberg; Joakim Lundeberg

    1998-01-01

    A rapidly growing area of genome research is the generation of expressed sequence tags (ESTs) in which large numbers of randomly selected cDNA clones are partially sequenced. The collection of ESTs reflects the level and complexity of gene expression in the sampled tissue. To date, the majority of plant ESTs are from nonwoody plants such as Arabidopsis, Brassica, maize, and

  17. Discovery of a gene involved in a third bacterial protoporphyrinogen oxidase activity through comparative genomic analysis and functional complementation.

    PubMed

    Boynton, Tye O; Gerdes, Svetlana; Craven, Sarah H; Neidle, Ellen L; Phillips, John D; Dailey, Harry A

    2011-07-01

    Tetrapyrroles are ubiquitous molecules in nearly all living organisms. Heme, an iron-containing tetrapyrrole, is widely distributed in nature, including most characterized aerobic and facultative bacteria. A large majority of bacteria that contain heme possess the ability to synthesize it. Despite this capability and the fact that the biosynthetic pathway has been well studied, enzymes catalyzing at least three steps have remained "missing" in many bacteria. In the current work, we have employed comparative genomics via the SEED genomic platform, coupled with experimental verification utilizing Acinetobacter baylyi ADP1, to identify one of the missing enzymes, a new protoporphyrinogen oxidase, the penultimate enzyme in heme biosynthesis. COG1981 was identified by genomic analysis as a candidate protein family for the missing enzyme in bacteria that lacked HemG or HemY, two known protoporphyrinogen oxidases. The predicted amino acid sequence of COG1981 is unlike those of the known enzymes HemG and HemY, but in some genomes, the gene encoding it is found neighboring other heme biosynthetic genes. When the COG1981 gene was deleted from the genome of A. baylyi, a bacterium that lacks both hemG and hemY, the organism became auxotrophic for heme. Cultures accumulated porphyrin intermediates, and crude cell extracts lacked protoporphyrinogen oxidase activity. The heme auxotrophy was rescued by the presence of a plasmid-borne protoporphyrinogen oxidase gene from a number of different organisms, such as hemG from Escherichia coli, hemY from Myxococcus xanthus, or the human gene for protoporphyrinogen oxidase. PMID:21642412

  18. 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

  19. Functional gene-based discovery of phenazines from the actinobacteria associated with marine sponges in the South China Sea.

    PubMed

    Karuppiah, Valliappan; Li, Yingxin; Sun, Wei; Feng, Guofang; Li, Zhiyong

    2015-07-01

    Phenazines represent a large group of nitrogen-containing heterocyclic compounds produced by the diverse group of bacteria including actinobacteria. In this study, a total of 197 actinobacterial strains were isolated from seven different marine sponge species in the South China Sea using five different culture media. Eighty-seven morphologically different actinobacterial strains were selected and grouped into 13 genera, including Actinoalloteichus, Kocuria, Micrococcus, Micromonospora, Mycobacterium, Nocardiopsis, Prauserella, Rhodococcus, Saccharopolyspora, Salinispora, Serinicoccus, and Streptomyces by the phylogenetic analysis of 16S rRNA gene. Based on the screening of phzE genes, ten strains, including five Streptomyces, two Nocardiopsis, one Salinispora, one Micrococcus, and one Serinicoccus were found to be potential for phenazine production. The level of phzE gene expression was highly expressed in Nocardiopsis sp. 13-33-15, 13-12-13, and Serinicoccus sp. 13-12-4 on the fifth day of fermentation. Finally, 1,6-dihydroxy phenazine (1) from Nocardiopsis sp. 13-33-15 and 13-12-13, and 1,6-dimethoxy phenazine (2) from Nocardiopsis sp. 13-33-15 were isolated and identified successfully based on ESI-MS and NMR analysis. The compounds 1 and 2 showed antibacterial activity against Bacillus mycoides SJ14, Staphylococcus aureus SJ51, Escherichia coli SJ42, and Micrococcus luteus SJ47. This study suggests that the integrated approach of gene screening and chemical analysis is an effective strategy to find the target compounds and lays the basis for the production of phenazine from the sponge-associated actinobacteria. PMID:25820602

  20. 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

  1. Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells

    PubMed Central

    Kim, Jeffrey J.; Khalid, Omar; Namazi, AmirHosien; Tu, Thanh G.; Elie, Omid; Lee, Connie; Kim, Yong

    2014-01-01

    Molecular markers defining self-renewing pluripotent embryonic stem cells (ESCs) have been identified by relative comparisons between undifferentiated and differentiated cells. Most of analysis has been done under a specific differentiation condition that may present significantly different molecular changes over others. Therefore, it is currently unclear if there are true consensus markers defining undifferentiated hESCs. To identify a set of key genes consistently altered during differentiation of hESCs regardless of differentiation conditions we have performed microarray analysis on undifferentiated hESCs (H1 and H9) and differentiated EB’s and validated our results using publicly available expression array data sets. We constructed consensus modules by Weighted Gene Correlation Analysis (WGCNA) and discovered novel markers that are consistently present in undifferentiated hESCs under various differentiation conditions. We have validated top markers (downregulated: LCK, KLKB1 and SLC7A3; upregulated: RhoJ, Zeb2 and Adam12) upon differentiation. Functional validation analysis of LCK in self-renewal of hESCs by using LCK inhibitor or gene silencing with siLCK resulted in a loss of undifferentiation characteristics- morphological change, reduced alkaline phosphatase activity and pluripotency gene expression, demonstrating a potential functional role of LCK in self-renewal of hESCs. We have designated hESC markers to interactive networks in the genome, identifying possible interacting partners and showing how new markers relate to each other. Furthermore, comparison of these data sets with available datasets from iPSCs revealed that the level of these newly identified markers were correlated to the establishment of iPSCs, which may imply a potential role of these markers in gaining of cellular potency. PMID:24519983

  2. Discovery of candidate genes and pathways that may help explain fertility cycle stage dependent post-resection breast cancer outcome

    Microsoft Academic Search

    Eun-Young Oh; Patricia A. Wood; Xiaoming Yang; William J. M. Hrushesky

    2009-01-01

    Breast cancer relapse and death occur more often and sooner among young pre-menopausal women. Breast cancer resected during\\u000a luteal phase cures about a quarter more women than if the operation is performed during follicular phase. We have identified\\u000a candidate breast cancer gene signatures that may point to the potential mechanisms of cycle stage-dependent surgical cure.\\u000a We performed whole murine genome

  3. First Discovery of Two Polyketide Synthase Genes for Mitorubrinic Acid and Mitorubrinol Yellow Pigment Biosynthesis and Implications in Virulence of Penicillium marneffei

    PubMed Central

    Leung, Chris K. F.; Wong, Samson S. Y.; Lau, Susanna K. P.; Yuen, Kwok-Yung

    2012-01-01

    Background The genome of P. marneffei, the most important thermal dimorphic fungus causing respiratory, skin and systemic mycosis in China and Southeast Asia, possesses 23 polyketide synthase (PKS) genes and 2 polyketide synthase nonribosomal peptide synthase hybrid (PKS-NRPS) genes, which is of high diversity compared to other thermal dimorphic pathogenic fungi. We hypothesized that the yellow pigment in the mold form of P. marneffei could also be synthesized by one or more PKS genes. Methodology/Principal Findings All 23 PKS and 2 PKS-NRPS genes of P. marneffei were systematically knocked down. A loss of the yellow pigment was observed in the mold form of the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants. Sequence analysis showed that PKS11 and PKS12 are fungal non-reducing PKSs. Ultra high performance liquid chromatography-photodiode array detector/electrospray ionization-quadruple time of flight-mass spectrometry (MS) and MS/MS analysis of the culture filtrates of wild type P. marneffei and the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants showed that the yellow pigment is composed of mitorubrinic acid and mitorubrinol. The survival of mice challenged with the pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants was significantly better than those challenged with wild type P. marneffei (P<0.05). There was also statistically significant decrease in survival of pks11 knockdown, pks12 knockdown and pks11pks12 double knockdown mutants compared to wild type P. marneffei in both J774 and THP1 macrophages (P<0.05). Conclusions/Significance The yellow pigment of the mold form of P. marneffei is composed of mitorubrinol and mitorubrinic acid. This represents the first discovery of PKS genes responsible for mitorubrinol and mitorubrinic acid biosynthesis. pks12 and pks11 are probably responsible for sequential use in the biosynthesis of mitorubrinol and mitorubrinic acid. Mitorubrinol and mitorubrinic acid are virulence factors of P. marneffei by improving its intracellular survival in macrophages. PMID:23094121

  4. 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

  5. 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

  6. A structural genomics pilot project based on gene targets selected from Escherichia coli

    NASA Astrophysics Data System (ADS)

    Sivaraman, J.; Li, Yunge; Plamondon, Josée; Larocque, Robert; Raymond, Stéphane; Sauvé, Véronique; Smith, Christopher; Boju, Lorena; Schrag, Joseph; Matte, Allan; Gaasterland, Terry; Cygler, Miroslaw

    2001-11-01

    A pilot project based on gene targets selected from the genome of E. coli has been initiated with 38 genes for initial cloning. Of these, 18 proteins have been purified to date and some crystals were obtained for twelve of them. Of these, four proteins yielded crystals diffracting to a sufficiently high resolution to warrant structural investigation. We have determined 3-D structures of three of these proteins using Se-Met labeling and MAD methods, while the structure of the fourth one was simultaneously determined by another group. To manage the parallel work on many proteins by several researchers it became necessary to create a searchable database containing the pertinent information about every stage of the work.

  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. 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

  9. 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

  10. High-Throughput Discovery of Mutations in Tef Semi-Dwarfing Genes by Next-Generation Sequencing Analysis

    PubMed Central

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

    2012-01-01

    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

  11. 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

  12. 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…

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

    PubMed

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

    2013-04-01

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

  14. Analysis of genes expressed in second stage juveniles of the potato cyst nematodes Globodera rostochiensis and G. pallida using the expressed sequence tag approach

    Microsoft Academic Search

    Herman Popeijus; Vivian C. Blok; Linda Cardle; Erin Bakker; Mark S. Phillips; Johannes Helder; Geert Smant; John T. Jones

    2000-01-01

    Summary - Expressed sequence tag(EST)projects offer a rapid route to the discovery of novel genes. Genes expressedina wide range of parasitic nematodes of medical or veterinary importance have been investigated using EST analysis but these techniques have not yet been applied to plant parasiticnematodes. We describe a small scale EST project using cDNA libraries made from the two species of

  15. Gene discovery in Eimeria tenella by immunoscreening cDNA expression libraries of sporozoites and schizonts with chicken intestinal antibodies.

    PubMed

    Réfega, Susana; Girard-Misguich, Fabienne; Bourdieu, Christiane; Péry, Pierre; Labbé, Marie

    2003-04-01

    Specific antibodies were produced ex vivo from intestinal culture of Eimeria tenella infected chickens. The specificity of these intestinal antibodies was tested against different parasite stages. These antibodies were used to immunoscreen first generation schizont and sporozoite cDNA libraries permitting the identification of new E. tenella antigens. We obtained a total of 119 cDNA clones which were subjected to sequence analysis. The sequences coding for the proteins inducing local immune responses were compared with nucleotide or protein databases and with expressed sequence tags (ESTs) databases. We identified new Eimeria genes coding for heat shock proteins, a ribosomal protein, a pyruvate kinase and a pyridoxine kinase. Specific features of other sequences are discussed. PMID:12651215

  16. 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).

  17. 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

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Gene discovery, evolutionary affinity and molecular detection of Oxyspirura petrowi, an eye worm parasite of game birds

    PubMed Central

    2013-01-01

    Background Oxyspirura petrowi appears to be emerging as a nematode parasite that could negatively impact Northern Bobwhite quail individuals and populations within Texas and other regions of the United States. Despite this eye worm's potential importance in the conservation of wild quail, little is known about the general biology and genome composition of O. petrowi. To fill the knowledge gap, we performed a small scale random genome sequence survey, sequenced its 18S rRNA and the intergenic region between the 18S and 28S rRNA genes, studied its phylogenetic affinity, and developed a PCR protocol for the detection of this eye worm. Results We have generated ~240 kb of genome sequence data derived from 348 clones by a random genome survey of an O. petrowi genomic library. The eye worm genome is AT-rich (i.e., 62.2% AT-content), and contains a high number of microsatellite sequences. The discovered genes encode a wide-range of proteins including hypothetical proteins, enzymes, nematode-specific proteins. Phylogenetic analysis based on 18S rRNA sequences indicate that the Spiruroidea is paraphyletic, in which Oxyspirura and its closely related species are sisters to the filarial nematodes. We have also developed a PCR protocol based on the ITS2 sequence that allows sensitive and specific detection of eye worm DNA in feces. Using this newly developed protocol, we have determined that ~28% to 33% of the fecal samples collected from Northern Bobwhites and Scaled Quail in Texas in the spring of 2013 are O. petrowi positive. Conclusions The O. petrowi genome is rich in microsatellite sequences that may be used in future genotyping and molecular fingerprinting analysis. This eye worm is evolutionarily close to the filarial nematodes, implying that therapeutic strategies for filariasis such as Loa loa would be referential in developing treatments for the Thelazoidea parasites. Our qPCR-based survey has confirmed that O. petrowi infection is of potential concern to quail managers in Texas. PMID:24144118

  1. 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

  2. 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

  3. 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

  4. Putative protease inhibitor gene discovery and transcript profiling during fruit development and leaf damage in grapefruit (Citrus paradisi Macf.).

