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Sample records for elliptica gene discovery

  1. Rice Genomics: Gene discovery

    Indian Academy of Sciences (India)

    There is a need for discovering candidate genes( a lot of them all over the genome indeed ) and the unlimited allelic variation that can productively take over rice metabolism when cellular water content falls below threshold levels.

  2. Transcriptome-Wide Analysis of Botrytis elliptica Responsive microRNAs and Their Targets in Lilium Regale Wilson by High-Throughput Sequencing and Degradome Analysis

    Directory of Open Access Journals (Sweden)

    Xue Gao

    2017-05-01

    Full Text Available MicroRNAs, as master regulators of gene expression, have been widely identified and play crucial roles in plant-pathogen interactions. A fatal pathogen, Botrytis elliptica, causes the serious folia disease of lily, which reduces production because of the high susceptibility of most cultivated species. However, the miRNAs related to Botrytis infection of lily, and the miRNA-mediated gene regulatory networks providing resistance to B. elliptica in lily remain largely unexplored. To systematically dissect B. elliptica-responsive miRNAs and their target genes, three small RNA libraries were constructed from the leaves of Lilium regale, a promising Chinese wild Lilium species, which had been subjected to mock B. elliptica treatment or B. elliptica infection for 6 and 24 h. By high-throughput sequencing, 71 known miRNAs belonging to 47 conserved families and 24 novel miRNA were identified, of which 18 miRNAs were downreguleted and 13 were upregulated in response to B. elliptica. Moreover, based on the lily mRNA transcriptome, 22 targets for 9 known and 1 novel miRNAs were identified by the degradome sequencing approach. Most target genes for elliptica-responsive miRNAs were involved in metabolic processes, few encoding different transcription factors, including ELONGATION FACTOR 1 ALPHA (EF1a and TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR 2 (TCP2. Furthermore, the expression patterns of a set of elliptica-responsive miRNAs and their targets were validated by quantitative real-time PCR. This study represents the first transcriptome-based analysis of miRNAs responsive to B. elliptica and their targets in lily. The results reveal the possible regulatory roles of miRNAs and their targets in B. elliptica interaction, which will extend our understanding of the mechanisms of this disease in lily.

  3. Independent Gene Discovery and Testing

    Science.gov (United States)

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

    2010-01-01

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

  4. Gene discovery in Triatoma infestans

    Directory of Open Access Journals (Sweden)

    de Burgos Nelia

    2011-03-01

    Full Text Available Abstract Background Triatoma infestans is the most relevant vector of Chagas disease in the southern cone of South America. Since its genome has not yet been studied, sequencing of Expressed Sequence Tags (ESTs is one of the most powerful tools for efficiently identifying large numbers of expressed genes in this insect vector. Results In this work, we generated 826 ESTs, resulting in an increase of 47% in the number of ESTs available for T. infestans. These ESTs were assembled in 471 unique sequences, 151 of which represent 136 new genes for the Reduviidae family. Conclusions Among the putative new genes for the Reduviidae family, we identified and described an interesting subset of genes involved in development and reproduction, which constitute potential targets for insecticide development.

  5. A new anthraquinone from Morinda elliptica Ridl.

    Science.gov (United States)

    Loonjang, Kiedparinya; Duangjinda, David; Phongpaichit, Souwalak; Sawangjaroen, Nongyao; Rattanaburi, Suthida; Mahabusarakam, Wilawan

    2015-01-01

    A new anthraquinone, morinquinone, together with 18 known anthraquinones were isolated from the stems of Morinda elliptica Ridl. Their structures were elucidated on the basis of spectroscopic data. They each showed weak inhibitory activity against a susceptible strain of Staphylococcus aureus and a methicillin-resistant S. aureus. Damnacanthal was effective against Microsporum gypseum (MIC 1 μg/mL). Lucidin was active against Entamoeba histolytica (MIC 31.25 μg/mL) and Giardia intestinalis (MIC 7.8 μg/mL).

  6. Chemical constituents of Salacia elliptica (Celastraceae

    Directory of Open Access Journals (Sweden)

    Lucienir Pains Duarte

    2010-01-01

    Full Text Available The chemical investigation of Salacia elliptica allowed to the isolation of 20 constituents: two polyols, one xanthone, a mixture of long chain hydrocarbons, one carboxylic acid, one polymer, two steroidal compounds, one aromatic ester and eleven pentacyclic triterpenes. These triterpenes include 3β-stearyloxy-oleanane, 3β-stearyloxy-ursane, one seco-friedelane, and eight compounds of the friedelane serie. The chemical structure and the relative configuration of a new triterpene 1,3-dioxo-16α-hydroxyfriedelane (15 were established through ¹H and 13C NMR including 2D experiments (HMBC, HMQC, COSY and NOESY and herein reported for the first time.

  7. Chemical constituents of Salacia elliptica (Celastraceae)

    Energy Technology Data Exchange (ETDEWEB)

    Duarte, Lucienir Pains; Figueiredo, Rute Cunha; Sousa, Grasiely Faria de; Soares, Debora Barbosa da Silva; Rodrigues, Salomao Bento Vasconcelos; Silva, Fernando Cesar; Silva, Gracia Divina de Fatima, E-mail: lucienir@ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Quimica; Vieira Filho, Sidney Augusto [Universidade Federal de Ouro Preto, MG (Brazil). Escola de Farmacia. Dept. de Farmacia

    2010-07-01

    The chemical investigation of Salacia elliptica allowed to the isolation of 20 constituents: two polyols, one xanthone, a mixture of long chain hydrocarbons, one carboxylic acid, one polymer, two steroidal compounds, one aromatic ester and eleven pentacyclic triterpenes. These triterpenes include 3{beta}-stearyloxy-oleanane, 3{beta}-stearyloxy-ursane, one seco-friedelane, and eight compounds of the friedelane series. The chemical structure and the relative configuration of a new triterpene 1,3-dioxo-16alpha-hydroxyfriedelane (15) were established through {sup 1}H and {sup 13}C NMR including 2D experiments (HMBC, HMQC, COSY and NOESY) and herein reported for the first time (author)

  8. Ocean acidification at high latitudes: potential effects on functioning of the Antarctic bivalve Laternula elliptica.

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    Vonda Cummings

    Full Text Available Ocean acidification is a well recognised threat to marine ecosystems. High latitude regions are predicted to be particularly affected due to cold waters and naturally low carbonate saturation levels. This is of concern for organisms utilising calcium carbonate (CaCO(3 to generate shells or skeletons. Studies of potential effects of future levels of pCO(2 on high latitude calcifiers are at present limited, and there is little understanding of their potential to acclimate to these changes. We describe a laboratory experiment to compare physiological and metabolic responses of a key benthic bivalve, Laternula elliptica, at pCO(2 levels of their natural environment (430 µatm, pH 7.99; based on field measurements with those predicted for 2100 (735 µatm, pH 7.78 and glacial levels (187 µatm, pH 8.32. Adult L. elliptica basal metabolism (oxygen consumption rates and heat shock protein HSP70 gene expression levels increased in response both to lowering and elevation of pH. Expression of chitin synthase (CHS, a key enzyme involved in synthesis of bivalve shells, was significantly up-regulated in individuals at pH 7.78, indicating L. elliptica were working harder to calcify in seawater undersaturated in aragonite (Ω(Ar = 0.71, the CaCO(3 polymorph of which their shells are comprised. The different response variables were influenced by pH in differing ways, highlighting the importance of assessing a variety of factors to determine the likely impact of pH change. In combination, the results indicate a negative effect of ocean acidification on whole-organism functioning of L. elliptica over relatively short terms (weeks-months that may be energetically difficult to maintain over longer time periods. Importantly, however, the observed changes in L. elliptica CHS gene expression provides evidence for biological control over the shell formation process, which may enable some degree of adaptation or acclimation to future ocean acidification scenarios.

  9. Biomarker Gene Signature Discovery Integrating Network Knowledge

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    Holger Fröhlich

    2012-02-01

    Full Text Available 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.

  10. Induction of programmed cell death in lily by the fungal pathogen Botrytis elliptica

    NARCIS (Netherlands)

    Baarlen, van P.; Staats, M.; Kan, van J.A.L.

    2004-01-01

    The genus Botrytis contains necrotrophic plant pathogens that have a wide host range (B. cinerea) or are specialized on a single host species, e.g. B. elliptica on lily. In this study, it was found that B. elliptica-induced cell death of lily displays hallmark features of animal programmed cell

  11. Maximizing biomarker discovery by minimizing gene signatures

    Directory of Open Access Journals (Sweden)

    Chang Chang

    2011-12-01

    Full Text Available Abstract Background The use of gene signatures can potentially be of considerable value in the field of clinical diagnosis. However, gene signatures defined with different methods can be quite various even when applied the same disease and the same endpoint. Previous studies have shown that the correct selection of subsets of genes from microarray data is key for the accurate classification of disease phenotypes, and a number of methods have been proposed for the purpose. However, these methods refine the subsets by only considering each single feature, and they do not confirm the association between the genes identified in each gene signature and the phenotype of the disease. We proposed an innovative new method termed Minimize Feature's Size (MFS based on multiple level similarity analyses and association between the genes and disease for breast cancer endpoints by comparing classifier models generated from the second phase of MicroArray Quality Control (MAQC-II, trying to develop effective meta-analysis strategies to transform the MAQC-II signatures into a robust and reliable set of biomarker for clinical applications. Results We analyzed the similarity of the multiple gene signatures in an endpoint and between the two endpoints of breast cancer at probe and gene levels, the results indicate that disease-related genes can be preferably selected as the components of gene signature, and that the gene signatures for the two endpoints could be interchangeable. The minimized signatures were built at probe level by using MFS for each endpoint. By applying the approach, we generated a much smaller set of gene signature with the similar predictive power compared with those gene signatures from MAQC-II. Conclusions Our results indicate that gene signatures of both large and small sizes could perform equally well in clinical applications. Besides, consistency and biological significances can be detected among different gene signatures, reflecting the

  12. Crowdsourcing the nodulation gene network discovery environment.

    Science.gov (United States)

    Li, Yupeng; Jackson, Scott A

    2016-05-26

    The Legumes (Fabaceae) are an economically and ecologically important group of plant species with the conspicuous capacity for symbiotic nitrogen fixation in root nodules, specialized plant organs containing symbiotic microbes. With the aim of understanding the underlying molecular mechanisms leading to nodulation, many efforts are underway to identify nodulation-related genes and determine how these genes interact with each other. In order to accurately and efficiently reconstruct nodulation gene network, a crowdsourcing platform, CrowdNodNet, was created. The platform implements the jQuery and vis.js JavaScript libraries, so that users are able to interactively visualize and edit the gene network, and easily access the information about the network, e.g. gene lists, gene interactions and gene functional annotations. In addition, all the gene information is written on MediaWiki pages, enabling users to edit and contribute to the network curation. Utilizing the continuously updated, collaboratively written, and community-reviewed Wikipedia model, the platform could, in a short time, become a comprehensive knowledge base of nodulation-related pathways. The platform could also be used for other biological processes, and thus has great potential for integrating and advancing our understanding of the functional genomics and systems biology of any process for any species. The platform is available at http://crowd.bioops.info/ , and the source code can be openly accessed at https://github.com/bioops/crowdnodnet under MIT License.

  13. Prostate Cancer Gene Discovery Using ROMA

    National Research Council Canada - National Science Library

    Isaacs, William B

    2007-01-01

    We hypothesized that a subset of men who develop prostate cancer (PCa) do so as a result of an inherited chromosomal deletion or amplification affecting the function of one or more critical prostate cancer susceptibility genes...

  14. Microarray Assisted Gene Discovery in Ulcerative Colitis

    DEFF Research Database (Denmark)

    Brusgaard, Klaus

    ), and microarray based expression studies. In IBD the increased production of chemo attractants from the inflamed microenvironment results in recruitment of activated CD4+ T lymphocytes which results in tissue damage. Where Th1 cell-derived cytokines has been reported to be essential mediators in CD with high (IFN...... on the activation of different downstream pathways. Thus it seems that different genetic backgrounds can lead to similar clinical manifestations, and as well determines the susceptibility to IBD. In the previous micro array based expression studies on UC the main target has been to point to new candidate genes...... based on analysis of the main up or down regulated genes in the dataset. The majority of the studies are hampered by a relatively shortcoming of the numbers of genes analysed on the particular array. In this study the main target has been to point to clusters of genes involved in biochemical pathways...

  15. SNP marker discovery in koala TLR genes.

    Directory of Open Access Journals (Sweden)

    Jian Cui

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

  16. SNP marker discovery in koala TLR genes.

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    2014-01-01

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

  18. Fusion genes and their discovery using high throughput sequencing.

    Science.gov (United States)

    Annala, M J; Parker, B C; Zhang, W; Nykter, M

    2013-11-01

    Fusion genes are hybrid genes that combine parts of two or more original genes. They can form as a result of chromosomal rearrangements or abnormal transcription, and have been shown to act as drivers of malignant transformation and progression in many human cancers. The biological significance of fusion genes together with their specificity to cancer cells has made them into excellent targets for molecular therapy. Fusion genes are also used as diagnostic and prognostic markers to confirm cancer diagnosis and monitor response to molecular therapies. High-throughput sequencing has enabled the systematic discovery of fusion genes in a wide variety of cancer types. In this review, we describe the history of fusion genes in cancer and the ways in which fusion genes form and affect cellular function. We also describe computational methodologies for detecting fusion genes from high-throughput sequencing experiments, and the most common sources of error that lead to false discovery of fusion genes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Barbara McClintock and the Discovery of Jumping Genes

    Indian Academy of Sciences (India)

    GENERAL I ARTICLE. Barbara McClintock and the Discovery of Jumping Genes. Vidyanand Nanjundiah works in the. Developmental Biology and Genetics Laboratory at the Indian Institute of. Science. After a Master's degree in physics he took up biology. He is interested in evolutionary biology and pattern formation during.

  20. Novel venom gene discovery in the platypus.

    Science.gov (United States)

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

    2010-01-01

    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. 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. 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.

  1. INTEGRATE: gene fusion discovery using whole genome and transcriptome data.

    Science.gov (United States)

    Zhang, Jin; White, Nicole M; Schmidt, Heather K; Fulton, Robert S; Tomlinson, Chad; Warren, Wesley C; Wilson, Richard K; Maher, Christopher A

    2016-01-01

    While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use. © 2016 Zhang et al.; Published by Cold Spring Harbor Laboratory Press.

  2. Developing integrated crop knowledge networks to advance candidate gene discovery.

    Science.gov (United States)

    Hassani-Pak, Keywan; Castellote, Martin; Esch, Maria; Hindle, Matthew; Lysenko, Artem; Taubert, Jan; Rawlings, Christopher

    2016-12-01

    The chances of raising crop productivity to enhance global food security would be greatly improved if we had a complete understanding of all the biological mechanisms that underpinned traits such as crop yield, disease resistance or nutrient and water use efficiency. With more crop genomes emerging all the time, we are nearer having the basic information, at the gene-level, to begin assembling crop gene catalogues and using data from other plant species to understand how the genes function and how their interactions govern crop development and physiology. Unfortunately, the task of creating such a complete knowledge base of gene functions, interaction networks and trait biology is technically challenging because the relevant data are dispersed in myriad databases in a variety of data formats with variable quality and coverage. In this paper we present a general approach for building genome-scale knowledge networks that provide a unified representation of heterogeneous but interconnected datasets to enable effective knowledge mining and gene discovery. We describe the datasets and outline the methods, workflows and tools that we have developed for creating and visualising these networks for the major crop species, wheat and barley. We present the global characteristics of such knowledge networks and with an example linking a seed size phenotype to a barley WRKY transcription factor orthologous to TTG2 from Arabidopsis, we illustrate the value of integrated data in biological knowledge discovery. The software we have developed (www.ondex.org) and the knowledge resources (http://knetminer.rothamsted.ac.uk) we have created are all open-source and provide a first step towards systematic and evidence-based gene discovery in order to facilitate crop improvement.

  3. Automated discovery of functional generality of human gene expression programs.

    Directory of Open Access Journals (Sweden)

    Georg K Gerber

    2007-08-01

    Full Text Available An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-kappaB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal

  4. Species-independent MicroRNA Gene Discovery

    KAUST Repository

    Kamanu, Timothy K.

    2012-12-01

    MicroRNA (miRNA) are a class of small endogenous non-coding RNA that are mainly negative transcriptional and post-transcriptional regulators in both plants and animals. Recent studies have shown that miRNA are involved in different types of cancer and other incurable diseases such as autism and Alzheimer’s. Functional miRNAs are excised from hairpin-like sequences that are known as miRNA genes. There are about 21,000 known miRNA genes, most of which have been determined using experimental methods. miRNA genes are classified into different groups (miRNA families). This study reports about 19,000 unknown miRNA genes in nine species whereby approximately 15,300 predictions were computationally validated to contain at least one experimentally verified functional miRNA product. The predictions are based on a novel computational strategy which relies on miRNA family groupings and exploits the physics and geometry of miRNA genes to unveil the hidden palindromic signals and symmetries in miRNA gene sequences. Unlike conventional computational miRNA gene discovery methods, the algorithm developed here is species-independent: it allows prediction at higher accuracy and resolution from arbitrary RNA/DNA sequences in any species and thus enables examination of repeat-prone genomic regions which are thought to be non-informative or ’junk’ sequences. The information non-redundancy of uni-directional RNA sequences compared to information redundancy of bi-directional DNA is demonstrated, a fact that is overlooked by most pattern discovery algorithms. A novel method for computing upstream and downstream miRNA gene boundaries based on mathematical/statistical functions is suggested, as well as cutoffs for annotation of miRNA genes in different miRNA families. Another tool is proposed to allow hypotheses generation and visualization of data matrices, intra- and inter-species chromosomal distribution of miRNA genes or miRNA families. Our results indicate that: miRNA and mi

  5. Chemical constituents and leishmanicidal activity of Gustavia elliptica (Lecythidaceae); Constituintes quimicos e atividade leishmanicida de Gustavia elliptica (Lecythidaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Maria de Fatima Oliveira; Melo, Ana Claudia Rodrigues de; Pinheiro, Maria Lucia Belem; Silva, Jefferson Rocha de Andrade; Souza, Afonso Duarte Leao de, E-mail: souzadq@ufam.edu.br [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil). Dept. de Quimica; Barison, Andersson; Campos, Francinete Ramos [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Quimica; Amaral, Ana Claudia Fernandes [Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto de Tecnologia de Farmacos. Farmanguinhos; Machado, Gerzia Maria de Carvalho; Leon, Leonor Laura Pinto [Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Dept. de Imunologia

    2011-07-01

    The phyto chemical investigation of the stem bark and leaves of G. elliptica provided a mixture of the norisoprenoids blumenol B and 6-epi blumenol B along with the triterpenes friedelin, as the major constituent, friedelan ol, ursa-9(11),12-dien-3-ol, a-amyrin, b-amyrin, morentenol, epifriedelanol, as well as the sesquiterpenes trans-caryophyllene, a-humulene, ethyl hydnocarpate and other fatty acid esters. The identification of the compounds was performed on basis of spectrometric methods such as GC-MS, IR, MS and 1D and 2D NMR. Stem bark extracts showed significant leishmanicidal activity against promastigote forms of Leishmania braziliensis, with the best results for the chloroform extract. (author)

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

    Science.gov (United States)

    Lin, Frank P Y; Coiera, Enrico; Lan, Ruiting; Sintchenko, Vitali

    2009-03-17

    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. 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. 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

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

    Directory of Open Access Journals (Sweden)

    Lan Ruiting

    2009-03-01

    Full Text Available Abstract 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

  8. Discovery of cancer common and specific driver gene sets

    Science.gov (United States)

    2017-01-01

    Abstract Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found. PMID:28168295

  9. Genome-enabled Discovery of Carbon Sequestration Genes

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-01-01

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

  10. Genome Enabled Discovery of Carbon Sequestration Genes in Poplar

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-02-22

    The goals of the S.H. Strauss laboratory portion of 'Genome-enabled discovery of carbon sequestration genes in poplar' are (1) to explore the functions of candidate genes using Populus transformation by inserting genes provided by Oakridge National Laboratory (ORNL) and the University of Florida (UF) into poplar; (2) to expand the poplar transformation toolkit by developing transformation methods for important genotypes; and (3) to allow induced expression, and efficient gene suppression, in roots and other tissues. As part of the transformation improvement effort, OSU developed transformation protocols for Populus trichocarpa 'Nisqually-1' clone and an early flowering P. alba clone, 6K10. Complete descriptions of the transformation systems were published (Ma et. al. 2004, Meilan et. al 2004). Twenty-one 'Nisqually-1' and 622 6K10 transgenic plants were generated. To identify root predominant promoters, a set of three promoters were tested for their tissue-specific expression patterns in poplar and in Arabidopsis as a model system. A novel gene, ET304, was identified by analyzing a collection of poplar enhancer trap lines generated at OSU (Filichkin et. al 2006a, 2006b). Other promoters include the pGgMT1 root-predominant promoter from Casuarina glauca and the pAtPIN2 promoter from Arabidopsis root specific PIN2 gene. OSU tested two induction systems, alcohol- and estrogen-inducible, in multiple poplar transgenics. Ethanol proved to be the more efficient when tested in tissue culture and greenhouse conditions. Two estrogen-inducible systems were evaluated in transgenic Populus, neither of which functioned reliably in tissue culture conditions. GATEWAY-compatible plant binary vectors were designed to compare the silencing efficiency of homologous (direct) RNAi vs. heterologous (transitive) RNAi inverted repeats. A set of genes was targeted for post transcriptional silencing in the model Arabidopsis system; these include the floral

  11. The Matchmaker Exchange: a platform for rare disease gene discovery.

    Science.gov (United States)

    Philippakis, Anthony A; Azzariti, Danielle R; Beltran, Sergi; Brookes, Anthony J; Brownstein, Catherine A; Brudno, Michael; Brunner, Han G; Buske, Orion J; Carey, Knox; Doll, Cassie; Dumitriu, Sergiu; Dyke, Stephanie O M; den Dunnen, Johan T; Firth, Helen V; Gibbs, Richard A; Girdea, Marta; Gonzalez, Michael; Haendel, Melissa A; Hamosh, Ada; Holm, Ingrid A; Huang, Lijia; Hurles, Matthew E; Hutton, Ben; Krier, Joel B; Misyura, Andriy; Mungall, Christopher J; Paschall, Justin; Paten, Benedict; Robinson, Peter N; Schiettecatte, François; Sobreira, Nara L; Swaminathan, Ganesh J; Taschner, Peter E; Terry, Sharon F; Washington, Nicole L; Züchner, Stephan; Boycott, Kym M; Rehm, Heidi L

    2015-10-01

    There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow. © 2015 WILEY PERIODICALS, INC.

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

    Directory of Open Access Journals (Sweden)

    Katrina Gwinn

    2007-12-01

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

  13. Canonical correlation analysis for gene-based pleiotropy discovery.

    Directory of Open Access Journals (Sweden)

    Jose A Seoane

    2014-10-01

    Full Text Available 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.

  14. Note on the rare terrestrial orchid Apostasia elliptica found in Borneo

    NARCIS (Netherlands)

    Poulsen, A.D.

    1993-01-01

    Apostasia elliptica J.J. Smith has only been collected twice before, in Sumatra and on the Malay Peninsula. The species has now been found in Borneo. The collection by Bünnemeijer (107) from Sumatra, Westcoast Reserve, Ophir District, N of Talu represents the type and is deposited in BO. The Malay

  15. Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource.

    Science.gov (United States)

    Shim, Hongseok; Kim, Ji Hyun; Kim, Chan Yeong; Hwang, Sohyun; Kim, Hyojin; Yang, Sunmo; Lee, Ji Eun; Lee, Insuk

    2016-11-16

    Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish (Danio rerio), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet (www.inetbio.org/danionet), which was constructed by Bayesian integration of genomics big data. Rigorous statistical assessment confirmed the high prediction capacity of DanioNet for a wide variety of human diseases. To demonstrate the feasibility of the function-driven disease gene discovery using DanioNet, we predicted genes for ciliopathies and performed experimental validation for eight candidate genes. We also validated the existence of heterozygous rare variants in the candidate genes of individuals with ciliopathies yet not in controls derived from the UK10K consortium, suggesting that these variants are potentially involved in enhancing the risk of ciliopathies. These results showed that an integrated genomics big data for a model animal of diseases can expand our opportunity for harnessing WES data in disease gene discovery. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    Gasser Robin B

    2007-06-01

    Full Text Available Abstract 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

  18. Protection of Vochysia elliptica (Vochysiaceae by a nectar-thieving ant

    Directory of Open Access Journals (Sweden)

    G. Q. ROMERO

    Full Text Available Vochysia elliptica (Vochysiaceae is a shrubby plant, which does not have EFNs. Camponotus ants thieve nectar, and can decrease plant fitness by making flowers less attractive to pollinators. However, ants remove herbivores, wich can be beneficial. Results show that plants from which ants were excluded had lower rates of termite (simulated herbivore removal than did plants visited by ants. Plants accessible to ants showed higher rates of termite removal in the base of leaves and in the inflorescence, than in the tip of leaves. This occurs because ants must pass through the principal axis to reach the inflorescence. Conclusive results of this cost/benefit analysis of the Camponotus sp. presence for V. elliptica can be obtained, with experimental manipulations.

  19. Anti-Inflammatory and Antibothropic Properties of Jatropha Elliptica, a Plant from Brazilian Cerrado Biome

    Directory of Open Access Journals (Sweden)

    Sára Costa Ferreira-Rodrigues

    2016-12-01

    Full Text Available Purpose: The aim of this study was to evaluate the antibothropic and anti-inflammatory properties of J. elliptica. Methods: Phytochemical screening and thin-layer chromatography (TLC assays were performed on J. elliptica hydroalcoholic extract (TE in order to observe its main constituents. The antibothropic activity of TE was evaluated by the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu, in a mouse phrenic nerve-diaphragm model (PND. A quantitative histological study was carried out to observe a possible protection of TE against the venom myotoxicity. The anti-inflammatory activity was also evaluated in two models, Bjssu-induced paw edema, and carrageenan-induced neutrophils migration in the peritoneal cavity. Results: TLC analysis revealed several compounds in TE, such as saponins, alkaloids, and phenolic constituents. TE was able to neutralize the blockade and the myotoxicity induced by venom, when it was pre-incubated for 30 min with venom. In addition, it showed anti-inflammatory activity, inducing less neutrophils migration and reducing paw edema. Conclusion: J. elliptica showed both antibothropic and anti-inflammatory properties.

  20. Gene-disease relationship discovery based on model-driven data integration and database view definition.

    Science.gov (United States)

    Yilmaz, S; Jonveaux, P; Bicep, C; Pierron, L; Smaïl-Tabbone, M; Devignes, M D

    2009-01-15

    Computational methods are widely used to discover gene-disease relationships hidden in vast masses of available genomic and post-genomic data. In most current methods, a similarity measure is calculated between gene annotations and known disease genes or disease descriptions. However, more explicit gene-disease relationships are required for better insights into the molecular bases of diseases, especially for complex multi-gene diseases. Explicit relationships between genes and diseases are formulated as candidate gene definitions that may include intermediary genes, e.g. orthologous or interacting genes. These definitions guide data modelling in our database approach for gene-disease relationship discovery and are expressed as views which ultimately lead to the retrieval of documented sets of candidate genes. A system called ACGR (Approach for Candidate Gene Retrieval) has been implemented and tested with three case studies including a rare orphan gene disease.

  1. Application of genefishing discovery system on differential gene ...

    African Journals Online (AJOL)

    GREGORY

    2010-08-30

    Aug 30, 2010 ... this discovery system for a prokaryotic system by modifying the eukaryotic protocol using the poly (A)- ... eukaryotic system mainly in humans, screening of ... RNA isolation. Total RNA extraction from the bacterial cells was performed at room temperature using RNeasy® Mini Kit (Qiagen). Initially, the cells.

  2. The Matchmaker Exchange: a platform for rare disease gene discovery

    NARCIS (Netherlands)

    Philippakis, A.A.; Azzariti, D.R.; Beltran, S.; Brookes, A.J.; Brownstein, C.A.; Brudno, M.; Brunner, H.G.; Buske, O.J.; Carey, K.; Doll, C.; Dumitriu, S.; Dyke, S.O.M.; Dunnen, J.T. den; Firth, H.V.; Gibbs, R.A.; Girdea, M.; Gonzalez, M.; Haendel, M.A.; Hamosh, A.; Holm, I.A.; Huang, L.; Hurles, M.E.; Hutton, B.; Krier, J.B.; Misyura, A.; Mungall, C.J.; Paschall, J.; Paten, B.; Robinson, P.N.; Schiettecatte, F.; Sobreira, N.L.; Swaminathan, G.J.; Taschner, P.E.M.; Terry, S.F.; Washington, N.L.; Zuchner, S.; Boycott, K.M.; Rehm, H.L.

    2015-01-01

    There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of

  3. Computational method for discovery of estrogen responsive genes

    DEFF Research Database (Denmark)

    Tang, Suisheng; Tan, Sin Lam; Ramadoss, Suresh Kumar

    2004-01-01

    of human genes are functionally well characterized. It is still unclear how many and which human genes respond to estrogen treatment. We propose a simple, economic, yet effective computational method to predict a subclass of estrogen responsive genes. Our method relies on the similarity of ERE frames...

  4. Comparative Oncogenomics for Peripheral Nerve Sheath Cancer Gene Discovery

    Science.gov (United States)

    2015-06-01

    and growth factor receptors potentially upstream of some of these signaling cascades (the growth hormone receptor gene Ghr, Il17a, Inhbe) were...Loss of p16 (INK4A) expression is associated with allelic imbalance /loss of heterozygosity of chromosome 9p21 in microdissected malignant peripheral...cell receptor genes) Antigen recognition Ghr (growth hormone receptor) Growth hormone receptor Myc (myelocytomatosis oncogene) Nuclear phosphoprotein

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Gene discovery in the horned beetle Onthophagus taurus

    Directory of Open Access Journals (Sweden)

    Yang Youngik

    2010-12-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

    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

  8. A Dynamic Energy Budget (DEB model to describe Laternula elliptica (King, 1832 seasonal feeding and metabolism.

    Directory of Open Access Journals (Sweden)

    Antonio Agüera

    Full Text Available Antarctic marine organisms are adapted to an extreme environment, characterized by a very low but stable temperature and a strong seasonality in food availability arousing from variations in day length. Ocean organisms are particularly vulnerable to global climate change with some regions being impacted by temperature increase and changes in primary production. Climate change also affects the biotic components of marine ecosystems and has an impact on the distribution and seasonal physiology of Antarctic marine organisms. Knowledge on the impact of climate change in key species is highly important because their performance affects ecosystem functioning. To predict the effects of climate change on marine ecosystems, a holistic understanding of the life history and physiology of Antarctic key species is urgently needed. DEB (Dynamic Energy Budget theory captures the metabolic processes of an organism through its entire life cycle as a function of temperature and food availability. The DEB model is a tool that can be used to model lifetime feeding, growth, reproduction, and their responses to changes in biotic and abiotic conditions. In this study, we estimate the DEB model parameters for the bivalve Laternula elliptica using literature-extracted and field data. The DEB model we present here aims at better understanding the biology of L. elliptica and its levels of adaptation to its habitat with a special focus on food seasonality. The model parameters describe a metabolism specifically adapted to low temperatures, with a low maintenance cost and a high capacity to uptake and mobilise energy, providing this organism with a level of energetic performance matching that of related species from temperate regions. It was also found that L. elliptica has a large energy reserve that allows enduring long periods of starvation. Additionally, we applied DEB parameters to time-series data on biological traits (organism condition, gonad growth to describe the

  9. Gene Discovery and Functional Analyses in the Model Plant Arabidopsis

    DEFF Research Database (Denmark)

    Feng, Cai-ping; Mundy, J.

    2006-01-01

    The present mini-review describes newer methods and strategies, including transposon and T-DNA insertions, TILLING, Deleteagene, and RNA interference, to functionally analyze genes of interest in the model plant Arabidopsis. The relative advantages and disadvantages of the systems are also...

  10. Discovery of Novel Gene Elements Associated with Prostate Cancer Progression

    Science.gov (United States)

    2014-12-01

    buffer [Tris-buffered saline, 0.1% Tween (TBS-T), 5% nonfat dry milk ] and incubated at 4C with the appropriate antibody. Following incubation, the...prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am. J. Pathol. 164, 217–227...proteins. Proteins were transferred onto PVDF membrane and blocked for 90 min in block- ing buffer (5% milk in a solution of 0.1% Tween-20 in Tris

  11. Improving functional modules discovery by enriching interaction networks with gene profiles

    KAUST Repository

    Salem, Saeed

    2013-05-01

    Recent advances in proteomic and transcriptomic technologies resulted in the accumulation of vast amount of high-throughput data that span multiple biological processes and characteristics in different organisms. Much of the data come in the form of interaction networks and mRNA expression arrays. An important task in systems biology is functional modules discovery where the goal is to uncover well-connected sub-networks (modules). These discovered modules help to unravel the underlying mechanisms of the observed biological processes. While most of the existing module discovery methods use only the interaction data, in this work we propose, CLARM, which discovers biological modules by incorporating gene profiles data with protein-protein interaction networks. We demonstrate the effectiveness of CLARM on Yeast and Human interaction datasets, and gene expression and molecular function profiles. Experiments on these real datasets show that the CLARM approach is competitive to well established functional module discovery methods.

  12. Knowledge Discovery in Biological Databases for Revealing Candidate Genes Linked to Complex Phenotypes.

    Science.gov (United States)

    Hassani-Pak, Keywan; Rawlings, Christopher

    2017-06-13

    Genetics and "omics" studies designed to uncover genotype to phenotype relationships often identify large numbers of potential candidate genes, among which the causal genes are hidden. Scientists generally lack the time and technical expertise to review all relevant information available from the literature, from key model species and from a potentially wide range of related biological databases in a variety of data formats with variable quality and coverage. Computational tools are needed for the integration and evaluation of heterogeneous information in order to prioritise candidate genes and components of interaction networks that, if perturbed through potential interventions, have a positive impact on the biological outcome in the whole organism without producing negative side effects. Here we review several bioinformatics tools and databases that play an important role in biological knowledge discovery and candidate gene prioritization. We conclude with several key challenges that need to be addressed in order to facilitate biological knowledge discovery in the future.

  13. Discovery of error-tolerant biclusters from noisy gene expression data.

    Science.gov (United States)

    Gupta, Rohit; Rao, Navneet; Kumar, Vipin

    2011-11-24

    An important analysis performed on microarray gene-expression data is to discover biclusters, which denote groups of genes that are coherently expressed for a subset of conditions. Various biclustering algorithms have been proposed to find different types of biclusters from these real-valued gene-expression data sets. However, these algorithms suffer from several limitations such as inability to explicitly handle errors/noise in the data; difficulty in discovering small bicliusters due to their top-down approach; inability of some of the approaches to find overlapping biclusters, which is crucial as many genes participate in multiple biological processes. Association pattern mining also produce biclusters as their result and can naturally address some of these limitations. However, traditional association mining only finds exact biclusters, which limits its applicability in real-life data sets where the biclusters may be fragmented due to random noise/errors. Moreover, as they only work with binary or boolean attributes, their application on gene-expression data require transforming real-valued attributes to binary attributes, which often results in loss of information. Many past approaches have tried to address the issue of noise and handling real-valued attributes independently but there is no systematic approach that addresses both of these issues together. In this paper, we first propose a novel error-tolerant biclustering model, 'ET-bicluster', and then propose a bottom-up heuristic-based mining algorithm to sequentially discover error-tolerant biclusters directly from real-valued gene-expression data. The efficacy of our proposed approach is illustrated by comparing it with a recent approach RAP in the context of two biological problems: discovery of functional modules and discovery of biomarkers. For the first problem, two real-valued S.Cerevisiae microarray gene-expression data sets are used to demonstrate that the biclusters obtained from ET

  14. Discovery AP2/ERF family genes in silico in Medicago truncatula

    African Journals Online (AJOL)

    aghomotsegin

    Discovery AP2/ERF family genes in silico in. Medicago truncatula. Zhifei Zhang*, Qian Zhou, Zhijian Yang and Jingpeng Jiang. College of Agronomy, Hunan Agricultural University, Furong District, Changsha, Hunan Province 410128, P.R. China. Accepted 27 May, 2013. Medicago truncatula is a legume model plant due to ...