    PubMed

    Shatters, Robert G; Bausher, Michael G; Hunter, Wayne B; Chaparro, José X; Dang, Phat M; Niedz, Randall P; Mayer, Richard T; McCollum, T Greg; Sinisterra, Xiomara

    2004-02-01

    Seven putative protease inhibitor (PPI) cDNAs, representing four protein families, were isolated from a grapefruit (Citrus paradisi Macf. Cv. Marsh) immature fruit flavedo cDNA library. Cloned open reading frames encoded proteins with similarity to, and protein signatures for: legume Kuntiz inhibitors (lkiL-1, lkiL-2, lkiL-3), potato trypsin inhibitor I (ptiIL-1), serpins (serpL-1), cystatins (cystL-1), and gamma thionins (gthL-1). Response of transcript abundance to fruit development and leaf wounding was determined for all but lkiL-1 using real-time RT-PCR. Immature leaves had the highest transcript levels for all PPIs. The gthL-1 transcript in immature leaves was the most abundant transcript but was absent from healthy mature leaves. In fruit flavedo, transcripts for all PPIs were most abundant in youngest fruit (<15 mm dia. fruit), and declined during development, but displayed different patterns of developmental change. Mechanical or Diaprepes root weevil (DRW) feeding damage to leaves caused a <10-fold reduction or had no effect on transcript level with the exception of gthL-1 which, as a result of damage, increased >50-fold in mature leaves and decreased >1400-fold in immature leaves. This developmental control of transcript response to wounding in a woody perennial is opposite of what has been observed for defensive proteinase inhibitors (PIs) in other plants (typically herbaceous and/or annual plants), where younger leaves typically invoke a higher defensive proteinase inhibitor transcript accumulation than older tissues. Except for gthL-1, the PPI transcripts were minimally responsive or unresponsive to wounding. Changes in PPI transcript levels suggest diverse roles for the products of these genes in citrus, with only gthL-1 responding in a defense-like manner. PMID:14729265

  5. 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

  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 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

  7. 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.

  8. 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<

  9. 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

  10. The Extragalactic Distance Scale Key Project. XVIII. The Discovery of Cepheids and a New Distance to NGC 4535 Using the Hubble Space Telescope

    NASA Astrophysics Data System (ADS)

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

    1999-08-01

    We report on the discovery of Cepheids in the Virgo spiral galaxy NGC 4535, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope (HST). NGC 4535 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. NGC 4535 was observed over 13 epochs using the F555W filter, and over 9 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 programs, DoPHOT and DAOPHOT II/ALLFRAME. Period-luminosity relations in the V and I bands were constructed using 39 high-quality Cepheids present in our set of 50 variable candidates. We obtain a distance modulus of 31.02+/-0.26 mag, corresponding to a distance of 16.0+/-1.9 Mpc. Our distance estimate is based on values of ?0=18.50+/-0.10 mag and E(V-I)=0.13 mag for the distance modulus and reddening of the LMC, respectively. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, operated by AURA, Inc., under NASA contract NAS 5-26555.

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

    NASA Astrophysics Data System (ADS)

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

    1997-12-01

    We report on the discovery of Cepheids in the field spiral galaxy NGC 3621, based on observations made with the Wide Field 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 over four 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 +/- 0.09 and 10.56 +/- 0.10 mag were obtained using the ALLFRAME and DoPHOT data, respectively. True distance moduli of 29.13 +/- 0.18 and 29.06 +/- 0.18 mag, corresponding to distances of 6.3 +/- 0.7 and 6.1 +/- 0.7 Mpc, were obtained by assuming values of ?0 = 18.50 +/- 0.10 mag and E(V - I) = 0.13 mag for the distance modulus and reddening of the LMC, respectively. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, operated by AURA, Inc. under NASA contract NAS 5-26555.

  12. Accidental Discoveries

    NSDL National Science Digital Library

    2012-08-03

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

  13. Rapid Annotation of Anonymous Sequences from Genome Projects Using Semantic Similarities and a Weighting Scheme in Gene Ontology

    Microsoft Academic Search

    Paolo Fontana; Alessandro Cestaro; Riccardo Velasco; Elide Formentin; Stefano Toppo; Sridhar Hannenhalli

    2009-01-01

    BackgroundLarge-scale sequencing projects have now become routine lab practice and this has led to the development of a new generation of tools involving function prediction methods, bringing the latter back to the fore. The advent of Gene Ontology, with its structured vocabulary and paradigm, has provided computational biologists with an appropriate means for this task.MethodologyWe present here a novel method

  14. Left ventricular structure in relation to the human SAH gene in the European Project on Genes in Hypertension

    Microsoft Academic Search

    Yu Jin; Tatiana Kuznetsova; Valérie Tikhonoff; Lutgarde Thijs; Sandra Hasenkamp; Veronika Bäumer; Katarzyna Stolarz-Skrzypek; Andrew Ryabikov; Tom Richart; Sofia Malyutina; Yuri Nikitin; Edoardo Casiglia; Kalina Kawecka-Jaszcz; Agnieszka Olszanecka; Stefan-Martin Brand-Herrmann; Eva Brand; Robert Fagard; Jan A Staessen

    2009-01-01

    Earlier studies showed association of the human SAH (Spontaneously hypertensive rat-clone A-Hypertension associated) gene with hypertension and obesity. Left ventricular mass index (LVMI) increases with blood pressure and body mass index. In a family-based population study (54.5% women; mean age, 43.1 years), we measured LVMI, mean wall thickness (MWT) and the left ventricular internal diameter (LVID) at end-diastole in 699

  15. The Hubble Space Telescope Extragalactic Distance Scale Key Project. VII. The Discovery of Cepheids in the Leo I Group Galaxy NGC 3351

    NASA Astrophysics Data System (ADS)

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

    1997-03-01

    We report of the discovery and properties of Cepheid variable stars in the barred spiral galaxy NGC 3351 which is a member of the Leo I group of galaxies. NGC 3351 is one of 18 galaxies being observed as part of the Hubble Space Telescope (HST) Key Project on the Extragalactic Distance Scale which aims to determine the Hubble constant to 10% accuracy. Our analysis is based on observations made with the Wide Field Planetary Camera 2 during 1994 and early 1995. The Leo I group contains several bright galaxies of diverse types and is very suitable for linking together a number of secondary calibrators which can be employed at much greater distances than the Cepheid variables. We identify 49 probable Cepheids within NGC 3351 in the period range 10-43 days which have been observed at 12 epochs with the F555W filter and 4 epochs using the F814W filter. The HST F555W and F814W data have been transformed to the Johnson V and Cousins I magnitude systems, respectively. Photometry has principally been carried out using the DAOPHOT/ALLFRAME package. Reference is made to parallel measurements being made with the DoPHOT package. Apparent period-luminosity functions for V and I have been constructed assuming values of ?0 = 18.50 +/- 0.10 mag and E(B - V) = 0.10 mag for the distance modulus and reddening of the Large Magellanic Cloud. A true distance modulus of 30.01 +/- 0.19 mag is derived corresponding to a distance of 10.05 +/- 0.88 Mpc with a reddening E(V - I) = 0.15 mag. A comparison is made with distances estimated for other galaxies in the Leo I group using various distance indicators. There is good agreement with the surface brightness fluctuation and planetary nebula luminosity function methods as calibrated by the Cepheids in M31. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, operated by AURA, Inc. under NASA contract No. NAS5-26555.

  16. 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

  17. Gene hunting in autoinflammation

    PubMed Central

    2013-01-01

    Steady progress in our understanding of the genetic basis of autoinflammatory diseases has been made over the past 16 years. Since the discovery of the familial Mediterranean fever gene MEFV (also known as marenostrin) in 1997, 18 other genes responsible for monogenic autoinflammatory diseases have been identified to date. The discovery of these genes was made through the utilisation of many genetic mapping techniques, including next generation sequencing platforms. This review article clearly describes the gene hunting approaches, methods of data analysis and the technological platforms used, which has relevance to all those working within the field of gene discovery for Mendelian disorders. PMID:24070009

  18. Discovery Channel: Extreme Engineering

    NSDL National Science Digital Library

    2003-01-01

    Extreme Engineering is a program on the Discovery Channel that unveils "some of the most ambitious architectural plans of our times." The projects highlighted in each episode come from locations around the world. Some are in the planning stages, while others are only theoretical. This Web site serves as a companion to the television broadcasts and has interactive multimedia tours that offer a glimpse of what the projects would look like when completed. An underwater train tunnel linking New York and London, a massive skyscraper city in Tokyo, and a bridge over the Bering Strait are just some of the remarkable projects featured. The online elements are added after the corresponding episode is aired.

  19. 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.

  20. De novo Transcriptome Assembly of Common Wild Rice (Oryza rufipogon Griff.) and Discovery of Drought-Response Genes in Root Tissue Based on Transcriptomic Data

    PubMed Central

    Zhang, Jing-wen; Wang, Yan-yan; Li, Wei-min; Peng, Yu-fa; Yuan, Qian-hua; Pei, Xin-wu

    2015-01-01

    Background The perennial O. rufipogon (common wild rice), which is considered to be the ancestor of Asian cultivated rice species, contains many useful genetic resources, including drought resistance genes. However, few studies have identified the drought resistance and tissue-specific genes in common wild rice. Results In this study, transcriptome sequencing libraries were constructed, including drought-treated roots (DR) and control leaves (CL) and roots (CR). Using Illumina sequencing technology, we generated 16.75 million bases of high-quality sequence data for common wild rice and conducted de novo assembly and annotation of genes without prior genome information. These reads were assembled into 119,332 unigenes with an average length of 715 bp. A total of 88,813 distinct sequences (74.42% of unigenes) significantly matched known genes in the NCBI NT database. Differentially expressed gene (DEG) analysis showed that 3617 genes were up-regulated and 4171 genes were down-regulated in the CR library compared with the CL library. Among the DEGs, 535 genes were expressed in roots but not in shoots. A similar comparison between the DR and CR libraries showed that 1393 genes were up-regulated and 315 genes were down-regulated in the DR library compared with the CR library. Finally, 37 genes that were specifically expressed in roots were screened after comparing the DEGs identified in the above-described analyses. Conclusion This study provides a transcriptome sequence resource for common wild rice plants and establishes a digital gene expression profile of wild rice plants under drought conditions using the assembled transcriptome data as a reference. Several tissue-specific and drought-stress-related candidate genes were identified, representing a fully characterized transcriptome and providing a valuable resource for genetic and genomic studies in plants. PMID:26134138

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

    Microsoft Academic Search

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

    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

  2. Stochastic analysis of gene regulatory networks using finite state projections and singular perturbation

    Microsoft Academic Search

    Brian Munsky; S. Peles; Mustafa Khammash

    2007-01-01

    Considerable recent experimental evidence suggests that significant stochastic fluctuations are present in gene regulatory networks. The investigation of stochastic properties in genetic systems involves the formulation of a mathematical representation of molecular noise and devising efficient computational algorithms for computing the relevant statistics of the modeled processes. However, the complexity of gene regulatory networks poses serious computational difficulties and makes

  3. Genome-wide ENU mutagenesis for the discovery of novel male fertility regulators.

    PubMed

    Jamsai, Duangporn; O'Bryan, Moira K

    2010-06-01

    The completion of genome sequencing projects has provided an extensive knowledge of the contents of the genomes of human, mouse, and many other organisms. Despite this, the function of most of the estimated 25,000 human genes remains largely unknown. Attention has now turned to elucidating gene function and identifying biological pathways that contribute to human diseases, including male infertility. Our understanding of the genetic regulation of male fertility has been accelerated through the use of genetically modified mouse models including knockout, knock-in, gene-trapped, and transgenic mice. Such reverse genetic approaches however, require some fore-knowledge of a gene's function and, as such, bias against the discovery of completely novel genes and biological pathways. To facilitate high throughput gene discovery, genome-wide mouse mutagenesis via the use of a potent chemical mutagen, N-ethyl-N-nitrosourea (ENU), has been developed over the past decade. This forward genetic, or phenotype-driven, approach relies upon observing a phenotype first, then subsequently defining the underlining genetic defect. Mutations are randomly introduced into the mouse genome via ENU exposure. Through a controlled breeding scheme, mutations causing a phenotype of interest (e.g., male infertility) are then identified by linkage analysis and candidate gene sequencing. This approach allows for the possibility of revealing comprehensive phenotype-genotype relationships for a range of genes and pathways i.e. in addition to null alleles, mice containing partial loss of function or gain-of-function mutations, can be recovered. Such point mutations are likely to be more reflective of those that occur within the human population. Many research groups have successfully used this approach to generate infertile mouse lines and some novel male fertility genes have been revealed. In this review, we focus on the utility of ENU mutagenesis for the discovery of novel male fertility regulators. PMID:20536324

  4. The Extragalactic Distance Scale Key Project III. Teh discovery of Cephids and a New Distance to M101 Using the Hubble Space Telescope

    NASA Technical Reports Server (NTRS)

    Kelson, Daniel D.; Madore, Barry

    1994-01-01

    We report on the discovery of 29 cephid variables in the galaxy M101 after using the original Wide Field Camera (WFC 1) and the new Wide Field and Planetary Camera (WFPC 2) on the Hubble Space Telescope (HST), to observe a field in M101 at 14 independent epochs in F555W.

  5. 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

  6. Discovery Channel: Science Fair Central

    NSDL National Science Digital Library

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

  7. Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas

    Microsoft Academic Search

    Michèl Schummer; WaiLap V. Ng; Roger E. Bumgarner; Peter S. Nelson; Bernhard Schummer; David W. Bednarski; Laurie Hassell; Rae Lynn Baldwin; Beth Y. Karlan; Leroy Hood

    1999-01-01

    Comparative hybridization of cDNA arrays is a powerful tool for the measurement of differences in gene expression between two or more tissues. We optimized this technique and employed it to discover genes with potential for the diagnosis of ovarian cancer. This cancer is rarely identified in time for a good prognosis after diagnosis. An array of 21500 unknown ovarian cDNAs

  8. Discovery's Edge

    NSDL National Science Digital Library

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

  9. STS-114: Discovery Impromptu Briefing

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Dr. Griffin, NASA Administrator, is accompanied by members of The U.S. House of Representatives in this STS-114 Discovery Impromptu briefing. The U.S. House of Representatives present include: Sherwood Boehlert, House Science Committee Chairman, Senator Hutchinson, Sheila Jackson, 18th Congressional District Texas, Al Green, 9th Congressional District, Representative Jim Davis, Florida, and Gene Green, 29th District, Texas. Griffin talks about the problem that occurred with the external fuel tank sensor of the Space Shuttle Discovery and the effort NASA is pursuing to track the problem, and identify the root cause. He answers questions from the news media about the next steps for the Space Shuttle Discovery, time frame for the launch, and activities for the astronauts for the next few days.

  10. Dynamic changes in gene expression profiles following axotomy of projection fibres in the Mammalian CNS.

    PubMed

    Abankwa, Daniel; Küry, Patrick; Müller, Hans Werner

    2002-11-01

    Following postcommissural fornix transection we have investigated the postaxotomy transcriptional program in the subiculum where the injured axons originate. cDNA array hybridization revealed 125 genes that were specifically regulated as the injured neurons passed through three distinct postlesion (PL) stages comprising (i). early phase of injury and axon degeneration, (ii). sprouting phase of the proximal stump, and (iii). axonal growth arrest at the lesion scar. Numerous genes were detected which have, so far, not been associated with axotomy or axonal growth. Following the early lesion response that is characterized predominantly by down-regulation of genes at 1 day PL, neurons switch to a sprouting program with the majority of genes up-regulated at 7 days PL. However, the latter program of gene expression is not maintained but largely reversed (at 3 weeks PL) to the initial profile as axonal growth is blocked at the lesion barrier, indicating retrograde signaling that leads to down-regulation of neuronal genes previously up-regulated during axon sprouting. PMID:12498784

  11. 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

  12. The MACHO Project LMC Variable Star Inventory. VII. The Discovery of RV Tauri Stars and New Type II Cepheids in the Large Magellanic Cloud

    Microsoft Academic Search

    C. Alcock; R. A. Allsman; D. R. Alves; T. S. Axelrod; A. Becker; D. P. Bennett; K. H. Cook; K. C. Freeman; K. Griest; W. A. Lawson; M. J. Lehner; S. L. Marshall; D. Minniti; Karen R. Pollard; M. R. Pratt; P. J. Quinn; A. W. Rodgers; W. Sutherland; A. Tomaney; D. L. Welch

    1998-01-01

    We report the discovery of RV Tauri stars in the Large Magellanic Cloud (LMC). In light- and color-curve behavior, the RV Tauri stars appear to be a direct extension of the type II Cepheids to longer periods. A single period-luminosity-color relationship is seen to describe both the type II Cepheids and the RV Tauri stars in the LMC. We derive

  13. 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

  14. 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

  15. Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Coelomocytes of Sea Cucumber (Apostichopus japonicus) after Vibrio splendidus Challenge.

    PubMed

    Gao, Qiong; Liao, Meijie; Wang, Yingeng; Li, Bin; Zhang, Zheng; Rong, Xiaojun; Chen, Guiping; Wang, Lan

    2015-01-01

    Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus), which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform) were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs) in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway. PMID:26193268

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

    PubMed Central

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

    2006-01-01

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

  17. 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

  18. Designing, optimizing, and implementing high-throughput siRNA genomic screening with glioma cells for the discovery of survival genes and novel drug targets.

    PubMed

    Thaker, Nikhil G; McDonald, Peter R; Zhang, Fang; Kitchens, Carolyn A; Shun, Tong Ying; Pollack, Ian F; Lazo, John S

    2010-01-15

    A major challenge for the treatment of cancers, such as glioblastoma multiforme (GBM), has been resistance to radiation and cancer chemotherapeutics. Short interfering RNA (siRNA) based screening may facilitate the identification of genes and pathways essential for cancer cell survival and could enable a more targeted therapeutic approach for the treatment of GBM. Although the commercial availability of siRNA libraries has expanded greatly, detailed methods for the implementation and analysis of genome-scale screens are largely lacking. To annotate the essential genes and pathways for glioma cell survival, we designed, optimized, and implemented a high-throughput siRNA screen in the highly drug and radiation resistant T98G glioma cell line. We developed a rapid, readily available, and simple strategy to optimize siRNA transfection assays in a 384-well plate format based on immunofluorescence studies and inhibition of the non-essential, endogenous gene lamin A/C. We used these transfection conditions to successfully screen a library of 1056 siRNAs targeting 352 unique human genes in a cell-based one gene per well format to identify the genes essential for glioma cell survival and assess the quality of the screening conditions prior to large-scale screening. After developing and applying a median-based outlier detection algorithm for post-screen analysis, we identified the Ras oncogene family member RAN as an essential gene for glioma cell survival. Successful implementation and analysis of this siRNA screen validates our transfection optimization approach and provides guidance for the rapid development of high-throughput siRNA screens in human glioma cells. PMID:19782703

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

    Boles, Melissa K; Wilkinson, Bonney M; Wilming, Laurens G; Liu, Bin; Probst, Frank J; Harrow, Jennifer; Grafham, Darren; Hentges, Kathryn E; Woodward, Lanette P; Maxwell, Andrea; Mitchell, Karen; Risley, Michael D; Johnson, Randy; Hirschi, Karen; Lupski, James R; Funato, Yosuke; Miki, Hiroaki; Marin-Garcia, Pablo; Matthews, Lucy; Coffey, Alison J; Parker, Anne; Hubbard, Tim J; Rogers, Jane; Bradley, Allan; Adams, David J; Justice, Monica J

    2009-12-01

    An accurate and precisely annotated genome assembly is a fundamental requirement for functional genomic analysis. Here, the complete DNA sequence and gene annotation of mouse Chromosome 11 was used to test the efficacy of large-scale sequencing for mutation identification. We re-sequenced the 14,000 annotated exons and boundaries from over 900 genes in 41 recessive mutant mouse lines that were isolated in an N-ethyl-N-nitrosourea (ENU) mutation screen targeted to mouse Chromosome 11. Fifty-nine sequence variants were identified in 55 genes from 31 mutant lines. 39% of the lesions lie in coding sequences and create primarily missense mutations. The other 61% lie in noncoding regions, many of them in highly conserved sequences. A lesion in the perinatal lethal line l11Jus13 alters a consensus splice site of nucleoredoxin (Nxn), inserting 10 amino acids into the resulting protein. We conclude that point mutations can be accurately and sensitively recovered by large-scale sequencing, and that conserved noncoding regions should be included for disease mutation identification. Only seven of the candidate genes we report have been previously targeted by mutation in mice or rats, showing that despite ongoing efforts to functionally annotate genes in the mammalian genome, an enormous gap remains between phenotype and function. Our data show that the classical positional mapping approach of disease mutation identification can be extended to large target regions using high-throughput sequencing. PMID:20011118

  1. Molecular studies on the aerolysin gene of Aeromonas species and discovery of a species-specific probe for Aeromonas trota species nova.

    PubMed

    Husslein, V; Chakraborty, T; Carnahan, A; Joseph, S W

    1992-05-01

    A large group of aeromonads and other enteric microorganisms were assayed for the presence of the aerolysin gene with use of DNA-DNA hybridization. Two DNA fragments corresponding to the regulatory region (aerC) and the structural gene (aerA) were used as probes for the detection of the aerolysin gene in these strains. Sequences corresponding to the aerolysin structural gene were widespread among Aeromonas isolates. In contrast, the aerC probe was much more selective, and sequences corresponding to the aerC region were detected in only a small subset of strains. Concurrent studies using numerical taxonomy and DNA hybridization with the aerC probe on a larger set of strains led to the identification of a distinct cluster of 14 presumed atypical Aeromonas sobria strains. These strains have recently been grouped into a new species designated Aeromonas trota. Hence, the DNA fragment aerC used in the study is a species-specific gene probe for A. trota. The ability of the aerC probe to detect strains belonging to a single species suggests that there is selection pressure to maintain the clonality of this species. These results have important implications with respect to the evolution of "pathogenic profiles" among these medically important bacteria. PMID:1600007

  2. A Roadmap for Natural Product Discovery Based on Large-Scale Genomics and Metabolomics

    PubMed Central

    Doroghazi, James R.; Albright, Jessica C.; Goering, Anthony W.; Ju, Kou-San; Haines, Robert R.; Tchalukov, Konstantin A.; Labeda, David P.; Kelleher, Neil L.; Metcalf, William W.

    2014-01-01

    Actinobacteria encode a wealth of natural product biosynthetic gene clusters (NPGCs), whose systematic study is complicated by numerous repetitive motifs. By combining several metrics we developed a method for global classification of these gene clusters into families (GCFs) and analyzed the biosynthetic capacity of Actinobacteria in 830 genome sequences, including 344 obtained for this project. The GCF network, comprised of 11,422 gene clusters grouped into 4,122 GCFs, was validated in hundreds of strains by correlating confident mass spectrometric detection of known small molecules with the presence/absence of their established biosynthetic gene clusters. The method also linked previously unassigned GCFs to known natural products, an approach that will enable de novo, bioassay-free discovery of novel natural products using large data sets. Extrapolation from the 830-genome dataset reveals that Actinobacteria encode hundreds of thousands of future drug leads, while the strong correlation between phylogeny and GCFs frames a roadmap to efficiently access them. PMID:25262415

  3. Dynamic Changes in Gene Expression Profiles Following Axotomy of Projection Fibres in the Mammalian CNS

    Microsoft Academic Search

    Daniel Abankwa; Patrick Küry; Hans Werner Müller

    2002-01-01

    Following postcommissural fornix transection we have investigated the postaxotomy transcriptional program in the subiculum where the injured axons originate. cDNA array hybridization revealed 125 genes that were specifically regulated as the injured neurons passed through three distinct postlesion (PL) stages comprising (i) early phase of injury and axon degeneration, (ii) sprouting phase of the proximal stump, and (iii) axonal growth

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

    PubMed Central

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

    2012-01-01

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

  5. Applications of Genomics in Melanoma Oncogene Discovery

    PubMed Central

    Berger, Michael F.; Garraway, Levi A.

    2009-01-01

    SYNOPSIS (for table of contents) The identification of recurrent alterations in the melanoma genome has provided key insights into the biology of melanoma genesis and progression. These discoveries have come about as a result of the systematic deployment and integration of diverse genomic technologies, including DNA sequencing, chromosomal copy number analysis, and gene expression profiling. Here, we chronicle the discoveries of several key melanoma oncogenes affecting critical cell pathways and examine the role played by evolving genomics technologies in melanoma oncogene discovery. These advances are being exploited to improve prognosis and treatment of melanoma patients through the development of genome-based diagnostic and targeted therapeutic avenues. PMID:19464593

  6. INTEGRATING COMPUTATIONAL PROTEIN FUNCTION PREDICTION INTO DRUG DISCOVERY INITIATIVES

    PubMed Central

    Grant, Marianne A.

    2014-01-01

    Pharmaceutical researchers must evaluate vast numbers of protein sequences and formulate innovative strategies for identifying valid targets and discovering leads against them as a way of accelerating drug discovery. The ever increasing number and diversity of novel protein sequences identified by genomic sequencing projects and the success of worldwide structural genomics initiatives have spurred great interest and impetus in the development of methods for accurate, computationally empowered protein function prediction and active site identification. Previously, in the absence of direct experimental evidence, homology-based protein function annotation remained the gold-standard for in silico analysis and prediction of protein function. However, with the continued exponential expansion of sequence databases, this approach is not always applicable, as fewer query protein sequences demonstrate significant homology to protein gene products of known function. As a result, several non-homology based methods for protein function prediction that are based on sequence features, structure, evolution, biochemical and genetic knowledge have emerged. Herein, we review current bioinformatic programs and approaches for protein function prediction/annotation and discuss their integration into drug discovery initiatives. The development of such methods to annotate protein functional sites and their application to large protein functional families is crucial to successfully utilizing the vast amounts of genomic sequence information available to drug discovery and development processes. PMID:25530654

  7. Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data.

    PubMed

    Brandt, Débora Y C; Aguiar, Vitor R C; Bitarello, Bárbara D; Nunes, Kelly; Goudet, Jérôme; Meyer, Diogo

    2015-01-01

    Next-generation sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known to be problematic when applied to highly polymorphic genomic regions, such as the human leukocyte antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population genomics analyses, it is important to assess the reliability of NGS data. Here, we evaluate the reliability of genotype calls and allele frequency estimates of the single-nucleotide polymorphisms (SNPs) reported by 1000G (phase I) at five HLA genes (HLA-A, -B, -C, -DRB1, and -DQB1). We take advantage of the availability of HLA Sanger sequencing of 930 of the 1092 1000G samples and use this as a gold standard to benchmark the 1000G data. We document that 18.6% of SNP genotype calls in HLA genes are incorrect and that allele frequencies are estimated with an error greater than ±0.1 at approximately 25% of the SNPs in HLA genes. We found a bias toward overestimation of reference allele frequency for the 1000G data, indicating mapping bias is an important cause of error in frequency estimation in this dataset. We provide a list of sites that have poor allele frequency estimates and discuss the outcomes of including those sites in different kinds of analyses. Because the HLA region is the most polymorphic in the human genome, our results provide insights into the challenges of using of NGS data at other genomic regions of high diversity. PMID:25787242

  8. 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

  9. 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

  10. VeloceGenomics: An Accelerated in Vivo Drug Discovery Approach to Rapidly Predict the Biologic, Drug-Like Activity of Compounds, Proteins, or Genes

    Microsoft Academic Search

    Ruben Papoian; Andreas Scherer; Muriel Saulnier; Frank Staedtler; André Cordier; Francois Legay; Gerard Maurer; Joerg Staeheli; Jacky Vonderscher; Salah-Dine Chibout

    2005-01-01

    :Purpose. The aim of this study is to test the predictive power of in vivo multiorgan RNA expression profiling in identifying the biologic activity of molecules. Methods. Animals were treated with compound A or B. At the end of the treatment period, in vivo multiorgan microarray-based gene expression data were collected. Investigators masked to the identity of the compounds analyzed

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. 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

    Wang, Wei; Wu, Xugan; 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

  13. 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

  14. 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

  15. Rapid Annotation of Anonymous Sequences from Genome Projects Using Semantic Similarities and a Weighting Scheme in Gene Ontology

    PubMed Central

    Fontana, Paolo; Cestaro, Alessandro; Velasco, Riccardo; Formentin, Elide; Toppo, Stefano

    2009-01-01

    Background Large-scale sequencing projects have now become routine lab practice and this has led to the development of a new generation of tools involving function prediction methods, bringing the latter back to the fore. The advent of Gene Ontology, with its structured vocabulary and paradigm, has provided computational biologists with an appropriate means for this task. Methodology We present here a novel method called ARGOT (Annotation Retrieval of Gene Ontology Terms) that is able to process quickly thousands of sequences for functional inference. The tool exploits for the first time an integrated approach which combines clustering of GO terms, based on their semantic similarities, with a weighting scheme which assesses retrieved hits sharing a certain number of biological features with the sequence to be annotated. These hits may be obtained by different methods and in this work we have based ARGOT processing on BLAST results. Conclusions The extensive benchmark involved 10,000 protein sequences, the complete S. cerevisiae genome and a small subset of proteins for purposes of comparison with other available tools. The algorithm was proven to outperform existing methods and to be suitable for function prediction of single proteins due to its high degree of sensitivity, specificity and coverage. PMID:19247487

  16. Discovery of gemfibrozil analogues that activate PPAR? and enhance the expression of gene CPT1A involved in fatty acids catabolism.