  15. Rule extraction in gene-disease relationship discovery.

    Science.gov (United States)

    Hou, Wen-Juan; Chen, Hsiao-Yuan

    2013-04-10

    Biomedical data available to researchers and clinicians have increased dramatically over the past years because of the exponential growth of knowledge in medical biology. It is difficult for curators to go through all of the unstructured documents so as to curate the information to the database. Associating genes with diseases is important because it is a fundamental challenge in human health with applications to understanding disease properties and developing new techniques for prevention, diagnosis and therapy. Our study uses the automatic rule-learning approach to gene-disease relationship extraction. We first prepare the experimental corpus from MEDLINE and OMIM. A parser is applied to produce some grammatical information. We then learn all possible rules that discriminate relevant from irrelevant sentences. After that, we compute the scores of the learned rules in order to select rules of interest. As a result, a set of rules is generated. We produce the learned rules automatically from the 1000 positive and 1000 negative sentences. The test set includes 400 sentences composed of 200 positives and 200 negatives. Precision, recall and F-score served as our evaluation metrics. The results reveal that the maximal precision rate is 77.8% and the maximal recall rate is 63.5%. The maximal F-score is 66.9% where the precision rate is 70.6% and the recall rate is 63.5%. We employ the rule-learning approach to extract gene-disease relationships. Our main contributions are to build rules automatically and to support a more complete set of rules than a manually generated one. The experiments show exhilarating results and some improving efforts will be made in the future. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  16. Context-driven discovery of gene cassettes in mobile integrons using a computational grammar.

    Science.gov (United States)

    Tsafnat, Guy; Coiera, Enrico; Partridge, Sally R; Schaeffer, Jaron; Iredell, Jon R

    2009-09-08

    Gene discovery algorithms typically examine sequence data for low level patterns. A novel method to computationally discover higher order DNA structures is presented, using a context sensitive grammar. The algorithm was applied to the discovery of gene cassettes associated with integrons. The discovery and annotation of antibiotic resistance genes in such cassettes is essential for effective monitoring of antibiotic resistance patterns and formulation of public health antibiotic prescription policies. We discovered two new putative gene cassettes using the method, from 276 integron features and 978 GenBank sequences. The system achieved kappa = 0.972 annotation agreement with an expert gold standard of 300 sequences. In rediscovery experiments, we deleted 789,196 cassette instances over 2030 experiments and correctly relabelled 85.6% (alpha > or = 95%, E analysis demonstrated that for 72,338 missed deletions, two adjacent deleted cassettes were labeled as a single cassette, increasing performance to 94.8% (mean sensitivity = 0.92, specificity = 1, F-score = 0.96). Using grammars we were able to represent heuristic background knowledge about large and complex structures in DNA. Importantly, we were also able to use the context embedded in the model to discover new putative antibiotic resistance gene cassettes. The method is complementary to existing automatic annotation systems which operate at the sequence level.

  17. Context-driven discovery of gene cassettes in mobile integrons using a computational grammar

    Directory of Open Access Journals (Sweden)

    Schaeffer Jaron

    2009-09-01

    Full Text Available Abstract Background Gene discovery algorithms typically examine sequence data for low level patterns. A novel method to computationally discover higher order DNA structures is presented, using a context sensitive grammar. The algorithm was applied to the discovery of gene cassettes associated with integrons. The discovery and annotation of antibiotic resistance genes in such cassettes is essential for effective monitoring of antibiotic resistance patterns and formulation of public health antibiotic prescription policies. Results We discovered two new putative gene cassettes using the method, from 276 integron features and 978 GenBank sequences. The system achieved κ = 0.972 annotation agreement with an expert gold standard of 300 sequences. In rediscovery experiments, we deleted 789,196 cassette instances over 2030 experiments and correctly relabelled 85.6% (α ≥ 95%, E ≤ 1%, mean sensitivity = 0.86, specificity = 1, F-score = 0.93, with no false positives. Error analysis demonstrated that for 72,338 missed deletions, two adjacent deleted cassettes were labeled as a single cassette, increasing performance to 94.8% (mean sensitivity = 0.92, specificity = 1, F-score = 0.96. Conclusion Using grammars we were able to represent heuristic background knowledge about large and complex structures in DNA. Importantly, we were also able to use the context embedded in the model to discover new putative antibiotic resistance gene cassettes. The method is complementary to existing automatic annotation systems which operate at the sequence level.

  18. Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery.

    Science.gov (United States)

    Verstraeten, Aline; Alaerts, Maaike; Van Laer, Lut; Loeys, Bart

    2016-06-01

    Marfan syndrome (MFS) is a rare, autosomal-dominant, multisystem disorder, presenting with skeletal, ocular, skin, and cardiovascular symptoms. Significant clinical overlap with other systemic connective tissue diseases, including Loeys-Dietz syndrome (LDS), Shprintzen-Goldberg syndrome (SGS), and the MASS phenotype, has been documented. In MFS and LDS, the cardiovascular manifestations account for the major cause of patient morbidity and mortality, rendering them the main target for therapeutic intervention. Over the past decades, gene identification studies confidently linked the aforementioned syndromes, as well as nonsyndromic aneurysmal disease, to genetic defects in proteins related to the transforming growth factor (TGF)-β pathway, greatly expanding our knowledge on the disease mechanisms and providing us with novel therapeutic targets. As a result, the focus of the developing pharmacological treatment strategies is shifting from hemodynamic stress management to TGF-β antagonism. In this review, we discuss the insights that have been gained in the molecular biology of MFS and related disorders over the past 25 years. © 2016 WILEY PERIODICALS, INC.

  19. Cross-pollination of research findings, although uncommon, may accelerate discovery of human disease genes

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    Duda Marlena

    2012-11-01

    Full Text Available Abstract Background Technological leaps in genome sequencing have resulted in a surge in discovery of human disease genes. These discoveries have led to increased clarity on the molecular pathology of disease and have also demonstrated considerable overlap in the genetic roots of human diseases. In light of this large genetic overlap, we tested whether cross-disease research approaches lead to faster, more impactful discoveries. Methods We leveraged several gene-disease association databases to calculate a Mutual Citation Score (MCS for 10,853 pairs of genetically related diseases to measure the frequency of cross-citation between research fields. To assess the importance of cooperative research, we computed an Individual Disease Cooperation Score (ICS and the average publication rate for each disease. Results For all disease pairs with one gene in common, we found that the degree of genetic overlap was a poor predictor of cooperation (r2=0.3198 and that the vast majority of disease pairs (89.56% never cited previous discoveries of the same gene in a different disease, irrespective of the level of genetic similarity between the diseases. A fraction (0.25% of the pairs demonstrated cross-citation in greater than 5% of their published genetic discoveries and 0.037% cross-referenced discoveries more than 10% of the time. We found strong positive correlations between ICS and publication rate (r2=0.7931, and an even stronger correlation between the publication rate and the number of cross-referenced diseases (r2=0.8585. These results suggested that cross-disease research may have the potential to yield novel discoveries at a faster pace than singular disease research. Conclusions Our findings suggest that the frequency of cross-disease study is low despite the high level of genetic similarity among many human diseases, and that collaborative methods may accelerate and increase the impact of new genetic discoveries. Until we have a better

  20. Gene-based SNP discovery and genetic mapping in pea.

    Science.gov (United States)

    Sindhu, Anoop; Ramsay, Larissa; Sanderson, Lacey-Anne; Stonehouse, Robert; Li, Rong; Condie, Janet; Shunmugam, Arun S K; Liu, Yong; Jha, Ambuj B; Diapari, Marwan; Burstin, Judith; Aubert, Gregoire; Tar'an, Bunyamin; Bett, Kirstin E; Warkentin, Thomas D; Sharpe, Andrew G

    2014-10-01

    Gene-based SNPs were identified and mapped in pea using five recombinant inbred line populations segregating for traits of agronomic importance. Pea (Pisum sativum L.) is one of the world's oldest domesticated crops and has been a model system in plant biology and genetics since the work of Gregor Mendel. Pea is the second most widely grown pulse crop in the world following common bean. The importance of pea as a food crop is growing due to its combination of moderate protein concentration, slowly digestible starch, high dietary fiber concentration, and its richness in micronutrients; however, pea has lagged behind other major crops in harnessing recent advances in molecular biology, genomics and bioinformatics, partly due to its large genome size with a large proportion of repetitive sequence, and to the relatively limited investment in research in this crop globally. The objective of this research was the development of a genome-wide transcriptome-based pea single-nucleotide polymorphism (SNP) marker platform using next-generation sequencing technology. A total of 1,536 polymorphic SNP loci selected from over 20,000 non-redundant SNPs identified using deep transcriptome sequencing of eight diverse Pisum accessions were used for genotyping in five RIL populations using an Illumina GoldenGate assay. The first high-density pea SNP map defining all seven linkage groups was generated by integrating with previously published anchor markers. Syntenic relationships of this map with the model legume Medicago truncatula and lentil (Lens culinaris Medik.) maps were established. The genic SNP map establishes a foundation for future molecular breeding efforts by enabling both the identification and tracking of introgression of genomic regions harbouring QTLs related to agronomic and seed quality traits.

  1. Biomarker discovery for colon cancer using a 761 gene RT-PCR assay

    Directory of Open Access Journals (Sweden)

    Hackett James R

    2007-08-01

    Full Text Available Abstract Background Reverse transcription PCR (RT-PCR is widely recognized to be the gold standard method for quantifying gene expression. Studies using RT-PCR technology as a discovery tool have historically been limited to relatively small gene sets compared to other gene expression platforms such as microarrays. We have recently shown that TaqMan® RT-PCR can be scaled up to profile expression for 192 genes in fixed paraffin-embedded (FPE clinical study tumor specimens. This technology has also been used to develop and commercialize a widely used clinical test for breast cancer prognosis and prediction, the Onco typeDX™ assay. A similar need exists in colon cancer for a test that provides information on the likelihood of disease recurrence in colon cancer (prognosis and the likelihood of tumor response to standard chemotherapy regimens (prediction. We have now scaled our RT-PCR assay to efficiently screen 761 biomarkers across hundreds of patient samples and applied this process to biomarker discovery in colon cancer. This screening strategy remains attractive due to the inherent advantages of maintaining platform consistency from discovery through clinical application. Results RNA was extracted from formalin fixed paraffin embedded (FPE tissue, as old as 28 years, from 354 patients enrolled in NSABP C-01 and C-02 colon cancer studies. Multiplexed reverse transcription reactions were performed using a gene specific primer pool containing 761 unique primers. PCR was performed as independent TaqMan® reactions for each candidate gene. Hierarchal clustering demonstrates that genes expected to co-express form obvious, distinct and in certain cases very tightly correlated clusters, validating the reliability of this technical approach to biomarker discovery. Conclusion We have developed a high throughput, quantitatively precise multi-analyte gene expression platform for biomarker discovery that approaches low density DNA arrays in numbers of

  2. Gene set-based module discovery in the breast cancer transcriptome

    Directory of Open Access Journals (Sweden)

    Zhang Michael Q

    2009-02-01

    Full Text Available Abstract Background Although microarray-based studies have revealed global view of gene expression in cancer cells, we still have little knowledge about regulatory mechanisms underlying the transcriptome. Several computational methods applied to yeast data have recently succeeded in identifying expression modules, which is defined as co-expressed gene sets under common regulatory mechanisms. However, such module discovery methods are not applied cancer transcriptome data. Results In order to decode oncogenic regulatory programs in cancer cells, we developed a novel module discovery method termed EEM by extending a previously reported module discovery method, and applied it to breast cancer expression data. Starting from seed gene sets prepared based on cis-regulatory elements, ChIP-chip data, and gene locus information, EEM identified 10 principal expression modules in breast cancer based on their expression coherence. Moreover, EEM depicted their activity profiles, which predict regulatory programs in each subtypes of breast tumors. For example, our analysis revealed that the expression module regulated by the Polycomb repressive complex 2 (PRC2 is downregulated in triple negative breast cancers, suggesting similarity of transcriptional programs between stem cells and aggressive breast cancer cells. We also found that the activity of the PRC2 expression module is negatively correlated to the expression of EZH2, a component of PRC2 which belongs to the E2F expression module. E2F-driven EZH2 overexpression may be responsible for the repression of the PRC2 expression modules in triple negative tumors. Furthermore, our network analysis predicts regulatory circuits in breast cancer cells. Conclusion These results demonstrate that the gene set-based module discovery approach is a powerful tool to decode regulatory programs in cancer cells.

  3. Literature-Based Discovery of IFN-γ and Vaccine-Mediated Gene Interaction Networks

    Directory of Open Access Journals (Sweden)

    Arzucan Özgür

    2010-01-01

    Full Text Available Interferon-gamma (IFN-γ regulates various immune responses that are often critical for vaccine-induced protection. In order to annotate the IFN-γ-related gene interaction network from a large amount of IFN-γ 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-γ (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-γ relatedness of 56 genes and vaccine development relatedness for 52 genes. This study also generated many new hypotheses worth further experimental studies.

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

    Science.gov (United States)

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

    2009-09-03

    linked to external data repositories. 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 http://cgs.pharm.kyoto-u.ac.jp/services/network.

  5. Gene signature critical to cancer phenotype as a paradigm for anticancer drug discovery.

    Science.gov (United States)

    Sampson, E R; McMurray, H R; Hassane, D C; Newman, L; Salzman, P; Jordan, C T; Land, H

    2013-08-15

    Malignant cell transformation commonly results in the deregulation of thousands of cellular genes, an observation that suggests a complex biological process and an inherently challenging scenario for the development of effective cancer interventions. To better define the genes/pathways essential to regulating the malignant phenotype, we recently described a novel strategy based on the cooperative nature of carcinogenesis that focuses on genes synergistically deregulated in response to cooperating oncogenic mutations. These so-called 'cooperation response genes' (CRGs) are highly enriched for genes critical for the cancer phenotype, thereby suggesting their causal role in the malignant state. Here, we show that CRGs have an essential role in drug-mediated anticancer activity and that anticancer agents can be identified through their ability to antagonize the CRG expression profile. These findings provide proof-of-concept for the use of the CRG signature as a novel means of drug discovery with relevance to underlying anticancer drug mechanisms.

  6. Differential gene expression analysis in ageing muscle and drug discovery perspectives.

    Science.gov (United States)

    Melouane, Aicha; Ghanemi, Abdelaziz; Aubé, Simon; Yoshioka, Mayumi; St-Amand, Jonny

    2018-01-01

    Identifying therapeutic target genes represents the key step in functional genomics-based therapies. Within this context, the disease heterogeneity, the exogenous factors and the complexity of genomic structure and function represent important challenges. The functional genomics aims to overcome such obstacles via identifying the gene functions and therefore highlight disease-causing genes as therapeutic targets. Genomic technologies promise to reshape the research on ageing muscle, exercise response and drug discovery. Herein, we describe the functional genomics strategies, mainly differential gene expression methods microarray, serial analysis of gene expression (SAGE), massively parallel signature sequence (MPSS), RNA sequencing (RNA seq), representational difference analysis (RDA), and suppression subtractive hybridization (SSH). Furthermore, we review these illustrative approaches that have been used to discover new therapeutic targets for some complex diseases along with the application of these tools to study the modulation of the skeletal muscle transcriptome. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Alternative Polyadenylation Patterns for Novel Gene Discovery and Classification in Cancer

    Directory of Open Access Journals (Sweden)

    Oguzhan Begik

    2017-07-01

    Full Text Available Certain aspects of diagnosis, prognosis, and treatment of cancer patients are still important challenges to be addressed. Therefore, we propose a pipeline to uncover patterns of alternative polyadenylation (APA, a hidden complexity in cancer transcriptomes, to further accelerate efforts to discover novel cancer genes and pathways. Here, we analyzed expression data for 1045 cancer patients and found a significant shift in usage of poly(A signals in common tumor types (breast, colon, lung, prostate, gastric, and ovarian compared to normal tissues. Using machine-learning techniques, we further defined specific subsets of APA events to efficiently classify cancer types. Furthermore, APA patterns were associated with altered protein levels in patients, revealed by antibody-based profiling data, suggesting functional significance. Overall, our study offers a computational approach for use of APA in novel gene discovery and classification in common tumor types, with important implications in basic research, biomarker discovery, and precision medicine approaches.

  8. Constituintes químicos e atividade Leishmanicida de Gustavia elliptica (Lecythidaceae

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    Maria de Fátima Oliveira Almeida

    2011-01-01

    Full Text Available The phytochemical investigation of the stem bark and leaves of G. elliptica provided a mixture of the norisoprenoids blumenol B and 6-epiblumenol B along with the triterpenes friedelin, as the major constituent, friedelanol, ursa-9(11,12-dien-3-ol, a-amyrin, β-amyrin, morentenol, epifriedelanol, as well as the sesquiterpenes trans-caryophyllene, α-humulene, ethyl hydnocarpate and other fatty acid esters. The identification of the compounds was performed on basis of spectrometric methods such as GC-MS, IR, MS and 1D and 2D NMR. Stem bark extracts showed significant leishmanicidal activity against promastigote forms of Leishmania braziliensis, with the best results for the chloroform extract.

  9. The golden era of ocular disease gene discovery: Race to the finish

    Science.gov (United States)

    Swaroop, A; Sieving, PA

    2014-01-01

    Within the last decade, technological advances have led to amazing genetic insights into Mendelian and multifactorial ocular diseases. We provide a perspective of the progress in gene discovery and discuss the implications. We believe that the time has come to redefine the goals and begin utilizing the genetic knowledge for clinical management and treatment design. The unbelievable opportunities now exist for those nimble enough to seize them. PMID:23713688

  10. Abiotic Stress Tolerance: From Gene Discovery in Model Organisms to Crop Improvement

    OpenAIRE

    Bressan, Ray; Bohnert, Hans; Zhu, Jian-Kang

    2009-01-01

    Productive and sustainable agriculture necessitates growing plants in sub-optimal environments with less input of precious resources such as fresh water. For a better understanding and rapid improvement of abiotic stress tolerance, it is important to link physiological and biochemical work to molecular studies in genetically tractable model organisms. With the use of several technologies for the discovery of stress tolerance genes and their appropriate alleles, transgenic approaches to improv...

  11. Exome sequencing for gene discovery in lethal fetal disorders--harnessing the value of extreme phenotypes.

    Science.gov (United States)

    Filges, Isabel; Friedman, Jan M

    2015-10-01

    Massively parallel sequencing has revolutionized our understanding of Mendelian disorders, and many novel genes have been discovered to cause disease phenotypes when mutant. At the same time, next-generation sequencing approaches have enabled non-invasive prenatal testing of free fetal DNA in maternal blood. However, little attention has been paid to using whole exome and genome sequencing strategies for gene identification in fetal disorders that are lethal in utero, because they can appear to be sporadic and Mendelian inheritance may be missed. We present challenges and advantages of applying next-generation sequencing approaches to gene discovery in fetal malformation phenotypes and review recent successful discovery approaches. We discuss the implication and significance of recessive inheritance and cross-species phenotyping in fetal lethal conditions. Whole exome sequencing can be used in individual families with undiagnosed lethal congenital anomaly syndromes to discover causal mutations, provided that prior to data analysis, the fetal phenotype can be correlated to a particular developmental pathway in embryogenesis. Cross-species phenotyping allows providing further evidence for causality of discovered variants in genes involved in those extremely rare phenotypes and will increase our knowledge about normal and abnormal human developmental processes. Ultimately, families will benefit from the option of early prenatal diagnosis. © 2014 John Wiley & Sons, Ltd.

  12. Estudo farmacognóstico comparativo das folhas de Davilla elliptica A. St.-Hil. e D. rugosa Poir., Dilleniaceae

    Directory of Open Access Journals (Sweden)

    Rose Lisieux R. Paiva Jácome

    Full Text Available As características farmacognósticas das folhas de Davilla elliptica A. St.-Hil. e D. rugosa Poir., Dilleniaceae, foram determinadas com objetivo de auxiliar na identificação taxonômica e no controle de qualidade das drogas vegetais e de produtos fitoterápicos. A espécie D. elliptica é um arbusto ereto, que ocorre naturalmente no cerrado e D. rugosa é um trepadeira lenhosa de beira de mata. Ambas são conhecidas popularmente como lixeirinha, sambaibinha e cipó-caboclo, empregadas na medicina tradicional como antiinflamatória e antiúlcera. As características microscópicas observadas em D. rugosa tais como tricomas estrelados e esclereídes no mesofilo e em D. elliptica de idioblastos contendo mucilagem e endoderme, são parâmetros que poderão ser utilizados na diferenciação das espécies. Os teores obtidos nos ensaios de pureza e nos doseamentos de taninos (9,4% e 7,2%, flavonoides (0,46% e 0,9% e mucilagens (2,2% e 4,1% de ambas as espécies, podem contribuir no controle de qualidade das drogas vegetais uma vez que são usadas indistintamente na produção de fitoterápicos.

  13. Gene expression, single nucleotide variant and fusion transcript discovery in archival material from breast tumors.

    Directory of Open Access Journals (Sweden)

    Nadine Norton

    Full Text Available 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

  14. Transcriptomic analysis and discovery of genes in the response of Arachis hypogaea to drought stress.

    Science.gov (United States)

    Zhao, Xiaobo; Li, Chunjuan; Wan, Shubo; Zhang, Tingting; Yan, Caixia; Shan, Shihua

    2018-04-01

    The peanut (Arachis hypogaea) is an important crop species that is threatened by drought stress. The genome sequences of peanut, which was officially released in 2016, may help explain the molecular mechanisms that underlie drought tolerance in this species. We report here a gene expression profiling of A. hypogaea to gain a global view of its drought resistance. Using whole-transcriptome sequencing, we analysed differential gene expression in response to drought stress in the drought-resistant peanut cultivar J11. Pooled samples obtained at 6, 12, 18, 24, and 48 h were compared with control samples at 0 h. In total, 51,554 genes were found, including 49,289 known genes and 2265 unknown genes. We identified 224 differentially expressed transcription factors, 296,335 SNPs and 28,391 InDELs. In addition, we detected significant differences in the gene expression profiles of the treatment and control groups. After comparing the two groups, 4648 genes were identified. An in-depth analysis of the data revealed that a large number of genes were associated with drought stress, including transcription factors and genes involved in photosynthesis-antenna proteins, carbon metabolism and the citrate cycle. The results of this study provide insights into the diverse mechanisms that underlie the successful establishment of drought resistance in the peanut, thereby facilitating the identification of important genes in the peanut related to drought management. Transcriptome analysis based on RNA-Seq is a powerful approach for gene discovery and molecular marker development for this species.

  15. Systematic discovery of unannotated genes in 11 yeast species using a database of orthologous genomic segments

    LENUS (Irish Health Repository)

    OhEigeartaigh, Sean S

    2011-07-26

    Abstract Background In standard BLAST searches, no information other than the sequences of the query and the database entries is considered. However, in situations where two genes from different species have only borderline similarity in a BLAST search, the discovery that the genes are located within a region of conserved gene order (synteny) can provide additional evidence that they are orthologs. Thus, for interpreting borderline search results, it would be useful to know whether the syntenic context of a database hit is similar to that of the query. This principle has often been used in investigations of particular genes or genomic regions, but to our knowledge it has never been implemented systematically. Results We made use of the synteny information contained in the Yeast Gene Order Browser database for 11 yeast species to carry out a systematic search for protein-coding genes that were overlooked in the original annotations of one or more yeast genomes but which are syntenic with their orthologs. Such genes tend to have been overlooked because they are short, highly divergent, or contain introns. The key features of our software - called SearchDOGS - are that the database entries are classified into sets of genomic segments that are already known to be orthologous, and that very weak BLAST hits are retained for further analysis if their genomic location is similar to that of the query. Using SearchDOGS we identified 595 additional protein-coding genes among the 11 yeast species, including two new genes in Saccharomyces cerevisiae. We found additional genes for the mating pheromone a-factor in six species including Kluyveromyces lactis. Conclusions SearchDOGS has proven highly successful for identifying overlooked genes in the yeast genomes. We anticipate that our approach can be adapted for study of further groups of species, such as bacterial genomes. More generally, the concept of doing sequence similarity searches against databases to which external

  16. Strategies for exome and genome sequence data analysis in disease-gene discovery projects.

    Science.gov (United States)

    Robinson, Peter N; Krawitz, P; Mundlos, S

    2011-08-01

    In whole-exome sequencing (WES), target capture methods are used to enrich the sequences of the coding regions of genes from fragmented total genomic DNA, followed by massively parallel, 'next-generation' sequencing of the captured fragments. Since its introduction in 2009, WES has been successfully used in several disease-gene discovery projects, but the analysis of whole-exome sequence data can be challenging. In this overview, we present a summary of the main computational strategies that have been applied to identify novel disease genes in whole-exome data, including intersect filters, the search for de novo mutations, and the application of linkage mapping or inference of identity-by-descent (IBD) in family studies. © 2011 John Wiley & Sons A/S.

  17. Abiotic stress tolerance: from gene discovery in model organisms to crop improvement.

    Science.gov (United States)

    Bressan, Ray; Bohnert, Hans; Zhu, Jian-Kang

    2009-01-01

    Productive and sustainable agriculture necessitates growing plants in sub-optimal environments with less input of precious resources such as fresh water. For a better understanding and rapid improvement of abiotic stress tolerance, it is important to link physiological and biochemical work to molecular studies in genetically tractable model organisms. With the use of several technologies for the discovery of stress tolerance genes and their appropriate alleles, transgenic approaches to improving stress tolerance in crops remarkably parallels breeding principles with a greatly expanded germplasm base and will succeed eventually.

  18. Evaluation of gene association methods for coexpression network construction and biological knowledge discovery.

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    Sapna Kumari

    Full Text Available BACKGROUND: Constructing coexpression networks and performing network analysis using large-scale gene expression data sets is an effective way to uncover new biological knowledge; however, the methods used for gene association in constructing these coexpression networks have not been thoroughly evaluated. Since different methods lead to structurally different coexpression networks and provide different information, selecting the optimal gene association method is critical. METHODS AND RESULTS: In this study, we compared eight gene association methods - Spearman rank correlation, Weighted Rank Correlation, Kendall, Hoeffding's D measure, Theil-Sen, Rank Theil-Sen, Distance Covariance, and Pearson - and focused on their true knowledge discovery rates in associating pathway genes and construction coordination networks of regulatory genes. We also examined the behaviors of different methods to microarray data with different properties, and whether the biological processes affect the efficiency of different methods. CONCLUSIONS: We found that the Spearman, Hoeffding and Kendall methods are effective in identifying coexpressed pathway genes, whereas the Theil-sen, Rank Theil-Sen, Spearman, and Weighted Rank methods perform well in identifying coordinated transcription factors that control the same biological processes and traits. Surprisingly, the widely used Pearson method is generally less efficient, and so is the Distance Covariance method that can find gene pairs of multiple relationships. Some analyses we did clearly show Pearson and Distance Covariance methods have distinct behaviors as compared to all other six methods. The efficiencies of different methods vary with the data properties to some degree and are largely contingent upon the biological processes, which necessitates the pre-analysis to identify the best performing method for gene association and coexpression network construction.

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

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    Yang Mark CK

    2006-01-01

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

  20. Gene discovery using next-generation pyrosequencing to develop ESTs for Phalaenopsis orchids

    Science.gov (United States)

    2011-01-01

    Background Orchids are one of the most diversified angiosperms, but few genomic resources are available for these non-model plants. In addition to the ecological significance, Phalaenopsis has been considered as an economically important floriculture industry worldwide. We aimed to use massively parallel 454 pyrosequencing for a global characterization of the Phalaenopsis transcriptome. Results To maximize sequence diversity, we pooled RNA from 10 samples of different tissues, various developmental stages, and biotic- or abiotic-stressed plants. We obtained 206,960 expressed sequence tags (ESTs) with an average read length of 228 bp. These reads were assembled into 8,233 contigs and 34,630 singletons. The unigenes were searched against the NCBI non-redundant (NR) protein database. Based on sequence similarity with known proteins, these analyses identified 22,234 different genes (E-value cutoff, e-7). Assembled sequences were annotated with Gene Ontology, Gene Family and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Among these annotations, over 780 unigenes encoding putative transcription factors were identified. Conclusion Pyrosequencing was effective in identifying a large set of unigenes from Phalaenopsis. The informative EST dataset we developed constitutes a much-needed resource for discovery of genes involved in various biological processes in Phalaenopsis and other orchid species. These transcribed sequences will narrow the gap between study of model organisms with many genomic resources and species that are important for ecological and evolutionary studies. PMID:21749684

  1. A genomics based discovery of secondary metabolite biosynthetic gene clusters in Aspergillus ustus.

    Directory of Open Access Journals (Sweden)

    Borui Pi

    Full Text Available 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.

  2. Discovery of Putative Herbicide Resistance Genes and Its Regulatory Network in Chickpea Using Transcriptome Sequencing

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    Mir A. Iquebal

    2017-06-01

    Full Text Available Background: Chickpea (Cicer arietinum L. contributes 75% of total pulse production. Being cheaper than animal protein, makes it important in dietary requirement of developing countries. Weed not only competes with chickpea resulting into drastic yield reduction but also creates problem of harboring fungi, bacterial diseases and insect pests. Chemical approach having new herbicide discovery has constraint of limited lead molecule options, statutory regulations and environmental clearance. Through genetic approach, transgenic herbicide tolerant crop has given successful result but led to serious concern over ecological safety thus non-transgenic approach like marker assisted selection is desirable. Since large variability in tolerance limit of herbicide already exists in chickpea varieties, thus the genes offering herbicide tolerance can be introgressed in variety improvement programme. Transcriptome studies can discover such associated key genes with herbicide tolerance in chickpea.Results: This is first transcriptomic studies of chickpea or even any legume crop using two herbicide susceptible and tolerant genotypes exposed to imidazoline (Imazethapyr. Approximately 90 million paired-end reads generated from four samples were processed and assembled into 30,803 contigs using reference based assembly. We report 6,310 differentially expressed genes (DEGs, of which 3,037 were regulated by 980 miRNAs, 1,528 transcription factors associated with 897 DEGs, 47 Hub proteins, 3,540 putative Simple Sequence Repeat-Functional Domain Marker (SSR-FDM, 13,778 genic Single Nucleotide Polymorphism (SNP putative markers and 1,174 Indels. Randomly selected 20 DEGs were validated using qPCR. Pathway analysis suggested that xenobiotic degradation related gene, glutathione S-transferase (GST were only up-regulated in presence of herbicide. Down-regulation of DNA replication genes and up-regulation of abscisic acid pathway genes were observed. Study further reveals

  3. TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available 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/.

  4. Leveraging gene-environment interactions and endotypes for asthma gene discovery

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Ober, Carole

    2016-01-01

    Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also...... heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes......, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms. We will discuss the challenges of considering GEIs...

  5. Anthraquinones with antiplasmodial activity from the roots of Rennellia elliptica Korth. (Rubiaceae).

    Science.gov (United States)

    Osman, Che Puteh; Ismail, Nor Hadiani; Ahmad, Rohaya; Ahmat, Norizan; Awang, Khalijah; Jaafar, Faridahanim Mohd

    2010-10-20

    Dichloromethane root extract of Rennellia elliptica Korth. showed strong inhibition of Plasmodium falciparum growth in vitro with an IC₅₀ value of 4.04 µg/mL. A phytochemical study of the dichloromethane root extract has led to the isolation and characterization of a new anthraquinone, 1,2-dimethoxy-6-methyl-9,10-anthraquinone (1), and ten known anthraquinones: 1-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (2), nordamnacanthal (3), 2-formyl-3-hydroxy-9,10-anthraquinone (4), damnacanthal (5), lucidin-ω-methyl ether (6), 3-hydroxy-2-methyl-9,10-anthraquinone (7), rubiadin (8), 3-hydroxy-2-methoxy-6-methyl-9,10-anthraquinone (9), rubiadin-1-methyl ether (10) and 3-hydroxy-2-hydroxymethyl-9,10-anthraquinone (11). Structural elucidation of all compounds was accomplished by modern spectroscopic methods, notably 1D and 2D NMR, IR, UV and HREIMS. The new anthraquinone 1, 2-formyl-3-hydroxy-9,10-anthraquinone (4) and 3-hydroxy-2-methyl-9,10-anthraquinone (7) possess strong antiplasmodial activity, with IC₅₀ values of 1.10, 0.63 and 0.34 µM, respectively.

  6. Bootstrapping of gene-expression data improves and controls the false discovery rate of differentially expressed genes

    Directory of Open Access Journals (Sweden)

    Goddard Mike E

    2004-03-01

    Full Text Available Abstract The ordinary-, penalized-, and bootstrap t-test, least squares and best linear unbiased prediction were compared for their false discovery rates (FDR, i.e. the fraction of falsely discovered genes, which was empirically estimated in a duplicate of the data set. The bootstrap-t-test yielded up to 80% lower FDRs than the alternative statistics, and its FDR was always as good as or better than any of the alternatives. Generally, the predicted FDR from the bootstrapped P-values agreed well with their empirical estimates, except when the number of mRNA samples is smaller than 16. In a cancer data set, the bootstrap-t-test discovered 200 differentially regulated genes at a FDR of 2.6%, and in a knock-out gene expression experiment 10 genes were discovered at a FDR of 3.2%. It is argued that, in the case of microarray data, control of the FDR takes sufficient account of the multiple testing, whilst being less stringent than Bonferoni-type multiple testing corrections. Extensions of the bootstrap simulations to more complicated test-statistics are discussed.

  7. Targeted SNP discovery in Atlantic salmon (Salmo salar genes using a 3'UTR-primed SNP detection approach

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    Høyheim Bjørn

    2010-12-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs represent the most widespread type of DNA variation in vertebrates and may be used as genetic markers for a range of applications. This has led to an increased interest in identification of SNP markers in non-model species and farmed animals. The in silico SNP mining method used for discovery of most known SNPs in Atlantic salmon (Salmo salar has applied a global (genome-wide approach. In this study we present a targeted 3'UTR-primed SNP discovery strategy that utilizes sequence data from Salmo salar full length sequenced cDNAs (FLIcs. We compare the efficiency of this new strategy to the in silico SNP mining method when using both methods for targeted SNP discovery. Results The SNP discovery efficiency of the two methods was tested in a set of FLIc target genes. The 3'UTR-primed SNP discovery method detected novel SNPs in 35% of the target genes while the in silico SNP mining method detected novel SNPs in 15% of the target genes. Furthermore, the 3'UTR-primed SNP discovery strategy was the less labor intensive one and revealed a higher success rate than the in silico SNP mining method in the initial amplification step. When testing the methods we discovered 112 novel bi-allelic polymorphisms (type I markers in 88 salmon genes [dbSNP: ss179319972-179320081, ss250608647-250608648], and three of the SNPs discovered were missense substitutions. Conclusions Full length insert cDNAs (FLIcs are important genomic resources that have been developed in many farmed animals. The 3'UTR-primed SNP discovery strategy successfully utilized FLIc data to detect novel SNPs in the partially tetraploid Atlantic salmon. This strategy may therefore be useful for targeted SNP discovery in several species, and particularly useful in species that, like salmonids, have duplicated genomes.

  8. Gene analysis techniques and susceptibility gene discovery in non-BRCA1/BRCA2 familial breast cancer.

    Science.gov (United States)

    Aloraifi, Fatima; Boland, Michael R; Green, Andrew J; Geraghty, James G

    2015-06-01

    Breast cancer is the leading cause of cancer deaths in females worldwide occurring in both hereditary and sporadic forms. Women with inherited pathogenic mutations in the BRCA1 or BRCA2 genes have up to an 85% risk of developing breast cancer in their lifetimes. These patients are candidates for risk-reduction measures such as intensive radiological screening, prophylactic surgery or chemoprevention. However, only about 20% of familial breast cancer cases are attributed to mutations in BRCA1 and BRCA2, while a further 5-10% are attributed to mutations in other rare susceptibility genes such as TP53, STK11, PTEN, ATM and CHEK2. A multitude of genome wide association studies (GWAS) have been conducted confirming low-risk common variants associated with breast cancer in excess of 90 loci, which may contribute to a further 23% of the heritability. We currently find ourselves in "the next generation", with technologies offering deep sequencing at a fraction of the cost. Starting off primarily in a research setting, multi-gene panel testing is now utilized in the clinic to sequence multiple predisposing genes simultaneously (otherwise known as multi-gene panel testing). In this review, we focus on the hereditary breast cancer discoveries, techniques and the challenges we face in this complex disease, especially in the light of the vast amount of data we now have at hand. It has been 20 years since the first breast cancer susceptibility gene has been discovered and there has been substantial progress in unraveling the genetic component of the disease. However, hereditary breast cancer remains a challenging topic subject to common debate. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Nicholas J. Talbot

    2006-04-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  11. SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate

    Science.gov (United States)

    Roffler, Gretchen H.; Amish, Stephen J.; Smith, Seth; Cosart, Ted F.; Kardos, Marty; Schwartz, Michael K.; Luikart, Gordon

    2016-01-01

    Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding and nearby 5′ and 3′ untranslated regions of chosen candidate genes. Targeted sequences were taken from bighorn sheep (Ovis canadensis) exon capture data and directly from the domestic sheep genome (Ovis aries v. 3; oviAri3). The bighorn sheep sequences used in the Dall's sheep (Ovis dalli dalli) exon capture aligned to 2350 genes on the oviAri3 genome with an average of 2 exons each. We developed a microfluidic qPCR-based SNP chip to genotype 476 Dall's sheep from locations across their range and test for patterns of selection. Using multiple corroborating approaches (lositan and bayescan), we detected 28 SNP loci potentially under selection. We additionally identified candidate loci significantly associated with latitude, longitude, precipitation and temperature, suggesting local environmental adaptation. The three methods demonstrated consistent support for natural selection on nine genes with immune and disease-regulating functions (e.g. Ovar-DRA, APC, BATF2, MAGEB18), cell regulation signalling pathways (e.g. KRIT1, PI3K, ORRC3), and respiratory health (CYSLTR1). Characterizing adaptive allele distributions from novel genetic techniques will facilitate investigation of the influence of environmental variation on local adaptation of a northern alpine ungulate throughout its range. This research demonstrated the utility of exon capture for gene-targeted SNP discovery and subsequent SNP chip genotyping using low-quality samples in a nonmodel species.

  12. Population dynamics of freshwater oyster Etheria elliptica (Bivalvia: Etheriidae in the Pendjari River (Benin-Western Africa

    Directory of Open Access Journals (Sweden)

    Akélé G.D.

    2015-01-01

    Full Text Available Etheria elliptica (Bivalvia: Etheriidae is the only freshwater oyster occurring in Africa. The current study provides the first data on the population structure, growth, age, mortality and exploitation status of this species in the Pendjari River. E. elliptica length-frequency data were collected monthly from January to December 2009 and analyzed with FiSAT software. Population parameters including the asymptotic length (L∞ and growth coefficient (K were assessed to evaluate the stock status. The recruitment pattern was modeled with a FiSAT routine. The asymptotic length (L∞ was 14.75 cm, while the growth coefficient (K was 0.38 year-1. The growth performance index (ø′ reached 1.92. Specimens of Etheria elliptica reached a mean size of 4.66 cm and 6.41 cm at the end of one year and 1.5 years, respectively. We estimated total mortality (Z, natural mortality (M and fishing mortality (F to be 2.90 year-1, 1.16 year-1 and 1.74 year-1, respectively. The recruitment pattern was continuous over the year with one major peak event during the rainy season (July. The exploitation rate (E = 0.60 revealed that the freshwater oyster was probably facing overexploitation due to lack of a minimum limit size and also due to an increase in the harvesting effort. Therefore, efficient management methods were urgently required to conserve the species. The return of empty shells into the water to increase the recruitment surface, rotation planning among harvesting sites and the imposition of a minimum limit size were recommendations made in order to ensure the sustainable exploitation of wild stocks.

  13. Iron assimilation by the clam Laternula elliptica: Do stable isotopes (δ⁵⁶Fe) help to decipher the sources?

    Science.gov (United States)

    Poigner, Harald; Wilhelms-Dick, Dorothee; Abele, Doris; Staubwasser, Michael; Henkel, Susann

    2015-09-01

    Iron stable isotope signatures (δ(56)Fe) in hemolymph (bivalve blood) of the Antarctic bivalve Laternula elliptica were analyzed by Multiple Collector-Inductively Coupled Plasma-Mass Spectrometry (MC-ICP-MS) to test whether the isotopic fingerprint can be tracked back to the predominant sources of the assimilated Fe. An earlier investigation of Fe concentrations in L. elliptica hemolymph suggested that an assimilation of reactive and bioavailable Fe (oxyhydr)oxide particles (i.e. ferrihydrite), precipitated from pore water Fe around the benthic boundary, is responsible for the high Fe concentration in L. elliptica (Poigner et al., 2013 b). At two stations in Potter Cove (King George Island, Antarctica) bivalve hemolymph showed mean δ(56)Fe values of -1.19 ± 0.34‰ and -1.04 ± 0.39 ‰, respectively, which is between 0.5‰ and 0.85‰ lighter than the pool of easily reducible Fe (oxyhydr)oxides of the surface sediments (-0.3‰ to -0.6‰). This is in agreement with the enrichment of lighter Fe isotopes at higher trophic levels, resulting from the preferential assimilation of light isotopes from nutrition. Nevertheless, δ(56)Fe hemolymph values from both stations showed a high variability, ranging between -0.21‰ (value close to unaltered/primary Fe(oxyhydr)oxide minerals) and -1.91‰ (typical for pore water Fe or diagenetic Fe precipitates), which we interpret as a "mixed" δ(56)Fe signature caused by Fe assimilation from different sources with varying Fe contents and δ(56)Fe values. Furthermore, mass dependent Fe fractionation related to physiological processes within the bivalve cannot be ruled out. This is the first study addressing the potential of Fe isotopes for tracing back food sources of bivalves. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A comparative review of estimates of the proportion unchanged genes and the false discovery rate

    Directory of Open Access Journals (Sweden)

    Broberg Per

    2005-08-01

    Full Text Available Abstract Background In the analysis of microarray data one generally produces a vector of p-values that for each gene give the likelihood of obtaining equally strong evidence of change by pure chance. The distribution of these p-values is a mixture of two components corresponding to the changed genes and the unchanged ones. The focus of this article is how to estimate the proportion unchanged and the false discovery rate (FDR and how to make inferences based on these concepts. Six published methods for estimating the proportion unchanged genes are reviewed, two alternatives are presented, and all are tested on both simulated and real data. All estimates but one make do without any parametric assumptions concerning the distributions of the p-values. Furthermore, the estimation and use of the FDR and the closely related q-value is illustrated with examples. Five published estimates of the FDR and one new are presented and tested. Implementations in R code are available. Results A simulation model based on the distribution of real microarray data plus two real data sets were used to assess the methods. The proposed alternative methods for estimating the proportion unchanged fared very well, and gave evidence of low bias and very low variance. Different methods perform well depending upon whether there are few or many regulated genes. Furthermore, the methods for estimating FDR showed a varying performance, and were sometimes misleading. The new method had a very low error. Conclusion The concept of the q-value or false discovery rate is useful in practical research, despite some theoretical and practical shortcomings. However, it seems possible to challenge the performance of the published methods, and there is likely scope for further developing the estimates of the FDR. The new methods provide the scientist with more options to choose a suitable method for any particular experiment. The article advocates the use of the conjoint information

  15. Genomics-Based Discovery of Plant Genes for Synthetic Biology of Terpenoid Fragrances: A Case Study in Sandalwood oil Biosynthesis.

    Science.gov (United States)

    Celedon, J M; Bohlmann, J

    2016-01-01

    Terpenoid fragrances are powerful mediators of ecological interactions in nature and have a long history of traditional and modern industrial applications. Plants produce a great diversity of fragrant terpenoid metabolites, which make them a superb source of biosynthetic genes and enzymes. Advances in fragrance gene discovery have enabled new approaches in synthetic biology of high-value speciality molecules toward applications in the fragrance and flavor, food and beverage, cosmetics, and other industries. Rapid developments in transcriptome and genome sequencing of nonmodel plant species have accelerated the discovery of fragrance biosynthetic pathways. In parallel, advances in metabolic engineering of microbial and plant systems have established platforms for synthetic biology applications of some of the thousands of plant genes that underlie fragrance diversity. While many fragrance molecules (eg, simple monoterpenes) are abundant in readily renewable plant materials, some highly valuable fragrant terpenoids (eg, santalols, ambroxides) are rare in nature and interesting targets for synthetic biology. As a representative example for genomics/transcriptomics enabled gene and enzyme discovery, we describe a strategy used successfully for elucidation of a complete fragrance biosynthetic pathway in sandalwood (Santalum album) and its reconstruction in yeast (Saccharomyces cerevisiae). We address questions related to the discovery of specific genes within large gene families and recovery of rare gene transcripts that are selectively expressed in recalcitrant tissues. To substantiate the validity of the approaches, we describe the combination of methods used in the gene and enzyme discovery of a cytochrome P450 in the fragrant heartwood of tropical sandalwood, responsible for the fragrance defining, final step in the biosynthesis of (Z)-santalols. © 2016 Elsevier Inc. All rights reserved.

  16. Discovery of group I introns in the nuclear small subunit ribosomal RNA genes of Acanthamoeba.

    Science.gov (United States)

    Gast, R J; Fuerst, P A; Byers, T J

    1994-01-01

    The discovery of group I introns in small subunit nuclear rDNA (nsrDNA) is becoming more common as the effort to generate phylogenies based upon nsrDNA sequences grows. In this paper we describe the discovery of the first two group I introns in the nsrDNA from the genus Acanthamoeba. The introns are in different locations in the genes, and have no significant primary sequence similarity to each other. They are identified as group I introns by the conserved P, Q, R and S sequences (1), and the ability to fit the sequences to a consensus secondary structure model for the group I introns (1, 2). Both introns are absent from the mature srRNA. A BLAST search (3) of nucleic acid sequences present in GenBank and EMBL revealed that the A. griffini intron was most similar to the nsrDNA group I intron of the green alga Dunaliella parva. A similar search found that the A. lenticulata intron was not similar to any of the other reported group I introns. Images PMID:8127708

  17. A new omics data resource of Pleurocybella porrigens for gene discovery.

    Directory of Open Access Journals (Sweden)

    Tomohiro Suzuki

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

  18. A New Omics Data Resource of Pleurocybella porrigens for Gene Discovery

    Science.gov (United States)

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

    2013-01-01

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

  19. Cracking the regulatory code of biosynthetic gene clusters as a strategy for natural product discovery.

    Science.gov (United States)

    Rigali, Sébastien; Anderssen, Sinaeda; Naômé, Aymeric; van Wezel, Gilles P

    2018-01-05

    The World Health Organization (WHO) describes antibiotic resistance as "one of the biggest threats to global health, food security, and development today", as the number of multi- and pan-resistant bacteria is rising dangerously. Acquired resistance phenomena also impair antifungals, antivirals, anti-cancer drug therapy, while herbicide resistance in weeds threatens the crop industry. On the positive side, it is likely that the chemical space of natural products goes far beyond what has currently been discovered. This idea is fueled by genome sequencing of microorganisms which unveiled numerous so-called cryptic biosynthetic gene clusters (BGCs), many of which are transcriptionally silent under laboratory culture conditions, and by the fact that most bacteria cannot yet be cultivated in the laboratory. However, brute force antibiotic discovery does not yield the same results as it did in the past, and researchers have had to develop creative strategies in order to unravel the hidden potential of microorganisms such as Streptomyces and other antibiotic-producing microorganisms. Identifying the cis elements and their corresponding transcription factors(s) involved in the control of BGCs through bioinformatic approaches is a promising strategy. Theoretically, we are a few 'clicks' away from unveiling the culturing conditions or genetic changes needed to activate the production of cryptic metabolites or increase the production yield of known compounds to make them economically viable. In this opinion article, we describe and illustrate the idea beyond 'cracking' the regulatory code for natural product discovery, by presenting a series of proofs of concept, and discuss what still should be achieved to increase the rate of success of this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Functional Gene Discovery and Characterization of Genes and Alleles Affecting Wood Biomass Yield and Quality in Populus

    Energy Technology Data Exchange (ETDEWEB)

    Busov, Victor [Michigan Technological Univ., Houghton, MI (United States)

    2017-02-12

    Adoption of biofuels as economically and environmentally viable alternative to fossil fuels would require development of specialized bioenergy varieties. A major goal in the breeding of such varieties is the improvement of lignocellulosic biomass yield and quality. These are complex traits and understanding the underpinning molecular mechanism can assist and accelerate their improvement. This is particularly important for tree bioenergy crops like poplars (species and hybrids from the genus Populus), for which breeding progress is extremely slow due to long generation cycles. A variety of approaches have been already undertaken to better understand the molecular bases of biomass yield and quality in poplar. An obvious void in these undertakings has been the application of mutagenesis. Mutagenesis has been instrumental in the discovery and characterization of many plant traits including such that affect biomass yield and quality. In this proposal we use activation tagging to discover genes that can significantly affect biomass associated traits directly in poplar, a premier bioenergy crop. We screened a population of 5,000 independent poplar activation tagging lines under greenhouse conditions for a battery of biomass yield traits. These same plants were then analyzed for changes in wood chemistry using pyMBMS. As a result of these screens we have identified nearly 800 mutants, which are significantly (P<0.05) different when compared to wild type. Of these majority (~700) are affected in one of ten different biomass yield traits and 100 in biomass quality traits (e.g., lignin, S/G ration and C6/C5 sugars). We successfully recovered the position of the tag in approximately 130 lines, showed activation in nearly half of them and performed recapitulation experiments with 20 genes prioritized by the significance of the phenotype. Recapitulation experiments are still ongoing for many of the genes but the results are encouraging. For example, we have shown successful

  1. Using Phenomic Analysis of Photosynthetic Function for Abiotic Stress Response Gene Discovery.

    Science.gov (United States)

    Rungrat, Tepsuda; Awlia, Mariam; Brown, Tim; Cheng, Riyan; Sirault, Xavier; Fajkus, Jiri; Trtilek, Martin; Furbank, Bob; Badger, Murray; Tester, Mark; Pogson, Barry J; Borevitz, Justin O; Wilson, Pip

    2016-01-01

    Monitoring the photosynthetic performance of plants is a major key to understanding how plants adapt to their growth conditions. Stress tolerance traits have a high genetic complexity as plants are constantly, and unavoidably, exposed to numerous stress factors, which limits their growth rates in the natural environment. Arabidopsis thaliana , with its broad genetic diversity and wide climatic range, has been shown to successfully adapt to stressful conditions to ensure the completion of its life cycle. As a result, A. thaliana has become a robust and renowned plant model system for studying natural variation and conducting gene discovery studies. Genome wide association studies (GWAS) in restructured populations combining natural and recombinant lines is a particularly effective way to identify the genetic basis of complex traits. As most abiotic stresses affect photosynthetic activity, chlorophyll fluorescence measurements are a potential phenotyping technique for monitoring plant performance under stress conditions. This review focuses on the use of chlorophyll fluorescence as a tool to study genetic variation underlying the stress tolerance responses to abiotic stress in A. thaliana .

  2. Using Phenomic Analysis of Photosynthetic Function for Abiotic Stress Response Gene Discovery

    KAUST Repository

    Rungrat, Tepsuda

    2016-09-09

    Monitoring the photosynthetic performance of plants is a major key to understanding how plants adapt to their growth conditions. Stress tolerance traits have a high genetic complexity as plants are constantly, and unavoidably, exposed to numerous stress factors, which limits their growth rates in the natural environment. Arabidopsis thaliana, with its broad genetic diversity and wide climatic range, has been shown to successfully adapt to stressful conditions to ensure the completion of its life cycle. As a result, A. thaliana has become a robust and renowned plant model system for studying natural variation and conducting gene discovery studies. Genome wide association studies (GWAS) in restructured populations combining natural and recombinant lines is a particularly effective way to identify the genetic basis of complex traits. As most abiotic stresses affect photosynthetic activity, chlorophyll fluorescence measurements are a potential phenotyping technique for monitoring plant performance under stress conditions. This review focuses on the use of chlorophyll fluorescence as a tool to study genetic variation underlying the stress tolerance responses to abiotic stress in A. thaliana.

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

    Science.gov (United States)

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

    2015-05-01

    As challenges to food security increase, the demand for lead genes for improving crop production is growing. However, genetic screens of plant mutants typically yield very low frequencies of desired phenotypes. Here, we present a powerful computational approach for selecting candidate genes for screening insertion mutants. We combined ranking of Arabidopsis thaliana regulatory genes according to their expression in response to multiple abiotic stresses (Multiple Stress [MST] score), with stress-responsive RNA co-expression network analysis to select candidate multiple stress regulatory (MSTR) genes. Screening of 62 T-DNA insertion mutants defective in candidate MSTR genes, for abiotic stress germination phenotypes yielded a remarkable hit rate of up to 62%; this gene discovery rate is 48-fold greater than that of other large-scale insertional mutant screens. Moreover, the MST score of these genes could be used to prioritize them for screening. To evaluate the contribution of the co-expression analysis, we screened 64 additional mutant lines of MST-scored genes that did not appear in the RNA co-expression network. The screening of these MST-scored genes yielded a gene discovery rate of 36%, which is much higher than that of classic mutant screens but not as high as when picking candidate genes from the co-expression network. The MSTR co-expression network that we created, AraSTressRegNet is publicly available at http://netbio.bgu.ac.il/arnet. This systems biology-based screening approach combining gene ranking and network analysis could be generally applicable to enhancing identification of genes regulating additional processes in plants and other organisms provided that suitable transcriptome data are available. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Coetzer, Nanette; Gazendam, Inge; Oelofse, Dean; Berger, Dave K

    2010-04-01

    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. 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 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

  5. Functional linkage between genes that regulate osmotic stress responses and multidrug resistance transporters: challenges and opportunities for antibiotic discovery.

    Science.gov (United States)

    Cohen, B Eleazar

    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.

  6. Preparative separation of flavonoids from the medicinal plant Davilla elliptica St. Hill. by high-speed counter-current chromatography

    Directory of Open Access Journals (Sweden)

    Daniel Rinaldo

    2006-10-01

    Full Text Available High-speed counter-current chromatography (HSCCC is a major tool for the fast separation of natural products from plants. It was used for the preparative isolation of the flavonoid monoglucosides present in the aerial parts of the Davilla elliptica St. Hill. (Dilleniaceae. This species is used in Brazilian folk medicine for the treatment of gastric disorders. The optimum solvent system used was composed of a mixture of ethyl acetate-n-propanol-water (140:8:80, v/v/v and led to a successful separation of quercetin-3-O-alpha-L-rhamnopyranoside and myricetin-3-O-alpha-L-rhamnopyranoside in approximately 3.0 hours with purity higher than 95%. Identification was performed by ¹H NMR, 13C NMR and HPLC-UV-DAD analyses.

  7. Preparative separation of flavonoids from the medicinal plant Davilla elliptica St. Hill. by high-speed counter-current chromatography

    Directory of Open Access Journals (Sweden)

    Rinaldo Daniel

    2006-01-01

    Full Text Available High-speed counter-current chromatography (HSCCC is a major tool for the fast separation of natural products from plants. It was used for the preparative isolation of the flavonoid monoglucosides present in the aerial parts of the Davilla elliptica St. Hill. (Dilleniaceae. This species is used in Brazilian folk medicine for the treatment of gastric disorders. The optimum solvent system used was composed of a mixture of ethyl acetate-n-propanol-water (140:8:80, v/v/v and led to a successful separation of quercetin-3-O-alpha-L-rhamnopyranoside and myricetin-3-O-alpha-L-rhamnopyranoside in approximately 3.0 hours with purity higher than 95%. Identification was performed by ¹H NMR, 13C NMR and HPLC-UV-DAD analyses.

  8. De novo assembly and characterization of the transcriptome of broomcorn millet (Panicum miliaceum L. for gene discovery and marker development

    Directory of Open Access Journals (Sweden)

    Hong Yue

    2016-07-01

    Full Text Available Broomcorn millet (Panicum miliaceum L. is one of the world’s oldest cultivated cereals, which is well adapted to extreme environments such as drought, heat and salinity with an efficient C4 carbon fixation. Discovery and identification of genes involved in these processes will provide valuable information to improve the crop for meeting the challenge of global climate change. However, the lack of genetic resources and genomic information make gene discovery and molecular mechanism studies very difficult. Here, we sequenced and assembled the transcriptome of broomcorn millet using Illumina sequencing technology. After sequencing, a total of 45,406,730 and 51,160,820 clean paired-end reads were obtained for two genotypes Yumi No.2 and Yumi No.3. These reads were mixed and then assembled into 113,643 unigenes, with the length ranging from 351 to 15,691 bp, of which 62,543 contings could be assigned to 315 gene ontology (GO categories. Cluster of orthologous groups and kyoto encyclopedia of genes and genomes (KEGG analyses assigned could map 15,514 unigenes into 202 KEGG pathways and 51,020 unigenes to 25 COG categories, respectively. Furthermore, 35,216 simple sequence repeats (SSRs were identified in 27,055 unigene sequences, of which trinucleotides were the most abundant repeat unit, accounting for 66.72% of SSRs. In addition, 292 differentially expressed genes (DEGs were identified between the two genotypes, which were significantly enriched in 88 GO terms and 12 KEGG pathways. Finally, the expression patterns of 4 selected transcripts were validated through quantitative reverse transcription PCR (qRT-PCR analysis. Our study for the first time sequenced and assembled the transcriptome of broomcorn millet, which not only provided a rich sequence resource for gene discovery and marker development in this important crop, but will also facilitate the further investigation of the molecular mechanism of its favored agronomic traits and beyond.

  9. Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study

    Science.gov (United States)

    Cao, Wuxiong; Epstein, Charles; Liu, Hong; DeLoughery, Craig; Ge, Nanxiang; Lin, Jieyi; Diao, Rong; Cao, Hui; Long, Fan; Zhang, Xin; Chen, Yangde; Wright, Paul S; Busch, Steve; Wenck, Michelle; Wong, Karen; Saltzman, Alan G; Tang, Zhihua; Liu, Li; Zilberstein, Asher

    2004-01-01

    Background Several high throughput technologies have been employed to identify differentially regulated genes that may be molecular targets for drug discovery. Here we compared the sets of differentially regulated genes discovered using two experimental approaches: a subtracted suppressive hybridization (SSH) cDNA library methodology and Affymetrix GeneChip® technology. In this "case study" we explored the transcriptional pattern changes during the in vitro differentiation of human monocytes to myeloid dendritic cells (DC), and evaluated the potential for novel gene discovery using the SSH methodology. Results The same RNA samples isolated from peripheral blood monocyte precursors and immature DC (iDC) were used for GeneChip microarray probing and SSH cDNA library construction. 10,000 clones from each of the two-way SSH libraries (iDC-monocytes and monocytes-iDC) were picked for sequencing. About 2000 transcripts were identified for each library from 8000 successful sequences. Only 70% to 75% of these transcripts were represented on the U95 series GeneChip microarrays, implying that 25% to 30% of these transcripts might not have been identified in a study based only on GeneChip microarrays. In addition, about 10% of these transcripts appeared to be "novel", although these have not yet been closely examined. Among the transcripts that are also represented on the chips, about a third were concordantly discovered as differentially regulated between iDC and monocytes by GeneChip microarray transcript profiling. The remaining two thirds were either not inferred as differentially regulated from GeneChip microarray data, or were called differentially regulated but in the opposite direction. This underscores the importance both of generating reciprocal pairs of SSH libraries, and of real-time RT-PCR confirmation of the results. Conclusions This study suggests that SSH could be used as an alternative and complementary transcript profiling tool to GeneChip microarrays

  10. ConGEMs: Condensed Gene Co-Expression Module Discovery Through Rule-Based Clustering and Its Application to Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Saurav Mallik

    2017-12-01

    Full Text Available For transcriptomic analysis, there are numerous microarray-based genomic data, especially those generated for cancer research. The typical analysis measures the difference between a cancer sample-group and a matched control group for each transcript or gene. Association rule mining is used to discover interesting item sets through rule-based methodology. Thus, it has advantages to find causal effect relationships between the transcripts. In this work, we introduce two new rule-based similarity measures—weighted rank-based Jaccard and Cosine measures—and then propose a novel computational framework to detect condensed gene co-expression modules ( C o n G E M s through the association rule-based learning system and the weighted similarity scores. In practice, the list of evolved condensed markers that consists of both singular and complex markers in nature depends on the corresponding condensed gene sets in either antecedent or consequent of the rules of the resultant modules. In our evaluation, these markers could be supported by literature evidence, KEGG (Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology annotations. Specifically, we preliminarily identified differentially expressed genes using an empirical Bayes test. A recently developed algorithm—RANWAR—was then utilized to determine the association rules from these genes. Based on that, we computed the integrated similarity scores of these rule-based similarity measures between each rule-pair, and the resultant scores were used for clustering to identify the co-expressed rule-modules. We applied our method to a gene expression dataset for lung squamous cell carcinoma and a genome methylation dataset for uterine cervical carcinogenesis. Our proposed module discovery method produced better results than the traditional gene-module discovery measures. In summary, our proposed rule-based method is useful for exploring biomarker modules from transcriptomic data.

  11. Discovery of CTCF-sensitive Cis-spliced fusion RNAs between adjacent genes in human prostate cells.

    Science.gov (United States)

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

    2015-02-01

    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.

  12. Helping Students Understand Gene Regulation with Online Tools: A Review of MEME and Melina II, Motif Discovery Tools for Active Learning in Biology

    Directory of Open Access Journals (Sweden)

    David Treves

    2012-08-01

    Full Text Available Review of: MEME and Melina II, which are two free and easy-to-use online motif discovery tools that can be employed to actively engage students in learning about gene regulatory elements.

  13. Metabologenomics: Correlation of Microbial Gene Clusters with Metabolites Drives Discovery of a Nonribosomal Peptide with an Unusual Amino Acid Monomer.

    Science.gov (United States)

    Goering, Anthony W; McClure, Ryan A; Doroghazi, James R; Albright, Jessica C; Haverland, Nicole A; Zhang, Yongbo; Ju, Kou-San; Thomson, Regan J; Metcalf, William W; Kelleher, Neil L

    2016-02-24

    For more than half a century the pharmaceutical industry has sifted through natural products produced by microbes, uncovering new scaffolds and fashioning them into a broad range of vital drugs. We sought a strategy to reinvigorate the discovery of natural products with distinctive structures using bacterial genome sequencing combined with metabolomics. By correlating genetic content from 178 actinomycete genomes with mass spectrometry-enabled analyses of their exported metabolomes, we paired new secondary metabolites with their biosynthetic gene clusters. We report the use of this new approach to isolate and characterize tambromycin, a new chlorinated natural product, composed of several nonstandard amino acid monomeric units, including a unique pyrrolidine-containing amino acid we name tambroline. Tambromycin shows antiproliferative activity against cancerous human B- and T-cell lines. The discovery of tambromycin via large-scale correlation of gene clusters with metabolites (a.k.a. metabologenomics) illuminates a path for structure-based discovery of natural products at a sharply increased rate.

  14. IMG-ABC: An Atlas of Biosynthetic Gene Clusters to Fuel the Discovery of Novel Secondary Metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Chen, I-Min; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Huang, Jinghua; Reddy, T. B.K.; Cimermancic, Peter; Fischbach, Michael; Ivanova, Natalia; Markowitz, Victor; Kyrpides, Nikos; Pati, Amrita

    2014-10-28

    In the discovery of secondary metabolites (SMs), large-scale analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of relevant computational resources. We present IMG-ABC (https://img.jgi.doe.gov/abc/) -- An Atlas of Biosynthetic gene Clusters within the Integrated Microbial Genomes (IMG) system1. IMG-ABC is a rich repository of both validated and predicted biosynthetic clusters (BCs) in cultured isolates, single-cells and metagenomes linked with the SM chemicals they produce and enhanced with focused analysis tools within IMG. The underlying scalable framework enables traversal of phylogenetic dark matter and chemical structure space -- serving as a doorway to a new era in the discovery of novel molecules.

  15. Cultivation of hard-to-culture subsurface mercury-resistant bacteria and discovery of new merA gene sequences

    DEFF Research Database (Denmark)

    Rasmussen, L D; Zawadsky, C; Binnerup, S J

    2008-01-01

    different 16S rRNA gene sequences were observed, including Alpha-, Beta-, and Gammaproteobacteria; Actinobacteria; Firmicutes; and Bacteroidetes. The diversity of isolates obtained by direct plating included eight different 16S rRNA gene sequences (Alpha- and Betaproteobacteria and Actinobacteria). Partial......Mercury-resistant bacteria may be important players in mercury biogeochemistry. To assess the potential for mercury reduction by two subsurface microbial communities, resistant subpopulations and their merA genes were characterized by a combined molecular and cultivation-dependent approach...... sequencing of merA of selected isolates led to the discovery of new merA sequences. With phylum-specific merA primers, PCR products were obtained for Alpha- and Betaproteobacteria and Actinobacteria but not for Bacteroidetes and Firmicutes. The similarity to known sequences ranged between 89 and 95%. One...

  16. Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

    Science.gov (United States)

    Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

    2017-06-01

    The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  17. Discovery of the porcine NGN3 gene and testing its endocrine function in the pig

    Science.gov (United States)

    Neurogenin 3 (NGN3) is a member of the basic helix-loop-helix transcription factor family. NGN3 is both necessary and sufficient to drive endocrine differentiation in the developing pancreas in mouse and humans. Until now, the sequence for NGN3 eluded discovery despite completion of the pig genome a...

  18. Ataxin1L is a regulator of HSC function highlighting the utility of cross-tissue comparisons for gene discovery.

    Directory of Open Access Journals (Sweden)

    Juliette J Kahle

    2013-03-01

    Full Text Available Hematopoietic stem cells (HSCs are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein-protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems.

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

    Directory of Open Access Journals (Sweden)

    Oelofse Dean

    2010-04-01

    Full Text Available Abstract 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 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

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

    Science.gov (United States)

    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 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

  1. Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study

    Directory of Open Access Journals (Sweden)

    Wright Paul S

    2004-04-01

    Full Text Available Abstract Background Several high throughput technologies have been employed to identify differentially regulated genes that may be molecular targets for drug discovery. Here we compared the sets of differentially regulated genes discovered using two experimental approaches: a subtracted suppressive hybridization (SSH cDNA library methodology and Affymetrix GeneChip® technology. In this "case study" we explored the transcriptional pattern changes during the in vitro differentiation of human monocytes to myeloid dendritic cells (DC, and evaluated the potential for novel gene discovery using the SSH methodology. Results The same RNA samples isolated from peripheral blood monocyte precursors and immature DC (iDC were used for GeneChip microarray probing and SSH cDNA library construction. 10,000 clones from each of the two-way SSH libraries (iDC-monocytes and monocytes-iDC were picked for sequencing. About 2000 transcripts were identified for each library from 8000 successful sequences. Only 70% to 75% of these transcripts were represented on the U95 series GeneChip microarrays, implying that 25% to 30% of these transcripts might not have been identified in a study based only on GeneChip microarrays. In addition, about 10% of these transcripts appeared to be "novel", although these have not yet been closely examined. Among the transcripts that are also represented on the chips, about a third were concordantly discovered as differentially regulated between iDC and monocytes by GeneChip microarray transcript profiling. The remaining two thirds were either not inferred as differentially regulated from GeneChip microarray data, or were called differentially regulated but in the opposite direction. This underscores the importance both of generating reciprocal pairs of SSH libraries, and of real-time RT-PCR confirmation of the results. Conclusions This study suggests that SSH could be used as an alternative and complementary transcript profiling tool to

  2. A hybrid computational method for the discovery of novel reproduction-related genes.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2013-06-01

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

  4. Discovery by the Epistasis Project of an epistatic interaction between the GSTM3 gene and the HHEX/IDE/KIF11 locus in the risk of Alzheimer's disease

    NARCIS (Netherlands)

    J.M. Bullock (James); C. Medway (Christopher); M. Cortina-Borja (Mario); J.C. Turton (James); J.A. Prince (Jonathan); C.A. Ibrahim-Verbaas (Carla); M. Schuur (Maaike); M.M.B. Breteler (Monique); C.M. van Duijn (Cornelia); P.G. Kehoe (Patrick); R. Barber (Rachel); E. Coto (Eliecer); V. Alvarez (Victoria); P. Deloukas (Panagiotis); N. Hammond (Naomi); O. Combarros (Onofre); I. Mateo (Ignacio); D.R. Warden (Donald); M.G. Lehmann (Michael); O. Belbin (Olivia); K. Brown (Kristelle); G.K. Wilcock (Gordon); R. Heun (Reinhard); H. Kölsch (Heike); A.D. Smith; D.J. Lehmann (Donald); K. Morgan (Kevin)

    2013-01-01

    textabstractDespite recent discoveries in the genetics of sporadic Alzheimer's disease, there remains substantial " hidden heritability." It is thought that some of this missing heritability may be because of gene-gene, i.e., epistatic, interactions. We examined potential epistasis between 110

  5. Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

    Science.gov (United States)

    Lovering, Ruth C; Roncaglia, Paola; Howe, Douglas G; Laulederkind, Stanley J F; Khodiyar, Varsha K; Berardini, Tanya Z; Tweedie, Susan; Foulger, Rebecca E; Osumi-Sutherland, David; Campbell, Nancy H; Huntley, Rachael P; Talmud, Philippa J; Blake, Judith A; Breckenridge, Ross; Riley, Paul R; Lambiase, Pier D; Elliott, Perry M; Clapp, Lucie; Tinker, Andrew; Hill, David P

    2018-02-01

    A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. © 2018 The Authors.

  6. High resolution microscopy reveals significant impacts of ocean acidification and warming on larval shell development in Laternula elliptica.

    Directory of Open Access Journals (Sweden)

    Christine H Bylenga

    Full Text Available Environmental stressors impact marine larval growth rates, quality and sizes. Larvae of the Antarctic bivalve, Laternula elliptica, were raised to the D-larvae stage under temperature and pH conditions representing ambient and end of century projections (-1.6°C to +0.4°C and pH 7.98 to 7.65. Previous observations using light microscopy suggested pH had no influence on larval abnormalities in this species. Detailed analysis of the shell using SEM showed that reduced pH is in fact a major stressor during development for this species, producing D-larvae with abnormal shapes, deformed shell edges and irregular hinges, cracked shell surfaces and even uncalcified larvae. Additionally, reduced pH increased pitting and cracking on shell surfaces. Thus, apparently normal larvae may be compromised at the ultrastructural level and these larvae would be in poor condition at settlement, reducing juvenile recruitment and overall survival. Elevated temperatures increased prodissoconch II sizes. However, the overall impacts on larval shell quality and integrity with concurrent ocean acidification would likely overshadow any beneficial results from warmer temperatures, limiting populations of this prevalent Antarctic species.