    PubMed

    De Filippis, Barbara; Giancristofaro, Antonella; Ammazzalorso, Alessandra; D'Angelo, Alessandra; Fantacuzzi, Marialuigia; Giampietro, Letizia; Maccallini, Cristina; Petruzzelli, Michele; Amoroso, Rosa

    2011-10-01

    A new series of gemfibrozil analogues conjugated with ?-asarone, trans-stilbene, chalcone, and their bioisosteric modifications were synthesized and evaluated to develop PPAR? agonists. In this attempt, we have removed the methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in para position synthesizing two series of derivatives, keeping the dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four compounds exhibited good activation of the PPAR? receptor and were also screened for their activity on PPAR?-regulated gene CPT1A. PMID:21889235

  17. Discovery of Cadmium, Indium, and Tin Isotopes

    NASA Astrophysics Data System (ADS)

    Amos, Stephanie; Thoennessen, Michael

    2009-10-01

    As of today, no comprehensive study has been made covering the initial observations and identifications of isotopes. A project has been undertaken at MSU to document the discovery of all the known isotopes. The criteria defining discovery of a given isotope is the publication of clear mass and element assignment in a refereed journal. Prior to the current work the documentation of the discovery of eleven elements had been completed^1. These elements are cerium^2, arsenic, gold, tungsten, krypton, silver, vanadium, einsteinium, iron, barium, and cobalt. We will present the new documentation for the cadmium, indium, and tin isotopes. Thirty-seven cadmium isotopes, thirty-eight indium isotopes, and thirty-eight tin isotopes have been discovered so far. The description for each discovered isotope includes the year of discovery, the article published on the discovery, the article's author, the method of production, the method of identification, and any previous information concerning the isotope discovery. A summary and overview of all ˜500 isotopes documented so far as a function of discovery year, method and place will also be presented. ^1http://www.nscl.msu.edu/˜thoennes/2009/discovery.htm ^2J.Q. Ginepro, J. Snyder, and M. Thoennessen, At. Data Nucl. Data. Tables, in press (2009), doi:10.1016/j.adt.2009.06.002

  18. Project

    Microsoft Academic Search

    E. Petersen; J. Ali-Adeeb; T. Cerling; M. Chan; D. Chapman; L. Cohen; M. Davis; D. Chapmandearing; S. Hill; S. Hynek; L. Millward; S. O'Grady; L. Richards; K. Solomon; S. Sampson; J. Schafer; L. Zanno; E. Zipser

    2004-01-01

    Project WEST (Water, the Environment, Science, and Teaching) is a graduate student fellowship program funded by a GK-12 grant from the National Science Foundation. WEST links the University of Utah, the Utah Museum of Natural History, and the Salt Lake City school district in enhancing inquiry based science teaching in grades 4, 8, and 9 and the interdisciplinary training of

  19. Role of ChIP-seq in the discovery of transcription factor binding sites, differential gene regulation mechanism, epigenetic marks and beyond.

    PubMed

    Mundade, Rasika; Ozer, Hatice Gulcin; Wei, Han; Prabhu, Lakshmi; Lu, Tao

    2014-01-01

    Many biologically significant processes, such as cell differentiation and cell cycle progression, gene transcription and DNA replication, chromosome stability and epigenetic silencing etc. depend on the crucial interactions between cellular proteins and DNA. Chromatin immunoprecipitation (ChIP) is an important experimental technique for studying interactions between specific proteins and DNA in the cell and determining their localization on a specific genomic locus. In recent years, the combination of ChIP with second generation DNA-sequencing technology (ChIP-seq) allows precise genomic functional assay. This review addresses the important applications of ChIP-seq with an emphasis on its role in genome-wide mapping of transcription factor binding sites, the revelation of underlying molecular mechanisms of differential gene regulation that are governed by specific transcription factors, and the identification of epigenetic marks. Furthermore, we also describe the ChIP-seq data analysis workflow and a perspective for the exciting potential advancement of ChIP-seq technology in the future. PMID:25486472

  20. 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; Montañés-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 ...

  1. 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

  2. Projection of gene-protein networks to the functional space of the proteome and its application to analysis of organism complexity

    Microsoft Academic Search

    Alexander A Kanapin; Nicola Mulder; Vladimir A Kuznetsov

    2010-01-01

    We consider the problem of biological complexity via a projection of protein-coding genes of complex organisms onto the functional space of the proteome. The latter can be defined as a set of all functions committed by proteins of an organism. Alternative splicing (AS) allows an organism to generate diverse mature RNA transcripts from a single mRNA strand and thus it

  3. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 mod...

  4. 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

  5. Discovery of Rare Variants via Sequencing: Implications for the Design of Complex Trait Association Studies

    PubMed Central

    Li, Bingshan; Leal, Suzanne M.

    2009-01-01

    There is strong evidence that rare variants are involved in complex disease etiology. The first step in implicating rare variants in disease etiology is their identification through sequencing in both randomly ascertained samples (e.g., the 1,000 Genomes Project) and samples ascertained according to disease status. We investigated to what extent rare variants will be observed across the genome and in candidate genes in randomly ascertained samples, the magnitude of variant enrichment in diseased individuals, and biases that can occur due to how variants are discovered. Although sequencing cases can enrich for casual variants, when a gene or genes are not involved in disease etiology, limiting variant discovery to cases can lead to association studies with dramatically inflated false positive rates. PMID:19436704

  6. The human decorin gene: Intron-exon organization, discovery of two alternatively spliced exons in the 5[prime] untralsated region, and mapping of the gene to chromosome 12q23

    SciTech Connect

    Danielson, K.G.; Fazzio, A.; Cohen, I.; Cannizzaro, L.A.; Eichstetter, I.; Iozzo, R.V. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1993-01-01

    Decorin is a chondroitin/dermatan sulfate proteoglycan expressed by most vascular and avascular connective tissues and, because of its ability to interact with collagen and growth factors, has been implicated in the control of matrix assembly and cellular growth. To understand the molecular mechanisms involved in regulating its tissue expression, we have isolated a number of genomic clones encoding the complete decorin gene. The human decorin gene spans over 38 kb of continuous DNA sequence and contains eight exons and very large introns, two of which are 5.4 and > 13.2 kb. We have discovered two alternatively spliced leader exons, exons Ia and Ib, in the 5[prime] untranslated region. These exons were identified by cloning and sequencing cDNAs obtained by polymerase chain reaction amplification of a fibroblast cDNA library. Using Northern blotting or reverse transcriptase PCR, we detected the two leader exons in a variety of mRNAs isolated from human cell lines and tissues. Interestingly, sequences highly (74-87%) homologous to exons Ia and lb are found in the 5[prime]untranslated region of avian and bovine decorin, respectively. This high degree of conservation among species suggests regulatory functions for these leader exons. In the 3' untranslated region there are several polyadenylation sites, and at least two of these sites could give rise to the transcripts of [approx]1.6 and [approx]1.9 kb, typically detected in a variety of tissues and cells. Using a genomic clone as the labeled probe and in situ hybridization of human metaphase chromosomes, we have mapped the decorin gene to the discrete region of human chromosome 12q23. This sturdy provides the molecular basis for discerning the transcriptional control of the decorin gene and offers the opportunity to investigate genetic disorders linked to this important human gene. 57 refs., 11 figs., 3 tabs.

  7. The Application of FAST-NMR for the Identification of Novel Drug Discovery Targets

    PubMed Central

    Powers, Robert; Mercier, Kelly A.; Copeland, Jennifer C.

    2009-01-01

    The continued success of genome sequencing projects has resulted in a wealth of information, but 40-50% of identified genes correspond to hypothetical proteins or proteins of unknown function. The Functional Annotation Screening Technology by NMR (FAST-NMR) screen was developed to assign a biological function for these unannotated proteins with a structure solved by the Protein Structure Initiative. FAST-NMR is based on the premise that a biological function can be described by a similarity in binding sites and ligand interactions with proteins of known function. The resulting co-structure and functional assignment may provide a starting point for a drug discovery effort. PMID:18275915

  8. 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

  9. 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

  10. Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.

    PubMed

    Huang, Xi-Ping; Mangano, Thomas; Hufeisen, Sandy; Setola, Vincent; Roth, Bryan L

    2010-12-01

    The human Ether-à-go-go related gene (hERG) potassium channel is responsible for the rapid delayed rectifier potassium current that plays a critical role in the repolarization of cardiomyocytes during the cardiac action potential. In humans, inhibition of hERG by drugs can prolong the electrocardiographic QT interval, which, in rare instance, leads to ventricular arrhythmia and sudden cardiac death. As such, several medications that block hERG channels in vitro have been withdrawn from the market due to QT prolongation and arrhythmias. The current FDA guidelines recommend that drug candidates destined for human use be evaluated for potential hERG activity ( www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm074963.pdf ). Here, we employed automated planar patch clamp (APPC), high-throughput fluorescent Tl(+) flux, and moderate-throughput [³H]dofetilide competition binding assays to characterize a panel of 49 drugs for their activities at the hERG channel. Notably, we used the same HEK293-hERG cell line for all assays, facilitating comparisons of hERG potencies across screening platforms. In general, hERG inhibitors were most potent in APPC assays, intermediate potent in [³H]dofetilide binding assays, and least potent in Tl(+) flux assays. Binding affinity constants (pK(i) values) and Tl(+) flux potencies (pEC?? values) correlated well with APPC pEC?? values. Further, the inhibitory potencies of many known hERG inhibitors in APPC matched literature values from manual and/or automated patch clamp systems. We also developed a novel fluorescent Tl(+) flux assays to measure the effects of drugs that modulate hERG trafficking and surface expression. PMID:21158687

  11. 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

  12. BioGraph: unsupervised biomedical knowledge discovery via automated hypothesis generation.

    PubMed

    Liekens, Anthony M L; De Knijf, Jeroen; Daelemans, Walter; Goethals, Bart; De Rijk, Peter; Del-Favero, Jurgen

    2011-01-01

    We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information. The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications beyond gene discovery. BioGraph is accessible at http://www.biograph.be. PMID:21696594

  13. BioGraph: unsupervised biomedical knowledge discovery via automated hypothesis generation

    PubMed Central

    2011-01-01

    We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information. The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications beyond gene discovery. BioGraph is accessible at http://www.biograph.be. PMID:21696594

  14. Learning through Projects.

    ERIC Educational Resources Information Center

    Borgia, Eileen

    1996-01-01

    Offers guidelines for creating and implementing an age-appropriate project that fits children's needs, interests, and surroundings. Using the example of a supermarket project, outlines the four stages of a project's development--preliminary planning, getting started, investigation and discovery, and wrapping up the project. Gives tips on learning…

  15. STS-92 Discovery Launch

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Viewed from across the waters of Banana Creek, clouds of smoke and steam are illuminated by the flames from Space Shuttle Discovery'''s perfect on-time launch at 7:17 p.m. EDT. Discovery carries a crew of seven on a construction flight to the International Space Station. Discovery also carries a payload that includes the Integrated Truss Structure Z-1, first of 10 trusses that will form the backbone of the Space Station, and the third Pressurized Mating Adapter that will provide a Shuttle docking port for solar array installation on the sixth Station flight and Lab installation on the seventh Station flight. Discovery'''s landing is expected Oct. 22 at 2:10 p.m. EDT.

  16. Improving the efficiency of gene replacements in Neurospora crassa: a first step towards a large-scale functional genomics project.

    PubMed

    Pratt, Robert J; Aramayo, Rodolfo

    2002-10-01

    Here, we report the use of the mating type heterokaryon incompatibility system as a counterselection to increase the probability of identifying gene replacements in Neurospora crassa. We compared the frequencies of gene replacements observed among transformants obtained by using plasmids with or without the mat a-1(+) gene (hereby called "Toxic Gene") placed adjacent to disruption cassettes. On an average, we were 20x more likely to identify a correct gene replacement by incorporating the toxic gene in our constructs. Using this strategy, we constructed strains containing a deletion of the inl (1L-myo-inositol-1-phosphate synthase) gene. Finally, we demonstrated that we were able to remove the transformation marker (the hygromycin B phosphotransferase- thymidine kinase gene fusion [hph(+)::tk(+)]) from the genome by using a strategy similar to the "URA-blaster" strategy used in yeast, which we call "tk-blaster." PMID:12223190

  17. 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.

  18. Knowledge Discovery from Graphs

    Microsoft Academic Search

    David Jensen

    Knowledge discovery is the process of discovering useful and previously unknown knowledge by analyzing large databases. Knowledge\\u000a discovery is also sometimes called “data mining” or “applied machine learning.” A new generation of knowledge discovery tools\\u000a are beginning to address data that can be expressed as large graphs. Example applications include fraud detection in telecommunication\\u000a networks and classifying Web pages based

  19. GENESTRACE: PHENOMIC KNOWLEDGE DISCOVERY VIA STRUCTURED TERMINOLOGY

    PubMed Central

    Cantor, Michael N.; Sarkar, Indra Neil; Bodenreider, Olivier

    2010-01-01

    The era of applied genomic medicine is quickly approaching accompanied by the increasing availability of detailed genetic information. Understanding the genetic etiology behind complex, multi-gene diseases remains an important challenge. In order to uncover the putative genetic etiology of complex diseases, we designed a method that explores the relationships between two major terminological and ontological resources: the Unified Medical Language System (UMLS) and the Gene Ontology (GO). The UMLS has a mainly clinical emphasis; Gene Ontology (GO) has become the standard for biological annotations of genes and gene products. Using statistical and semantic relationships within and between the two resources, we are able to infer relationships between disease concepts in the UMLS and gene products annotated using GO and its associated databases. We validated our inferences by comparing them to the known gene-disease relationships, as defined in the Online Mendelian Inheritance in Man1s morbidmap. The proof-of-concept methods presented here are unique in that they bypass the ambiguity of the direct extraction of gene or disease term from MEDLINE. Additionally, our methods provide direct links to clinically significant diseases through established terminologies or ontologies. The preliminary results presented here indicate the potential utility of exploiting the existing, manually curated relationships in biomedical resources as a tool for the discovery of potentially valuable new gene-disease relationships. The GenesTrace system may be accessed at the following URL: http://phene .cpmc.columbia.edu:8080/genesTrace/index.jsp PMID:15759618

  20. 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).

  1. Whole-genome Comparative Annotation and Regulatory Motif Discovery in Multiple Yeast Species

    E-print Network

    Kellis, Manolis

    Whole-genome Comparative Annotation and Regulatory Motif Discovery in Multiple Yeast Species these three yeast species to their close relative, S. cerevisiae. Genome-wide comparative analysis allowed than 90% of genes despite the large number of duplicated genes in the yeast genome, and the discovery

  2. 2014 PhD Scholarships: ARC funded projects at The University of Technology, Sydney As a result of outstanding success in recent ARC funding rounds two Future Fellowships and four Discovery Projects

    E-print Network

    University of Technology, Sydney

    2014 PhD Scholarships: ARC funded projects at The University of Technology, Sydney As a result ­ the UTS Plant Functional Biology and Climate Change Cluster (C3) is seeking applications from suitably qualified candidates for 9 PhD scholarships. Established in 2008, C3 is a dynamic, multidisciplinary

  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. DIMENSIONS of DISCOVERY Sponsored Program Awards

    E-print Network

    Ginzel, Matthew

    , "Instrumentation Van Project." Beckerman, Janna L; botany & plant pathol- ogy, from Indiana Arborists Association -- Voluntary Support." Blatchley, Ernest R; civil engineering, from Citizens Energy Group, $24,290, "Design with Improved Plasmonic Materials; Modi- fication 2 for Grant 105573." (a Discovery Parkaward

  5. 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.

  6. 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 ...

  7. 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 Dahlbæk; 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

  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. Topology discovery in PROFINET

    Microsoft Academic Search

    I. Schafer; M. Felser

    2007-01-01

    PROFINET, an automation network based on Ethernet, includes the automatic discovery of the physical topology with the link layer discovery protocol (LLDP) in its newest specifications. In this paper we present the objectives of LLDP in PROFINET and general information about the protocol and other parts of IEEE 802.1AB, which describes LLDP. During the analysis of different implementations on the

  10. Simulating an Automated Approach to Discovery and Modeling of Open Source Software Development Processes

    Microsoft Academic Search

    Chris Jensen; Walt Scacchi

    Process discovery has been shown to be challenging offering limited results, however, most work has been conducted in closed source systems. This paper describes a new approach to process discovery that examines the Internet information spaces of open source software development projects. In searching for an automated solution to the process discovery problem, we first have simulated it by having

  11. Wyre Community Discovery Centre Wyre Community Discovery

    E-print Network

    of Scientific Special Interest (SSSI). The forest is a popular natural attraction and 250,000 visitors per year to ensure long-term social, environmental and economic sustainability in the area saw the development designed to equip people with traditional and practical land management skills. The Discovery Centre

  12. Gene discovery and engineering for biomass degradation

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. 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.

  14. Metagenomic gene discovery: past, present and future

    Microsoft Academic Search

    Don Cowan; Quinton Meyer; William Stafford; Samson Muyanga; Rory Cameron; Pia Wittwer

    2005-01-01

    It is now widely accepted that the application of standard microbiological methods for the recovery of microorganisms from the environment has had limited success in providing access to the true extent of microbial biodiversity. It follows that much of the extant microbial genetic diversity (collectively termed the metagenome) remains unexploited, an issue of con- siderable relevance to a wider understanding

  15. Purposive discovery of operations

    NASA Technical Reports Server (NTRS)

    Sims, Michael H.; Bresina, John L.

    1992-01-01

    The Generate, Prune & Prove (GPP) methodology for discovering definitions of mathematical operators is introduced. GPP is a task within the IL exploration discovery system. We developed GPP for use in the discovery of mathematical operators with a wider class of representations than was possible with the previous methods by Lenat and by Shen. GPP utilizes the purpose for which an operator is created to prune the possible definitions. The relevant search spaces are immense and there exists insufficient information for a complete evaluation of the purpose constraint, so it is necessary to perform a partial evaluation of the purpose (i.e., pruning) constraint. The constraint is first transformed so that it is operational with respect to the partial information, and then it is applied to examples in order to test the generated candidates for an operator's definition. In the GPP process, once a candidate definition survives this empirical prune, it is passed on to a theorem prover for formal verification. We describe the application of this methodology to the (re)discovery of the definition of multiplication for Conway numbers, a discovery which is difficult for human mathematicians. We successfully model this discovery process utilizing information which was reasonably available at the time of Conway's original discovery. As part of this discovery process, we reduce the size of the search space from a computationally intractable size to 3468 elements.

  16. The Greatest Mathematical Discovery?

    SciTech Connect

    Bailey, David H.; Borwein, Jonathan M.

    2010-05-12

    What mathematical discovery more than 1500 years ago: (1) Is one of the greatest, if not the greatest, single discovery in the field of mathematics? (2) Involved three subtle ideas that eluded the greatest minds of antiquity, even geniuses such as Archimedes? (3) Was fiercely resisted in Europe for hundreds of years after its discovery? (4) Even today, in historical treatments of mathematics, is often dismissed with scant mention, or else is ascribed to the wrong source? Answer: Our modern system of positional decimal notation with zero, together with the basic arithmetic computational schemes, which were discovered in India about 500 CE.

  17. Metastasis Suppressor Genes

    PubMed Central

    Yan, Jinchun; Yang, Qin; Huang, Qihong

    2014-01-01

    Metastasis is a major cause of cancer mortality. Metastasis is a complex process that requires the regulation of both metastasis-promoting and metastasis suppressor genes. The discovery of metastasis suppressor genes contributes significantly to our understanding of metastasis mechanisms and provides prognostic markers and therapeutic targets in clinical cancer management. In this review, we summarize the methods that have been used to identify metastasis suppressors and the potential clinical impact of these genes. PMID:23348381

  18. 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

  19. 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

  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. THEMOSELYSNOWFLAKESPONGE A USC LIBRARIES DISCOVERY FELLOW PROJECT

    E-print Network

    Valero-Cuevas, Francisco

    -dimensional fractal, which came to be called, in his honor, the Menger Sponge. Eighty years later Dr. Jeannine Mosely, an MIT-trained engineer, built a model of this extraordinary object using 66,000 business cards. Now Dr. Mosely has discovered a relative of Menger's original fractal--the Mosely Snowflake Sponge. USC Libraries

  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. 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.

  4. History of Saturn Discoveries

    NSDL National Science Digital Library

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

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

    PubMed Central

    Lee, Y.; Tsai, J.; Sunkara, S.; Karamycheva, S.; Pertea, G.; Sultana, R.; Antonescu, V.; Chan, A.; Cheung, F.; Quackenbush, J.

    2005-01-01

    Although the list of completed genome sequencing projects has expanded rapidly, sequencing and analysis 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 and EST sequences in an attempt to identify and characterize expressed transcripts and to present them on the Web in a user-friendly, consistent fashion. A Gene Index database is constructed for each selected organism by first clustering, then assembling EST and annotated cDNA and gene sequences from GenBank. This process produces a set of unique, high-fidelity virtual transcripts, or tentative consensus (TC) sequences. The TC sequences can be used to provide putative genes with functional annotation, to link the transcripts to genetic and physical maps, to provide links to orthologous and paralogous genes, and as a resource for comparative and functional genomic analysis. PMID:15608288

  6. 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 ...

  7. Recent Genetic Discoveries Implicating Ion Channels in Human Cardiovascular Diseases

    PubMed Central

    George, Alfred L.

    2014-01-01

    The term channelopathy refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets. PMID:24721653

  8. 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.

  9. Physical activity correlates with glutamate receptor gene expression in spinally-projecting RVLM neurons: a laser capture microdissection study.

    PubMed

    Subramanian, Madhan; Holt, Avril G; Mueller, Patrick J

    2014-10-17

    Physical inactivity is an important risk factor in the development of cardiovascular disease. The rostral ventrolateral portion of the medulla (RVLM) is composed of heterogeneous populations of neurons that are involved in the regulation of the cardiovascular system. Because of functional heterogeneity, studying the changes in the gene expression of this specific population of neurons within the RVLM is challenging. In the present study, a fluorescent retrograde tracer was injected into the spinal cord to specifically label bulbospinal RVLM neurons in sedentary and active rats. Laser capture microdissection (LCM) was then employed to collect the fluorescently labeled neurons from sections encompassing the rostrocaudal extent of the RVLM. RNA extracted from the neurons was used in qRT-PCR analysis. Changes in gene expression levels of glutamate and GABA receptor subunits were compared between sedentary and physically active rats. GLUR3 subunit showed a significant negative correlation between total running distance and its relative gene expression in active rats. There were no significant difference in the gene expression of NMDA (NR1, NR2A, NR2B, NR2C and NR2D), AMPA (GLUR1, GLUR2 and GLUR3) and GABAA (GABAA1 and GABAA2) receptor subunits. Overall, the present study demonstrates the feasibility of utilizing LCM to investigate the gene expression changes in a specific population of neurons in the RVLM. Correlation studies suggest that physical activity could contribute to neuroplasticity in the RVLM. PMID:25173073

  10. Assessment of Materials for Engaging Students in Statistical Discovery*

    E-print Network

    Froelich, Amy G.

    1 Assessment of Materials for Engaging Students in Statistical Discovery* Amy G. Froelich W. Robert of Materials · Course Project ­ Experiment and Regression Analysis ­ Experimental and Control Group Students randomly assigned to project groups. Assessment of Materials · Grading of Exam Questions ­ Rubric ­ Graded

  11. Science Fun with Electricity...Discoveries and Innovations.

    ERIC Educational Resources Information Center

    Horton, Robert L.

    This project manual is written for 4-H member children who are in the fifth grade or older. This project is designed to familiarize members with the scientific history concerning the discovery and application of electric energy through the 1800's. Readers can conduct experiments similar to the ones performed by the scientists and inventors of that…

  12. Knowledge Discovery in Data with selected Java Open Source Software

    Microsoft Academic Search

    Carlos Rojas; Olfa Nasraoui; Nurcan Durak; Leyla Zuhadar; Sofiane Sellah; Zhiyong Zhang; Basheer Hawwash; Esin Saka; Elizabeth Leon; Jonatan Gomez; Fabio Gonzalez; Maha Soliman

    2008-01-01

    We give an overview of our experience in utilizing sev- eral open source packages and composing them into sophis- ticated applications to solve several challenging problems as part of some of the research projects at the Knowledge Dis- covery & Web Mining lab at the Universe of Louisville. The projects have a common theme of knowledge discovery, how- ever their

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Inosine Alters Gene Expression and Axonal Projections in Neurons Contralateral to a Cortical Infarct and Improves Skilled Use of the Impaired Limb

    PubMed Central

    Zai, Laila; Ferrari, Christina; Subbaiah, Sathish; Havton, Leif A.; Coppola, Giovanni; Strittmatter, Stephen; Irwin, Nina; Geschwind, Daniel; Benowitz, Larry I.

    2010-01-01

    Recovery after stroke and other types of brain injury is restricted in part by the limited ability of undamaged neurons to form compensatory connections. Inosine, a naturally occurring purine nucleoside, stimulates neurons to extend axons in culture and, in vivo, enhances the ability of undamaged neurons to form axon collaterals after brain damage. The molecular changes induced by inosine are unknown, as is the ability of inosine to restore complex functions associated with a specific cortical area. Using a unilateral injury model limited to the sensorimotor cortex, we show that inosine triples the number of corticospinal tract axons that project from the unaffected hemisphere and form synaptic bouton-like structures in the denervated half of the spinal cord. These changes correlate with improved recovery in animals’ ability to grasp and consume food pellets with the affected forepaw. Studies using laser-capture microdissection and microarray analysis show that inosine profoundly affects gene expression in corticospinal neurons contralateral to the injury. Inosine attenuates transcriptional changes caused by the stroke, while upregulating the expression of genes associated with axon growth and the complement cascade. Thus, inosine alters gene expression in neurons contralateral to a stroke, enhances the ability of these neurons to form connections on the denervated side of the spinal cord, and improves performance with the impaired limb. PMID:19553458

  18. Evolution of Melanopsin Photoreceptors: Discovery and Characterization of a New Melanopsin in Nonmammalian Vertebrates

    Microsoft Academic Search

    James Bellingham; Shyam S. Chaurasia; Zara Melyan; Cuimei Liu; Morven A. Cameron; Emma E. Tarttelin; P. Michael Iuvone; Mark W. Hankins; Gianluca Tosini; Robert J. Lucas

    2006-01-01

    In mammals, the melanopsin gene (Opn4) encodes a sensory photopigment that underpins newly discovered inner retinal photoreceptors. Since its first discovery in Xenopus laevis and subsequent description in humans and mice, melanopsin genes have been described in all vertebrate classes. Until now, all of these sequences have been considered representatives of a single orthologous gene (albeit with duplications in the

  19. 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.

  20. 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

  1. 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.

  2. 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)

  3. Stories of Discovery

    Cancer.gov

    Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. This collection of Stories of Discovery portrays how NCI's role in cancer research has led to landmark developments in cancer prevention and treatment, improved the lives of those fighting cancer, and continues to create hope for tomorrow.