  7. Effect of Gamma Irradiation and Its Convergent Treatments on Lily Leaf Blight Pathogen, Botrytis elliptica, and the Disease Development

    Directory of Open Access Journals (Sweden)

    Ji-Hoon Kim

    2014-06-01

    Full Text Available Gamma irradiation and its convergence with nano-silver particles and sodium dichloroisocyanurate (NaDCC were investigated to inhibit germination and mycelial growth of Botrytis elliptica, the pathogen of lily leaf blight. In addition, the same treatments were studied on the process of disease development with detached leaf of lily cv. Siberia. Spray inoculation, which is closer to natural infection than wound inoculation, can be a way to investigate infection ability of the treated pathogen. The irradiating dose required to reduce the population by 90%, D10, was 526 Gy irradiating with 0-2000 Gy gamma ray on the conidial suspension as well as the growing mycelia. Even at 2000 Gy, the mycelium was not killed but just delayed its growth at 1–2 days behind. Convergent treatment with 40 mg/l of NaDCC just before 200 Gy gamma irradiation was the best way to decrease the conidial germination about 1/1000 times. The control values of gamma irradiation were 23% and 19.5% at wound inoculation and spray inoculation, respectively. On wound-inoculation, the control value of NaDCC only was 89%, and that of NaDCC convergent with 200 Gy gamma irradiation was 32%. On sprayinoculation, the highest control value was NaDCC at 50%, and that of NaDCC convergent with gamma irradiation was 24%.

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

    Science.gov (United States)

    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

  9. Discovery of functional genes for systemic acquired resistance in Arabidopsis thaliana through integrated data mining.

    Science.gov (United States)

    Pan, Youlian; Pylatuik, Jeffrey D; Ouyang, Junjun; Famili, A Fazel; Fobert, Pierre R

    2004-12-01

    Various data mining techniques combined with sequence motif information in the promoter region of genes were applied to discover functional genes that are involved in the defense mechanism of systemic acquired resistance (SAR) in Arabidopsis thaliana. A series of K-Means clustering with difference-in-shape as distance measure was initially applied. A stability measure was used to validate this clustering process. A decision tree algorithm with the discover-and-mask technique was used to identify a group of most informative genes. Appearance and abundance of various transcription factor binding sites in the promoter region of the genes were studied. Through the combination of these techniques, we were able to identify 24 candidate genes involved in the SAR defense mechanism. The candidate genes fell into 2 highly resolved categories, each category showing significantly unique profiles of regulatory elements in their promoter regions. This study demonstrates the strength of such integration methods and suggests a broader application of this approach.

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

    Directory of Open Access Journals (Sweden)

    Chung I-Fang

    2008-10-01

    Full Text Available Abstract 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

  11. Discovery and replication of gene influences on brain structure using LASSO regression

    Directory of Open Access Journals (Sweden)

    Omid eKohannim

    2012-08-01

    Full Text Available We implemented LASSO (least absolute shrinkage and selection operator 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. In exploratory analyses, three selected SNPs in the MACROD2 gene were also significantly associated with performance intelligence quotient (PIQ. Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.

  12. IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites.

    Science.gov (United States)

    Hadjithomas, Michalis; Chen, I-Min Amy; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Szeto, Ernest; Huang, Jinghua; Reddy, T B K; Cimermančič, Peter; Fischbach, Michael A; Ivanova, Natalia N; Markowitz, Victor M; Kyrpides, Nikos C; Pati, Amrita

    2015-07-14

    In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of "big" genomic data for discovering small molecules. IMG-ABC relies on IMG's comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC's focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in Alphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG's extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to

  13. Discovery of differentially expressed genes in cashmere goat (Capra hircus) hair follicles by RNA sequencing.

    Science.gov (United States)

    Qiao, X; Wu, J H; Wu, R B; Su, R; Li, C; Zhang, Y J; Wang, R J; Zhao, Y H; Fan, Y X; Zhang, W G; Li, J Q

    2016-09-02

    The mammalian hair follicle (HF) is a unique, highly regenerative organ with a distinct developmental cycle. Cashmere goat (Capra hircus) HFs can be divided into two categories based on structure and development time: primary and secondary follicles. To identify differentially expressed genes (DEGs) in the primary and secondary HFs of cashmere goats, the RNA sequencing of six individuals from Arbas, Inner Mongolia, was performed. A total of 617 DEGs were identified; 297 were upregulated while 320 were downregulated. Gene ontology analysis revealed that the main functions of the upregulated genes were electron transport, respiratory electron transport, mitochondrial electron transport, and gene expression. The downregulated genes were mainly involved in cell autophagy, protein complexes, neutrophil aggregation, and bacterial fungal defense reactions. According to the Kyoto Encyclopedia of Genes and Genomes database, these genes are mainly involved in the metabolism of cysteine and methionine, RNA polymerization, and the MAPK signaling pathway, and were enriched in primary follicles. A microRNA-target network revealed that secondary follicles are involved in several important biological processes, such as the synthesis of keratin-associated proteins and enzymes involved in amino acid biosynthesis. In summary, these findings will increase our understanding of the complex molecular mechanisms of HF development and cycling, and provide a basis for the further study of the genes and functions of HF development.

  14. SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate

    Science.gov (United States)

    Gretchen H. Roffler; Stephen J. Amish; Seth Smith; Ted Cosart; Marty Kardos; Michael K. Schwartz; Gordon Luikart

    2016-01-01

    Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding...

  15. Network-Guided Key Gene Discovery for a Given Cellular Process

    DEFF Research Database (Denmark)

    He, Feng Q; Ollert, Markus

    2018-01-01

    and the following-up network analysis, opens up new avenues to predict key genes driving a given biological process or cellular function. Here we review and compare the current approaches in predicting key genes, which have no chances to stand out by classic differential expression analysis, from gene......Identification of key genes for a given physiological or pathological process is an essential but still very challenging task for the entire biomedical research community. Statistics-based approaches, such as genome-wide association study (GWAS)- or quantitative trait locus (QTL)-related analysis...... have already made enormous contributions to identifying key genes associated with a given disease or phenotype, the success of which is however very much dependent on a huge number of samples. Recent advances in network biology, especially network inference directly from genome-scale data...

  16. The Utility of Next-Generation Sequencing in Gene Discovery for Mutation-Negative Patients with Rett Syndrome

    Science.gov (United States)

    Gold, Wendy Anne; Christodoulou, John

    2015-01-01

    Rett syndrome (RTT) is a rare, severe disorder of neuronal plasticity that predominantly affects girls. Girls with RTT usually appear asymptomatic in the first 6–18 months of life, but gradually develop severe motor, cognitive, and behavioral abnormalities that persist for life. A predominance of neuronal and synaptic dysfunction, with altered excitatory–inhibitory neuronal synaptic transmission and synaptic plasticity, are overarching features of RTT in children and in mouse models. Over 90% of patients with classical RTT have mutations in the X-linked methyl-CpG-binding (MECP2) gene, while other genes, including cyclin-dependent kinase-like 5 (CDKL5), Forkhead box protein G1 (FOXG1), myocyte-specific enhancer factor 2C (MEF2C), and transcription factor 4 (TCF4), have been associated with phenotypes overlapping with RTT. However, there remain a proportion of patients who carry a clinical diagnosis of RTT, but who are mutation negative. In recent years, next-generation sequencing technologies have revolutionized approaches to genetic studies, making whole-exome and even whole-genome sequencing possible strategies for the detection of rare and de novo mutations, aiding the discovery of novel disease genes. Here, we review the recent progress that is emerging in identifying pathogenic variations, specifically from exome sequencing in RTT patients, and emphasize the need for the use of this technology to identify known and new disease genes in RTT patients. PMID:26236194

  17. Discovery of Unusual Biaryl Polyketides by Activation of a Silent Streptomyces venezuelae Biosynthetic Gene Cluster.

    Science.gov (United States)

    Thanapipatsiri, Anyarat; Gomez-Escribano, Juan Pablo; Song, Lijiang; Bibb, Maureen J; Al-Bassam, Mahmoud; Chandra, Govind; Thamchaipenet, Arinthip; Challis, Gregory L; Bibb, Mervyn J

    2016-11-17

    Comparative transcriptional profiling of a ΔbldM mutant of Streptomyces venezuelae with its unmodified progenitor revealed that the expression of a cryptic biosynthetic gene cluster containing both type I and type III polyketide synthase genes is activated in the mutant. The 29.5 kb gene cluster, which was predicted to encode an unusual biaryl metabolite, which we named venemycin, and potentially halogenated derivatives, contains 16 genes including one-vemR-that encodes a transcriptional activator of the large ATP-binding LuxR-like (LAL) family. Constitutive expression of vemR in the ΔbldM mutant led to the production of sufficient venemycin for structural characterisation, confirming its unusual biaryl structure. Co-expression of the venemycin biosynthetic gene cluster and vemR in the heterologous host Streptomyces coelicolor also resulted in venemycin production. Although the gene cluster encodes two halogenases and a flavin reductase, constitutive expression of all three genes led to the accumulation only of a monohalogenated venemycin derivative, both in the native producer and the heterologous host. A competition experiment in which equimolar quantities of sodium chloride and sodium bromide were fed to the venemycin-producing strains resulted in the preferential incorporation of bromine, thus suggesting that bromide is the preferred substrate for one or both halogenases. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

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

    Directory of Open Access Journals (Sweden)

    Robertson Gordon

    2010-10-01

    Full Text Available Abstract 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.

  19. Challenges in microarray class discovery: a comprehensive examination of normalization, gene selection and clustering

    Science.gov (United States)

    2010-01-01

    Background Cluster analysis, and in particular hierarchical clustering, is widely used to extract information from gene expression data. The aim is to discover new classes, or sub-classes, of either individuals or genes. Performing a cluster analysis commonly involve decisions on how to; handle missing values, standardize the data and select genes. In addition, pre-processing, involving various types of filtration and normalization procedures, can have an effect on the ability to discover biologically relevant classes. Here we consider cluster analysis in a broad sense and perform a comprehensive evaluation that covers several aspects of cluster analyses, including normalization. Result We evaluated 2780 cluster analysis methods on seven publicly available 2-channel microarray data sets with common reference designs. Each cluster analysis method differed in data normalization (5 normalizations were considered), missing value imputation (2), standardization of data (2), gene selection (19) or clustering method (11). The cluster analyses are evaluated using known classes, such as cancer types, and the adjusted Rand index. The performances of the different analyses vary between the data sets and it is difficult to give general recommendations. However, normalization, gene selection and clustering method are all variables that have a significant impact on the performance. In particular, gene selection is important and it is generally necessary to include a relatively large number of genes in order to get good performance. Selecting genes with high standard deviation or using principal component analysis are shown to be the preferred gene selection methods. Hierarchical clustering using Ward's method, k-means clustering and Mclust are the clustering methods considered in this paper that achieves the highest adjusted Rand. Normalization can have a significant positive impact on the ability to cluster individuals, and there are indications that background correction is

  20. Challenges in microarray class discovery: a comprehensive examination of normalization, gene selection and clustering

    Directory of Open Access Journals (Sweden)

    Landfors Mattias

    2010-10-01

    Full Text Available Abstract Background Cluster analysis, and in particular hierarchical clustering, is widely used to extract information from gene expression data. The aim is to discover new classes, or sub-classes, of either individuals or genes. Performing a cluster analysis commonly involve decisions on how to; handle missing values, standardize the data and select genes. In addition, pre-processing, involving various types of filtration and normalization procedures, can have an effect on the ability to discover biologically relevant classes. Here we consider cluster analysis in a broad sense and perform a comprehensive evaluation that covers several aspects of cluster analyses, including normalization. Result We evaluated 2780 cluster analysis methods on seven publicly available 2-channel microarray data sets with common reference designs. Each cluster analysis method differed in data normalization (5 normalizations were considered, missing value imputation (2, standardization of data (2, gene selection (19 or clustering method (11. The cluster analyses are evaluated using known classes, such as cancer types, and the adjusted Rand index. The performances of the different analyses vary between the data sets and it is difficult to give general recommendations. However, normalization, gene selection and clustering method are all variables that have a significant impact on the performance. In particular, gene selection is important and it is generally necessary to include a relatively large number of genes in order to get good performance. Selecting genes with high standard deviation or using principal component analysis are shown to be the preferred gene selection methods. Hierarchical clustering using Ward's method, k-means clustering and Mclust are the clustering methods considered in this paper that achieves the highest adjusted Rand. Normalization can have a significant positive impact on the ability to cluster individuals, and there are indications that

  1. Analysis of cassava (Manihot esculenta) ESTs: A tool for the discovery of genes

    International Nuclear Information System (INIS)

    Zapata, Andres; Neme, Rafik; Sanabria, Carolina; Lopez, Camilo

    2011-01-01

    Cassava (Manihot esculenta) is the main source of calories for more than 1,000 millions of people around the world and has been consolidated as the fourth most important crop after rice, corn and wheat. Cassava is considered tolerant to abiotic and biotic stress conditions; nevertheless these characteristics are mainly present in non-commercial varieties. Genetic breeding strategies represent an alternative to introduce the desirable characteristics into commercial varieties. A fundamental step for accelerating the genetic breeding process in cassava requires the identification of genes associated to these characteristics. One rapid strategy for the identification of genes is the possibility to have a large collection of ESTs (expressed sequence tag). In this study, a complete analysis of cassava ESTs was done. The cassava ESTs represent 80,459 sequences which were assembled in a set of 29,231 unique genes (unigen), comprising 10,945 contigs and 18,286 singletones. These 29,231 unique genes represent about 80% of the genes of the cassava's genome. Between 5% and 10% of the unigenes of cassava not show similarity to any sequences present in the NCBI database and could be consider as cassava specific genes. a functional category was assigned to a group of sequences of the unigen set (29%) following the Gene Ontology Vocabulary. the molecular function component was the best represented with 43% of the sequences, followed by the biological process component (38%) and finally the cellular component with 19%. in the cassava ESTs collection, 3,709 microsatellites were identified and they could be used as molecular markers. this study represents an important contribution to the knowledge of the functional genomic structure of cassava and constitutes an important tool for the identification of genes associated to agricultural characteristics of interest that could be employed in cassava breeding programs.

  2. Discovery and characterization of two new stem rust resistance genes in Aegilops sharonensis.

    Science.gov (United States)

    Yu, Guotai; Champouret, Nicolas; Steuernagel, Burkhard; Olivera, Pablo D; Simmons, Jamie; Williams, Cole; Johnson, Ryan; Moscou, Matthew J; Hernández-Pinzón, Inmaculada; Green, Phon; Sela, Hanan; Millet, Eitan; Jones, Jonathan D G; Ward, Eric R; Steffenson, Brian J; Wulff, Brande B H

    2017-06-01

    We identified two novel wheat stem rust resistance genes, Sr-1644-1Sh and Sr-1644-5Sh in Aegilops sharonensis that are effective against widely virulent African races of the wheat stem rust pathogen. Stem rust is one of the most important diseases of wheat in the world. When single stem rust resistance (Sr) genes are deployed in wheat, they are often rapidly overcome by the pathogen. To this end, we initiated a search for novel sources of resistance in diverse wheat relatives and identified the wild goatgrass species Aegilops sharonesis (Sharon goatgrass) as a rich reservoir of resistance to wheat stem rust. The objectives of this study were to discover and map novel Sr genes in Ae. sharonensis and to explore the possibility of identifying new Sr genes by genome-wide association study (GWAS). We developed two biparental populations between resistant and susceptible accessions of Ae. sharonensis and performed QTL and linkage analysis. In an F 6 recombinant inbred line and an F 2 population, two genes were identified that mapped to the short arm of chromosome 1S sh , designated as Sr-1644-1Sh, and the long arm of chromosome 5S sh , designated as Sr-1644-5Sh. The gene Sr-1644-1Sh confers a high level of resistance to race TTKSK (a member of the Ug99 race group), while the gene Sr-1644-5Sh conditions strong resistance to TRTTF, another widely virulent race found in Yemen. Additionally, GWAS was conducted on 125 diverse Ae. sharonensis accessions for stem rust resistance. The gene Sr-1644-1Sh was detected by GWAS, while Sr-1644-5Sh was not detected, indicating that the effectiveness of GWAS might be affected by marker density, population structure, low allele frequency and other factors.

  3. Discovery and characterization of novel vascular and hematopoietic genes downstream of etsrp in zebrafish.

    Directory of Open Access Journals (Sweden)

    Gustavo A Gomez

    Full Text Available The transcription factor Etsrp is required for vasculogenesis and primitive myelopoiesis in zebrafish. When ectopically expressed, etsrp is sufficient to induce the expression of many vascular and myeloid genes in zebrafish. The mammalian homolog of etsrp, ER71/Etv2, is also essential for vascular and hematopoietic development. To identify genes downstream of etsrp, gain-of-function experiments were performed for etsrp in zebrafish embryos followed by transcription profile analysis by microarray. Subsequent in vivo expression studies resulted in the identification of fourteen genes with blood and/or vascular expression, six of these being completely novel. Regulation of these genes by etsrp was confirmed by ectopic induction in etsrp overexpressing embryos and decreased expression in etsrp deficient embryos. Additional functional analysis of two newly discovered genes, hapln1b and sh3gl3, demonstrates their importance in embryonic vascular development. The results described here identify a group of genes downstream of etsrp likely to be critical for vascular and/or myeloid development.

  4. [Unexpected discovery of a fetus with DMD gene deletion using single nucleotide polymorphism array].

    Science.gov (United States)

    Lin, Shaobin; Zhou, Yu; Zhou, Bingyi; Gu, Heng

    2017-08-10

    To investigate the value of single nucleotide polymorphism array (SNP array) for the identification of de novo mutations in the DMD gene among fetuses. G-banded karyotyping and SNP array were performed on a fetus with intrauterine growth restriction but without family history of Duchenne/Becker muscular dystrophy (DMD/BMD). Multiplex ligation-dependent probe amplification (MLPA) was subsequently applied on amniocytes and maternal peripheral blood sample to detect DMD gene deletion/duplication mutations. Karyotyping of amniocytes showed a normal 46, XY karyotype. SNP array on amniocytes detected a 116 kb deletion (chrX: 32 455 741-32 571 504) at Xp21.1 with breakpoints at introns 16 and 30 respectively, encompassing exons 17-29 of the DMD gene. In addition, MLPA analysis of the DMD gene on amniocytes confirmed the deletion of exons 17 to 29 identified by SNP array. However, no deletion/duplication mutation was detected by MLPA in the mother. The de novo deletion of exons 17 to 29 of the DMD gene detected in the fetus may result in BMD or DMD. SNP array can improve the efficiency for detecting genomic disorders in fetuses with unidentified pathogenic genes, negative family history and nonspecific phenotypes.

  5. Heavy metals in sediments and soft tissues of the Antarctic clam Laternula elliptica: more evidence as a possible biomonitor of coastal marine pollution at high latitudes?

    Science.gov (United States)

    Vodopivez, Cristian; Curtosi, Antonio; Villaamil, Edda; Smichowski, Patricia; Pelletier, Emilien; Mac Cormack, Walter P

    2015-01-01

    Studies on metal contamination in 25 de Mayo Island, Antarctica, yielded controversial results. In this work, we analyzed Antarctic marine sediments and Antarctic clam (Laternula elliptica) tissues to investigate the possible use of this mollusk as a biomonitor of metals and to identify the sources of metal pollution. Different types of paint from several buildings from Carlini Station were examined to assess their contribution to the local and random metal pollution. Five sediment samples, 105 L. elliptica specimens (40.2-78.0mm length) and four types of paint were analyzed to quantify Cd, Cr, Cu, Fe, Mn, Pb and Zn using inductively coupled plasma-optical emission spectrometry. Metal concentrations in sediments were lower than the global averages of the earth's crust, with the exception of Cd and Cu. These results were related to the contribution of the local fresh-water runoff. The different varieties of paint showed low levels of Cu, Mn, Fe and Zn, whereas a broad range of values were found in the case of Cr and Pb (20-15,100 μg·g(-1) and 153-115,500 μg·g(-1) respectively). The remains of the paint would be responsible for the significant increases in Cr and Pb which are randomly detected by us and by other authors. High levels of Fe and Cd, in comparison to other Antarctic areas, appear to be related to the terrigenous materials transported by the local streams. Accumulation indexes suggested that kidney tissue from L. elliptica could be an adequate material for biomonitoring pollution with Cd, Zn and probably also Pb. In general, relationships between size and metal contents reported by other authors were not verified, suggesting that this issue should be revised. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling.

    Science.gov (United States)

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

    2014-02-01

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Ethnobotanical review and pharmacological properties of selected medicinal plants in Brunei Darussalam: Litsea elliptica, Dillenia suffruticosa, Dillenia excelsa, Aidia racemosa, Vitex pinnata and Senna alata

    Directory of Open Access Journals (Sweden)

    May Poh Yik Goh

    2017-02-01

    Full Text Available The aim of the current study is to review the medicinal properties of the plants found in Brunei Darussalam namely Litsea elliptica, Dillenia suffruticosa, Dillenia excelsa, Aidia racemosa, Vitex pinnata and Senna alata. The known phytochemical constituents of these plants and their ability to bring about a range of biological activities are included in this review. These plants have been used traditionally for a multitude of diseases and illnesses. There is a lot of untapped potential in these medicinal plants which could cure multiple diseases.

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

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    Warden Craig H

    2010-07-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

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

    2010-01-01

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

  13. Discovery of Phytophthora infestans genes expressed in planta through mining of cDNA libraries.

    Directory of Open Access Journals (Sweden)

    Roberto Sierra

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

  14. Gene-Expression-Guided Selection of Candidate Loci and Molecular Phenotype Analyses Enhance Genetic Discovery in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Yelena Koldobskaya

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-α. In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs for validation. The top 200 GWAS SNPs were searched in a database which compares genome-wide expression data to genome-wide SNP genotype data in HapMap cell lines. SNPs were chosen for validation if they were associated with differential expression of 15 or more genes at a significance of P<9×10−5. This resulted in 11 SNPs which were genotyped in 453 SLE patients and 418 matched controls. Three SNPs were associated with SLE-associated autoantibodies, and one of these SNPs was also associated with serum IFN-α (P<4.5×10−3 for all. One additional SNP was associated exclusively with serum IFN-α. Case-control analysis was insensitive to these molecular subphenotype associations. This study illustrates the use of gene expression data to rationally select candidate loci in autoimmune disease, and the utility of stratification by molecular phenotypes in the discovery of additional genetic associations in SLE.

  15. Gene-expression-guided selection of candidate loci and molecular phenotype analyses enhance genetic discovery in systemic lupus erythematosus.

    Science.gov (United States)

    Koldobskaya, Yelena; Ko, Kichul; Kumar, Akaash A; Agik, Sandra; Arrington, Jasmine; Kariuki, Silvia N; Franek, Beverly S; Kumabe, Marissa; Utset, Tammy O; Jolly, Meenakshi; Skol, Andrew D; Niewold, Timothy B

    2012-01-01

    Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS) of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-α). In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs) for validation. The top 200 GWAS SNPs were searched in a database which compares genome-wide expression data to genome-wide SNP genotype data in HapMap cell lines. SNPs were chosen for validation if they were associated with differential expression of 15 or more genes at a significance of P < 9 × 10(-5). This resulted in 11 SNPs which were genotyped in 453 SLE patients and 418 matched controls. Three SNPs were associated with SLE-associated autoantibodies, and one of these SNPs was also associated with serum IFN-α (P < 4.5 × 10(-3) for all). One additional SNP was associated exclusively with serum IFN-α. Case-control analysis was insensitive to these molecular subphenotype associations. This study illustrates the use of gene expression data to rationally select candidate loci in autoimmune disease, and the utility of stratification by molecular phenotypes in the discovery of additional genetic associations in SLE.

  16. Transcriptome analysis and discovery of genes involved in immune pathways from hepatopancreas of microbial challenged mitten crab Eriocheir sinensis.

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    Xihong Li

    Full Text Available 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; 10(8 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.

  17. Gene/QTL discovery for Anthracnose in common bean (Phaseolus vulgaris L.) from North-western Himalayas.

    Science.gov (United States)

    Choudhary, Neeraj; Bawa, Vanya; Paliwal, Rajneesh; Singh, Bikram; Bhat, Mohd Ashraf; Mir, Javid Iqbal; Gupta, Moni; Sofi, Parvaze A; Thudi, Mahendar; Varshney, Rajeev K; Mir, Reyazul Rouf

    2018-01-01

    Common bean (Phaseolus vulgaris L.) is one of the most important grain legume crops in the world. The beans grown in north-western Himalayas possess huge diversity for seed color, shape and size but are mostly susceptible to Anthracnose disease caused by seed born fungus Colletotrichum lindemuthianum. Dozens of QTLs/genes have been already identified for this disease in common bean world-wide. However, this is the first report of gene/QTL discovery for Anthracnose using bean germplasm from north-western Himalayas of state Jammu & Kashmir, India. A core set of 96 bean lines comprising 54 indigenous local landraces from 11 hot-spots and 42 exotic lines from 10 different countries were phenotyped at two locations (SKUAST-Jammu and Bhaderwah, Jammu) for Anthracnose resistance. The core set was also genotyped with genome-wide (91) random and trait linked SSR markers. The study of marker-trait associations (MTAs) led to the identification of 10 QTLs/genes for Anthracnose resistance. Among the 10 QTLs/genes identified, two MTAs are stable (BM45 & BM211), two MTAs (PVctt1 & BM211) are major explaining more than 20% phenotypic variation for Anthracnose and one MTA (BM211) is both stable and major. Six (06) genomic regions are reported for the first time, while as four (04) genomic regions validated the already known QTL/gene regions/clusters for Anthracnose. The major, stable and validated markers reported during the present study associated with Anthracnose resistance will prove useful in common bean molecular breeding programs aimed at enhancing Anthracnose resistance of local bean landraces grown in north-western Himalayas of state Jammu and Kashmir.

  18. A probabilistic approach for automated discovery of perturbed genes using expression data from microarray or RNA-Seq.

    Science.gov (United States)

    Sundaramurthy, Gopinath; Eghbalnia, Hamid R

    2015-12-01

    In complex diseases, alterations of multiple molecular and cellular components in response to perturbations are indicative of disease physiology. While expression level of genes from high-throughput analysis can vary among patients, the common path among disease progression suggests that the underlying cellular sub-processes involving associated genes follow similar fates. Motivated by the interconnected nature of sub-processes, we have developed an automated methodology that combines ideas from biological networks, statistical models, and game theory, to probe connected cellular processes. The core concept in our approach uses probability of change (POC) to indicate the probability that a gene's expression level has changed between two conditions. POC facilitates the definition of change at the neighborhood, pathway, and network levels and enables evaluation of the influence of diseases on the expression. The 'connected' disease-related genes (DRG) identified display coherent and concomitant differential expression levels along paths. RNA-Seq and microarray breast cancer subtyping expression data sets were used to identify DRG between subtypes. A machine-learning algorithm was trained for subtype discrimination using the DRG, and the training yielded a set of biomarkers. The discriminative power of the biomarkers was tested using an unseen data set. Biomarkers identified overlaps with disease-specific identified genes, and we were able to classify disease subtypes with 100% and 80% agreement with PAM50, for microarray and RNA-Seq data set respectively. We present an automated probabilistic approach that offers unbiased and reproducible results, thus complementing existing methods in DRG and biomarker discovery for complex diseases. Copyright © 2015. Published by Elsevier Ltd.

  19. The CHRNA5-A3-B4 Gene Cluster and Smoking: From Discovery to Therapeutics.

    Science.gov (United States)

    Lassi, Glenda; Taylor, Amy E; Timpson, Nicholas J; Kenny, Paul J; Mather, Robert J; Eisen, Tim; Munafò, Marcus R

    2016-12-01

    Genome-wide association studies (GWASs) have identified associations between the CHRNA5-CHRNA3-CHRNB4 gene cluster and smoking heaviness and nicotine dependence. Studies in rodents have described the anatomical localisation and function of the nicotinic acetylcholine receptors (nAChRs) formed by the subunits encoded by this gene cluster. Further investigations that complemented these studies highlighted the variability of individuals' smoking behaviours and their ability to adjust nicotine intake. GWASs of smoking-related health outcomes have also identified this signal in the CHRNA5-CHRNA3-CHRNB4 gene cluster. This insight underpins approaches to strengthen causal inference in observational data. Combining genetic and mechanistic studies of nicotine dependence and smoking heaviness may reveal novel targets for medication development. Validated targets can inform genetic therapeutic interventions for smoking cessation and tobacco-related diseases. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Discovery and characterization of two new stem rust resistance genes in Aegilops sharonensis

    OpenAIRE

    Yu, Guotai; Champouret, Nicolas; Steuernagel, Burkhard; Olivera, Pablo D.; Simmons, Jamie; Williams, Cole; Johnson, Ryan; Moscou, Matthew J.; Hern?ndez-Pinz?n, Inmaculada; Green, Phon; Sela, Hanan; Millet, Eitan; Jones, Jonathan D. G.; Ward, Eric R.; Steffenson, Brian J.

    2017-01-01

    Key message We identified two novel wheat stem rust resistance genes, Sr-1644-1Sh and Sr-1644-5Sh in Aegilops sharonensis that are effective against widely virulent African races of the wheat stem rust pathogen. Abstract Stem rust is one of the most important diseases of wheat in the world. When single stem rust resistance (Sr) genes are deployed in wheat, they are often rapidly overcome by the pathogen. To this end, we initiated a search for novel sources of resistance in diverse wheat relat...

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

    Science.gov (United States)

    Wyatt, Sarah

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

  2. A new essential protein discovery method based on the integration of protein-protein interaction and gene expression data

    Directory of Open Access Journals (Sweden)

    Li Min

    2012-03-01

    Full Text Available Abstract Background Identification of essential proteins is always a challenging task since it requires experimental approaches that are time-consuming and laborious. With the advances in high throughput technologies, a large number of protein-protein interactions are available, which have produced unprecedented opportunities for detecting proteins' essentialities from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. However, the network topology-based centrality measures are very sensitive to the robustness of network. Therefore, a new robust essential protein discovery method would be of great value. Results In this paper, we propose a new centrality measure, named PeC, based on the integration of protein-protein interaction and gene expression data. The performance of PeC is validated based on the protein-protein interaction network of Saccharomyces cerevisiae. The experimental results show that the predicted precision of PeC clearly exceeds that of the other fifteen previously proposed centrality measures: Degree Centrality (DC, Betweenness Centrality (BC, Closeness Centrality (CC, Subgraph Centrality (SC, Eigenvector Centrality (EC, Information Centrality (IC, Bottle Neck (BN, Density of Maximum Neighborhood Component (DMNC, Local Average Connectivity-based method (LAC, Sum of ECC (SoECC, Range-Limited Centrality (RL, L-index (LI, Leader Rank (LR, Normalized α-Centrality (NC, and Moduland-Centrality (MC. Especially, the improvement of PeC over the classic centrality measures (BC, CC, SC, EC, and BN is more than 50% when predicting no more than 500 proteins. Conclusions We demonstrate that the integration of protein-protein interaction network and gene expression data can help improve the precision of predicting essential proteins. The new centrality measure, PeC, is an effective essential protein discovery method.

  3. Controlling Botrytis elliptica Leaf Blight on Hybrid Lilies through the Application of Convergent Chemical X-ray Irradiation

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    Sung-Jun Hong

    2016-04-01

    Full Text Available X-ray irradiation with convergent chemicals such as nano-silver particles or sodium dichloroisocyanurate (NaDCC has been used to control leaf blight on cut lilies. The oriental hybrid lily cultivars Siberia, Le Reve, and Sorbonne were irradiated five times by 200 Gy of X-rays in 2014. In 2015, Siberia and Sorbonne were irradiated three times by 150 Gy of X-rays. After artificial infection with Botrytis elliptica on the leaves and petals of cut lilies, this study used convergent chemical X-ray irradiation of 200 Gy or 150 Gy. Leaf and petal blight was measured in terms of incidence and severity at 8 days after infection using total 552 cuttings. Results indicate that the treatments of X-ray irradiation and NaDCC in 2014 and 2015 slightly decreased the severity of petal blight on Siberia and Sorbonne. However, the results were not significant and severity did not decrease as NaDCC concentration increased. Vase-life was observed separately after X-ray irradiation of 270 cut lilies in 2014 and 108 cut lilies in 2015. Chlorophyll content was not affected by either 200 Gy or 150 Gy of X-rays. The number of days of fully opened flowers at Siberia of 150 Gy and Le Revu of 200 Gy increased by 1–2 days. In addition, the relative fresh weights of the X-rayed flowers were 10% drier than the non-irradiated controls. Overall, leaf blight control by X-ray was inferior to the control by gamma rays, and petal color was bleached in Sorbonne and Le Reve cvs. by 150 Gy of X-rays.

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

    Science.gov (United States)

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

    2010-01-01

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

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

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    Adam Y Ye

    Full Text Available 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.

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

    Science.gov (United States)

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

    2014-02-01

    Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis-eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis-eQTLs provided mechanistic evidence for two genome-wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role. © 2013 WILEY PERIODICALS, INC.

  7. Molecular mapping of soybean rust (Phakopsora pachyrhizi) resistance genes: discovery of a novel locus and alleles.

    Science.gov (United States)

    Garcia, Alexandre; Calvo, Eberson Sanches; de Souza Kiihl, Romeu Afonso; Harada, Arlindo; Hiromoto, Dario Minoru; Vieira, Luiz Gonzaga Esteves

    2008-08-01

    Soybean production in South and North America has recently been threatened by the widespread dissemination of soybean rust (SBR) caused by the fungus Phakopsora pachyrhizi. Currently, chemical spray containing fungicides is the only effective method to control the disease. This strategy increases production costs and exposes the environment to higher levels of fungicides. As a first step towards the development of SBR resistant cultivars, we studied the genetic basis of SBR resistance in five F2 populations derived from crossing the Brazilian-adapted susceptible cultivar CD 208 to each of five different plant introductions (PI 200487, PI 200526, PI 230970, PI 459025, PI 471904) carrying SBR-resistant genes (Rpp). Molecular mapping of SBR-resistance genes was performed in three of these PIs (PI 459025, PI 200526, PI 471904), and also in two other PIs (PI 200456 and 224270). The strategy mapped two genes present in PI 230970 and PI 459025, the original sources of Rpp2 and Rpp4, to linkage groups (LG) J and G, respectively. A new SBR resistance locus, rpp5 was mapped in the LG-N. Together, the genetic and molecular analysis suggested multiple alleles or closely linked genes that govern SBR resistance in soybean.

  8. Genome-Wide Discovery of Genes Required for Capsule Production by UropathogenicEscherichia coli.

    Science.gov (United States)

    Goh, Kelvin G K; Phan, Minh-Duy; Forde, Brian M; Chong, Teik Min; Yin, Wai-Fong; Chan, Kok-Gan; Ulett, Glen C; Sweet, Matthew J; Beatson, Scott A; Schembri, Mark A

    2017-10-24

    Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract and bloodstream infections and possesses an array of virulence factors for colonization, survival, and persistence. One such factor is the polysaccharide K capsule. Among the different K capsule types, the K1 serotype is strongly associated with UPEC infection. In this study, we completely sequenced the K1 UPEC urosepsis strain PA45B and employed a novel combination of a lytic K1 capsule-specific phage, saturated Tn 5 transposon mutagenesis, and high-throughput transposon-directed insertion site sequencing (TraDIS) to identify the complement of genes required for capsule production. Our analysis identified known genes involved in capsule biosynthesis, as well as two additional regulatory genes ( mprA and lrhA ) that we characterized at the molecular level. Mutation of mprA resulted in protection against K1 phage-mediated killing, a phenotype restored by complementation. We also identified a significantly increased unidirectional Tn 5 insertion frequency upstream of the lrhA gene and showed that strong expression of LrhA induced by a constitutive Pcl promoter led to loss of capsule production. Further analysis revealed loss of MprA or overexpression of LrhA affected the transcription of capsule biosynthesis genes in PA45B and increased sensitivity to killing in whole blood. Similar phenotypes were also observed in UPEC strains UTI89 (K1) and CFT073 (K2), demonstrating that the effects were neither strain nor capsule type specific. Overall, this study defined the genome of a UPEC urosepsis isolate and identified and characterized two new regulatory factors that affect UPEC capsule production. IMPORTANCE Urinary tract infections (UTIs) are among the most common bacterial infections in humans and are primarily caused by uropathogenic Escherichia coli (UPEC). Many UPEC strains express a polysaccharide K capsule that provides protection against host innate immune factors and contributes to survival

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

    LENUS (Irish Health Repository)

    Perry, Antoinette S

    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.