  4. 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…

  5. 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

  6. Knowledge Discovery in Databases.

    ERIC Educational Resources Information Center

    Norton, M. Jay

    1999-01-01

    Knowledge discovery in databases (KDD) revolves around the investigation and creation of knowledge, processes, algorithms, and mechanisms for retrieving knowledge from data collections. The article is an introductory overview of KDD. The rationale and environment of its development and applications are discussed. Issues related to database design…

  7. 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

  8. Interoperability and information discovery

    USGS Publications Warehouse

    Christian, E.

    2001-01-01

    In the context of information systems, there is interoperability when the distinctions between separate information systems are not a barrier to accomplishing a task that spans those systems. Interoperability so defined implies that there are commonalities among the systems involved and that one can exploit such commonalities to achieve interoperability. The challenge of a particular interoperability task is to identify relevant commonalities among the systems involved and to devise mechanisms that exploit those commonalities. The present paper focuses on the particular interoperability task of information discovery. The Global Information Locator Service (GILS) is described as a policy, standards, and technology framework for addressing interoperable information discovery on a global and long-term basis. While there are many mechanisms for people to discover and use all manner of data and information resources, GILS initiatives exploit certain key commonalities that seem to be sufficient to realize useful information discovery interoperability at a global, long-term scale. This paper describes ten of the specific commonalities that are key to GILS initiatives. It presents some of the practical implications for organizations in various roles: content provider, system engineer, intermediary, and searcher. The paper also provides examples of interoperable information discovery as deployed using GILS in four types of information communities: bibliographic, geographic, environmental, and government.

  9. Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

    Microsoft Academic Search

    R Keers; R Uher; P Huezo-Diaz; R Smith; S Jaffee; M Rietschel; N Henigsberg; D Kozel; O Mors; W Maier; A Zobel; J Hauser; D Souery; A Placentino; E R Larsen; M Dmitrzak-Weglarz; B Gupta; F Hoda; I Craig; P McGuffin; A E Farmer; K J Aitchison

    2011-01-01

    There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report

  10. Discovery planetary mission operations concepts

    Microsoft Academic Search

    Richard C. Coffin

    1995-01-01

    The NASA Discovery Program of small planetary missions will provide opportunities to continue scientific exploration of the solar system in today's cost-constrained environment. Using a multidisciplinary team, the Jet Propulsion Laboratory is developing plans to provide mission operations within the financial parameters established by the Discovery Program. This paper describes experiences and methods that show promise of allowing Discovery missions

  11. 24 CFR 180.500 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...voluntary discovery procedures. Discovery shall be conducted as expeditiously...ALJ, the parties may obtain discovery regarding any matter...documents or persons having knowledge of any discoverable matter...calculated to lead to the discovery of admissible evidence....

  12. 42 CFR 405.1037 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...to request discovery or conduct discovery only if the requesting party establishes...fault in not meeting the original discovery deadline. (5) If the ALJ grants...extension request, it must impose a new discovery deadline and, if necessary,...

  13. 42 CFR 405.1037 - Discovery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...to request discovery or conduct discovery only if the requesting party establishes...fault in not meeting the original discovery deadline. (5) If the ALJ grants...extension request, it must impose a new discovery deadline and, if necessary,...

  14. The Human Genome Project and biology education

    SciTech Connect

    McInerney, J.D. [Biological Sciences Curriculum Study, Colorado Springs, CO (United States)

    1995-12-01

    Within the last several years, biologists celebrated the fortieth anniversary of the Watson-Crick model of DNA and the fiftieth anniversary of the demonstration that DNA is the genetic material, discoveries that began a pervasive and ongoing revolution in biology and medicine. Nobelist Joshua Lederberg, for example, called the work of Avery`s group {open_quotes}the most important discovery in biology in the twentieth century.{close_quotes} This early work on DNA also contributed to a revolution in biology education, beginning in the 1960s. Like the biological revolution that is its counterpart, however, the educational revolution is incomplete, in part because the science continues to evolve, but primarily because scientists and science educators have not yet responded completely to the challenges of genetics and molecular biology. These challenges are made even more obvious by the scope and visibility of the Human Genome Project, the international project intended to map and sequence all human genes. Science educators face 4 challenges discussed in this article and using the Genome project as an example: teach for conceptual understanding; the nature of science; the personal and social impact of science and technology; the principles of technology.

  15. Chapter 19: Gene: A Directory of Genes Donna Maglott

    E-print Network

    Levin, Judith G.

    Chapter 19: Gene: A Directory of Genes Donna Maglott Kim Pruitt Tatiana Tatusova Summary A major goal of genomic sequencing projects is to identify and characterize genes. Gene (1) has been genes, serving as a major node in the nexus of genomic map, sequence, expression, protein structure

  16. Lynch Syndrome Genes

    Microsoft Academic Search

    Päivi Peltomäki

    2005-01-01

    Since the discovery of the major human genes with DNA mismatch repair (MMR) function in 1993--1995, mutations in four, MSH2, MLH1, MSH6, and PMS2, have been convincingly linked to susceptibility of hereditary nonpolyposis colorectal cancer (HNPCC)\\/Lynch syndrome. Among these, PMS2 mutations are associated with diverse clinical features, including those of the Turcot syndrome. Two additional MMR genes, MLH3 and PMS1,

  17. Neurobiology expert Zoghbi set for next Discovery Lecture

    E-print Network

    Palmeri, Thomas

    Neurobiology expert Zoghbi set for next Discovery Lecture BY: LEIGH MACMILLAN 3/17/2011 - Huda and MECP2 Disorders: Linking Epigenetics to Neurobiology," will begin at 4 p.m. in 208 Light Hall. Zoghbi. The investigators have developed mouse models with MECP2 mutations to explore the gene's function in neurobiology

  18. Evidence of efficient stop codon readthrough in four mammalian genes

    E-print Network

    Loughran, Gary

    Stop codon readthrough is used extensively by viruses to expand their gene expression. Until recent discoveries in Drosophila, only a very limited number of readthrough cases in chromosomal genes had been reported. Analysis ...

  19. Horizontal Gene Transfer

    NSDL National Science Digital Library

    Citizendium

    This Citizendium article offers a comprehensive review of horizontal gene transfer (HGT). Topics include main features of HGT in nature, HGT in prokaryotes, HGT in eukaryotes, history and discovery of HGT, and decoding the tree of life from genomes scrambled by HGT. The image-rich text includes a list of related articles, a bibliography and external links of interest.

  20. Discovery of antiepileptic drugs.

    PubMed

    Smith, Misty; Wilcox, Karen S; White, H Steve

    2007-01-01

    Since 1993, the Anticonvulsant Drug Development Program has contributed to the successful development of nine clinically effective drugs for the symptomatic treatment of epilepsy. These include felbamate (1993), gabapentin (1994), lamotrigine (1994), fosphenytoin (1996), topiramate (1996), tiagabine (1997), levetiracetam (1999), zonisamide (2000), and oxcarbazepine (2000). Despite the apparent success of the current discovery process, a significant need persists for more efficacious and less toxic antiepileptic drugs (AEDs). This is particularly true for patients whose seizures remain refractory to the currently available AEDs. This chapter will review the current process for AED discovery employed by the Anticonvulsant Drug Development Program at the University of Utah and other laboratories working toward the common goal of discovering better therapeutic options for patients living with epilepsy. It will discuss some of the inherent advantages and limitations of the primary animal models employed, while offering insight into potential future directions as we seek to better understand the pathophysiology underlying acquired epilepsy, therapy resistance, and epileptogenesis. PMID:17199014

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Discovery of new enzymes and metabolic pathways by using structure and genome context.

    PubMed

    Zhao, Suwen; Kumar, Ritesh; Sakai, Ayano; Vetting, Matthew W; Wood, B McKay; Brown, Shoshana; Bonanno, Jeffery B; Hillerich, Brandan S; Seidel, Ronald D; Babbitt, Patricia C; Almo, Steven C; Sweedler, Jonathan V; Gerlt, John A; Cronan, John E; Jacobson, Matthew P

    2013-10-31

    Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns. We and others are developing computation-guided strategies for functional discovery with 'metabolite docking' to experimentally derived or homology-based three-dimensional structures. Bacterial metabolic pathways often are encoded by 'genome neighbourhoods' (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by 'predicting' the intermediates in the glycolytic pathway in Escherichia coli. Metabolite docking to multiple binding proteins and enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. Here we report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-L-proline betaine (tHyp-B) and cis-4-hydroxy-D-proline betaine (cHyp-B), and also the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt concentrations was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guided functional predictions to enable the discovery of new metabolic pathways. PMID:24056934

  6. Advanced Energy Projects, FY 1993

    NASA Astrophysics Data System (ADS)

    1993-09-01

    AEP has been supporting research on novel materials for energy technology, renewable and biodegradable materials, new uses for scientific discoveries, alternate pathways to energy efficiency, alternative energy sources, innovative approaches to waste treatment and reduction, etc. The summaries are grouped according to projects active in FY 1993, Phase 1 SBIR projects, and Phase 2 SBIR projects. Investigator and institutional indexes are included.

  7. Discovery of chemically induced mutations in rice by TILLING

    PubMed Central

    Till, Bradley J; Cooper, Jennifer; Tai, Thomas H; Colowit, Peter; Greene, Elizabeth A; Henikoff, Steven; Comai, Luca

    2007-01-01

    Background Rice is both a food source for a majority of the world's population and an important model system. Available functional genomics resources include targeted insertion mutagenesis and transgenic tools. While these can be powerful, a non-transgenic, unbiased targeted mutagenesis method that can generate a range of allele types would add considerably to the analysis of the rice genome. TILLING (Targeting Induced Local Lesions in Genomes), a general reverse genetic technique that combines traditional mutagenesis with high throughput methods for mutation discovery, is such a method. Results To apply TILLING to rice, we developed two mutagenized rice populations. One population was developed by treatment with the chemical mutagen ethyl methanesulphonate (EMS), and the other with a combination of sodium azide plus methyl-nitrosourea (Az-MNU). To find induced mutations, target regions of 0.7–1.5 kilobases were PCR amplified using gene specific primers labeled with fluorescent dyes. Heteroduplexes were formed through denaturation and annealing of PCR products, mismatches digested with a crude preparation of CEL I nuclease and cleaved fragments visualized using denaturing polyacrylamide gel electrophoresis. In 10 target genes screened, we identified 27 nucleotide changes in the EMS-treated population and 30 in the Az-MNU population. Conclusion We estimate that the density of induced mutations is two- to threefold higher than previously reported rice populations (about 1/300 kb). By comparison to other plants used in public TILLING services, we conclude that the populations described here would be suitable for use in a large scale TILLING project. PMID:17428339

  8. Epigenetics--gene silencing.

    PubMed

    Lele, R D

    2009-01-01

    The discovery of the mechanism of RNA interference by ds RNA by Prof. Andrew Fire and Prof. Craig Mello in 1998, gave them the Nobel Prize in 2006. This discovery revealed a new mechanism for gene regulation through "gene silencing" at the transcriptional level (TGS) or at the post-transcriptional level (PTGS), which play a key role in many essential cellular processes. Today dsRNA is used as a powerful tool to experimentally elucidate the function of essentially any gene in a cell. The immense impact of the discovery of RNA interference (RNAi) on biomedical research and its novel medical applications in the future are reviewed in this article, with particular stress on therapeutic applications of radio-labeled antisense oligonucleotides (RASONs) for diagnosis and treatment of various cancers and neurodegenerative diseases by "gene silencing". Antisense oligonucleotides (ASONs) can also modulate alternative splicing which 74% of all human genes undergo. The most effective targeting strategy employs simultaneous blocking SnRNP binding sites and splice junctions. Correction of splicing by ASONs can be used to silence mutations causing aberrant splicing as in thalassemia, Duchenne muscular dystrophy and cystic fibrosis. PMID:19753761

  9. Overview of the Coastal Marine Discovery Service: data discovery, visualization, and understanding

    NASA Astrophysics Data System (ADS)

    Armstrong, E. M.; Mattmann, C. A.; Cinquini, L.; O'Brien, F. J.; Resneck, G.; Siegrist, Z.

    2012-12-01

    Many resources available for coastal ocean research and management remain underutilized. Typically, the emphasis in the past has been on increasing access and usability of remote sensing satellite products from NASA data centers. Significant progress has been made in this regard although access and discovery mechanisms still remain disjointed. Less attention has been paid to discovery and usability to ocean in situ records and circulation model products, because typically these are organized and maintained on a smaller regional level such as a university or smaller division of a larger national agency. The NASA Coastal Marine Discovery Service, a NASA ACCESS funded activity, focuses on improving discovery of these regional coastal ocean web services and data portals, including databases for satellite imagery, in situ and field measurements, ocean circulation models, and GIS coverages as a few examples. Beyond resource discovery, the CMDS integrated system (http://cmds.jpl.nasa.gov) leverages open source technology for unifying coastal ocean data within the framework on a GIS web client, the Easy GIS Net Viewer. In sum, CMDS consists of an online catalog of coastal resources that allows users to quickly discover the availability of data for their region of interest, physical parameter of interest or specific regional project of interest, or any combination of these. After discovery, data can be transparently linked to Netviewer client to view, overlay and interrogate products, and make GIS-like queries on the data layers to investigate statistical relationships. In this presentation, we will review the CMDS system, it architecture and resource harvesting approach, and more importantly demonstrate real world use of cases of data exploration, visualization and ultimately understanding.

  10. OntologicalDiscovery.org: A web resource for the empirical discovery of phenotypic relations across species and experimental systems

    SciTech Connect

    Baker, Erich J [Baylor University; Li, Zuopan [University of Tennessee, Knoxville (UTK); Jay, Jeremy J [ORNL; Philip, Vivek M [ORNL; Zhang, Yun [University of Tennessee, Knoxville (UTK); Langston, Michael A [University of Tennessee, Knoxville (UTK); Chesler, Elissa J [ORNL

    2009-01-01

    The Ontological Discovery Environment ( http://ontologicaldiscovery.org ) is a free, public Internet resource for the storage, sharing, retrieval and analysis of phenotype-centered genomic data sets. The intent of this resource is to allow the creation of user-defined phenotype categories based on naturally and experimentally observed biological networks, pathways and systems rather than on externally manifested constructs and semantics such as disease names and processes. By extracting the relationships of complex processes from the technology that produces those relationships, this resource meets a growing demand for data integration and hypothesis discovery across multiple experimental contexts, including broad species and phenotype domains. At a highly processed level, analyses of set similarity, distance and hierarchical relations are performed through a modular suite of tools. The core pivot point of analysis is the creation of a bipartite network of gene-phenotype relations, a unique discrete graph approach to gene-set analysis which enables set-set matching of non-referential data. The central organizing metaphor of a gene set may be created, stored and curated by individual users, shared among virtual working groups, or made publicly available. Gene sets submission incorporates a variety of accession numbers, microarray feature IDs, and gene symbols from model organisms, allowing integration across experimental platforms, literature reviews and other genomic analyses. The sets themselves are annotated with several levels of metadata which may include an unstructured description, publication information and structured community ontologies for anatomy, process and function. Gene set translation to user chosen reference species through gene homology allows translational comparison of models regardless of the face validity of the experimental systems. In addition, computationally derived gene sets can be integrated into phenome interdependency and similarity hierarchy graphs, which are hierarchical trees of phenotypes based on the genes to which they are associated. This provides an empirical discovery of the natural phenotype ontology.

  11. 18 CFR 385.908 - Discovery (Rule 908).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...discovery, where such discovery: (1) Relates to new facts or issues raised...conduct discovery where such discovery relates to new facts or issues raised...conduct discovery where such discovery: (1) Relates to new facts or issues...

  12. 18 CFR 385.908 - Discovery (Rule 908).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...discovery, where such discovery: (1) Relates to new facts or issues raised...conduct discovery where such discovery relates to new facts or issues raised...conduct discovery where such discovery: (1) Relates to new facts or issues...

  13. Discovery Channel - Mars

    NSDL National Science Digital Library

    This Discovery Channel website furnishes news articles and interactive modules about the latest information on the NASA mission to Mars and the rovers. Using Macromedia Flash Player, students can explore the equipment on the rover, view videos of the rover landing on Mars, and examine panoramas of Mars. The stereo images of the Martian landscape are amazing, especially when viewed with 3D glasses. The website offers answers to the common questions related to NASA's mission. While many of the links on the side panel were not working at the time of this review, the same headings are presented within the main part of the website and function properly.

  14. 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.

  15. Cytomics and drug discovery.

    PubMed

    Van Osta, Peter; Ver Donck, Kris; Bols, Luc; Geysen, Johan

    2006-03-01

    Pharmaceutical companies try to develop new drugs that have a high success rate of reaching the market. However, current disease models lack a strong correlation to clinical reality, because of the underestimation of the complexity and variability of clinical disease processes. This leads to high attrition rates late in drug development and soaring costs. Improvement of disease models is an important issue to reduce the high attrition rates in drug development. Using cell-based disease models, which should take into account the molecular diversity of the human cytome, will improve the predictive value of drug discovery. PMID:16496374

  16. 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

  17. 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.

  18. Discovery Planetary Mission Operations Concepts

    NASA Technical Reports Server (NTRS)

    Coffin, R.

    1994-01-01

    The NASA Discovery Program of small planetary missions will provide opportunities to continue scientific exploration of the solar system in today's cost-constrained environment. Using a multidisciplinary team, JPL has developed plans to provide mission operations within the financial parameters established by the Discovery Program. This paper describes experiences and methods that show promise of allowing the Discovery Missions to operate within the program cost constraints while maintaining low mission risk, high data quality, and reponsive operations.

  19. Formative Evaluation of the Intel[R] Design and Discovery Curriculum Report. CCT Reports

    ERIC Educational Resources Information Center

    Culp, Katie McMillan; Keane, Julie Thompson; Meade, Terri; Nudell, Hannah

    2004-01-01

    Between May 2003 and January 2004, Education Development Center's Center for Children and Technology (CCT) undertook a formative evaluation of Design and Discovery, a hands-on, project-based design and engineering curriculum being disseminated as part of the Intel Innovation in Education initiatives. The Design and Discovery curriculum invites 11-…

  20. School of Science and Technology An integrative approach to a cancer biomarker discovery and validation pipeline

    E-print Network

    Evans, Paul

    School of Science and Technology An integrative approach to a cancer biomarker discovery a strategic, multi-platform assessment/validation of cancer biomarkers that have been reported for cancer biomarker discovery and translation. This project has been selected for consideration for a fully

  1. RELATIONAL CLUSTERING FOR KNOWLEDGE DISCOVERY

    E-print Network

    Fernandez, Thomas

    RELATIONAL CLUSTERING FOR KNOWLEDGE DISCOVERY IN LIFE SCIENCES A dissertation presented by ILARIA............................................................................................................................... 9 1. Clustering Analysis ..................................................................................................... 12 1.2 Clustering as an Optimization Problem

  2. Causality discovery technology

    NASA Astrophysics Data System (ADS)

    Chen, M.; Ertl, T.; Jirotka, M.; Trefethen, A.; Schmidt, A.; Coecke, B.; Bañares-Alcántara, R.

    2012-11-01

    Causality is the fabric of our dynamic world. We all make frequent attempts to reason causation relationships of everyday events (e.g., what was the cause of my headache, or what has upset Alice?). We attempt to manage causality all the time through planning and scheduling. The greatest scientific discoveries are usually about causality (e.g., Newton found the cause for an apple to fall, and Darwin discovered natural selection). Meanwhile, we continue to seek a comprehensive understanding about the causes of numerous complex phenomena, such as social divisions, economic crisis, global warming, home-grown terrorism, etc. Humans analyse and reason causality based on observation, experimentation and acquired a priori knowledge. Today's technologies enable us to make observations and carry out experiments in an unprecedented scale that has created data mountains everywhere. Whereas there are exciting opportunities to discover new causation relationships, there are also unparalleled challenges to benefit from such data mountains. In this article, we present a case for developing a new piece of ICT, called Causality Discovery Technology. We reason about the necessity, feasibility and potential impact of such a technology.

  3. What's that gene (or protein)? Online resources for exploring functions of genes, transcripts, and proteins

    PubMed Central

    Hutchins, James R. A.

    2014-01-01

    The genomic era has enabled research projects that use approaches including genome-scale screens, microarray analysis, next-generation sequencing, and mass spectrometry–based proteomics to discover genes and proteins involved in biological processes. Such methods generate data sets of gene, transcript, or protein hits that researchers wish to explore to understand their properties and functions and thus their possible roles in biological systems of interest. Recent years have seen a profusion of Internet-based resources to aid this process. This review takes the viewpoint of the curious biologist wishing to explore the properties of protein-coding genes and their products, identified using genome-based technologies. Ten key questions are asked about each hit, addressing functions, phenotypes, expression, evolutionary conservation, disease association, protein structure, interactors, posttranslational modifications, and inhibitors. Answers are provided by presenting the latest publicly available resources, together with methods for hit-specific and data set–wide information retrieval, suited to any genome-based analytical technique and experimental species. The utility of these resources is demonstrated for 20 factors regulating cell proliferation. Results obtained using some of these are discussed in more depth using the p53 tumor suppressor as an example. This flexible and universally applicable approach for characterizing experimental hits helps researchers to maximize the potential of their projects for biological discovery. PMID:24723265

  4. Discovery of Business Opportunities on the Internet with Information Extraction

    Microsoft Academic Search

    Arman Tajarobi

    In this paper we describe a tool for the discovery of business opportunities on the Web. The aim of our system is to help a user decide which call for tenders should be examined further. The project and its goals will be presented. We then focus on one aspect, named entity extraction, and its use to improve classication and user

  5. An Interactive Guide to Self-Discovery for Women

    Microsoft Academic Search

    Elaine J. Taylor

    2012-01-01

    This project is a translation of ideas I have encountered in my journey through Women's Studies. With this interactive book, I offer a concise, understandable, and empowering method for self-discovery from one feminist's perspective. Traditional self-help materials often set the reader up as the one with the issue or problem and they rarely call out the functioning systems of oppression

  6. Knowledge Discovery from Structured Mammography Reports Using Inductive Logic Programming

    E-print Network

    Page Jr., C. David

    1 Knowledge Discovery from Structured Mammography Reports Using Inductive Logic Programming of Wisconsin, Milwaukee, WI 4 The development of large mammography databases provides an opportunity. In this project, we use a large collection of mammography reports to test the feasibility of using specific

  7. 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

  8. Mapping the Disease Protein Interactome: Toward a Molecular Medicine GPS to Accelerate Drug and Biomarker Discovery

    PubMed Central

    Coulombe, Benoit

    2015-01-01

    Genomic approaches such as genome-wide association studies (GWAS), disease genome sequencing projects, and genome-wide expression profiling analyses, in conjunction with classical genetic approaches, can identify human genes that are altered in disease, thereby suggesting a role for the encoded protein (or RNA) in the establishment and/or progression of the disease. However, many technical difficulties challenge our ability to validate the role of these disease-associated genes and gene products. Moreover, many identified genes contain open reading frames (ORFs) that have yet to be annotated, that is, the function (or activity) of the encoded protein is unknown. As a result, translating the genomic information available in public databases into useful tools for understanding and curing disease is a very slow and inefficient process. To overcome these difficulties, we have developed a technology platform, termed the “molecular medicine GPS” (mm-GPS), which is aimed at defining high-quality maps of interaction networks involving disease proteins. These maps are used to identify network dysfunctions in disease cells or models and to develop molecular tools such as RNA interference (RNAi) and small-molecule inhibitors to further characterize the molecular basis of disease. In this article, I review our progress in producing high-quality maps of human protein interaction networks, and I describe how we used this information to identify new factors and pathways that regulate the RNA polymerase II transcription machinery. I also describe how we utilize the mm-GPS platform to guide more efficient efforts leading from disease-associated genes to protein interaction networks to small-molecule inhibitors, and consequently, to accelerate drug and biomarker discovery. PMID:20939596

  9. 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,

  10. 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…

  11. Advances in Nuclear Magnetic Resonance for Drug Discovery

    PubMed Central

    Powers, Robert

    2010-01-01

    Background Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exasperated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project time-lines. Recent advances in nuclear magnetic resonance are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. Objective/Method A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process will be presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein-ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by FAST-NMR. Conclusion NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques, and the expansion of NMR amenable targets. PMID:20333269

  12. 22 CFR 521.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...REMEDIES ACT § 521.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  13. 40 CFR 27.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...CIVIL REMEDIES § 27.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  14. 20 CFR 355.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...ACT OF 1986 § 355.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  15. 34 CFR 33.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...REMEDIES ACT § 33.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  16. 14 CFR 1264.120 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...ACT OF 1986 § 1264.120 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  17. 22 CFR 224.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...REMEDIES ACT § 224.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  18. 41 CFR 105-70.021 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...1986 § 105-70.021 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  19. 38 CFR 42.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...REMEDIES ACT § 42.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  20. 22 CFR 35.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...CIVIL REMEDIES § 35.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  1. 45 CFR 79.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...CIVIL REMEDIES § 79.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  2. 28 CFR 71.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...Department of Justice § 71.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  3. 12 CFR 308.520 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Procedures § 308.520 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data or documentary evidence...agreed to by the parties, discovery is available only as...

  4. 31 CFR 16.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...ACT OF 1986 § 16.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data, either paper or electronic...agreed to by the parties, discovery is available only as...

  5. 10 CFR 13.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...CIVIL REMEDIES § 13.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  6. 10 CFR 1013.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...PROCEDURES § 1013.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  7. 49 CFR 31.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...CIVIL REMEDIES § 31.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  8. 5 CFR 185.122 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...CIVIL REMEDIES § 185.122 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  9. 43 CFR 35.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...AND STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  10. 15 CFR 25.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...Civil Remedies § 25.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  11. 29 CFR 22.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...ACT OF 1986 § 22.21 Discovery. (a) The following types of discovery are authorized: (1...accounts, papers, and other data and documentary evidence...agreed to by the parties, discovery is available only as...

  12. 12 CFR 19.170 - Discovery depositions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 false Discovery depositions. 19.170...PRACTICE AND PROCEDURE Discovery Depositions and Subpoenas § 19.170 Discovery depositions. (a) General...party, who has direct knowledge of matters that...

  13. 12 CFR 263.53 - Discovery depositions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... In addition to the discovery permitted in subpart A of this part, limited discovery by means of depositions...allowed for individuals with knowledge of facts material to...are not protected from discovery by any...

  14. 24 CFR 26.18 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...encouraged to engage in voluntary discovery procedures, which may commence...filed. Parties may obtain discovery regarding any matter...location of persons having knowledge of any discoverable matter...hearing officer may order discovery of any matter relevant...

  15. 28 CFR 76.21 - Discovery.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...CONTROLLED SUBSTANCES § 76.21 Discovery. (a) Scope. Discovery under this part covers...location of persons having knowledge of relevant facts. To the...used as a general guide for discovery practices in...

  16. Introduction The problem and Archimedes' discovery

    E-print Network

    Little, John B.

    Introduction The problem and Archimedes' discovery Some conclusions Archimedes' Quadrature, 2013 John B. Little Archimedes' Quadrature of the Parabola #12;Introduction The problem and Archimedes' discovery Some conclusions Outline 1 Introduction 2 The problem and Archimedes' discovery 3 Some conclusions

  17. Discovery | NCI Experimental Therapeutics (NExT)

    Cancer.gov

    Skip to Content Search this site DISCOVERY NCINExTInfo@mail.nih.gov Overview Chemical Biology Consortium NExT Diversity Library Discovery Activities in DTP Discovery Activities in CCR Other NCI Programs Last Updated: 10/28/10 North

  18. Discovery of Superconductive Tunneling

    NASA Astrophysics Data System (ADS)

    Giaever, Ivar

    2011-03-01

    Some times unlikely events happens: How can a mechanical engineer from Norway end up with a Nobel Prize in Physics? I had the great fortune to receive the prize in Physics for using electron tunneling to measure the energy gap in superconductors. In this talk I will recollect some of the events that led to this discovery and hopefully be able to convey to you some of the fun and excitement of that area. My great fortune was really to be at the right place at the right time, where I had access to outstanding and helpful physicists. If you become real interested, you may look up the talk at the web site http://nobelprize.org/ .