  10. Gene discovery in the threatened elkhorn coral: 454 sequencing of the Acropora palmata transcriptome.

    Directory of Open Access Journals (Sweden)

    Nicholas R Polato

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

  11. Gene discovery in the threatened elkhorn coral: 454 sequencing of the Acropora palmata transcriptome.

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Srinivasan Ramamurthy

    2009-11-01

    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.

  13. InFusion: Advancing Discovery of Fusion Genes and Chimeric Transcripts from Deep RNA-Sequencing Data.

    Directory of Open Access Journals (Sweden)

    Konstantin Okonechnikov

    Full Text Available Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found. The ability to detect gene fusions of different types, including isoform fusions and fusions involving non-coding regions, has not been thoroughly studied yet. Here, we propose a novel computational toolkit called InFusion for fusion gene detection from RNA-seq data. InFusion introduces several unique features, such as discovery of fusions involving intergenic regions, and detection of anti-sense transcription in chimeric RNAs based on strand-specificity. Our approach demonstrates superior detection accuracy on simulated data and several public RNA-seq datasets. This improved performance was also evident when evaluating data from RNA deep-sequencing of two well-established prostate cancer cell lines. InFusion identified 26 novel fusion events that were validated in vitro, including alternatively spliced gene fusion isoforms and chimeric transcripts that include intergenic regions. The toolkit is freely available to download from http:/bitbucket.org/kokonech/infusion.

  14. InFusion: Advancing Discovery of Fusion Genes and Chimeric Transcripts from Deep RNA-Sequencing Data.

    Science.gov (United States)

    Okonechnikov, Konstantin; Imai-Matsushima, Aki; Paul, Lukas; Seitz, Alexander; Meyer, Thomas F; Garcia-Alcalde, Fernando

    2016-01-01

    Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found. The ability to detect gene fusions of different types, including isoform fusions and fusions involving non-coding regions, has not been thoroughly studied yet. Here, we propose a novel computational toolkit called InFusion for fusion gene detection from RNA-seq data. InFusion introduces several unique features, such as discovery of fusions involving intergenic regions, and detection of anti-sense transcription in chimeric RNAs based on strand-specificity. Our approach demonstrates superior detection accuracy on simulated data and several public RNA-seq datasets. This improved performance was also evident when evaluating data from RNA deep-sequencing of two well-established prostate cancer cell lines. InFusion identified 26 novel fusion events that were validated in vitro, including alternatively spliced gene fusion isoforms and chimeric transcripts that include intergenic regions. The toolkit is freely available to download from http:/bitbucket.org/kokonech/infusion.

  15. NASA's GeneLab Phase II: Federated Search and Data Discovery

    Science.gov (United States)

    Berrios, Daniel C.; Costes, Sylvain V.; Tran, Peter B.

    2017-01-01

    GeneLab is currently being developed by NASA to accelerate 'open science' biomedical research in support of the human exploration of space and the improvement of life on earth. Phase I of the four-phase GeneLab Data Systems (GLDS) project emphasized capabilities for submission, curation, search, and retrieval of genomics, transcriptomics and proteomics ('omics') data from biomedical research of space environments. The focus of development of the GLDS for Phase II has been federated data search for and retrieval of these kinds of data across other open-access systems, so that users are able to conduct biological meta-investigations using data from a variety of sources. Such meta-investigations are key to corroborating findings from many kinds of assays and translating them into systems biology knowledge and, eventually, therapeutics.

  16. NASAs GeneLab Phase II: Federated Search and Data Discovery

    Science.gov (United States)

    Berrios, Daniel C.; Costes, Sylvain; Tran, Peter

    2017-01-01

    GeneLab is currently being developed by NASA to accelerate open science biomedical research in support of the human exploration of space and the improvement of life on earth. Phase I of the four-phase GeneLab Data Systems (GLDS) project emphasized capabilities for submission, curation, search, and retrieval of genomics, transcriptomics and proteomics (omics) data from biomedical research of space environments. The focus of development of the GLDS for Phase II has been federated data search for and retrieval of these kinds of data across other open-access systems, so that users are able to conduct biological meta-investigations using data from a variety of sources. Such meta-investigations are key to corroborating findings from many kinds of assays and translating them into systems biology knowledge and, eventually, therapeutics.

  17. Gene discovery for improvement of kernel quality-related traits in maize

    Directory of Open Access Journals (Sweden)

    Motto M.

    2010-01-01

    Full Text Available Developing maize plants with improved kernel quality traits involves the ability to use existing genetic variation and to identify and manipulate commercially important genes. This will open avenues for designing novel variation in grain composition and will provide the basis for the development of the next generation of specialty maize. This paper provides an overview of current knowledge on the identification and exploitation of genes affecting the composition, development, and structure of the maize kernel with particular emphasis on pathways relevant to endosperm growth and development, differentiation of starch-filled cells, and biosynthesis of starches, storage proteins, lipids, and carotenoids. The potential that the new technologies of cell and molecular biology will provide for the creation of new variation in the future are also indicated and discussed.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Yu Robert K

    2011-03-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

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

    2011-03-30

    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. 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. 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.

  1. Diversity of ribulose-1,5-bisphosphate carboxylase/oxygenase large-subunit genes in the MgCl2-dominated deep hypersaline anoxic basin discovery

    NARCIS (Netherlands)

    van der Wielen, PWJJ

    Partial sequences of the form I (cbbL) and form II (cbbM) of the ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) large subunit genes were obtained from the brine and interface of the MgCl2-dominated deep hypersaline anoxic basin Discovery. CbbL and cbbM genes were found in both brine and

  2. Transcriptomics Analysis of Crassostrea hongkongensis for the Discovery of Reproduction-Related Genes.

    Directory of Open Access Journals (Sweden)

    Ying Tong

    Full Text Available The reproductive mechanisms of mollusk species have been interesting targets in biological research because of the diverse reproductive strategies observed in this phylum. These species have also been studied for the development of fishery technologies in molluscan aquaculture. Although the molecular mechanisms underlying the reproductive process have been well studied in animal models, the relevant information from mollusks remains limited, particularly in species of great commercial interest. Crassostrea hongkongensis is the dominant oyster species that is distributed along the coast of the South China Sea and little genomic information on this species is available. Currently, high-throughput sequencing techniques have been widely used for investigating the basis of physiological processes and facilitating the establishment of adequate genetic selection programs.The C.hongkongensis transcriptome included a total of 1,595,855 reads, which were generated by 454 sequencing and were assembled into 41,472 contigs using de novo methods. Contigs were clustered into 33,920 isotigs and further grouped into 22,829 isogroups. Approximately 77.6% of the isogroups were successfully annotated by the Nr database. More than 1,910 genes were identified as being related to reproduction. Some key genes involved in germline development, sex determination and differentiation were identified for the first time in C.hongkongensis (nanos, piwi, ATRX, FoxL2, β-catenin, etc.. Gene expression analysis indicated that vasa, nanos, piwi, ATRX, FoxL2, β-catenin and SRD5A1 were highly or specifically expressed in C.hongkongensis gonads. Additionally, 94,056 single nucleotide polymorphisms (SNPs and 1,699 simple sequence repeats (SSRs were compiled.Our study significantly increased C.hongkongensis genomic information based on transcriptomics analysis. The group of reproduction-related genes identified in the present study constitutes a new tool for research on bivalve

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

    Science.gov (United States)

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

    2011-01-01

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

  4. Cultivation of Hard-To-Culture Subsurface Mercury-Resistant Bacteria and Discovery of New merA Gene Sequences▿

    Science.gov (United States)

    Rasmussen, L. D.; Zawadsky, C.; Binnerup, S. J.; Øregaard, G.; Sørensen, S. J.; Kroer, N.

    2008-01-01

    Mercury-resistant bacteria may be important players in mercury biogeochemistry. To assess the potential for mercury reduction by two subsurface microbial communities, resistant subpopulations and their merA genes were characterized by a combined molecular and cultivation-dependent approach. The cultivation method simulated natural conditions by using polycarbonate membranes as a growth support and a nonsterile soil slurry as a culture medium. Resistant bacteria were pregrown to microcolony-forming units (mCFU) before being plated on standard medium. Compared to direct plating, culturability was increased up to 2,800 times and numbers of mCFU were similar to the total number of mercury-resistant bacteria in the soils. Denaturing gradient gel electrophoresis analysis of DNA extracted from membranes suggested stimulation of growth of hard-to-culture bacteria during the preincubation. A total of 25 different 16S rRNA gene sequences were observed, including Alpha-, Beta-, and Gammaproteobacteria; Actinobacteria; Firmicutes; and Bacteroidetes. The diversity of isolates obtained by direct plating included eight different 16S rRNA gene sequences (Alpha- and Betaproteobacteria and Actinobacteria). Partial sequencing of merA of selected isolates led to the discovery of new merA sequences. With phylum-specific merA primers, PCR products were obtained for Alpha- and Betaproteobacteria and Actinobacteria but not for Bacteroidetes and Firmicutes. The similarity to known sequences ranged between 89 and 95%. One of the sequences did not result in a match in the BLAST search. The results illustrate the power of integrating advanced cultivation methodology with molecular techniques for the characterization of the diversity of mercury-resistant populations and assessing the potential for mercury reduction in contaminated environments. PMID:18441111

  5. Discovery of Metastatic Breast Cancer Suppressor Genes Using Functional Genome Analysis

    Science.gov (United States)

    2012-07-01

    al., 2008; Cheung,H.W., et al., 2011; Barbie ,D.A., et al., 2009]. To identify genes whose essentiality could be associated specifically with...Reference Barbie ,D.A., Tamayo,P., Boehm,J.S., Kim,S.Y., Moody,S.E., Dunn,I.F., Schinzel,A.C., Sandy,P., Meylan,E., Scholl,C., Frohling,S., Chan,E.M... Barbie ,D.A., Awad,T., Zhou,X., Nguyen,T., Piqani,B., Li,C., Golub,T.R., Meyerson,M., Hacohen,N., Hahn,W.C., Lander,E.S., Sabatini,D.M., and Root

  6. The long (and winding) road to gene discovery for canine hip dysplasia.

    Science.gov (United States)

    Zhu, Lan; Zhang, Zhiwu; Friedenberg, Steven; Jung, Seung-Woo; Phavaphutanon, Janjira; Vernier-Singer, Margaret; Corey, Elizabeth; Mateescu, Raluca; Dykes, Nathan; Sandler, Jody; Acland, Gregory; Lust, George; Todhunter, Rory

    2009-08-01

    Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.

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

    Science.gov (United States)

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

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Hahn Daniel A

    2009-05-01

    Full Text Available Abstract 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 (ES. 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

  9. Discovery of Gene Sources for Economic Traits in Hanwoo by Whole-genome Resequencing

    Directory of Open Access Journals (Sweden)

    Younhee Shin

    2016-09-01

    Full Text Available Hanwoo, a Korean native cattle (Bos taurus coreana, has great economic value due to high meat quality. Also, the breed has genetic variations that are associated with production traits such as health, disease resistance, reproduction, growth as well as carcass quality. In this study, next generation sequencing technologies and the availability of an appropriate reference genome were applied to discover a large amount of single nucleotide polymorphisms (SNPs in ten Hanwoo bulls. Analysis of whole-genome resequencing generated a total of 26.5 Gb data, of which 594,716,859 and 592,990,750 reads covered 98.73% and 93.79% of the bovine reference genomes of UMD 3.1 and Btau 4.6.1, respectively. In total, 2,473,884 and 2,402,997 putative SNPs were discovered, of which 1,095,922 (44.3% and 982,674 (40.9% novel SNPs were discovered against UMD3.1 and Btau 4.6.1, respectively. Among the SNPs, the 46,301 (UMD 3.1 and 28,613 SNPs (Btau 4.6.1 that were identified as Hanwoo-specific SNPs were included in the functional genes that may be involved in the mechanisms of milk production, tenderness, juiciness, marbling of Hanwoo beef and yellow hair. Most of the Hanwoo-specific SNPs were identified in the promoter region, suggesting that the SNPs influence differential expression of the regulated genes relative to the relevant traits. In particular, the non-synonymous (ns SNPs found in CORIN, which is a negative regulator of Agouti, might be a causal variant to determine yellow hair of Hanwoo. Our results will provide abundant genetic sources of variation to characterize Hanwoo genetics and for subsequent breeding.

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

    Directory of Open Access Journals (Sweden)

    Saville Barry J

    2007-09-01

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

  11. Métodos de superação de dormência em sementes de croada (Mouriri elliptica Mart Dormancy breaking methods in croada (Mouriri elliptica Mart seeds

    Directory of Open Access Journals (Sweden)

    Jaqueline Martins Vasconcelos

    2010-10-01

    Full Text Available Sementes de croada (Mouriri elliptica Mart. Melastomataceae, espécie frutífera nativa do cerrado, foram submetidas aos seguintes tratamentos, visando a superação de dormência: pré-resfriamento a 5° C por 7 dias; pré-aquecimento em estufa com circulação de ar a 40º C por 7 dias; escarificação química em ácido sulfúrico concentrado por 5 e 15 minutos; imersão em água fervente por 5 e 15 minutos; imersão em ácido giberélico a 100 e 200 mg L-1 por 48 horas; imersão em água destilada por 24 e 48 horas; escarificação mecânica com lixa nº 80 na parte superior e oposta ao eixo embrionário e testemunha (sementes sem tratamento prévio. Quatro repetições de quinze sementes foram colocadas para germinar sobre papel umedecido com água destilada ou nitrato de potássio a 0,2%, em temperatura de 30º C em presença de luz. Foram realizadas contagens diárias do 2º dia após a implantação do experimento até a estabilização da porcentagem de germinação, que acorreu no 60º dia. A germinação foi mais rápida em sementes pré-embebidas em ácido giberélico (em substrato umedecido com água ou com solução de nitrato de potássio 0,2%, pré-embebidas em água por 24 horas, em substrato umedecido com água, e pré-embebidas em água por 48 horas ou escarificadas mecanicamente e colocadas para germinar em substrato umedecido com água. Taxas de germinação mais elevadas ocorreram em sementes pré-embebidas em ácido giberélico a 100 ou 200 mg L-1, em substrato umedecido com solução de nitrato de potássio 0,2%.Croada seeds (Mouriri elliptica Mart. Melastomataceae, a fruit-bearing species native of the cerrado (savannah-like vegetation, were submitted to the following dormancy breaking methods: pre-cooling at 5° C for 7 days; pre-heating in a oven air circualtion at 40º C for 7 days; chemical escarification in concentrated sulfuric acid for 5 and 15 min; soaking in boiling water for 5 and 15 min; soaking in gibbereli

  12. Discovery of PPi-type Phosphoenolpyruvate Carboxykinase Genes in Eukaryotes and Bacteria*

    Science.gov (United States)

    Chiba, Yoko; Kamikawa, Ryoma; Nakada-Tsukui, Kumiko; Saito-Nakano, Yumiko; Nozaki, Tomoyoshi

    2015-01-01

    Phosphoenolpyruvate carboxykinase (PEPCK) is one of the pivotal enzymes that regulates the carbon flow of the central metabolism by fixing CO2 to phosphoenolpyruvate (PEP) to produce oxaloacetate or vice versa. Whereas ATP- and GTP-type PEPCKs have been well studied, and their protein identities are established, inorganic pyrophosphate (PPi)-type PEPCK (PPi-PEPCK) is poorly characterized. Despite extensive enzymological studies, its protein identity and encoding gene remain unknown. In this study, PPi-PEPCK has been identified for the first time from a eukaryotic human parasite, Entamoeba histolytica, by conventional purification and mass spectrometric identification of the native enzyme, followed by demonstration of its enzymatic activity. A homolog of the amebic PPi-PEPCK from an anaerobic bacterium Propionibacterium freudenreichii subsp. shermanii also exhibited PPi-PEPCK activity. The primary structure of PPi-PEPCK has no similarity to the functional homologs ATP/GTP-PEPCKs and PEP carboxylase, strongly suggesting that PPi-PEPCK arose independently from the other functional homologues and very likely has unique catalytic sites. PPi-PEPCK homologs were found in a variety of bacteria and some eukaryotes but not in archaea. The molecular identification of this long forgotten enzyme shows us the diversity and functional redundancy of enzymes involved in the central metabolism and can help us to understand the central metabolism more deeply. PMID:26269598

  13. Discovery of PPi-type Phosphoenolpyruvate Carboxykinase Genes in Eukaryotes and Bacteria.

    Science.gov (United States)

    Chiba, Yoko; Kamikawa, Ryoma; Nakada-Tsukui, Kumiko; Saito-Nakano, Yumiko; Nozaki, Tomoyoshi

    2015-09-25

    Phosphoenolpyruvate carboxykinase (PEPCK) is one of the pivotal enzymes that regulates the carbon flow of the central metabolism by fixing CO2 to phosphoenolpyruvate (PEP) to produce oxaloacetate or vice versa. Whereas ATP- and GTP-type PEPCKs have been well studied, and their protein identities are established, inorganic pyrophosphate (PPi)-type PEPCK (PPi-PEPCK) is poorly characterized. Despite extensive enzymological studies, its protein identity and encoding gene remain unknown. In this study, PPi-PEPCK has been identified for the first time from a eukaryotic human parasite, Entamoeba histolytica, by conventional purification and mass spectrometric identification of the native enzyme, followed by demonstration of its enzymatic activity. A homolog of the amebic PPi-PEPCK from an anaerobic bacterium Propionibacterium freudenreichii subsp. shermanii also exhibited PPi-PEPCK activity. The primary structure of PPi-PEPCK has no similarity to the functional homologs ATP/GTP-PEPCKs and PEP carboxylase, strongly suggesting that PPi-PEPCK arose independently from the other functional homologues and very likely has unique catalytic sites. PPi-PEPCK homologs were found in a variety of bacteria and some eukaryotes but not in archaea. The molecular identification of this long forgotten enzyme shows us the diversity and functional redundancy of enzymes involved in the central metabolism and can help us to understand the central metabolism more deeply. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

    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

  15. Ação do extrato metanólico e etanólico de Davilla elliptica St. Hill. (Malpighiaceae na resposta imune

    Directory of Open Access Journals (Sweden)

    I.Z. Carlos

    Full Text Available Plantas têm contribuído no tratamento da maioria das doenças. Considerando a importância terapêutica das plantas medicinais, foi avaliada a atividade imunológica dos extratos metanólico e etanólico de Davilla elliptica. Macrófagos estão envolvidos em todos estágios da resposta imune, podendo liberar componentes como: peróxido de hidrogênio (H2O2, óxido nítrico (NO e fator de necrose tumoral-alfa (TNF-alfa. A estimulação dos macrófagos foi avaliada pela determinação de H2O2, NO e TNF-alfa em culturas de macrófagos peritoneais de camundongos na presença dos extratos da D. elliptica. IC50 foi determinado através de ensaio utilizando MTT. Os estudos fitoquímicos realizados mostraram a presença de flavonóides derivados da quercetina e miricetina entre outros compostos. A produção de H2O2 não foi muito expressiva em ambos extratos, contudo a de NO foi significativa. Os dois extratos induziram a produção de TNF-alfa, sendo que a liberação dessa citocina pelo extrato metanólico foi quase cinco vezes maior do que pelo extrato etanólico. Uma relação entre as sínteses de NO e TNF-alfa foi observada. O aumento na produção de NO está relacionado com a indução de citocinas pró-inflamatórias como TNF-alfa. Analisando os resultados, sugere-se que os extratos metanólico e etanólico de D. elliptica podem modular a ativação de macrófagos.

  16. Interestingness measures and strategies for mining multi-ontology multi-level association rules from gene ontology annotations for the discovery of new GO relationships.

    Science.gov (United States)

    Manda, Prashanti; McCarthy, Fiona; Bridges, Susan M

    2013-10-01

    The Gene Ontology (GO), a set of three sub-ontologies, is one of the most popular bio-ontologies used for describing gene product characteristics. GO annotation data containing terms from multiple sub-ontologies and at different levels in the ontologies is an important source of implicit relationships between terms from the three sub-ontologies. Data mining techniques such as association rule mining that are tailored to mine from multiple ontologies at multiple levels of abstraction are required for effective knowledge discovery from GO annotation data. We present a data mining approach, Multi-ontology data mining at All Levels (MOAL) that uses the structure and relationships of the GO to mine multi-ontology multi-level association rules. We introduce two interestingness measures: Multi-ontology Support (MOSupport) and Multi-ontology Confidence (MOConfidence) customized to evaluate multi-ontology multi-level association rules. We also describe a variety of post-processing strategies for pruning uninteresting rules. We use publicly available GO annotation data to demonstrate our methods with respect to two applications (1) the discovery of co-annotation suggestions and (2) the discovery of new cross-ontology relationships. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  17. A dual transcript-discovery approach to improve the delimitation of gene features from RNA-seq data in the chicken model

    Directory of Open Access Journals (Sweden)

    Mickael Orgeur

    2018-01-01

    Full Text Available The sequence of the chicken genome, like several other draft genome sequences, is presently not fully covered. Gaps, contigs assigned with low confidence and uncharacterized chromosomes result in gene fragmentation and imprecise gene annotation. Transcript abundance estimation from RNA sequencing (RNA-seq data relies on read quality, library complexity and expression normalization. In addition, the quality of the genome sequence used to map sequencing reads, and the gene annotation that defines gene features, must also be taken into account. A partially covered genome sequence causes the loss of sequencing reads from the mapping step, while an inaccurate definition of gene features induces imprecise read counts from the assignment step. Both steps can significantly bias interpretation of RNA-seq data. Here, we describe a dual transcript-discovery approach combining a genome-guided gene prediction and a de novo transcriptome assembly. This dual approach enabled us to increase the assignment rate of RNA-seq data by nearly 20% as compared to when using only the chicken reference annotation, contributing therefore to a more accurate estimation of transcript abundance. More generally, this strategy could be applied to any organism with partial genome sequence and/or lacking a manually-curated reference annotation in order to improve the accuracy of gene expression studies.

  18. A dual transcript-discovery approach to improve the delimitation of gene features from RNA-seq data in the chicken model.

    Science.gov (United States)

    Orgeur, Mickael; Martens, Marvin; Börno, Stefan T; Timmermann, Bernd; Duprez, Delphine; Stricker, Sigmar

    2018-01-17

    The sequence of the chicken genome, like several other draft genome sequences, is presently not fully covered. Gaps, contigs assigned with low confidence and uncharacterized chromosomes result in gene fragmentation and imprecise gene annotation. Transcript abundance estimation from RNA sequencing (RNA-seq) data relies on read quality, library complexity and expression normalization. In addition, the quality of the genome sequence used to map sequencing reads, and the gene annotation that defines gene features, must also be taken into account. A partially covered genome sequence causes the loss of sequencing reads from the mapping step, while an inaccurate definition of gene features induces imprecise read counts from the assignment step. Both steps can significantly bias interpretation of RNA-seq data. Here, we describe a dual transcript-discovery approach combining a genome-guided gene prediction and a de novo transcriptome assembly. This dual approach enabled us to increase the assignment rate of RNA-seq data by nearly 20% as compared to when using only the chicken reference annotation, contributing therefore to a more accurate estimation of transcript abundance. More generally, this strategy could be applied to any organism with partial genome sequence and/or lacking a manually-curated reference annotation in order to improve the accuracy of gene expression studies. © 2018. Published by The Company of Biologists Ltd.

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

    Directory of Open Access Journals (Sweden)

    Wynhoven Brian

    2011-03-01

    Full Text Available Abstract Background Rust fungi are biotrophic basidiomycete plant pathogens that cause major diseases on plants and trees world-wide, affecting agriculture and forestry. Their biotrophic nature precludes many established molecular genetic manipulations and lines of research. The generation of genomic resources for these microbes is leading to novel insights into biology such as interactions with the hosts and guiding directions for breakthrough research in plant pathology. Results To support gene discovery and gene model verification in the genome of the wheat leaf rust fungus, Puccinia triticina (Pt, we have generated Expressed Sequence Tags (ESTs by sampling several life cycle stages. We focused on several spore stages and isolated haustorial structures from infected wheat, generating 17,684 ESTs. We produced sequences from both the sexual (pycniospores, aeciospores and teliospores and asexual (germinated urediniospores stages of the life cycle. From pycniospores and aeciospores, produced by infecting the alternate host, meadow rue (Thalictrum speciosissimum, 4,869 and 1,292 reads were generated, respectively. We generated 3,703 ESTs from teliospores produced on the senescent primary wheat host. Finally, we generated 6,817 reads from haustoria isolated from infected wheat as well as 1,003 sequences from germinated urediniospores. Along with 25,558 previously generated ESTs, we compiled a database of 13,328 non-redundant sequences (4,506 singlets and 8,822 contigs. Fungal genes were predicted using the EST version of the self-training GeneMarkS algorithm. To refine the EST database, we compared EST sequences by BLASTN to a set of 454 pyrosequencing-generated contigs and Sanger BAC-end sequences derived both from the Pt genome, and to ESTs and genome reads from wheat. A collection of 6,308 fungal genes was identified and compared to sequences of the cereal rusts, Puccinia graminis f. sp. tritici (Pgt and stripe rust, P. striiformis f. sp

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

    Science.gov (United States)

    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…

  1. An integrative data analysis platform for gene set analysis and knowledge discovery in a data warehouse framework.

    Science.gov (United States)

    Chen, Yi-An; Tripathi, Lokesh P; Mizuguchi, Kenji

    2016-01-01

    Data analysis is one of the most critical and challenging steps in drug discovery and disease biology. A user-friendly resource to visualize and analyse high-throughput data provides a powerful medium for both experimental and computational biologists to understand vastly different biological data types and obtain a concise, simplified and meaningful output for better knowledge discovery. We have previously developed TargetMine, an integrated data warehouse optimized for target prioritization. Here we describe how upgraded and newly modelled data types in TargetMine can now survey the wider biological and chemical data space, relevant to drug discovery and development. To enhance the scope of TargetMine from target prioritization to broad-based knowledge discovery, we have also developed a new auxiliary toolkit to assist with data analysis and visualization in TargetMine. This toolkit features interactive data analysis tools to query and analyse the biological data compiled within the TargetMine data warehouse. The enhanced system enables users to discover new hypotheses interactively by performing complicated searches with no programming and obtaining the results in an easy to comprehend output format. Database URL: http://targetmine.mizuguchilab.org. © The Author(s) 2016. Published by Oxford University Press.

  2. In-depth cDNA library sequencing provides quantitative gene expression profiling in cancer biomarker discovery.

    Science.gov (United States)

    Yang, Wanling; Ying, Dingge; Lau, Yu-Lung

    2009-06-01

    Quantitative gene expression analysis plays an important role in identifying differentially expressed genes in various pathological states, gene expression regulation and co-regulation, shedding light on gene functions. Although microarray is widely used as a powerful tool in this regard, it is suboptimal quantitatively and unable to detect unknown gene variants. Here we demonstrated effective detection of differential expression and co-regulation of certain genes by expressed sequence tag analysis using a selected subset of cDNA libraries. We discussed the issues of sequencing depth and library preparation, and propose that increased sequencing depth and improved preparation procedures may allow detection of many expression features for less abundant gene variants. With the reduction of sequencing cost and the emerging of new generation sequencing technology, in-depth sequencing of cDNA pools or libraries may represent a better and powerful tool in gene expression profiling and cancer biomarker detection. We also propose using sequence-specific subtraction to remove hundreds of the most abundant housekeeping genes to increase sequencing depth without affecting relative expression ratio of other genes, as transcripts from as few as 300 most abundantly expressed genes constitute about 20% of the total transcriptome. In-depth sequencing also represents a unique advantage of detecting unknown forms of transcripts, such as alternative splicing variants, fusion genes, and regulatory RNAs, as well as detecting mutations and polymorphisms that may play important roles in disease pathogenesis.

  3. Volatility Discovery

    DEFF Research Database (Denmark)

    Dias, Gustavo Fruet; Scherrer, Cristina; Papailias, Fotis

    The price discovery literature investigates how homogenous securities traded on different markets incorporate information into prices. We take this literature one step further and investigate how these markets contribute to stochastic volatility (volatility discovery). We formally show...... that the realized measures from homogenous securities share a fractional stochastic trend, which is a combination of the price and volatility discovery measures. Furthermore, we show that volatility discovery is associated with the way that market participants process information arrival (market sensitivity......). Finally, we compute volatility discovery for 30 actively traded stocks in the U.S. and report that Nyse and Arca dominate Nasdaq....

  4. The Analysis of Multiple Genome Comparisons in Genus Escherichia and Its Application to the Discovery of Uncharacterised Metabolic Genes in Uropathogenic Escherichia coli CFT073

    Directory of Open Access Journals (Sweden)

    William A. Bryant

    2009-01-01

    Full Text Available A survey of a complete gene synteny comparison has been carried out between twenty fully sequenced strains from the genus Escherichia with the aim of finding yet uncharacterised genes implicated in the metabolism of uropathogenic strains of E. coli (UPEC. Several sets of adjacent colinear genes have been identified which are present in all four UPEC included in this study (CFT073, F11, UTI89, and 536, annotated with putative metabolic functions, but are not found in any other strains considered. An operon closely homologous to that encoding the L-sorbose degradation pathway in Klebsiella pneumoniae has been identified in E. coli CFT073; this operon is present in all of the UPEC considered, but only in 7 of the other 16 strains. The operon's function has been confirmed by cloning the genes into E. coli DH5α and testing for growth on L-sorbose. The functional genomic approach combining in silico and in vitro work presented here can be used as a basis for the discovery of other uncharacterised genes contributing to bacterial survival in specific environments.

  5. QTL mapping and candidate gene discovery in potato for resistance to the Verticillium wilt pathogen Verticillium dahliae

    Science.gov (United States)

    Verticillium wilt (VW) of potato (Solanum tuberosum), caused by fungal pathogens, Verticillium dahliae and V. albo atrum, is a disease of major significance throughout the potato growing regions in the world. In the past, researchers have focused on the Ve gene, which is a major dominant gene that c...

  6. From mutation identification to therapy: discovery and origins of the first approved gene therapy in the Western world

    NARCIS (Netherlands)

    Kastelein, John J. P.; Ross, Colin J. D.; Hayden, Michael R.

    2013-01-01

    On November 2, 2012, Glybera® (alipogene tipovarvec) was the first human gene therapy to receive long awaited market approval in the Western world. This important milestone is expected to open the door to additional gene therapies for the treatment of many diseases in the future. The development of

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-20

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

  8. Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products.

    Science.gov (United States)

    Gubbens, Jacob; Zhu, Hua; Girard, Geneviève; Song, Lijiang; Florea, Bogdan I; Aston, Philip; Ichinose, Koji; Filippov, Dmitri V; Choi, Young H; Overkleeft, Herman S; Challis, Gregory L; van Wezel, Gilles P

    2014-06-19

    Information on gene clusters for natural product biosynthesis is accumulating rapidly because of the current boom of available genome sequencing data. However, linking a natural product to a specific gene cluster remains challenging. Here, we present a widely applicable strategy for the identification of gene clusters for specific natural products, which we name natural product proteomining. The method is based on using fluctuating growth conditions that ensure differential biosynthesis of the bioactivity of interest. Subsequent combination of metabolomics and quantitative proteomics establishes correlations between abundance of natural products and concomitant changes in the protein pool, which allows identification of the relevant biosynthetic gene cluster. We used this approach to elucidate gene clusters for different natural products in Bacillus and Streptomyces, including a novel juglomycin-type antibiotic. Natural product proteomining does not require prior knowledge of the gene cluster or secondary metabolite and therefore represents a general strategy for identification of all types of gene clusters. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. A comparison of digital gene expression profiling and methyl DNA immunoprecipitation as methods for gene discovery in honeybee (Apis mellifera behavioural genomic analyses.

    Directory of Open Access Journals (Sweden)

    Cui Guan

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

  10. Cogena, a novel tool for co-expressed gene-set enrichment analysis, applied to drug repositioning and drug mode of action discovery.

    Science.gov (United States)

    Jia, Zhilong; Liu, Ying; Guan, Naiyang; Bo, Xiaochen; Luo, Zhigang; Barnes, Michael R

    2016-05-27

    Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the "black box" nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context. We demonstrate that the analysis of co-expressed genes may be a critical first step towards illumination of both disease pathology and mode of drug action. We achieve this using a novel framework, co-expressed gene-set enrichment analysis (cogena) for co-expression analysis of gene expression signatures and gene set enrichment analysis of co-expressed genes. The cogena framework enables simultaneous, pathway driven, disease and drug repositioning analysis. Cogena can be used to illuminate coordinated changes within disease transcriptomes and identify drugs acting mechanistically within this framework. We illustrate this using a psoriatic skin transcriptome, as an exemplar, and recover two widely used Psoriasis drugs (Methotrexate and Ciclosporin) with distinct modes of action. Cogena out-performs the results of Connectivity Map and NFFinder webservers in similar disease transcriptome analyses. Furthermore, we investigated the literature support for the other top-ranked compounds to treat psoriasis and showed how the outputs of cogena analysis can contribute new insight to support the progression of drugs into the clinic. We have made cogena freely available within Bioconductor or https://github.com/zhilongjia/cogena . In conclusion, by targeting co-expressed genes within disease transcriptomes, cogena offers novel biological insight, which can be effectively harnessed for drug discovery and

  11. De novo assembly, gene annotation, and marker discovery in stored-product pest Liposcelis entomophila (Enderlein using transcriptome sequences.

    Directory of Open Access Journals (Sweden)

    Dan-Dan Wei

    Full Text Available 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

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

    Directory of Open Access Journals (Sweden)

    Ju-Chun Hsu

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

  13. Beyond Discovery

    DEFF Research Database (Denmark)

    Korsgaard, Steffen; Sassmannshausen, Sean Patrick

    2017-01-01

    In this chapter we explore four alternatives to the dominant discovery view of entrepreneurship; the development view, the construction view, the evolutionary view, and the Neo-Austrian view. We outline the main critique points of the discovery presented in these four alternatives, as well as the...

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

    Directory of Open Access Journals (Sweden)

    Sugantham Priyanka Annabel

    2010-10-01

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

  15. Whole genome shotgun sequencing of Brassica oleracea and its application to gene discovery and annotation in Arabidopsis.

    Science.gov (United States)

    Ayele, Mulu; Haas, Brian J; Kumar, Nikhil; Wu, Hank; Xiao, Yongli; Van Aken, Susan; Utterback, Teresa R; Wortman, Jennifer R; White, Owen R; Town, Christopher D

    2005-04-01

    Through comparative studies of the model organism Arabidopsis thaliana and its close relative Brassica oleracea, we have identified conserved regions that represent potentially functional sequences overlooked by previous Arabidopsis genome annotation methods. A total of 454,274 whole genome shotgun sequences covering 283 Mb (0.44 x) of the estimated 650 Mb Brassica genome were searched against the Arabidopsis genome, and conserved Arabidopsis genome sequences (CAGSs) were identified. Of these 229,735 conserved regions, 167,357 fell within or intersected existing gene models, while 60,378 were located in previously unannotated regions. After removal of sequences matching known proteins, CAGSs that were close to one another were chained together as potentially comprising portions of the same functional unit. This resulted in 27,347 chains of which 15,686 were sufficiently distant from existing gene annotations to be considered a novel conserved unit. Of 192 conserved regions examined, 58 were found to be expressed in our cDNA populations. Rapid amplification of cDNA ends (RACE) was used to obtain potentially full-length transcripts from these 58 regions. The resulting sequences led to the creation of 21 gene models at 17 new Arabidopsis loci and the addition of splice variants or updates to another 19 gene structures. In addition, CAGSs overlapping already annotated genes in Arabidopsis can provide guidance for manual improvement of existing gene models. Published genome-wide expression data based on whole genome tiling arrays and massively parallel signature sequencing were overlaid on the Brassica-Arabidopsis conserved sequences, and 1399 regions of intersection were identified. Collectively our results and these data sets suggest that several thousand new Arabidopsis genes remain to be identified and annotated.

  16. A Population of Deletion Mutants and an Integrated Mapping and Exome-seq Pipeline for Gene Discovery in Maize

    Science.gov (United States)

    Jia, Shangang; Li, Aixia; Morton, Kyla; Avoles-Kianian, Penny; Kianian, Shahryar F.; Zhang, Chi; Holding, David

    2016-01-01

    To better understand maize endosperm filling and maturation, we used γ-irradiation of the B73 maize reference line to generate mutants with opaque endosperm and reduced kernel fill phenotypes, and created a population of 1788 lines including 39 Mo17 × F2s showing stable, segregating, and viable kernel phenotypes. For molecular characterization of the mutants, we developed a novel functional genomics platform that combined bulked segregant RNA and exome sequencing (BSREx-seq) to map causative mutations and identify candidate genes within mapping intervals. To exemplify the utility of the mutants and provide proof-of-concept for the bioinformatics platform, we present detailed characterization of line 937, an opaque mutant harboring a 6203 bp in-frame deletion covering six exons within the Opaque-1 gene. In addition, we describe mutant line 146 which contains a 4.8 kb intragene deletion within the Sugary-1 gene and line 916 in which an 8.6 kb deletion knocks out a Cyclin A2 gene. The publically available algorithm developed in this work improves the identification of causative deletions and its corresponding gaps within mapping peaks. This study demonstrates the utility of γ-irradiation for forward genetics in large nondense genomes such as maize since deletions often affect single genes. Furthermore, we show how this classical mutagenesis method becomes applicable for functional genomics when combined with state-of-the-art genomics tools. PMID:27261000

  17. Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets.

    Science.gov (United States)

    Goonesekere, Nalin C W; Andersen, Wyatt; Smith, Alex; Wang, Xiaosheng

    2018-02-01

    The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines. This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC. While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.

  18. Functional gene-guided discovery of type II polyketides from culturable actinomycetes associated with soft coral Scleronephthya sp.

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    Wei Sun

    Full Text Available 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(α (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.

  19. Discovery, Annotation, and Functional Analysis of Long Noncoding RNAs Controlling Cell Cycle Gene Expression and Proliferation in Breast Cancer Cells

    Science.gov (United States)

    Sun, Miao; Gadad, Shrikanth S.; Kim, Dae-Seok; Kraus, W. Lee

    2015-01-01

    SUMMARY We describe a computational approach that integrates GRO-seq and RNA-seq data to annotate long noncoding RNAs (lncRNAs), with increased sensitivity for low abundance lncRNAs. We used this approach to characterize the lncRNA transcriptome in MCF-7 human breast cancer cells, including >700 previously unannotated lncRNAs. We then used information about the (1) transcription of lncRNA genes from GRO-seq, (2) steady-state levels of lncRNA transcripts in cell lines and patient samples from RNA-seq, and (3) histone modifications and factor binding at lncRNA gene promoters from ChIP-seq to explore lncRNA gene structure and regulation, as well as lncRNA transcript stability, regulation, and function. Functional analysis of selected lncRNAs with altered expression in breast cancers revealed roles in cell proliferation, regulation of an E2F-dependent cell cycle gene expression program, and estrogen-dependent mitogenic growth. Collectively, our studies demonstrate the use of an integrated genomic and molecular approach to identify and characterize growth-regulating lncRNAs in cancers. PMID:26236012

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

    Science.gov (United States)

    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 KSα (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

  1. Transcriptome analysis of the white body of the squid Euprymna tasmanica with emphasis on immune and hematopoietic gene discovery.

    Directory of Open Access Journals (Sweden)

    Karla A Salazar

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

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

    NARCIS (Netherlands)

    Kema, G.H.J.; Lee, van der T.A.J.; Mendes, O.; Verstappen, E.C.P.; Klein Lankhorst, R.M.; Sandbrink, H.; Burgt, van der A.; Zwiers, L.H.; Csukai, M.; Waalwijk, C.

    2008-01-01

    The foliar disease septoria tritici blotch, caused by the fungus Mycosphaerella graminicola, is currently the most important wheat disease in Europe. Gene expression was examined under highly different conditions, using 10 expressed sequence tag libraries generated from M. graminicola isolate IPO323

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

    Science.gov (United States)

    Gaur, Rashmi; Bhatia, Sabhyata; Gupta, Meetu

    2014-07-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  5. Comprehensive analysis of differential genes and miRNA profiles for discovery of topping-responsive genes in flue-cured tobacco roots.

    Science.gov (United States)

    Qi, Yuancheng; Guo, Hongxiang; Li, Ke; Liu, Weiqun

    2012-03-01

    Decapitation/topping is an important cultivating measure for flue-cured tobacco, and diverse biology processes are changed to respond to the topping, such as hormonal balance, root development, source-sink relationship, ability of nicotine synthesis and stress tolerance. The purpose of this study was to clarify the molecular mechanism involved in the response of flue-cured tobacco to topping. The differentially expressed genes and micro RNAs (miRNAs) before and after topping were screened with a combination of suppression subtractive hybridization (SSH) and miRNA deep sequencing. In all, 560 differently expressed clones were sequenced by SSH, and then 129 high quality expressed sequence tags were acquired. These expressed sequence tags were mainly involved in secondary metabolism (13.5%), hormone metabolism (4%), signaling/transcription (17.5%), stress/defense (20%), protein metabolism (13%), carbon metabolism (7%), other metabolism (12%) and unknown function (13%). The results contribute new data to the list of possible candidate genes involved in the response of flue-cured tobacco to topping. NAC transcription factor, a differential gene identified by SSH, had been proved to have a role in the regulation of nicotine biosynthesis. High-throughput sequencing of two small RNA libraries in combination with SSH screening revealed 15 differential miRNAs whose target genes were identical to some differential genes identified in SSH, suggesting that miRNAs play a critical role in post-transcriptional gene regulation in the response of flue-cured tobacco to decapitation. Based on the role of these miRNAs and differential genes identified from SSH in response to topping, an miRNA mediated model for flue-cured tobacco in response to topping is proposed. © 2012 The Authors Journal compilation © 2012 FEBS.

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

    Science.gov (United States)

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

    2012-01-01

    Background Eustigmatos 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 non-model microalgae species, E. cf. polyphem, and identify pathways and genes of importance related to biofuel production. Results We performed the de novo assembly of E. cf. polyphem transcriptome using Illumina paired-end sequencing technology. In a single run, we produced 29,199,432 sequencing reads corresponding to 2.33 Gb total nucleotides. These reads were assembled into 75,632 unigenes with a mean size of 503 bp and an N50 of 663 bp, ranging from 100 bp to >3,000 bp. Assembled unigenes were subjected to BLAST similarity searches and annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology identifiers. These analyses identified the majority of carbohydrate, fatty acids, TAG and carotenoids biosynthesis and catabolism pathways in E. cf. polyphem. Conclusions Our data provides the construction of metabolic pathways involved in the biosynthesis and catabolism of carbohydrate, fatty acids, TAG and carotenoids in E. cf. polyphem and provides 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:22536352

  7. Gene Discovery and Advances in Finger Millet [Eleusine coracana (L.) Gaertn.] Genomics-An Important Nutri-Cereal of Future.

    Science.gov (United States)

    Sood, Salej; Kumar, Anil; Babu, B Kalyana; Gaur, Vikram S; Pandey, Dinesh; Kant, Lakshmi; Pattnayak, Arunava

    2016-01-01

    The rapid strides in molecular marker technologies followed by genomics, and next generation sequencing advancements in three major crops (rice, maize and wheat) of the world have given opportunities for their use in the orphan, but highly valuable future crops, including finger millet [ Eleusine coracana (L.) Gaertn.]. Finger millet has many special agronomic and nutritional characteristics, which make it an indispensable crop in arid, semi-arid, hilly and tribal areas of India and Africa. The crop has proven its adaptability in harsh conditions and has shown resilience to climate change. The adaptability traits of finger millet have shown the advantage over major cereal grains under stress conditions, revealing it as a storehouse of important genomic resources for crop improvement. Although new technologies for genomic studies are now available, progress in identifying and tapping these important alleles or genes is lacking. RAPDs were the default choice for genetic diversity studies in the crop until the last decade, but the subsequent development of SSRs and comparative genomics paved the way for the marker assisted selection in finger millet. Resistance gene homologs from NBS-LRR region of finger millet for blast and sequence variants for nutritional traits from other cereals have been developed and used invariably. Population structure analysis studies exhibit 2-4 sub-populations in the finger millet gene pool with separate grouping of Indian and exotic genotypes. Recently, the omics technologies have been efficiently applied to understand the nutritional variation, drought tolerance and gene mining. Progress has also occurred with respect to transgenics development. This review presents the current biotechnological advancements along with research gaps and future perspective of genomic research in finger millet.

  8. Gene Discovery and Advances in Finger millet [Eleusine coracana (L. Gaertn.] Genomics - An Important Nutri-cereal of Future

    Directory of Open Access Journals (Sweden)

    Salej Sood

    2016-11-01

    Full Text Available The rapid strides in molecular marker technologies followed by genomics, and next generation sequencing advancements in three major crops (rice, maize and wheat of the world have given opportunities for their use in the orphan, but highly valuable future crops, including finger millet [Eleusine coracana (L. Gaertn.]. Finger millet has many special agronomic and nutritional characteristics, which make it an indispensable crop in arid, semi-arid, hilly and tribal areas of India and Africa. The crop has proven its adaptability in harsh conditions and has shown resilience to climate change. The adaptability traits of finger millet have shown the advantage over major cereal grains under stress conditions, revealing it as a storehouse of important genomic resources for crop improvement. Although new technologies for genomic studies are now available, progress in identifying and tapping these important alleles or genes is lacking. RAPDs were the default choice for genetic diversity studies in the crop until the last decade, but the subsequent development of SSRs and comparative genomics paved the way for the marker assisted selection in finger millet. Resistance gene homologues from NBS-LRR region of finger millet for blast and sequence variants for nutritional traits from other cereals have been developed and used invariably. Population structure analysis studies exhibit 2-4 sub-populations in the finger millet gene pool with separate grouping of Indian and exotic genotypes. Recently, the omics technologies have been efficiently applied to understand the nutritional variation, drought tolerance and gene mining. Progress has also occurred with respect to transgenics development. This review presents the current biotechnological advancements along with research gaps and future perspective of genomic research in finger millet.

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

    Directory of Open Access Journals (Sweden)

    Sivaganesan Siva

    2007-08-01

    Full Text Available Abstract 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, with the goal of identifying and characterizing TMs, is an important open problem in computational biomedicine. Results We developed and validated a novel probabilistic model and related computational procedure for identifying TMs by jointly modeling gene expression and ChIP-chip binding data. We demonstrate an improved functional coherence of the TMs produced by the new method when compared to either analyzing expression or ChIP-chip data separately or to alternative approaches for joint analysis. We also demonstrate the ability of the new algorithm to identify novel regulatory relationships not revealed by ChIP-chip data alone. The new computational procedure can be used in more or less the same way as one would use simple hierarchical clustering without performing any special transformation of data prior to the analysis. The R and C-source code for implementing our algorithm is incorporated within the R package gimmR which is freely available at http://eh3.uc.edu/gimm. Conclusion Our results indicate that, whenever available, ChIP-chip and expression data should be analyzed within the unified probabilistic modeling framework, which will likely result in improved clusters of co-regulated genes and improved ability to detect meaningful regulatory relationships. Given the good statistical properties and the ease of use, the new computational procedure offers a worthy new tool for reconstructing transcriptional regulatory networks.

  10. Using gene expression databases for classical trait QTL candidate gene discovery in the BXD recombinant inbred genetic reference population: Mouse forebrain weight

    Directory of Open Access Journals (Sweden)

    Zhou Jianhua

    2008-09-01

    Full Text Available Abstract Background Successful strategies for QTL gene identification benefit from combined experimental and bioinformatic approaches. Unique design aspects of the BXD recombinant inbred line mapping panel allow use of archived gene microarray expression data to filter likely from unlikely candidates. This prompted us to propose a simple five-filter protocol for candidate nomination. To filter more likely from less likely candidates, we required candidate genes near to the QTL to have mRNA abundance that correlated with the phenotype among the BXD lines as well as differed between the parental lines C57BL/6J and DBA/2J. We also required verification of mRNA abundance by an independent method, and finally we required either differences in protein levels or confirmed DNA sequence differences. Results QTL mapping of mouse forebrain weight in 34 BXD RI lines found significant association on chromosomes 1 and 11, with each C57BL/6J allele increasing weight by more than half a standard deviation. The intersection of gene lists that were within ± 10 Mb of the strongest associated location, that had forebrain mRNA abundance correlated with forebrain weight among the BXD, and that had forebrain mRNA abundance differing between C57BL/6J and DBA/2J, produced two candidates, Tnni1 (troponin 1 and Asb3 (ankyrin repeat and SOCS box-containing protein 3. Quantitative RT-PCR confirmed the direction of an increased expression in C57BL/6J genotype over the DBA/2J genotype for both genes, a difference that translated to a 2-fold difference in Asb3 protein. Although Tnni1 protein differences could not be confirmed, a 273 bp indel polymorphism was discovered 1 Kb upstream of the transcription start site. Conclusion Delivery of well supported candidate genes following a single quantitative trait locus mapping experiment is difficult. However, by combining available gene expression data with QTL mapping, we illustrated a five-filter protocol that nominated Asb3 and

  11. Gene-based therapies of neuromuscular disorders: an update and the pivotal role of patient organizations in their discovery and implementation.

    Science.gov (United States)

    Braun, Serge

    2013-01-01

    This review updates the state-of-the art accomplishments of the multifaceted gene-based therapies, which include DNA or RNA as either therapeutic tools or targets for the treatment of neuromuscular diseases. It also provides insights into the key role that patient organizations have played in research and development; in particular, by addressing bottlenecks and generating boundary conditions that have contributed to scientific breakthroughs, and the effectiveness of innovation processes. Several gene therapy methods have reached the clinical stage and are now addressing both specific and classical issues related to this novel technology. Not ready yet for clinical application, genome editing is at its infancy. More rapidly progressing, RNA-based therapeutics, and especially exon skipping, exon inclusion and stop codon readthrough strategies, are about to move to the market. Most importantly, patients were at the forefront of this discovery process, from basic knowledge to innovation and translational research in a rapidly growing field of unmet medical needs. In recent years, Duchenne muscular dystrophy was the fertile ground for new therapeutic concepts that have been extended to other neuromuscular disorders, such as spinal muscular atrophy, myotonic dystrophies or fascioscapulohumeral dystrophy. In line with their longstanding policy, patient organizations will keep working in a proactive manner to bring together all stakeholders with a view to working out truly therapeutic solutions over a long-term perspective. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Discovery of MYH14 as an important and unique deafness gene causing prelingually severe autosomal dominant nonsyndromic hearing loss.

    Science.gov (United States)

    Kim, Bong Jik; Kim, Ah Reum; Han, Jin Hee; Lee, Chung; Oh, Doo Yi; Choi, Byung Yoon

    2017-04-01

    Pathogenic variants of MYH14 are known to be associated (in either a syndromic or nonsyndromic manner) with hearing loss. Interestingly, all reported cases to date of MYH14-related nonsyndromic hearing loss with detailed phenotypes have demonstrated mild-to-moderate progressive hearing loss with postlingual onset. In the present study, targeted resequencing (TRS) of known deafness genes was performed to identify the causative variant in two multiplex families segregating autosomal dominant (AD) inherited hearing loss. TRS uncovered two novel variants of MYH14 (c.A572G: p.Asp191Gly in the myosin head domain and c.C73T:p.Gln25* in exon 2) from two multiplex deafness Korean families. Notably, both probands showed phenotypes of congenital or prelingual severe hearing loss. It is remarkably uncommon to encounter such a severe-to-profound, prelingual, AD hearing loss. Given that the first variant, p. Asp191Gly, was the first documented missense allele discovered in the myosin head domain of this gene related to either congenital or prelingual severe nonsyndromic hearing loss, and also that the second variant, p. Gln25*, lead to a null allele, more severe phenotypes from our probands may have been the result of either genotype-phenotype correlation or genetic backgrounds, or both. In the present study, we report that MYH14 can manifest as nonsyndromic prelingual severe sensorineural hearing loss in an AD fashion in Koreans. The results of the present study suggest that further genetic studies of similar patients should consider MYH14 as a causative gene, and cochlear implantation during infant or early childhood should be indicated for those patients with certain MYH14 pathogenic variants. Copyright © 2017 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2012-01-01

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

  15. Transcriptome analysis of the oriental river prawn, Macrobrachium nipponense using 454 pyrosequencing for discovery of genes and markers.

    Directory of Open Access Journals (Sweden)

    Keyi Ma

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

  16. Low-coverage, whole-genome sequencing of Artocarpus camansi (Moraceae) for phylogenetic marker development and gene discovery.

    Science.gov (United States)

    Gardner, Elliot M; Johnson, Matthew G; Ragone, Diane; Wickett, Norman J; Zerega, Nyree J C

    2016-07-01

    We used moderately low-coverage (17×) whole-genome sequencing of Artocarpus camansi (Moraceae) to develop genomic resources for Artocarpus and Moraceae. A de novo assembly of Illumina short reads (251,378,536 pairs, 2 × 100 bp) accounted for 93% of the predicted genome size. Predicted coding regions were used in a three-way orthology search with published genomes of Morus notabilis and Cannabis sativa. Phylogenetic markers for Moraceae were developed from 333 inferred single-copy exons. Ninety-eight putative MADS-box genes were identified. Analysis of all predicted coding regions resulted in preliminary annotation of 49,089 genes. An analysis of synonymous substitutions for pairs of orthologs (Ks analysis) in M. notabilis and A. camansi strongly suggested a lineage-specific whole-genome duplication in Artocarpus. This study substantially increases the genomic resources available for Artocarpus and Moraceae and demonstrates the value of low-coverage de novo assemblies for nonmodel organisms with moderately large genomes.

  17. Low-coverage, whole-genome sequencing of Artocarpus camansi (Moraceae) for phylogenetic marker development and gene discovery1

    Science.gov (United States)

    Gardner, Elliot M.; Johnson, Matthew G.; Ragone, Diane; Wickett, Norman J.; Zerega, Nyree J. C.

    2016-01-01

    Premise of the study: We used moderately low-coverage (17×) whole-genome sequencing of Artocarpus camansi (Moraceae) to develop genomic resources for Artocarpus and Moraceae. Methods and Results: A de novo assembly of Illumina short reads (251,378,536 pairs, 2 × 100 bp) accounted for 93% of the predicted genome size. Predicted coding regions were used in a three-way orthology search with published genomes of Morus notabilis and Cannabis sativa. Phylogenetic markers for Moraceae were developed from 333 inferred single-copy exons. Ninety-eight putative MADS-box genes were identified. Analysis of all predicted coding regions resulted in preliminary annotation of 49,089 genes. An analysis of synonymous substitutions for pairs of orthologs (Ks analysis) in M. notabilis and A. camansi strongly suggested a lineage-specific whole-genome duplication in Artocarpus. Conclusions: This study substantially increases the genomic resources available for Artocarpus and Moraceae and demonstrates the value of low-coverage de novo assemblies for nonmodel organisms with moderately large genomes. PMID:27437173

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

    Science.gov (United States)

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

    2014-02-01

    The citrus whitefly, Dialeurodes citri (Ashmead), is one of the three economically important whitefly species that infest citrus plants around the world; however, limited genetic research has been focused on D. citri, partly because of lack of genomic resources. In this study, we performed de novo assembly of a transcriptome using Illumina paired-end sequencing technology (Illumina Inc., San Diego, CA, USA). In total, 36,766 unigenes with a mean length of 497 bp were identified. Of these unigenes, we identified 17,788 matched known proteins in the National Center for Biotechnology Information database, as determined by Blast search, with 5731, 4850 and 14,441 unigenes assigned to clusters of orthologous groups (COG), gene ontology (GO), and SwissProt, respectively. In total, 7507 unigenes were assigned to 308 known pathways. In-depth analysis of the data showed that 117 unigenes were identified as potentially involved in the detoxification of xenobiotics and 67 heat shock protein (Hsp) genes were associated with environmental stress. In addition, these enzymes were searched against the GO and COG database, and the results showed that the three major detoxification enzymes and Hsps were classified into 18 and 3, 6, and 8 annotations, respectively. In addition, 149 simple sequence repeats were detected. The results facilitate the investigation of molecular resistance mechanisms to insecticides and environmental stress, and contribute to molecular marker development. The findings greatly improve our genetic understanding of D. citri, and lay the foundation for future functional genomics studies on this species. © 2013 The Royal Entomological Society.

  19. Cynomolgus monkey testicular cDNAs for discovery of novel human genes in the human genome sequence

    Directory of Open Access Journals (Sweden)

    Terao Keiji

    2002-12-01

    Full Text Available Abstract Background In order to contribute to the establishment of a complete map of transcribed regions of the human genome, we constructed a testicular cDNA library for the cynomolgus monkey, and attempted to find novel transcripts for identification of their human homologues. Result The full-insert sequences of 512 cDNA clones were determined. Ultimately we found 302 non-redundant cDNAs carrying open reading frames of 300 bp-length or longer. Among them, 89 cDNAs were found not to be annotated previously in the Ensembl human database. After searching against the Ensembl mouse database, we also found 69 putative coding sequences have no homologous cDNAs in the annotated human and mouse genome sequences in Ensembl. We subsequently designed a DNA microarray including 396 non-redundant cDNAs (with and without open reading frames to examine the expression of the full-sequenced genes. With the testicular probe and a mixture of probes of 10 other tissues, 316 of 332 effective spots showed intense hybridized signals and 75 cDNAs were shown to be expressed very highly in the cynomolgus monkey testis, but not ubiquitously. Conclusions In this report, we determined 302 full-insert sequences of cynomolgus monkey cDNAs with enough length of open reading frames to discover novel transcripts as human homologues. Among 302 cDNA sequences, human homologues of 89 cDNAs have not been predicted in the annotated human genome sequence in the Ensembl. Additionally, we identified 75 dominantly expressed genes in testis among the full-sequenced clones by using a DNA microarray. Our cDNA clones and analytical results will be valuable resources for future functional genomic studies.

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

    Science.gov (United States)

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

    2014-06-01

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

  1. RNAi-Mediated Specific Gene Silencing as a Tool for the Discovery of New Drug Targets in Giardia lamblia; Evaluation Using the NADH Oxidase Gene

    Directory of Open Access Journals (Sweden)

    Jaime Marcial-Quino

    2017-11-01

    Full Text Available The microaerophilic protozoan Giardia lamblia is the agent causing giardiasis, an intestinal parasitosis of worldwide distribution. Different pharmacotherapies have been employed against giardiasis; however, side effects in the host and reports of drug resistant strains generate the need to develop new strategies that identify novel biological targets for drug design. To support this requirement, we have designed and evaluated a vector containing a cassette for the synthesis of double-stranded RNA (dsRNA, which can silence expression of a target gene through the RNA interference (RNAi pathway. Small silencing RNAs were detected and quantified in transformants expressing dsRNA by a stem-loop RT-qPCR approach. The results showed that, in transformants expressing dsRNA of 100–200 base pairs, the level of NADHox mRNA was reduced by around 30%, concomitant with a decrease in enzyme activity and a reduction in the number of trophozoites with respect to the wild type strain, indicating that NADHox is indeed an important enzyme for Giardia viability. These results suggest that it is possible to induce the G. lamblia RNAi machinery for attenuating the expression of genes encoding proteins of interest. We propose that our silencing strategy can be used to identify new potential drug targets, knocking down genes encoding different structural proteins and enzymes from a wide variety of metabolic pathways.

  2. RNAi-Mediated Specific Gene Silencing as a Tool for the Discovery of New Drug Targets in Giardia lamblia; Evaluation Using the NADH Oxidase Gene

    Science.gov (United States)

    Marcial-Quino, Jaime; Rufino-González, Yadira; Sierra-Palacios, Edgar; Vanoye-Carlo, America; González-Valdez, Abigail; Torres-Arroyo, Angélica; Oria-Hernández, Jesús; Reyes-Vivas, Horacio

    2017-01-01

    The microaerophilic protozoan Giardia lamblia is the agent causing giardiasis, an intestinal parasitosis of worldwide distribution. Different pharmacotherapies have been employed against giardiasis; however, side effects in the host and reports of drug resistant strains generate the need to develop new strategies that identify novel biological targets for drug design. To support this requirement, we have designed and evaluated a vector containing a cassette for the synthesis of double-stranded RNA (dsRNA), which can silence expression of a target gene through the RNA interference (RNAi) pathway. Small silencing RNAs were detected and quantified in transformants expressing dsRNA by a stem-loop RT-qPCR approach. The results showed that, in transformants expressing dsRNA of 100–200 base pairs, the level of NADHox mRNA was reduced by around 30%, concomitant with a decrease in enzyme activity and a reduction in the number of trophozoites with respect to the wild type strain, indicating that NADHox is indeed an important enzyme for Giardia viability. These results suggest that it is possible to induce the G. lamblia RNAi machinery for attenuating the expression of genes encoding proteins of interest. We propose that our silencing strategy can be used to identify new potential drug targets, knocking down genes encoding different structural proteins and enzymes from a wide variety of metabolic pathways. PMID:29099754

  3. Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing.

    Directory of Open Access Journals (Sweden)

    Jinong Feng

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

  4. Developmental gene discovery in a hemimetabolous insect: de novo assembly and annotation of a transcriptome for the cricket Gryllus bimaculatus.

    Directory of Open Access Journals (Sweden)

    Victor Zeng

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

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

    Science.gov (United States)

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

    2013-01-01

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

  6. Use of arbitrary DNA primers, polyacrylamide gel electrophoresis and silver staining for identity testing, gene discovery and analysis of gene expression

    International Nuclear Information System (INIS)

    Gresshoff, P.

    1998-01-01

    To understand chemically-induced genomic differences in soybean mutants differing in their ability to enter the nitrogen-fixing symbiosis involving Bradyrhizobium japonicum, molecular techniques were developed to aid the map-based, or positional, cloning. DNA marker technology involving single arbitrary primers was used to enrich regional RFLP linkage data. Molecular techniques, including two-dimensional pulse field gel electrophoresis, were developed to ascertain the first physical mapping in soybean, leading to the conclusion that in the region of marker pA-36 on linkage group H, 1 cM equals about 500 cM. High molecular weight DNA was isolated and cloned into yeast or bacterial artificial chromosomes (YACs/ BACs). YACs were used to analyze soybean genome structure, revealing that over half of the genome contains repetitive DNA. Genetic and molecular tools are now available to facilitate the isolation of plant genes directly involved in symbiosis. The further characterization of these genes, along with the determination of the mechanisms that lead to the mutation, will be of value to other plants and induced mutation research. (author)

  7. Discovery of precursor and mature microRNAs and their putative gene targets using high-throughput sequencing in pineapple (Ananas comosus var. comosus).

    Science.gov (United States)

    Yusuf, Noor Hydayaty Md; Ong, Wen Dee; Redwan, Raimi Mohamed; Latip, Mariam Abd; Kumar, S Vijay

    2015-10-15

    MicroRNAs (miRNAs) are a class of small, endogenous non-coding RNAs that negatively regulate gene expression, resulting in the silencing of target mRNA transcripts through mRNA cleavage or translational inhibition. MiRNAs play significant roles in various biological and physiological processes in plants. However, the miRNA-mediated gene regulatory network in pineapple, the model tropical non-climacteric fruit, remains largely unexplored. Here, we report a complete list of pineapple mature miRNAs obtained from high-throughput small RNA sequencing and precursor miRNAs (pre-miRNAs) obtained from ESTs. Two small RNA libraries were constructed from pineapple fruits and leaves, respectively, using Illumina's Solexa technology. Sequence similarity analysis using miRBase revealed 579,179 reads homologous to 153 miRNAs from 41 miRNA families. In addition, a pineapple fruit transcriptome library consisting of approximately 30,000 EST contigs constructed using Solexa sequencing was used for the discovery of pre-miRNAs. In all, four pre-miRNAs were identified (MIR156, MIR399, MIR444 and MIR2673). Furthermore, the same pineapple transcriptome was used to dissect the function of the miRNAs in pineapple by predicting their putative targets in conjunction with their regulatory networks. In total, 23 metabolic pathways were found to be regulated by miRNAs in pineapple. The use of high-throughput sequencing in pineapples to unveil the presence of miRNAs and their regulatory pathways provides insight into the repertoire of miRNA regulation used exclusively in this non-climacteric model plant. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Data Discovery

    Directory of Open Access Journals (Sweden)

    Gerhard Weikum

    2013-07-01

    Full Text Available Discovery of documents, data sources, facts, and opinions is at the very heart of digital information and knowledge services. Being able to search, discover, compile, and analyse relevant information for a user’s specific tasks is of utmost importance in science (e.g., computational life sciences, digital humanities, etc., business (e.g., market and media analytics, customer relationship management, etc. , and society at large (e.g., consumer information, traffic logistics, health discussions, etc..

  9. Cosmic Discovery

    Science.gov (United States)

    Harwit, Martin

    1984-04-01

    In the remarkable opening section of this book, a well-known Cornell astronomer gives precise thumbnail histories of the 43 basic cosmic discoveries - stars, planets, novae, pulsars, comets, gamma-ray bursts, and the like - that form the core of our knowledge of the universe. Many of them, he points out, were made accidentally and outside the mainstream of astronomical research and funding. This observation leads him to speculate on how many more major phenomena there might be and how they might be most effectively sought out in afield now dominated by large instruments and complex investigative modes and observational conditions. The book also examines discovery in terms of its political, financial, and sociological context - the role of new technologies and of industry and the military in revealing new knowledge; and methods of funding, of peer review, and of allotting time on our largest telescopes. It concludes with specific recommendations for organizing astronomy in ways that will best lead to the discovery of the many - at least sixty - phenomena that Harwit estimates are still waiting to be found.

  10. Discovery Mondays

    CERN Multimedia

    2003-01-01

    Many people don't realise quite how much is going on at CERN. Would you like to gain first-hand knowledge of CERN's scientific and technological activities and their many applications? Try out some experiments for yourself, or pick the brains of the people in charge? If so, then the «Lundis Découverte» or Discovery Mondays, will be right up your street. Starting on May 5th, on every first Monday of the month you will be introduced to a different facet of the Laboratory. CERN staff, non-scientists, and members of the general public, everyone is welcome. So tell your friends and neighbours and make sure you don't miss this opportunity to satisfy your curiosity and enjoy yourself at the same time. You won't have to listen to a lecture, as the idea is to have open exchange with the expert in question and for each subject to be illustrated with experiments and demonstrations. There's no need to book, as Microcosm, CERN's interactive museum, will be open non-stop from 7.30 p.m. to 9 p.m. On the first Discovery M...

  11. 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.

    Science.gov (United States)

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

    2012-10-12

    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.

  12. 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

    Directory of Open Access Journals (Sweden)

    Jun-Feng Li

    2012-10-01

    Full Text Available 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.

  13. A two-genome microarray for the rice pathogens Xanthomonas oryzae pv. oryzae and X. oryzae pv. oryzicola and its use in the discovery of a difference in their regulation of hrp genes

    Directory of Open Access Journals (Sweden)

    Lin Ye

    2008-06-01

    Full Text Available Abstract Background Xanthomonas oryzae pv. oryzae (Xoo and X. oryzae pv. oryzicola (Xoc are bacterial pathogens of the worldwide staple and grass model, rice. Xoo and Xoc are closely related but Xoo invades rice vascular tissue to cause bacterial leaf blight, a serious disease of rice in many parts of the world, and Xoc colonizes the mesophyll parenchyma to cause bacterial leaf streak, a disease of emerging importance. Both pathogens depend on hrp genes for type III secretion to infect their host. We constructed a 50–70 mer oligonucleotide microarray based on available genome data for Xoo and Xoc and compared gene expression in Xoo strains PXO99A and Xoc strain BLS256 grown in the rich medium PSB vs. XOM2, a minimal medium previously reported to induce hrp genes in Xoo strain T7174. Results Three biological replicates of the microarray experiment to compare global gene expression in representative strains of Xoo and Xoc grown in PSB vs. XOM2 were carried out. The non-specific error rate and the correlation coefficients across biological replicates and among duplicate spots revealed that the microarray data were robust. 247 genes of Xoo and 39 genes of Xoc were differentially expressed in the two media with a false discovery rate of 5% and with a minimum fold-change of 1.75. Semi-quantitative-RT-PCR assays confirmed differential expression of each of 16 genes each for Xoo and Xoc selected for validation. The differentially expressed genes represent 17 functional categories. Conclusion We describe here the construction and validation of a two-genome microarray for the two pathovars of X. oryzae. Microarray analysis revealed that using representative strains, a greater number of Xoo genes than Xoc genes are differentially expressed in XOM2 relative to PSB, and that these include hrp genes and other genes important in interactions with rice. An exception was the rax genes, which are required for production of the host resistance elicitor AvrXa21

  14. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women

    DEFF Research Database (Denmark)

    Vrijens, Karen; Winckelmans, Ellen; Tsamou, Maria

    2017-01-01

    Background: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. Objectives: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. Methods: Microarray analyses were performed in ...... of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects....

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

    Science.gov (United States)

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

    2009-01-01

    Background Interpretation of ever-increasing raw sequence information generated by modern genome sequencing technologies faces multiple challenges, such as gene function analysis and genome annotation. Indeed, nearly 40% of genes in plants encode proteins of unknown function. Functional characterization of these genes is one of the main challenges in modern biology. In this regard, the availability of full-length cDNA clones may fill in the gap created between sequence information and biological knowledge. Full-length cDNA clones facilitate functional analysis of the corresponding genes enabling manipulation of their expression in heterologous systems and the generation of a variety of tagged versions of the native protein. In addition, the development of full-length cDNA sequences has the power to improve the quality of genome annotation. Results We developed an integrated method to generate a new normalized EST collection enriched in full-length and rare transcripts of different citrus species from multiple tissues and developmental stages. We constructed a total of 15 cDNA libraries, from which we isolated 10,898 high-quality ESTs representing 6142 different genes. Percentages of redundancy and proportion of full-length clones range from 8 to 33, and 67 to 85, respectively, indicating good efficiency of the approach employed. The new EST collection adds 2113 new citrus ESTs, representing 1831 unigenes, to the collection of citrus genes available in the public databases. To facilitate functional analysis, cDNAs were introduced in a Gateway-based cloning vector for high-throughput functional analysis of genes in planta. Herein, we describe the technical methods used in the library construction, sequence analysis of clones and the overexpression of CitrSEP, a citrus homolog to the Arabidopsis SEP3 gene, in Arabidopsis as an example of a practical application of the engineered Gateway vector for functional analysis. Conclusion The new EST collection denotes an

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

    Directory of Open Access Journals (Sweden)

    Alamar Santiago

    2009-09-01

    Full Text Available Abstract Background Interpretation of ever-increasing raw sequence information generated by modern genome sequencing technologies faces multiple challenges, such as gene function analysis and genome annotation. Indeed, nearly 40% of genes in plants encode proteins of unknown function. Functional characterization of these genes is one of the main challenges in modern biology. In this regard, the availability of full-length cDNA clones may fill in the gap created between sequence information and biological knowledge. Full-length cDNA clones facilitate functional analysis of the corresponding genes enabling manipulation of their expression in heterologous systems and the generation of a variety of tagged versions of the native protein. In addition, the development of full-length cDNA sequences has the power to improve the quality of genome annotation. Results We developed an integrated method to generate a new normalized EST collection enriched in full-length and rare transcripts of different citrus species from multiple tissues and developmental stages. We constructed a total of 15 cDNA libraries, from which we isolated 10,898 high-quality ESTs representing 6142 different genes. Percentages of redundancy and proportion of full-length clones range from 8 to 33, and 67 to 85, respectively, indicating good efficiency of the approach employed. The new EST collection adds 2113 new citrus ESTs, representing 1831 unigenes, to the collection of citrus genes available in the public databases. To facilitate functional analysis, cDNAs were introduced in a Gateway-based cloning vector for high-throughput functional analysis of genes in planta. Herein, we describe the technical methods used in the library construction, sequence analysis of clones and the overexpression of CitrSEP, a citrus homolog to the Arabidopsis SEP3 gene, in Arabidopsis as an example of a practical application of the engineered Gateway vector for functional analysis. Conclusion The new

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

    Science.gov (United States)

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

    2009-09-11

    Interpretation of ever-increasing raw sequence information generated by modern genome sequencing technologies faces multiple challenges, such as gene function analysis and genome annotation. Indeed, nearly 40% of genes in plants encode proteins of unknown function. Functional characterization of these genes is one of the main challenges in modern biology. In this regard, the availability of full-length cDNA clones may fill in the gap created between sequence information and biological knowledge. Full-length cDNA clones facilitate functional analysis of the corresponding genes enabling manipulation of their expression in heterologous systems and the generation of a variety of tagged versions of the native protein. In addition, the development of full-length cDNA sequences has the power to improve the quality of genome annotation. We developed an integrated method to generate a new normalized EST collection enriched in full-length and rare transcripts of different citrus species from multiple tissues and developmental stages. We constructed a total of 15 cDNA libraries, from which we isolated 10,898 high-quality ESTs representing 6142 different genes. Percentages of redundancy and proportion of full-length clones range from 8 to 33, and 67 to 85, respectively, indicating good efficiency of the approach employed. The new EST collection adds 2113 new citrus ESTs, representing 1831 unigenes, to the collection of citrus genes available in the public databases. To facilitate functional analysis, cDNAs were introduced in a Gateway-based cloning vector for high-throughput functional analysis of genes in planta. Herein, we describe the technical methods used in the library construction, sequence analysis of clones and the overexpression of CitrSEP, a citrus homolog to the Arabidopsis SEP3 gene, in Arabidopsis as an example of a practical application of the engineered Gateway vector for functional analysis. The new EST collection denotes an important step towards the

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

    Directory of Open Access Journals (Sweden)

    Qiong Gao

    2015-07-01

    Full Text Available 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.