  19. Minnesota Discovery Center

    NSDL National Science Digital Library

    The Minnesota Discovery Center has many different programs, and their Iron Range Research Center website is a fine way to learn about this rather unique cultural and geographical region. Located in the far northern reaches of Minnesota, the area was center of a vast natural resource extraction economy for well over a century. On the right-hand side of this page, visitors can look over the "Genealogy", "Archives", and "Events & Programs" area. The "Archives" area contains over 960 items (including photographs, postcards, and maps) that the folks at the Center have digitized thus far. The archive contains images of drilling stations, iron ore production, and conveyor belts. Also, visitors can search their online genealogy database, which contains Census information, passenger arrival records, and mining company newsletters. Finally, visitors can use the "Events & Programs" section to learn about upcoming programs of note.

  20. Key drivers of biomedical innovation in cancer drug discovery

    PubMed Central

    Huber, Margit A; Kraut, Norbert

    2015-01-01

    Discovery and translational research has led to the identification of a series of “cancer drivers”—genes that, when mutated or otherwise misregulated, can drive malignancy. An increasing number of drugs that directly target such drivers have demonstrated activity in clinical trials and are shaping a new landscape for molecularly targeted cancer therapies. Such therapies rely on molecular and genetic diagnostic tests to detect the presence of a biomarker that predicts response. Here, we highlight some of the key discoveries bringing precision oncology to cancer patients. Large-scale “omics” approaches as well as modern, hypothesis-driven science in both academic and industry settings have significantly contributed to the field. Based on these insights, we discuss current challenges and how to foster future biomedical innovation in cancer drug discovery and development. PMID:25422355

  1. Identifying bacterial genes and endosymbiont DNA with Glimmer

    PubMed Central

    Delcher, Arthur L.; Bratke, Kirsten A.; Powers, Edwin C.; Salzberg, Steven L.

    2008-01-01

    Motivation: The Glimmer gene-finding software has been successfully used for finding genes in bacteria, archæa and viruses representing hundreds of species. We describe several major changes to the Glimmer system, including improved methods for identifying both coding regions and start codons. We also describe a new module of Glimmer that can distinguish host and endosymbiont DNA. This module was developed in response to the discovery that eukaryotic genome sequencing projects sometimes inadvertently capture the DNA of intracellular bacteria living in the host. Results: The new methods dramatically reduce the rate of false-positive predictions, while maintaining Glimmer's 99% sensitivity rate at detecting genes in most species, and they find substantially more correct start sites, as measured by comparisons to known and well-curated genes. We show that our interpolated Markov model (IMM) DNA discriminator correctly separated 99% of the sequences in a recent genome project that produced a mixture of sequences from the bacterium Prochloron didemni and its sea squirt host, Lissoclinum patella. PMID:17237039

  2. Integrative Discovery of Epigenetically Derepressed Cancer Testis Antigens in NSCLC

    PubMed Central

    Glazer, Chad A.; Smith, Ian M.; Ochs, Michael F.; Begum, Shahnaz; Westra, William; Chang, Steven S.; Sun, Wenyue; Bhan, Sheetal; Khan, Zubair; Ahrendt, Steven; Califano, Joseph A.

    2009-01-01

    Background Cancer/testis antigens (CTAs) were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC) whose transcription is driven by promoter demethylation. Methodology/Principal Findings Our screening approach found 290 significant genes from the over 47,000 transcripts incorporated in the Affymetrix Human Genome U133 Plus 2.0 expression array. Of the top 55 candidates, 10 showed both differential overexpression and promoter region hypomethylation in NSCLC. Surprisingly, 6 of the 10 genes discovered by this approach were CTAs. Using a separate cohort of primary tumor and normal tissue, we validated NSCLC promoter hypomethylation and increased expression by quantitative RT-PCR for all 10 genes. We noted significant, coordinated coexpression of multiple target genes, as well as coordinated promoter demethylation, in a large set of individual tumors that was associated with the SCC subtype of NSCLC. In addition, we identified 2 novel target genes that exhibited growth-promoting effects in multiple cell lines. Conclusions/Significance Coordinated promoter demethylation in NSCLC is associated with aberrant expression of CTAs and potential, novel candidate protooncogenes that can be identified using integrative discovery techniques. These findings have significant implications for discovery of novel CTAs and CT antigen directed immunotherapy. PMID:19997593

  3. Towards pharmacogenomics knowledge discovery with the semantic web.

    PubMed

    Dumontier, Michel; Villanueva-Rosales, Natalia

    2009-03-01

    Pharmacogenomics aims to understand pharmacological response with respect to genetic variation. Essential to the delivery of better health care is the use of pharmacogenomics knowledge to answer questions about therapeutic, pharmacological or genetic aspects. Several XML markup languages have been developed to capture pharmacogenomic and related information so as to facilitate data sharing. However, recent advances in semantic web technologies have presented exciting new opportunities for pharmacogenomics knowledge discovery by representing the information with machine understandable semantics. Progress in this area is illustrated with reference to the personalized medicine project that aims to facilitate pharmacogenomics knowledge discovery through intuitive knowledge capture and sophisticated question answering using automated reasoning over expressive ontologies. PMID:19240125

  4. INSPIRING RESEARCHERS Project Information

    E-print Network

    Shepard, Kenneth

    INSPIRING RESEARCHERS ACTIONS Project Information Human resources & mobility E U R O P E A N these discoveries can improve our health, protect the environment, allow us to communicate better, or look beyond and stable career path while ensuring that they receive competitive salaries with full social security rights

  5. Bio-crude transcriptomics: Gene discovery and metabolic network reconstruction for the biosynthesis of the terpenome of the hydrocarbon oil-producing green alga, Botryococcus braunii race B (Showa)

    DOE PAGESBeta

    Molnár, István [Univ. of Arizona, Tucson, AZ (United States). Natural Products Center and Bio5 Institute; Lopez, David [Univ. of California, Los Angeles, CA (United States). Dept. of Molecular, Cell and Developmental Biology; Wisecaver, Jennifer H. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Ecology and Evolutionary Biology; Devarenne, Timothy P. [Texas A & M Univ., College Station, TX (United States). Dept. of Biochemistry and Biophysics; Weiss, Taylor L. [Texas A & M Univ., College Station, TX (United States). Dept. of Biochemistry and Biophysics; Pellegrini, Matteo [Univ. of California, Los Angeles, CA (United States). Dept. of Molecular, Cell and Developmental Biology; Hackett, Jeremiah D. [Univ. of Arizona, Tucson, AZ (United States). Bio5 Institute and Dept. of Ecology and Evolutionary Biology

    2012-01-01

    Microalgae hold promise for yielding a biofuel feedstock that is sustainable, carbon-neutral, distributed, and only minimally disruptive for the production of food and feed by traditional agriculture. Amongst oleaginous eukaryotic algae, the B race of Botryococcus braunii is unique in that it produces large amounts of liquid hydrocarbons of terpenoid origin. These are comparable to fossil crude oil, and are sequestered outside the cells in a communal extracellular polymeric matrix material. Biosynthetic engineering of terpenoid bio-crude production requires identification of genes and reconstruction of metabolic pathways responsible for production of both hydrocarbons and other metabolites of the alga that compete for photosynthetic carbon and energy.

  6. Bio-crude transcriptomics: Gene discovery and metabolic network reconstruction for the biosynthesis of the terpenome of the hydrocarbon oil-producing green alga, Botryococcus braunii race B (Showa)

    DOE PAGESBeta

    Molnár, István; Lopez, David; Wisecaver, Jennifer H.; Devarenne, Timothy P.; Weiss, Taylor L.; Pellegrini, Matteo; Hackett, Jeremiah D.

    2012-01-01

    Microalgae hold promise for yielding a biofuel feedstock that is sustainable, carbon-neutral, distributed, and only minimally disruptive for the production of food and feed by traditional agriculture. Amongst oleaginous eukaryotic algae, the B race of Botryococcus braunii is unique in that it produces large amounts of liquid hydrocarbons of terpenoid origin. These are comparable to fossil crude oil, and are sequestered outside the cells in a communal extracellular polymeric matrix material. Biosynthetic engineering of terpenoid bio-crude production requires identification of genes and reconstruction of metabolic pathways responsible for production of both hydrocarbons and other metabolites of the alga that competemore »for photosynthetic carbon and energy.« less

  7. Torpor induction in mammals: Recent discoveries fueling new ideas

    PubMed Central

    Melvin, Richard G.; Andrews, Matthew T.

    2009-01-01

    When faced with a harsh climate or inadequate food, some mammals enter a state of suspended animation known as torpor. A major goal of torpor research is to determine mechanisms that integrate environmental cues, gene expression and metabolism to produce periods of torpor lasting from hours to weeks. Recent discoveries spanning the metazoa suggest that sirtuins, the mammalian circadian clock, fibroblast growth factor 21 (FGF21) and lipids are involved in torpor induction. For example, sirtuins link cellular energy status to the mammalian circadian clock, oxidative stress, and metabolic fuel selection. In this review, we discuss how these recent discoveries form a new hypothesis linking changes in the physical environment with changes in the expression of genes that regulate torpor induction. PMID:19864159

  8. A new approach to the rationale discovery of polymeric biomaterials

    PubMed Central

    Kohn, Joachim; Welsh, William J.; Knight, Doyle

    2007-01-01

    This paper attempts to illustrate both the need for new approaches to biomaterials discovery as well as the significant promise inherent in the use of combinatorial and computational design strategies. The key observation of this Leading Opinion Paper is that the biomaterials community has been slow to embrace advanced biomaterials discovery tools such as combinatorial methods, high throughput experimentation, and computational modeling in spite of the significant promise shown by these discovery tools in materials science, medicinal chemistry and the pharmaceutical industry. It seems that the complexity of living cells and their interactions with biomaterials has been a conceptual as well as a practical barrier to the use of advanced discovery tools in biomaterials science. However, with the continued increase in computer power, the goal of predicting the biological response of cells in contact with biomaterials surfaces is within reach. Once combinatorial synthesis, high throughput experimentation, and computational modeling are integrated into the biomaterials discovery process, a significant acceleration is possible in the pace of development of improved medical implants, tissue regeneration scaffolds, and gene/drug delivery systems. PMID:17644176

  9. Drug discovery with engineered zinc-finger proteins

    Microsoft Academic Search

    Andrew C. Jamieson; Jeffrey C. Miller; Carl O. Pabo

    2003-01-01

    Zinc-finger proteins (ZFPs) that recognize novel DNA sequences are the basis of a powerful technology platform with many uses in drug discovery and therapeutics. These proteins have been used as the DNA-binding domains of novel transcription factors (ZFP TFs), which are useful for validating genes as drug targets and for engineering cell lines for small-molecule screening and protein production. Recently,

  10. Discovery of the Titanium Isotopes

    E-print Network

    D. Meierfrankenfeld; M. Thoennessen

    2010-09-08

    Twentyfive titanium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  11. Cancer Target Discovery and Development

    Cancer.gov

    Published on Office of Cancer Genomics (http://ocg.cancer.gov) Home > CTD² Cancer Target Discovery and Development [1] Program Body:  Network Centers The CTD2 Network Centers work both independently and collaboratively to advance the understanding of

  12. Discovery of the Indium Isotopes

    E-print Network

    S. Amos; M. Thoennessen

    2010-09-08

    Thirty-eight indium isotopes (A = 98-135) have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  13. PLATYPUS: Inheritance and Scientific Discovery

    Microsoft Academic Search

    Roger E. Ghormley; David L. Sallach

    1990-01-01

    PLATYPUS is a prototype of a knowledge base system designed to facilitate scientific discovery in complex domains. PLATYPUS incorporates semantic data modeling capabilities, implementing Codd's RM\\/T model in innovative ways.

  14. Discovery of the Cerium Isotopes

    E-print Network

    Ginepro, J Q; Thoennessen, M

    2008-01-01

    The discovery of the 35 cerium isotopes discovered up to date is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  15. Discovery of the Cerium Isotopes

    E-print Network

    J. Q. Ginepro; J. Snyder; M. Thoennessen

    2008-12-24

    The discovery of the 35 cerium isotopes discovered up to date is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  16. Drug discovery: lessons from evolution

    PubMed Central

    Warren, John

    2011-01-01

    A common view within the pharmaceutical industry is that there is a problem with drug discovery and we should do something about it. There is much sympathy for this from academics, regulators and politicians. In this article I propose that lessons learnt from evolution help identify those factors that favour successful drug discovery. This personal view is influenced by a decade spent reviewing drug development programmes submitted for European regulatory approval. During the prolonged gestation of a new medicine few candidate molecules survive. This process of elimination of many variants and the survival of so few has much in common with evolution, an analogy that encourages discussion of the forces that favour, and those that hinder, successful drug discovery. Imagining a world without vaccines, anaesthetics, contraception and anti-infectives reveals how medicines revolutionized humanity. How to manipulate conditions that favour such discoveries is worth consideration. PMID:21395642

  17. Discovery of the Einsteinium Isotopes

    Microsoft Academic Search

    A. Bury; A. Fritsch; J. Q. Ginepro; M. Heim; A. Schuh; A. Shore; M. Thoennessen

    2009-01-01

    Seventeen einsteinium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  18. Motif discovery in sequential data

    E-print Network

    Jensen, Kyle L. (Kyle Lawrence)

    2006-01-01

    In this thesis, I discuss the application and development of methods for the automated discovery of motifs in sequential data. These data include DNA sequences, protein sequences, and real-valued sequential data such as ...

  19. Discovery of the Gold Isotopes

    E-print Network

    A. Schuh; A. Fritsch; J. Q. Ginepro; M. Heim; A. Shore; M. Thoennessen

    2009-03-10

    Thirty-six gold isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  20. Discovery of the Calcium Isotopes

    E-print Network

    J. L. Gross; M. Thoennessen

    2010-09-08

    Twenty four calcium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.