  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

    Directory of Open Access Journals (Sweden)

    Richardson Annette C

    2008-07-01

    Full Text Available Abstract 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.

  20. Discovery and introgression of the wild sunflower-derived novel downy mildew resistance gene Pl 19 in confection sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Zhang, Z W; Ma, G J; Zhao, J; Markell, S G; Qi, L L

    2017-01-01

    A new downy mildew resistance gene, Pl 19 , was identified from wild Helianthus annuus accession PI 435414, introduced to confection sunflower, and genetically mapped to linkage group 4 of the sunflower genome. Wild Helianthus annuus accession PI 435414 exhibited resistance to downy mildew, which is one of the most destructive diseases to sunflower production globally. Evaluation of the 140 BC 1 F 2:3 families derived from the cross of CMS CONFSCLB1 and PI 435414 against Plasmopara halstedii race 734 revealed that a single dominant gene controls downy mildew resistance in the population. Bulked segregant analysis conducted in the BC 1 F 2 population with 860 simple sequence repeat (SSR) markers indicated that the resistance derived from wild H. annuus was associated with SSR markers located on linkage group (LG) 4 of the sunflower genome. To map and tag this resistance locus, designated Pl 19 , 140 BC 1 F 2 individuals were used to construct a linkage map of the gene region. Two SSR markers, ORS963 and HT298, were linked to Pl 19 within a distance of 4.7 cM. After screening 27 additional single nucleotide polymorphism (SNP) markers previously mapped to this region, two flanking SNP markers, NSA_003564 and NSA_006089, were identified as surrounding the Pl 19 gene at a distance of 0.6 cM from each side. Genetic analysis indicated that Pl 19 is different from Pl 17 , which had previously been mapped to LG4, but is closely linked to Pl 17 . This new gene is highly effective against the most predominant and virulent races of P. halstedii currently identified in North America and is the first downy mildew resistance gene that has been transferred to confection sunflower. The selected resistant germplasm derived from homozygous BC 2 F 3 progeny provides a novel gene for use in confection sunflower breeding programs.

  1. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans.

    Science.gov (United States)

    Bieganowski, Pawel; Brenner, Charles

    2004-05-14

    NAD+ is essential for life in all organisms, both as a coenzyme for oxidoreductases and as a source of ADPribosyl groups used in various reactions, including those that retard aging in experimental systems. Nicotinic acid and nicotinamide were defined as the vitamin precursors of NAD+ in Elvehjem's classic discoveries of the 1930s. The accepted view of eukaryotic NAD+ biosynthesis, that all anabolism flows through nicotinic acid mononucleotide, was challenged experimentally and revealed that nicotinamide riboside is an unanticipated NAD+ precursor in yeast. Nicotinamide riboside kinases from yeast and humans essential for this pathway were identified and found to be highly specific for phosphorylation of nicotinamide riboside and the cancer drug tiazofurin. Nicotinamide riboside was discovered as a nutrient in milk, suggesting that nicotinamide riboside is a useful compound for elevation of NAD+ levels in humans.

  2. A stress-enhanced model for discovery of disease-modifying gene: Ece1-suppresses the toxicity of α-synuclein A30P.

    Science.gov (United States)

    Chen, Alex Yen-Yu; Tully, Tim

    2018-03-07

    Parkinson's disease (PD) is a progressive motor neurodegenerative disorder, characterized by a selective loss of dopaminergic neurons in the substantia nigra. The complexity of disease etiology includes both genetic and environmental factors. No effective drug that can modify disease progression and protect dopamine neurons from degeneration is presently available. Human α-Synuclein A30P (A30P) is a mutant gene identified in early onset PD and showed to result selective dopamine neuron loss in transgenic A30P flies and mice. Paraquat (PQ) is an herbicide and an oxidative stress generator, linked to sporadic PD. We hypothesized that vital PD modifier genes are conserved across species and would show unique transcriptional changes to oxidative stress in animals expressing a PD-associated gene, such as A30P. We also hypothesized that manipulation of PD modifier genes would provide neuroprotection across species. To identify disease modifier genes, we performed two independently-duplicated experiments of microarray, capturing genome-wide transcriptional changes in A30P flies, chronically fed with PQ-contaminated food. We hypothesized that the best time point of identifying a disease modifier gene is at time when flies showed maximal combined toxicity of A30P transgene and PQ treatment during an early stage of disease and that effective disease modifiers gene are those showing transcriptional changes to oxidative stress in A30P expressing and not in wild type animals. Fly Neprilysin3 (Nep3) is one identified gene that is highly conserved. Its mouse and human homolog is endothelin-converting enzyme-1 (Ece1). To investigate the neuroprotective effect of Ece1, we used NS1 cells and mouse midbrain neurons expressing A30P, treated with or without PQ. We found that ECE1 expression protected against A30P toxicity on cell viability, on neurite outgrowth and ameliorated A30P accumulation in vitro. Expression of ECE1 in vivo suppressed dopamine neuron loss and alleviated the

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

    Directory of Open Access Journals (Sweden)

    Melissa K Boles

    2009-12-01

    Full Text Available 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.

  4. Discovery of MicroRNAs and Their Target Genes Related to Drought in Paulownia “Yuza 1” by High-Throughput Sequencing

    Directory of Open Access Journals (Sweden)

    Minjie Deng

    2017-01-01

    Full Text Available Understanding the role of miRNAs in regulating the molecular mechanisms responsive to drought stress was studied in Paulownia “yuza 1.” Two small RNA libraries and two degradome libraries were, respectively, constructed and sequenced in order to detect miRNAs and their target genes associated with drought stress. A total of 107 miRNAs and 42 putative target genes were identified in this study. Among them, 77 miRNAs were differentially expressed between drought-treated Paulownia “yuza 1” and the control (60 downregulated and 17 upregulated. The predicted target genes were annotated using the GO, KEGG, and Nr databases. According to the functional classification of the target genes, Paulownia “yuza 1” may respond to drought stress via plant hormone signal transduction, photosynthesis, and osmotic adjustment. Furthermore, the expression levels of seven miRNAs (ptf-miR157b, ptf-miR159b, ptf-miR398a, ptf-miR9726a, ptf-M2153, ptf-M2218, and ptf-M24a and their corresponding target genes were validated by quantitative real-time PCR. The results provide relevant information for understanding the molecular mechanism of Paulownia resistance to drought and reference data for researching drought resistance of other trees.

  5. Sequencing, de novo assembly and characterization of the spotted scat Scatophagus argus (Linnaeus 1766) transcriptome for discovery of reproduction related genes and SSRs

    Science.gov (United States)

    Yang, Wei; Chen, Huapu; Cui, Xuefan; Zhang, Kewei; Jiang, Dongneng; Deng, Siping; Zhu, Chunhua; Li, Guangli

    2017-09-01

    Spotted scat (Scatophagus argus) is an economically important farmed fish, particularly in East and Southeast Asia. Because there has been little research on reproductive development and regulation in this species, the lack of a mature artificial reproduction technology remains a barrier for the sustainable development of the aquaculture industry. More genetic and genomic background knowledge is urgently needed for an in-depth understanding of the molecular mechanism of reproductive process and identification of functional genes related to sexual differentiation, gonad maturation and gametogenesis. For these reasons, we performed transcriptomic analysis on spotted scat using a multiple tissue sample mixing strategy. The Illumina RNA sequencing generated 118 510 486 raw reads. After trimming, de novo assembly was performed and yielded 99 888 unigenes with an average length of 905.75 bp. A total of 45 015 unigenes were successfully annotated to the Nr, Swiss-Prot, KOG and KEGG databases. Additionally, 23 783 and 27 183 annotated unigenes were assigned to 56 Gene Ontology (GO) functional groups and 228 KEGG pathways, respectively. Subsequently, 2 474 transcripts associated with reproduction were selected using GO term and KEGG pathway assignments, and a number of reproduction-related genes involved in sex differentiation, gonad development and gametogenesis were identified. Furthermore, 22 279 simple sequence repeat (SSR) loci were discovered and characterized. The comprehensive transcript dataset described here greatly increases the genetic information available for spotted scat and contributes valuable sequence resources for functional gene mining and analysis. Candidate transcripts involved in reproduction would make good starting points for future studies on reproductive mechanisms, and the putative sex differentiation-related genes will be helpful for sex-determining gene identification and sex-specific marker isolation. Lastly, the SSRs can serve as marker

  6. Discovery of MicroRNAs and Their Target Genes Related to Drought in Paulownia ?Yuza 1? by High-Throughput Sequencing

    OpenAIRE

    Deng, Minjie; Cao, Yabing; Zhao, Zhenli; Yang, Lu; Zhang, Yanfang; Dong, Yanpeng; Fan, Guoqiang

    2017-01-01

    Understanding the role of miRNAs in regulating the molecular mechanisms responsive to drought stress was studied in Paulownia “yuza 1.” Two small RNA libraries and two degradome libraries were, respectively, constructed and sequenced in order to detect miRNAs and their target genes associated with drought stress. A total of 107 miRNAs and 42 putative target genes were identified in this study. Among them, 77 miRNAs were differentially expressed between drought-treated Paulownia “yuza 1” and t...

  7. Discovery, Annotation, and Functional Analysis of Long Noncoding RNAs Controlling Cell-Cycle Gene Expression and Proliferation in Breast Cancer Cells.

    Science.gov (United States)

    Sun, Miao; Gadad, Shrikanth S; Kim, Dae-Seok; Kraus, W Lee

    2015-08-20

    We describe a computational approach that integrates GRO-seq and RNA-seq data to annotate long noncoding RNAs (lncRNAs), with increased sensitivity for low-abundance lncRNAs. We used this approach to characterize the lncRNA transcriptome in MCF-7 human breast cancer cells, including >700 previously unannotated lncRNAs. We then used information about the (1) transcription of lncRNA genes from GRO-seq, (2) steady-state levels of lncRNA transcripts in cell lines and patient samples from RNA-seq, and (3) histone modifications and factor binding at lncRNA gene promoters from ChIP-seq to explore lncRNA gene structure and regulation, as well as lncRNA transcript stability, regulation, and function. Functional analysis of selected lncRNAs with altered expression in breast cancers revealed roles in cell proliferation, regulation of an E2F-dependent cell-cycle gene expression program, and estrogen-dependent mitogenic growth. Collectively, our studies demonstrate the use of an integrated genomic and molecular approach to identify and characterize growth-regulating lncRNAs in cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Then and now: use of 16S rDNA gene sequencing for bacterial identification and discovery of novel bacteria in clinical microbiology laboratories.

    Science.gov (United States)

    Woo, P C Y; Lau, S K P; Teng, J L L; Tse, H; Yuen, K-Y

    2008-10-01

    In the last decade, as a result of the widespread use of PCR and DNA sequencing, 16S rDNA sequencing has played a pivotal role in the accurate identification of bacterial isolates and the discovery of novel bacteria in clinical microbiology laboratories. For bacterial identification, 16S rDNA sequencing is particularly important in the case of bacteria with unusual phenotypic profiles, rare bacteria, slow-growing bacteria, uncultivable bacteria and culture-negative infections. Not only has it provided insights into aetiologies of infectious disease, but it also helps clinicians in choosing antibiotics and in determining the duration of treatment and infection control procedures. With the use of 16S rDNA sequencing, 215 novel bacterial species, 29 of which belong to novel genera, have been discovered from human specimens in the past 7 years of the 21st century (2001-2007). One hundred of the 215 novel species, 15 belonging to novel genera, have been found in four or more subjects. The largest number of novel species discovered were of the genera Mycobacterium (n = 12) and Nocardia (n = 6). The oral cavity/dental-related specimens (n = 19) and the gastrointestinal tract (n = 26) were the most important sites for discovery and/or reservoirs of novel species. Among the 100 novel species, Streptococcus sinensis, Laribacter hongkongensis, Clostridium hathewayi and Borrelia spielmanii have been most thoroughly characterized, with the reservoirs and routes of transmission documented, and S. sinensis, L. hongkongensis and C. hathewayi have been found globally. One of the greatest hurdles in putting 16S rDNA sequencing into routine use in clinical microbiology laboratories is automation of the technology. The only step that can be automated at the moment is input of the 16S rDNA sequence of the bacterial isolate for identification into one of the software packages that will generate the result of the identity of the isolate on the basis of its sequence database. However

  9. Topology Discovery Using Cisco Discovery Protocol

    OpenAIRE

    Rodriguez, Sergio R.

    2009-01-01

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

  10. Evaluation of putative reference genes for quantitative real-time PCR normalization in Lilium regale during development and under stress

    Science.gov (United States)

    Zhang, Ming-Fang

    2016-01-01

    Normalization to reference genes is the most common method to avoid bias in real-time quantitative PCR (qPCR), which has been widely used for quantification of gene expression. Despite several studies on gene expression, Lilium, and particularly L. regale, has not been fully investigated regarding the evaluation of reference genes suitable for normalization. In this study, nine putative reference genes, namely 18S rRNA, ACT, BHLH, CLA, CYP, EF1, GAPDH, SAND and TIP41, were analyzed for accurate quantitative PCR normalization at different developmental stages and under different stress conditions, including biotic (Botrytis elliptica), drought, salinity, cold and heat stress. All these genes showed a wide variation in their Cq (quantification Cycle) values, and their stabilities were calculated by geNorm, NormFinder and BestKeeper. In a combination of the results from the three algorithms, BHLH was superior to the other candidates when all the experimental treatments were analyzed together; CLA and EF1 were also recommended by two of the three algorithms. As for specific conditions, EF1 under various developmental stages, SAND under biotic stress, CYP/GAPDH under drought stress, and TIP41 under salinity stress were generally considered suitable. All the algorithms agreed on the stability of SAND and GAPDH under cold stress, while only CYP was selected under heat stress by all of them. Additionally, the selection of optimal reference genes under biotic stress was further verified by analyzing the expression level of LrLOX in leaves inoculated with B. elliptica. Our study would be beneficial for future studies on gene expression and molecular breeding of Lilium. PMID:27019788

  11. Transcriptome analysis and discovery of genes involved in immune pathways in large yellow croaker (Larimichthys crocea) under high stocking density stress.

    Science.gov (United States)

    Sun, Peng; Bao, Peibo; Tang, Baojun

    2017-09-01

    The large yellow croaker, Larimichthys crocea, is an economically important maricultured species in southeast China. Owing to the importance of stocking densities in commercial fish production, it is crucial to establish the physiological responses and molecular mechanisms that govern adaptation to crowding in order to optimize welfare and health. In the present study, an extensive immunity-related analysis was performed at the transcriptome level in L. crocea in response to crowding stress. Over 145 million high-quality reads were generated and de novo assembled into a final set of 40,123 unigenes. Gene Ontology and genome analyses revealed that molecular function, biological process, intracellular, ion binding, and cell process were the most highly enriched pathways among genes that were differentially expressed under stress. Among all of the pathways involved, 16 pathways were related to the immune system, among which the complement and coagulation cascades pathway was the most enriched for differentially expressed immunity-related genes, followed by the chemokine signaling pathway, toll-like receptor signaling pathway, and leukocyte transendothelial migration pathway. The consistently high expression of immune-related genes in the complement and coagulation cascades pathway (from 24 to 96 h after being subjected to stress) suggested its importance in both response to stress and resistance against bacterial invasion at an early stage. These results also demonstrated that crowding can significantly induce immunological responses in fish. However, long-term exposure to stress eventually impairs the defense capability in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  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.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available 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

  13. De novo sequencing and comparative transcriptome analysis of white petals and red labella in Phalaenopsis for discovery of genes related to flower color and floral differentation

    Directory of Open Access Journals (Sweden)

    Yuxia Yang

    2014-09-01

    Full Text Available Phalaenopsis is one of the world’s most popular and important epiphytic monopodial orchids. The extraordinary floral diversity of Phalaenopsis is a reflection of its evolutionary success. As a consequence of this diversity, and of the complexity of flower color development in Phalaenopsis, this species is a valuable research material for developmental biology studies. Nevertheless, research on the molecular mechanisms underlying flower color and floral organ formation in Phalaenopsis is still in the early phases. In this study, we generated large amounts of data from Phalaenopsis flowers by combining Illumina sequencing with differentially expressed gene (DEG analysis. We obtained 37 723 and 34 020 unigenes from petals and labella, respectively. A total of 2736 DEGs were identified, and the functions of many DEGs were annotated by BLAST-searching against several public databases. We mapped 837 up-regulated DEGs (432 from petals and 405 from labella to 102 Kyoto Encyclopedia of Genes and Genomes pathways. Almost all pathways were represented in both petals (102 pathways and labella (99 pathways. DEGs involved in energy metabolism were significantly differentially distributed between labella and petals, and various DEGs related to flower color and floral differentiation were found in the two organs. Interestingly, we also identified genes encoding several key enzymes involved in carotenoid synthesis. These genes were differentially expressed between petals and labella, suggesting that carotenoids may influence Phalaenopsis flower color. We thus conclude that a combination of anthocyanins and/or carotenoids determine flower color formation in Phalaenopsis. These results broaden our understanding of the mechanisms controlling flower color and floral organ differentiation in Phalaenopsis and other orchids.

  14. A statistical framework for genome-wide discovery of biomarker splice variations with GeneChip Human Exon 1.0 ST Arrays.

    Science.gov (United States)

    Yoshida, Ryo; Numata, Kazuyuki; Imoto, Seiya; Nagasaki, Masao; Doi, Atsushi; Ueno, Kazuko; Miyano, Satoru

    2006-01-01

    Alternative splicing is an important regulatory mechanism that generates multiple mRNA transcripts which are transcribed into functionally diverse proteins. According to the current studies, aberrant transcripts due to splicing mutations are known to cause for 15% of genetic diseases. Therefore understanding regulatory mechanism of alternative splicing is essential for identifying potential biomarkers for several types of human diseases. Most recently, advent of GeneChip Human Exon 1.0 ST Array enables us to measure genome-wide expression profiles of over one million exons. With this new microarray platform, analysis of functional gene expressions could be extended to detect not only differentially expressed genes, but also a set of specific-splicing events that are differentially observed between one or more experimental conditions, e.g. tumor or normal control cells. In this study, we address the statistical problems to identify differentially observed splicing variations from exon expression profiles. The proposed method is organized according to the following process: (1) Data preprocessing for removing systematic biases from the probe intensities. (2) Whole transcript analysis with the analysis of variance (ANOVA) to identify a set of loci that cause the alternative splicing-related to a certain disease. We test the proposed statistical approach on exon expression profiles of colorectal carcinoma. The applicability is verified and discussed in relation to the existing biological knowledge. This paper intends to highlight the potential role of statistical analysis of all exon microarray data. Our work is an important first step toward development of more advanced statistical technology. Supplementary information and materials are available from http://bonsai.ims.u-tokyo.ac.jp/~yoshidar/IBSB2006_ExonArray.htm.

  15. A genome-wide transcriptome map of pistachio (Pistacia vera L.) provides novel insights into salinity-related genes and marker discovery.

    Science.gov (United States)

    Moazzzam Jazi, Maryam; Seyedi, Seyed Mahdi; Ebrahimie, Esmaeil; Ebrahimi, Mansour; De Moro, Gianluca; Botanga, Christopher

    2017-08-17

    Pistachio (Pistacia vera L.) is one of the most important commercial nut crops worldwide. It is a salt-tolerant and long-lived tree, with the largest cultivation area in Iran. Climate change and subsequent increased soil salt content have adversely affected the pistachio yield in recent years. However, the lack of genomic/global transcriptomic sequences on P. vera impedes comprehensive researches at the molecular level. Hence, whole transcriptome sequencing is required to gain insight into functional genes and pathways in response to salt stress. RNA sequencing of a pooled sample representing 24 different tissues of two pistachio cultivars with contrasting salinity tolerance under control and salt treatment by Illumina Hiseq 2000 platform resulted in 368,953,262 clean 100 bp paired-ends reads (90 Gb). Following creating several assemblies and assessing their quality from multiple perspectives, we found that using the annotation-based metrics together with the length-based parameters allows an improved assessment of the transcriptome assembly quality, compared to the solely use of the length-based parameters. The generated assembly by Trinity was adopted for functional annotation and subsequent analyses. In total, 29,119 contigs annotated against all of five public databases, including NR, UniProt, TAIR10, KOG and InterProScan. Among 279 KEGG pathways supported by our assembly, we further examined the pathways involved in the plant hormone biosynthesis and signaling as well as those to be contributed to secondary metabolite biosynthesis due to their importance under salinity stress. In total, 11,337 SSRs were also identified, which the most abundant being dinucleotide repeats. Besides, 13,097 transcripts as candidate stress-responsive genes were identified. Expression of some of these genes experimentally validated through quantitative real-time PCR (qRT-PCR) that further confirmed the accuracy of the assembly. From this analysis, the contrasting expression pattern

  16. Advanced cell culture technology for essential oil production and micro array studies leading to discovery of genes for fragrance compounds in Michelia alba (Cempaka Putih)

    International Nuclear Information System (INIS)

    Rusli Ibrahim; Norazlina Nordin; Edrina Azlan

    2006-01-01

    Michelia spp. is known to produce high value essential oil for perfumery industry. The essence of world's most expensive perfumes, such as JOY and Jadore, is based on the oil of Michelia spp. One major problem anticipated in this approach, based on our early experiments, is limited amount of fragrance produced in cell cultures. The appropriate strategy is to superimpose DNA micro array studies on top of the cell culture project. The study covers natural flower development phases that led to the identification of genes or sets of genes that regulate the production of the fragrance. Seven developmental stages of Michelia alba flower namely Stage 5 to 11 were investigated for their volatile constituents. The essential oil was isolated by Simultaneous Distillation Extraction technique and the oil obtained was subjected to GC-MS analysis. In total, seventy-seven compounds representing 93-98% of the overall volatiles compounds were identified on the basis of mass spectra and retention indices. Thirty-three of these compounds belonged to isoprenoids group which comprised 30-50% of the total volatile compounds whereas the remaining belonged to fatty acid derivatives, benzenoid, phenylpropanoid and other hydrocarbon compounds. Studies were conducted to optimize culture parameters for scaling-up the production of callus, suspension cell cultures and somatic and product accumulation of essential oils using bioreactor technology. (Author)

  17. Sequencing, De Novo Assembly, and Annotation of the Transcriptome of the Endangered Freshwater Pearl Bivalve, Cristaria plicata, Provides Novel Insights into Functional Genes and Marker Discovery.

    Directory of Open Access Journals (Sweden)

    Bharat Bhusan Patnaik

    Full Text Available The freshwater mussel Cristaria plicata (Bivalvia: Eulamellibranchia: Unionidae, is an economically important species in molluscan aquaculture due to its use in pearl farming. The species have been listed as endangered in South Korea due to the loss of natural habitats caused by anthropogenic activities. The decreasing population and a lack of genomic information on the species is concerning for environmentalists and conservationists. In this study, we conducted a de novo transcriptome sequencing and annotation analysis of C. plicata using Illumina HiSeq 2500 next-generation sequencing (NGS technology, the Trinity assembler, and bioinformatics databases to prepare a sustainable resource for the identification of candidate genes involved in immunity, defense, and reproduction.The C. plicata transcriptome analysis included a total of 286,152,584 raw reads and 281,322,837 clean reads. The de novo assembly identified a total of 453,931 contigs and 374,794 non-redundant unigenes with average lengths of 731.2 and 737.1 bp, respectively. Furthermore, 100% coverage of C. plicata mitochondrial genes within two unigenes supported the quality of the assembler. In total, 84,274 unigenes showed homology to entries in at least one database, and 23,246 unigenes were allocated to one or more Gene Ontology (GO terms. The most prominent GO biological process, cellular component, and molecular function categories (level 2 were cellular process, membrane, and binding, respectively. A total of 4,776 unigenes were mapped to 123 biological pathways in the KEGG database. Based on the GO terms and KEGG annotation, the unigenes were suggested to be involved in immunity, stress responses, sex-determination, and reproduction. A total of 17,251 cDNA simple sequence repeats (cSSRs were identified from 61,141 unigenes (size of >1 kb with the most abundant being dinucleotide repeats.This dataset represents the first transcriptome analysis of the endangered mollusc, C. plicata

  18. Transcriptome analysis of androgenic gland for discovery of novel genes from the oriental river prawn, Macrobrachium nipponense, using Illumina Hiseq 2000.

    Directory of Open Access Journals (Sweden)

    Shubo Jin

    Full Text Available 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

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

    Science.gov (United States)

    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

  20. Academic Drug Discovery Centres

    DEFF Research Database (Denmark)

    Kirkegaard, Henriette Schultz; Valentin, Finn

    2014-01-01

    Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic and organi......Academic drug discovery centres (ADDCs) are seen as one of the solutions to fill the innovation gap in early drug discovery, which has proven challenging for previous organisational models. Prior studies of ADDCs have identified the need to analyse them from the angle of their economic...... their performance....

  1. Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies

    DEFF Research Database (Denmark)

    Thorsen, Jonathan; Brejnrod, Asker Daniel; Mortensen, Martin Steen

    2016-01-01

    detection power. For beta-diversity-based sample separation, we show that library size normalization has very little effect and that the distance metric is the most important factor in terms of separation power. CONCLUSIONS: Our results, generalizable to datasets from different sequencing platforms......, demonstrate how the choice of method considerably affects analysis outcome. Here, we give recommendations for tools that exhibit low false positive rates, have good retrieval power across effect sizes and case/control proportions, and have low sparsity bias. Result output from some commonly used methods......BACKGROUND: There is an immense scientific interest in the human microbiome and its effects on human physiology, health, and disease. A common approach for examining bacterial communities is high-throughput sequencing of 16S rRNA gene hypervariable regions, aggregating sequence-similar amplicons...

  2. Generation of expressed sequence tags for discovery of genes responsible for floral traits of Chrysanthemum morifolium by next-generation sequencing technology.

    Science.gov (United States)

    Sasaki, Katsutomo; Mitsuda, Nobutaka; Nashima, Kenji; Kishimoto, Kyutaro; Katayose, Yuichi; Kanamori, Hiroyuki; Ohmiya, Akemi

    2017-09-04

    Chrysanthemum morifolium is one of the most economically valuable ornamental plants worldwide. Chrysanthemum is an allohexaploid plant with a large genome that is commercially propagated by vegetative reproduction. New cultivars with different floral traits, such as color, morphology, and scent, have been generated mainly by classical cross-breeding and mutation breeding. However, only limited genetic resources and their genome information are available for the generation of new floral traits. To obtain useful information about molecular bases for floral traits of chrysanthemums, we read expressed sequence tags (ESTs) of chrysanthemums by high-throughput sequencing using the 454 pyrosequencing technology. We constructed normalized cDNA libraries, consisting of full-length, 3'-UTR, and 5'-UTR cDNAs derived from various tissues of chrysanthemums. These libraries produced a total number of 3,772,677 high-quality reads, which were assembled into 213,204 contigs. By comparing the data obtained with those of full genome-sequenced species, we confirmed that our chrysanthemum contig set contained the majority of all expressed genes, which was sufficient for further molecular analysis in chrysanthemums. We confirmed that our chrysanthemum EST set (contigs) contained a number of contigs that encoded transcription factors and enzymes involved in pigment and aroma compound metabolism that was comparable to that of other species. This information can serve as an informative resource for identifying genes involved in various biological processes in chrysanthemums. Moreover, the findings of our study will contribute to a better understanding of the floral characteristics of chrysanthemums including the myriad cultivars at the molecular level.

  3. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

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

    Directory of Open Access Journals (Sweden)

    Andrew C. Kotze

    2014-12-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  6. Service discovery at home

    NARCIS (Netherlands)

    Sundramoorthy, V.; Scholten, Johan; Jansen, P.G.; Hartel, Pieter H.

    2003-01-01

    Service discovery is a fairly new field that kicked off since the advent of ubiquitous computing and has been found essential in the making of intelligent networks by implementing automated discovery and remote control between devices. This paper provides an overview and comparison of several

  7. Service Discovery At Home

    NARCIS (Netherlands)

    Sundramoorthy, V.; Scholten, Johan; Jansen, P.G.; Hartel, Pieter H.

    Service discovery is a fady new field that kicked off since the advent of ubiquitous computing and has been found essential in the making of intelligent networks by implementing automated discovery and remote control between deviies. This paper provides an ovewiew and comparison of several prominent

  8. Promoter region of the bovine growth hormone receptor gene: single nucleotide polymorphism discovery in cattle and association with performance in Brangus bulls.

    Science.gov (United States)

    Garrett, A J; Rincon, G; Medrano, J F; Elzo, M A; Silver, G A; Thomas, M G

    2008-12-01

    Expression of the GH receptor (GHR) gene and its binding with GH is essential for growth and fat metabolism. A GT microsatellite exists in the promoter of bovine GHR segregating short (11 bp) and long (16 to 20 bp) allele sequences. To detect SNP and complete an association study of genotype to phenotype, we resequenced a 1,195-bp fragment of DNA including the GT microsatellite and exon 1A. Resequencing was completed in 48 familialy unrelated Holstein, Jersey, Brown Swiss, Simmental, Angus, Brahman, and Brangus cattle. Nine SNP were identified. Phylogeny analyses revealed minor distance (i.e., Brahman cattle averaged 27.4 +/- 0.07% divergence from the Bos taurus breeds, whereas divergence of Brangus was intermediate. An association study of genotype to phenotype was completed with data from growing Brangus bulls (n = 553 from 96 sires) and data from 4 of the SNP flanking the GT microsatellite. These SNP were found to be in Hardy-Weinberg equilibrium and in phase based on linkage disequilibrium analyses (r(2) = 0.84 and D'= 0.92). An A/G tag SNP was identified (ss86273136) and was located in exon 1A, which began 88 bp downstream from the GT microsatellite. Minor allele frequency of the tag SNP was greater than 10%, and Mendelian segregation was verified in 3 generation pedigrees. The A allele was derived from Brahman, and the G allele was derived from Angus. This tag SNP genotype was a significant effect in analyses of rib fat data collected with ultrasound when bulls were ~365 d of age. Specifically, bulls of the GG genotype had 6.1% more (P = 0.0204) rib fat than bulls of the AA and AG genotypes, respectively. Tag SNP (ss86273136), located in the promoter of GHR, appears to be associated with a measure of corporal fat in Bos taurus x Bos indicus composite cattle.

  9. "Eureka, Eureka!" Discoveries in Science

    Science.gov (United States)

    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…

  10. Biomimicry as a basis for drug discovery.

    Science.gov (United States)

    Kolb, V M

    1998-01-01

    Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term "natural product" is often used synonymously with "secondary metabolite." Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed "inventive evolution." It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products ("unnatural natural products"), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.

  11. The Greatest Mathematical Discovery?

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. On reliable discovery of molecular signatures

    Directory of Open Access Journals (Sweden)

    Björkegren Johan

    2009-01-01

    Full Text Available Abstract Background Molecular signatures are sets of genes, proteins, genetic variants or other variables that can be used as markers for a particular phenotype. Reliable signature discovery methods could yield valuable insight into cell biology and mechanisms of human disease. However, it is currently not clear how to control error rates such as the false discovery rate (FDR in signature discovery. Moreover, signatures for cancer gene expression have been shown to be unstable, that is, difficult to replicate in independent studies, casting doubts on their reliability. Results We demonstrate that with modern prediction methods, signatures that yield accurate predictions may still have a high FDR. Further, we show that even signatures with low FDR may fail to replicate in independent studies due to limited statistical power. Thus, neither stability nor predictive accuracy are relevant when FDR control is the primary goal. We therefore develop a general statistical hypothesis testing framework that for the first time provides FDR control for signature discovery. Our method is demonstrated to be correct in simulation studies. When applied to five cancer data sets, the method was able to discover molecular signatures with 5% FDR in three cases, while two data sets yielded no significant findings. Conclusion Our approach enables reliable discovery of molecular signatures from genome-wide data with current sample sizes. The statistical framework developed herein is potentially applicable to a wide range of prediction problems in bioinformatics.

  13. Target discovery from data mining approaches.

    Science.gov (United States)

    Yang, Yongliang; Adelstein, S James; Kassis, Amin I

    2012-02-01

    Data mining of available biomedical data and information has greatly boosted target discovery in the 'omics' era. Target discovery is the key step in the biomarker and drug discovery pipeline to diagnose and fight human diseases. In biomedical science, the 'target' is a broad concept ranging from molecular entities (such as genes, proteins and miRNAs) to biological phenomena (such as molecular functions, pathways and phenotypes). Within the context of biomedical science, data mining refers to a bioinformatics approach that combines biological concepts with computer tools or statistical methods that are mainly used to discover, select and prioritize targets. In response to the huge demand of data mining for target discovery in the 'omics' era, this review explicates various data mining approaches and their applications to target discovery with emphasis on text and microarray data analysis. Two emerging data mining approaches, chemogenomic data mining and proteomic data mining, are briefly introduced. Also discussed are the limitations of various data mining approaches found in the level of database integration, the quality of data annotation, sample heterogeneity and the performance of analytical and mining tools. Tentative strategies of integrating different data sources for target discovery, such as integrated text mining with high-throughput data analysis and integrated mining with pathway databases, are introduced. Published by Elsevier Ltd.

  14. Fateful discovery almost forgotten

    CERN Multimedia

    1989-01-01

    "The discovery of the fission of uranium exactly half a century ago is at risk of passing unremarked because of the general ambivalence towards the consequences of this development. Can that be wise?" (4 pages)

  15. On the antiproton discovery

    International Nuclear Information System (INIS)

    Piccioni, O.

    1989-01-01

    The author of this article describes his own role in the discovery of the antiproton. Although Segre and Chamberlain received the Nobel Prize in 1959 for its discovery, the author claims that their experimental method was his idea which he communicated to them informally in December 1954. He describes how his application for citizenship (he was Italian), and other scientists' manipulation, prevented him from being at Berkeley to work on the experiment himself. (UK)

  16. Análise multielementar da mucosa gástrica de roedores tratados com Alchornea glandulosa, Davilla elliptica e Davilla nitida pela técnica de fluorescência de raios-x por reflexão total

    OpenAIRE

    Vieira, Letícia Diniz [UNESP

    2010-01-01

    As úlceras pépticas são lesões provocadas pelo desequilíbrio entre fatores lesivos e protetores das mucosas gástrica e duodenal. Existe um grande número de plantas que são empregadas popularmente para o tratamento deste tipo de doença. Com este trabalho, pretende-se contribuir para a compreensão da ação farmacológica dos extratos de duas dessas plantas: a Alchornea glandulosa e a Davilla elliptica, assim como a Davilla nitida, que não é empregada na etnofarmacologia, mas pertence ao mesmo gên...

  17. Gene discovery in the Acanthamoeba castellanii genome

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Bioinformatics for discovery of microbiome variation

    DEFF Research Database (Denmark)

    Brejnrod, Asker Daniel

    two conditions. The purpose is to assess the false discovery rate, recovery of truly differential abundant bacteria and the impact of beta diversity exploration strategies commonly used in microbiome research. We assess these differences by simulation and by making biological assumptions about...... of various molecular methods to build hypotheses about the impact of a copper contaminated soil. The introduction is a broad introduction to the field of microbiome research with a focus on the technologies that enable these discoveries and how some of the broader issues have related to this thesis...... 1 ,“Large-scale benchmarking reveals false discoveries and count transformation sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome studies”, benchmarked the performance of a variety of popular statistical methods for discovering differentially abundant bacteria . between...

  19. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities

    OpenAIRE

    Chong, Jessica X.; Buckingham, Kati J.; Jhangiani, Shalini N.; Boehm, Corinne; Sobreira, Nara; Smith, Joshua D.; Harrell, Tanya M.; McMillin, Margaret J.; Wiszniewski, Wojciech; Gambin, Tomasz; Coban Akdemir, Zeynep H.; Doheny, Kimberly; Scott, Alan F.; Avramopoulos, Dimitri; Chakravarti, Aravinda

    2015-01-01

    Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of...

  20. Transgenic parasites accelerate drug discovery

    Science.gov (United States)

    Rodriguez, Ana; Tarleton, Rick L.

    2013-01-01

    Parasitic neglected diseases are in dire need of new drugs either to replace old drugs rendered ineffective because of resistance development, to cover clinical needs that had never been addressed or to tackle other associated problems of existing drugs such as high cost, difficult administration, restricted coverage or toxicity. The availability of transgenic parasites expressing reporter genes facilitates the discovery of new drugs through high throughput screenings, but also by allowing rapid screening in animal models of disease. Taking advantage of these, we propose an alternative pathway of drug development for neglected diseases, going from high throughput screening directly into in vivo testing of the top ranked compounds selected by medicinal chemistry. Rapid assessment animal models allow for identification of compounds with bona fide activity in vivo early in the development chain, constituting a solid basis for further development and saving valuable time and resources. PMID:22277131

  1. Discovery of Fullerenes

    Indian Academy of Sciences (India)

    ... Journal of Science Education; Volume 2; Issue 1. Discovery of Fullerenes Giving a New Shape to Carbon Chemistry. Rathna Ananthaiah. Research News Volume 2 Issue 1 January 1997 pp 68-73. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/01/0068-0073 ...

  2. Landmark Discoveries in Neurosciences

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 11. Landmark Discoveries in Neurosciences. Niranjan Kambi Neeraj Jain. General Article Volume 17 Issue 11 November 2012 pp 1054-1064. Fulltext. Click here to view fulltext PDF. Permanent link:

  3. The discovery of fission

    International Nuclear Information System (INIS)

    McKay, H.A.C.

    1978-01-01

    In this article by the retired head of the Separation Processes Group of the Chemistry Division, Atomic Energy Research Establishment, Harwell, U.K., the author recalls what he terms 'an exciting drama, the unravelling of the nature of the atomic nucleus' in the years before the Second World War, including the discovery of fission. 12 references. (author)

  4. Important discoveries from analysing bacterial phenotypes

    OpenAIRE

    Bochner, Barry R; Giovannetti, Luciana; Viti, Carlo

    2008-01-01

    The ability to test hundreds to thousands of cellular phenotypes in a single experiment has opened up new avenues of investigation and exploration and led to important discoveries in very diverse applications of microbiological research and development. The information provided by global phenotyping is complementary to, and often more easily interpretable than information provided by global molecular analytical methods such as gene chips and proteomics. This report summarizes advances present...

  5. CLARM: An integrative approach for functional modules discovery

    KAUST Repository

    Salem, Saeed M.

    2011-01-01

    Functional module discovery aims to find well-connected subnetworks which can serve as candidate protein complexes. Advances in High-throughput proteomic technologies have enabled the collection of large amount of interaction data as well as gene expression data. We propose, CLARM, a clustering algorithm that integrates gene expression profiles and protein protein interaction network for biological modules discovery. The main premise is that by enriching the interaction network by adding interactions between genes which are highly co-expressed over a wide range of biological and environmental conditions, we can improve the quality of the discovered modules. Protein protein interactions, known protein complexes, and gene expression profiles for diverse environmental conditions from the yeast Saccharomyces cerevisiae were used for evaluate the biological significance of the reported modules. Our experiments show that the CLARM approach is competitive to wellestablished module discovery methods. Copyright © 2011 ACM.

  6. Orphan diseases: state of the drug discovery art.

    Science.gov (United States)

    Volmar, Claude-Henry; Wahlestedt, Claes; Brothers, Shaun P

    2017-06-01

    Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.

  7. The neutron discovery

    International Nuclear Information System (INIS)

    Six, J.

    1987-01-01

    The neutron: who had first the idea, who discovered it, who established its main properties. To these apparently simple questions, multiple answers exist. The progressive discovery of the neutron is a marvellous illustration of some characteristics of the scientific research, where the unforeseen may be combined with the expected. This discovery is replaced in the context of the 1930's scientific effervescence that succeeded the revolutionary introduction of quantum mechanics. This book describes the works of Bothe, the Joliot-Curie and Chadwick which led to the neutron in an unexpected way. A historical analysis allows to give a new interpretation on the hypothesis suggested by the Joliot-Curie. Some texts of these days will help the reader to revive this fascinating story [fr

  8. Discovery of charm

    Energy Technology Data Exchange (ETDEWEB)

    Goldhaber, G.

    1984-11-01

    In my talk I will cover the period 1973 to 1976 which saw the discoveries of the J/psi and psi' resonances and most of the Psion spectroscopy, the tau lepton and the D/sup 0/,D/sup +/ charmed meson doublet. Occasionally I will refer briefly to more recent results. Since this conference is on the history of the weak-interactions I will deal primarily with the properties of naked charm and in particular the weakly decaying doublet of charmed mesons. Most of the discoveries I will mention were made with the SLAC-LBL Magnetic Detector or MARK I which we operated at SPEAR from 1973 to 1976. 27 references.

  9. Atlas of Astronomical Discoveries

    CERN Document Server

    Schilling, Govert

    2011-01-01

    Four hundred years ago in Middelburg, in the Netherlands, the telescope was invented. The invention unleashed a revolution in the exploration of the universe. Galileo Galilei discovered mountains on the Moon, spots on the Sun, and moons around Jupiter. Christiaan Huygens saw details on Mars and rings around Saturn. William Herschel discovered a new planet and mapped binary stars and nebulae. Other astronomers determined the distances to stars, unraveled the structure of the Milky Way, and discovered the expansion of the universe. And, as telescopes became bigger and more powerful, astronomers delved deeper into the mysteries of the cosmos. In his Atlas of Astronomical Discoveries, astronomy journalist Govert Schilling tells the story of 400 years of telescopic astronomy. He looks at the 100 most important discoveries since the invention of the telescope. In his direct and accessible style, the author takes his readers on an exciting journey encompassing the highlights of four centuries of astronomy. Spectacul...

  10. Biomedical Information Extraction: Mining Disease Associated Genes from Literature

    Science.gov (United States)

    Huang, Zhong

    2014-01-01

    Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to…

  11. Discoveries of isotopes by fission

    Indian Academy of Sciences (India)

    also contributed to the discovery of new isotopes. More recently, most of the very neutron- rich isotopes have been discovered by projectile fission. After a brief summary of the discovery of fission process itself, these production mechanisms will be discussed. The paper concludes with an outlook on future discoveries of ...

  12. Recent Discoveries and Bible Translation.

    Science.gov (United States)

    Harrelson, Walter

    1990-01-01

    Discusses recent discoveries for "Bible" translation with a focus on the "Dead Sea Scrolls." Examines recent discoveries that provide direct support for alternative reading of biblical passages and those discoveries that have contributed additional insight to knowledge of cultural practices, especially legal and religious…

  13. Fateful discovery almost forgotten

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    The paper reviews the discovery of the fission of uranium, which took place fifty years ago. A description is given of the work of Meitner and Frisch in interpreting the Fermi data on the bombardment of uranium nuclei with neutrons, i.e. proposing fission. The historical events associated with the development and exploitation of uranium fission are described, including the Manhattan Project, Hiroshima and Nagasaki, Shippingport, and Chernobyl. (U.K.)

  14. Discovery as a process

    Energy Technology Data Exchange (ETDEWEB)

    Loehle, C.

    1994-05-01

    The three great myths, which form a sort of triumvirate of misunderstanding, are the Eureka! myth, the hypothesis myth, and the measurement myth. These myths are prevalent among scientists as well as among observers of science. The Eureka! myth asserts that discovery occurs as a flash of insight, and as such is not subject to investigation. This leads to the perception that discovery or deriving a hypothesis is a moment or event rather than a process. Events are singular and not subject to description. The hypothesis myth asserts that proper science is motivated by testing hypotheses, and that if something is not experimentally testable then it is not scientific. This myth leads to absurd posturing by some workers conducting empirical descriptive studies, who dress up their study with a ``hypothesis`` to obtain funding or get it published. Methods papers are often rejected because they do not address a specific scientific problem. The fact is that many of the great breakthroughs in silence involve methods and not hypotheses or arise from largely descriptive studies. Those captured by this myth also try to block funding for those developing methods. The third myth is the measurement myth, which holds that determining what to measure is straightforward, so one doesn`t need a lot of introspection to do science. As one ecologist put it to me ``Don`t give me any of that philosophy junk, just let me out in the field. I know what to measure.`` These myths lead to difficulties for scientists who must face peer review to obtain funding and to get published. These myths also inhibit the study of science as a process. Finally, these myths inhibit creativity and suppress innovation. In this paper I first explore these myths in more detail and then propose a new model of discovery that opens the supposedly miraculous process of discovery to doser scrutiny.

  15. Discovery of TUG-770

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Hansen, Steffen Vissing Fahnøe; Urban, Christian

    2013-01-01

    Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical...... and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing....

  16. Discovery concepts for Mars

    Science.gov (United States)

    Luhmann, J. G.; Russell, C. T.; Brace, L. H.; Nagy, A. F.; Jakosky, B. M.; Barth, C. A.; Waite, J. H.

    1992-01-01

    Two focused Mars missions that would fit within the guidelines for the proposed Discovery line are discussed. The first mission would deal with the issue of the escape of the atmosphere (Mars') to space. A complete understanding of this topic is crucial to deciphering the evolution of the atmosphere, climate change, and volatile inventories. The second mission concerns the investigation of remanent magnetization of the crust and its relationship to the ionosphere and the atmosphere.

  17. Natural product discovery: past, present, and future.

    Science.gov (United States)

    Katz, Leonard; Baltz, Richard H

    2016-03-01

    Microorganisms have provided abundant sources of natural products which have been developed as commercial products for human medicine, animal health, and plant crop protection. In the early years of natural product discovery from microorganisms (The Golden Age), new antibiotics were found with relative ease from low-throughput fermentation and whole cell screening methods. Later, molecular genetic and medicinal chemistry approaches were applied to modify and improve the activities of important chemical scaffolds, and more sophisticated screening methods were directed at target disease states. In the 1990s, the pharmaceutical industry moved to high-throughput screening of synthetic chemical libraries against many potential therapeutic targets, including new targets identified from the human genome sequencing project, largely to the exclusion of natural products, and discovery rates dropped dramatically. Nonetheless, natural products continued to provide key scaffolds for drug development. In the current millennium, it was discovered from genome sequencing that microbes with large genomes have the capacity to produce about ten times as many secondary metabolites as was previously recognized. Indeed, the most gifted actinomycetes have the capacity to produce around 30-50 secondary metabolites. With the precipitous drop in cost for genome sequencing, it is now feasible to sequence thousands of actinomycete genomes to identify the "biosynthetic dark matter" as sources for the discovery of new and novel secondary metabolites. Advances in bioinformatics, mass spectrometry, proteomics, transcriptomics, metabolomics and gene expression are driving the new field of microbial genome mining for applications in natural product discovery and development.

  18. Bayesian centroid estimation for motif discovery.

    Science.gov (United States)

    Carvalho, Luis

    2013-01-01

    Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators.

  19. Bayesian centroid estimation for motif discovery.

    Directory of Open Access Journals (Sweden)

    Luis Carvalho

    Full Text Available Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators.

  20. Automated Supernova Discovery (Abstract)

    Science.gov (United States)

    Post, R. S.

    2015-12-01

    (Abstract only) We are developing a system of robotic telescopes for automatic recognition of Supernovas as well as other transient events in collaboration with the Puckett Supernova Search Team. At the SAS2014 meeting, the discovery program, SNARE, was first described. Since then, it has been continuously improved to handle searches under a wide variety of atmospheric conditions. Currently, two telescopes are used to build a reference library while searching for PSN with a partial library. Since data is taken every night without clouds, we must deal with varying atmospheric and high background illumination from the moon. Software is configured to identify a PSN, reshoot for verification with options to change the run plan to acquire photometric or spectrographic data. The telescopes are 24-inch CDK24, with Alta U230 cameras, one in CA and one in NM. Images and run plans are sent between sites so the CA telescope can search while photometry is done in NM. Our goal is to find bright PSNs with magnitude 17.5 or less which is the limit of our planned spectroscopy. We present results from our first automated PSN discoveries and plans for PSN data acquisition.

  1. Bioinformatics Tools for the Discovery of New Nonribosomal Peptides

    DEFF Research Database (Denmark)

    Leclère, Valérie; Weber, Tilmann; Jacques, Philippe

    2016-01-01

    This chapter helps in the use of bioinformatics tools relevant to the discovery of new nonribosomal peptides (NRPs) produced by microorganisms. The strategy described can be applied to draft or fully assembled genome sequences. It relies on the identification of the synthetase genes and the decip......This chapter helps in the use of bioinformatics tools relevant to the discovery of new nonribosomal peptides (NRPs) produced by microorganisms. The strategy described can be applied to draft or fully assembled genome sequences. It relies on the identification of the synthetase genes...

  2. Oncogene Discovery in Schwannomas

    Science.gov (United States)

    2013-07-01

    cytogenetic anomalies in these tumors are located elsewhere, most frequently in chromosomes 19 (35%), 16 (30%) and 9q (10%). Interestingly, alterations in...gene on chromosome 22.5-8 Proposed mechanisms for the activity of the merlin/schwannomin tumor suppressor gene include its association with the p21...recurrent DNA aberration outside chromosome 22.12-14 Loss of 22q (containing NF2) occurs reproducibly in 24-29% of tumors, but nearly half of the

  3. Representation Discovery using Harmonic Analysis

    CERN Document Server

    Mahadevan, Sridhar

    2008-01-01

    Representations are at the heart of artificial intelligence (AI). This book is devoted to the problem of representation discovery: how can an intelligent system construct representations from its experience? Representation discovery re-parameterizes the state space - prior to the application of information retrieval, machine learning, or optimization techniques - facilitating later inference processes by constructing new task-specific bases adapted to the state space geometry. This book presents a general approach to representation discovery using the framework of harmonic analysis, in particu

  4. Optogenetics enlightens neuroscience drug discovery.

    Science.gov (United States)

    Song, Chenchen; Knöpfel, Thomas

    2016-02-01

    Optogenetics - the use of light and genetics to manipulate and monitor the activities of defined cell populations - has already had a transformative impact on basic neuroscience research. Now, the conceptual and methodological advances associated with optogenetic approaches are providing fresh momentum to neuroscience drug discovery, particularly in areas that are stalled on the concept of 'fixing the brain chemistry'. Optogenetics is beginning to translate and transit into drug discovery in several key domains, including target discovery, high-throughput screening and novel therapeutic approaches to disease states. Here, we discuss the exciting potential of optogenetic technologies to transform neuroscience drug discovery.

  5. Discovery of neptunium

    International Nuclear Information System (INIS)

    Abelson, P.H.

    1990-01-01

    A number of distinguished scientists irradiated uranium with neutrons during 1934-1938. All were knowledgeable about the periodic table. They observed a number of beta-emitting activities that seemed to be from transuranic elements. They assumed that elements 93 and 94 would have chemical properties similar to rhenium and osmium respectively. In consequence discovery of fission and neptunium was delayed. After fission was finally demonstrated, a new search for element 93 was initiated by McMillan. He showed that when thin films of uranium are exposed to neutrons, high energy fission products leave the film - 23 minute and 2.3 day activities. The 23 minute activity was known to be an isotope of uranium. Chemistry performed by Abelson in May 1940 produced conclusive evidence that the 2.3 day activity was from the transuranic element 93 later named neptunium

  6. Hippocampus discovery First steps

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available The first steps of the discovery, and the main discoverers, of the hippocampus are outlined. Arantius was the first to describe a structure he named "hippocampus" or "white silkworm". Despite numerous controversies and alternate designations, the term hippocampus has prevailed until this day as the most widely used term. Duvernoy provided an illustration of the hippocampus and surrounding structures, considered the first by most authors, which appeared more than one and a half century after Arantius' description. Some authors have identified other drawings and texts which they claim predate Duvernoy's depiction, in studies by Vesalius, Varolio, Willis, and Eustachio, albeit unconvincingly. Considering the definition of the hippocampal formation as comprising the hippocampus proper, dentate gyrus and subiculum, Arantius and Duvernoy apparently described the gross anatomy of this complex. The pioneering studies of Arantius and Duvernoy revealed a relatively small hidden formation that would become one of the most valued brain structures.

  7. Towards Robot Scientists for autonomous scientific discovery.

    Science.gov (United States)

    Sparkes, Andrew; Aubrey, Wayne; Byrne, Emma; Clare, Amanda; Khan, Muhammed N; Liakata, Maria; Markham, Magdalena; Rowland, Jem; Soldatova, Larisa N; Whelan, Kenneth E; Young, Michael; King, Ross D

    2010-01-04

    We review the main components of autonomous scientific discovery, and how they lead to the concept of a Robot Scientist. This is a system which uses techniques from artificial intelligence to automate all aspects of the scientific discovery process: it generates hypotheses from a computer model of the domain, designs experiments to test these hypotheses, runs the physical experiments using robotic systems, analyses and interprets the resulting data, and repeats the cycle. We describe our two prototype Robot Scientists: Adam and Eve. Adam has recently proven the potential of such systems by identifying twelve genes responsible for catalysing specific reactions in the metabolic pathways of the yeast Saccharomyces cerevisiae. This work has been formally recorded in great detail using logic. We argue that the reporting of science needs to become fully formalised and that Robot Scientists can help achieve this. This will make scientific information more reproducible and reusable, and promote the integration of computers in scientific reasoning. We believe the greater automation of both the physical and intellectual aspects of scientific investigations to be essential to the future of science. Greater automation improves the accuracy and reliability of experiments, increases the pace of discovery and, in common with conventional laboratory automation, removes tedious and repetitive tasks from the human scientist.

  8. Discoveries of isotopes by fission

    Indian Academy of Sciences (India)

    2015-08-28

    Aug 28, 2015 ... Of the about 3000 isotopes presently known, about 20% have been discovered in fission. The history of fission as it relates to the discovery of isotopes as well as the various reaction mechanisms leading to isotope discoveries involving fission are presented.

  9. Recent development of computational resources for new antibiotics discovery

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Blin, Kai; Lee, Sang Yup

    2017-01-01

    Understanding a complex working mechanism of biosynthetic gene clusters (BGCs) encoding secondary metabolites is a key to discovery of new antibiotics. Computational resources continue to be developed in order to better process increasing volumes of genome and chemistry data, and thereby better...

  10. Discovery Mondays: Surveyors' Tools

    CERN Multimedia

    2003-01-01

    Surveyors of all ages, have your rulers and compasses at the ready! This sixth edition of Discovery Monday is your chance to learn about the surveyor's tools - the state of the art in measuring instruments - and see for yourself how they work. With their usual daunting precision, the members of CERN's Surveying Group have prepared some demonstrations and exercises for you to try. Find out the techniques for ensuring accelerator alignment and learn about high-tech metrology systems such as deviation indicators, tracking lasers and total stations. The surveyors will show you how they precisely measure magnet positioning, with accuracy of a few thousandths of a millimetre. You can try your hand at precision measurement using different types of sensor and a modern-day version of the Romans' bubble level, accurate to within a thousandth of a millimetre. You will learn that photogrammetry techniques can transform even a simple digital camera into a remarkable measuring instrument. Finally, you will have a chance t...

  11. Supernovae Discovery Efficiency

    Science.gov (United States)

    John, Colin

    2018-01-01

    Abstract:We present supernovae (SN) search efficiency measurements for recent Hubble Space Telescope (HST) surveys. Efficiency is a key component to any search, and is important parameter as a correction factor for SN rates. To achieve an accurate value for efficiency, many supernovae need to be discoverable in surveys. This cannot be achieved from real SN only, due to their scarcity, so fake SN are planted. These fake supernovae—with a goal of realism in mind—yield an understanding of efficiency based on position related to other celestial objects, and brightness. To improve realism, we built a more accurate model of supernovae using a point-spread function. The next improvement to realism is planting these objects close to galaxies and of various parameters of brightness, magnitude, local galactic brightness and redshift. Once these are planted, a very accurate SN is visible and discoverable by the searcher. It is very important to find factors that affect this discovery efficiency. Exploring the factors that effect detection yields a more accurate correction factor. Further inquires into efficiency give us a better understanding of image processing, searching techniques and survey strategies, and result in an overall higher likelihood to find these events in future surveys with Hubble, James Webb, and WFIRST telescopes. After efficiency is discovered and refined with many unique surveys, it factors into measurements of SN rates versus redshift. By comparing SN rates vs redshift against the star formation rate we can test models to determine how long star systems take from the point of inception to explosion (delay time distribution). This delay time distribution is compared to SN progenitors models to get an accurate idea of what these stars were like before their deaths.

  12. Model-driven discovery of underground metabolic functions in Escherichia coli

    DEFF Research Database (Denmark)

    Guzmán, Gabriela I.; Utrilla, José; Nurk, Sergey

    2015-01-01

    -scale models, which have been widely used for predicting growth phenotypes in various environments or following a genetic perturbation; however, these predictions occasionally fail. Failed predictions of gene essentiality offer an opportunity for targeting biological discovery, suggesting the presence...

  13. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  14. Discovery of the cadmium isotopes

    International Nuclear Information System (INIS)

    Amos, S.; Thoennessen, M.

    2010-01-01

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

  15. Synthetic biology of antimicrobial discovery

    Science.gov (United States)

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  16. Scientific discovery through weighted sampling

    NARCIS (Netherlands)

    E. Sidirourgos (Eleftherios); M.L. Kersten (Martin); P.A. Boncz (Peter)

    2013-01-01

    textabstractScientific discovery has shifted from being an exercise of theory and computation, to become the exploration of an ocean of observational data. Scientists explore data originated from modern scientific instruments in order to discover

  17. Exosomes in urine biomarker discovery.

    Science.gov (United States)

    Huebner, Alyssa R; Somparn, Poorichaya; Benjachat, Thitima; Leelahavanichkul, Asada; Avihingsanon, Yingyos; Fenton, Robert A; Pisitkun, Trairak

    2015-01-01

    Nanovesicles present in urine the so-called urinary exosomes have been found to be secreted by every epithelial cell type lining the urinary tract system in human. Urinary exosomes are an appealing source for biomarker discovery as they contain molecular constituents of their cell of origin, including proteins and genetic materials, and they can be isolated in a non-invasive manner. Following the discovery of urinary exosomes in 2004, many studies have been performed using urinary exosomes as a starting material to identify biomarkers in various renal, urogenital, and systemic diseases. Here, we describe the discovery of urinary exosomes and address the issues on the collection, isolation, and normalization of urinary exosomes as well as delineate the systems biology approach to biomarker discovery using urinary exosomes.

  18. Radioactivity. Centenary of radioactivity discovery

    International Nuclear Information System (INIS)

    Charpak, G.; Tubiana, M.; Bimbot, R.

    1997-01-01

    This small booklet was edited for the occasion of the exhibitions of the celebration of the centenary of radioactivity discovery which took place in various locations in France from 1996 to 1998. It recalls some basic knowledge concerning radioactivity and its applications: history of discovery, atoms and isotopes, radiations, measurement of ionizing radiations, natural and artificial radioactivity, isotope dating and labelling, radiotherapy, nuclear power and reactors, fission and fusion, nuclear wastes, dosimetry, effects and radioprotection. (J.S.)

  19. Large-scale discovery of enhancers from human heart tissue.

    Science.gov (United States)

    May, Dalit; Blow, Matthew J; Kaplan, Tommy; McCulley, David J; Jensen, Brian C; Akiyama, Jennifer A; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Afzal, Veena; Simpson, Paul C; Rubin, Edward M; Black, Brian L; Bristow, James; Pennacchio, Len A; Visel, Axel

    2011-12-04

    Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.

  20. Computational methods in drug discovery

    Directory of Open Access Journals (Sweden)

    Sumudu P. Leelananda

    2016-12-01

    Full Text Available The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed.

  1. Genetic regulation and manipulation for natural product discovery.

    Science.gov (United States)

    Chen, Jianwei; Wu, Qihao; Hawas, Usama W; Wang, Hong

    2016-04-01

    Natural products are an important source of modern medical development, e.g., antibiotics, anticancers, immune modulators, etc. and will continue to be a powerful driving force for the discovery of novel potential drugs. In the heterologous hosts, natural products are biosynthesized using dedicated metabolic networks. By gene engineering, pathway reconstructing, and enzyme engineering, metabolic networks can be modified to synthesize novel compounds containing enhanced structural feature or produce a large quantity of known valuable bioactive compounds. The review introduces some important technical platforms and relevant examples of genetic regulation and manipulation to improve natural product titers or drive novel secondary metabolite discoveries.

  2. Universal Knowledge Discovery from Big Data: Towards a Paradigm Shift from 'Knowledge Discovery' to 'Wisdom Discovery'

    OpenAIRE

    Shen, Bin

    2014-01-01

    Many people hold a vision that big data will provide big insights and have a big impact in the future, and big-data-assisted scientific discovery is seen as an emerging and promising scientific paradigm. However, how to turn big data into deep insights with tremendous value still remains obscure. To meet the challenge, universal knowledge discovery from big data (UKD) is proposed. The new concept focuses on discovering universal knowledge, which exists in the statistical analyses of big data ...

  3. Gene and enhancer trap tagging of vascular-expressed genes in poplar trees

    Science.gov (United States)

    Andrew Groover; Joseph R. Fontana; Gayle Dupper; Caiping Ma; Robert Martienssen; Steven Strauss; Richard Meilan

    2004-01-01

    We report a gene discovery system for poplar trees based on gene and enhancer traps. Gene and enhancer trap vectors carrying the β-glucuronidase (GUS) reporter gene were inserted into the poplar genome via Agrobacterium tumefaciens transformation, where they reveal the expression pattern of genes at or near the insertion sites. Because GUS...

  4. The web server of IBM's Bioinformatics and Pattern Discovery group.

    Science.gov (United States)

    Huynh, Tien; Rigoutsos, Isidore; Parida, Laxmi; Platt, Daniel; Shibuya, Tetsuo

    2003-07-01

    We herein present and discuss the services and content which are available on the web server of IBM's Bioinformatics and Pattern Discovery group. The server is operational around the clock and provides access to a variety of methods that have been published by the group's members and collaborators. The available tools correspond to applications ranging from the discovery of patterns in streams of events and the computation of multiple sequence alignments, to the discovery of genes in nucleic acid sequences and the interactive annotation of amino acid sequences. Additionally, annotations for more than 70 archaeal, bacterial, eukaryotic and viral genomes are available on-line and can be searched interactively. The tools and code bundles can be accessed beginning at http://cbcsrv.watson.ibm.com/Tspd.html whereas the genomics annotations are available at http://cbcsrv.watson.ibm.com/Annotations/.

  5. The Europa Ocean Discovery mission

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, B.C. [Los Alamos National Lab., NM (United States); Chyba, C.F. [Univ. of Arizona, Tucson, AZ (United States); Abshire, J.B. [National Aeronautics and Space Administration, Greenbelt, MD (United States). Goddard Space Flight Center] [and others

    1997-06-01

    Since it was first proposed that tidal heating of Europa by Jupiter might lead to liquid water oceans below Europa`s ice cover, there has been speculation over the possible exobiological implications of such an ocean. Liquid water is the essential ingredient for life as it is known, and the existence of a second water ocean in the Solar System would be of paramount importance for seeking the origin and existence of life beyond Earth. The authors present here a Discovery-class mission concept (Europa Ocean Discovery) to determine the existence of a liquid water ocean on Europa and to characterize Europa`s surface structure. The technical goal of the Europa Ocean Discovery mission is to study Europa with an orbiting spacecraft. This goal is challenging but entirely feasible within the Discovery envelope. There are four key challenges: entering Europan orbit, generating power, surviving long enough in the radiation environment to return valuable science, and complete the mission within the Discovery program`s launch vehicle and budget constraints. The authors will present here a viable mission that meets these challenges.

  6. Exploration and Exploitation of Novel SSR Markers for Candidate Transcription Factor Genes in Lilium Species

    Directory of Open Access Journals (Sweden)

    Manosh Kumar Biswas

    2018-02-01

    Full Text Available Lilies (Lilium sp. are commercially important horticultural crops widely cultivated for their flowers and bulbs. Here, we conducted large-scale data mining of the lily transcriptome to develop transcription factor (TF-associated microsatellite markers (TFSSRs. Among 216,768 unigenes extracted from our sequence data, 6966 unigenes harbored simple sequence repeats (SSRs. Seventy-one SSRs were associated with TF genes, and these were used to design primers and validate their potential as markers. These 71 SSRs were accomplished with 31 transcription factor families; including bHLH, MYB, C2H2, ERF, C3H, NAC, bZIP, and so on. Fourteen highly polymorphic SSRs were selected based on Polymorphic Information Content (PIC values and used to study genetic diversity and population structure in lily accessions. Higher genetic diversity was observed in Longiflorum compared to Oriental and Asiatic populations. Lily accessions were divided into three sub-populations based in our structure analysis, and an un-rooted neighbor-joining tree effectively separated the accessions according to Asiatic, Oriental, and Longiflorum subgroups. Finally, we showed that 46 of the SSR-associated genes were differentially expressed in response to Botrytis elliptica infection. Thus, our newly developed TFSSR markers represent a powerful tool for large-scale genotyping, high-density and comparative mapping, marker-aided backcrossing, and molecular diversity analysis of Lilium sp.

  7. New genetic discoveries and primary immune deficiencies.

    Science.gov (United States)

    Hernandez-Trujillo, Vivian

    2014-04-01

    The field of immunology has undergone recent discoveries of genetic causes for many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has led to increased understanding behind the pathophysiology of these diseases. Since these diseases are rare, the patients are frequently misdiagnosed early in the presentation of their illnesses. The identification of new genes has increased our opportunities for recognizing and making the diagnosis in patients with PIDD before they succumb to infections that may result secondary to their PIDD. Some mutations lead to a variety of presentations of severe combined immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead to SCID phenotypes have been identified in recent years. Other mutations associated with some genetic syndromes have associated immunodeficiency and are important for making the diagnosis of primary immunodeficiency in patients with some syndromes, who may otherwise be missed within the larger context of their syndromes. A variety of mutations also lead to increased susceptibility to infections due to particular organisms. These patterns of infections due to specific organisms are important keys in properly identifying the part of the immune system which is affected in these patients. This review will discuss recent genetic discoveries that enhance our understanding of these complex diseases.

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

    Directory of Open Access Journals (Sweden)

    Douglas Carl J

    2008-01-01

    Full Text Available Abstract Background The genus Populus includes poplars, aspens and cottonwoods, which will be collectively referred to as poplars hereafter unless otherwise specified. Poplars are the dominant tree species in many forest ecosystems in the Northern Hemisphere and are of substantial economic value in plantation forestry. Poplar has been established as a model system for genomics studies of growth, development, and adaptation of woody perennial plants including secondary xylem formation, dormancy, adaptation to local environments, and biotic interactions. Results As part of the poplar genome sequencing project and the development of genomic resources for poplar, we have generated a full-length (FL-cDNA collection using the biotinylated CAP trapper method. We constructed four FLcDNA libraries using RNA from xylem, phloem and cambium, and green shoot tips and leaves from the P. trichocarpa Nisqually-1 genotype, as well as insect-attacked leaves of the P. trichocarpa × P. deltoides hybrid. Following careful selection of candidate cDNA clones, we used a combined strategy of paired end reads and primer walking to generate a set of 4,664 high-accuracy, sequence-verified FLcDNAs, which clustered into 3,990 putative unique genes. Mapping FLcDNAs to the poplar genome sequence combined with BLAST comparisons to previously predicted protein coding sequences in the poplar genome identified 39 FLcDNAs that likely localize to gaps in the current genome sequence assembly. Another 173 FLcDNAs mapped to the genome sequence but were not included among the previously predicted genes in the poplar genome. Comparative sequence analysis against Arabidopsis thaliana and other species in the non-redundant database of GenBank revealed that 11.5% of the poplar FLcDNAs display no significant sequence similarity to other plant proteins. By mapping the poplar FLcDNAs against transcriptome data previously obtained with a 15.5 K cDNA microarray, we identified 153 FLcDNA clones

  9. Development of Molecular Markers Linked to Powdery Mildew Resistance Gene Pm4b by Combining SNP Discovery from Transcriptome Sequencing Data with Bulked Segregant Analysis (BSR-Seq) in Wheat

    Science.gov (United States)

    Wu, Peipei; Xie, Jingzhong; Hu, Jinghuang; Qiu, Dan; Liu, Zhiyong; Li, Jingting; Li, Miaomiao; Zhang, Hongjun; Yang, Li; Liu, Hongwei; Zhou, Yang; Zhang, Zhongjun; Li, Hongjie

    2018-01-01

    Powdery mildew resistance gene Pm4b, originating from Triticum persicum, is effective against the prevalent Blumeria graminis f. sp. tritici (Bgt) isolates from certain regions of wheat production in China. The lack of tightly linked molecular markers with the target gene prevents the precise identification of Pm4b during the application of molecular marker-assisted selection (MAS). The strategy that combines the RNA-Seq technique and the bulked segregant analysis (BSR-Seq) was applied in an F2:3 mapping population (237 families) derived from a pair of isogenic lines VPM1/7∗Bainong 3217 F4 (carrying Pm4b) and Bainong 3217 to develop more closely linked molecular markers. RNA-Seq analysis of the two phenotypically contrasting RNA bulks prepared from the representative F2:3 families generated 20,745,939 and 25,867,480 high-quality read pairs, and 82.8 and 80.2% of them were uniquely mapped to the wheat whole genome draft assembly for the resistant and susceptible RNA bulks, respectively. Variant calling identified 283,866 raw single nucleotide polymorphisms (SNPs) and InDels between the two bulks. The SNPs that were closely associated with the powdery mildew resistance were concentrated on chromosome 2AL. Among the 84 variants that were potentially associated with the disease resistance trait, 46 variants were enriched in an about 25 Mb region at the distal end of chromosome arm 2AL. Four Pm4b-linked SNP markers were developed from these variants. Based on the sequences of Chinese Spring where these polymorphic SNPs were located, 98 SSR primer pairs were designed to develop distal markers flanking the Pm4b gene. Three SSR markers, Xics13, Xics43, and Xics76, were incorporated in the new genetic linkage map, which located Pm4b in a 3.0 cM genetic interval spanning a 6.7 Mb physical genomic region. This region had a collinear relationship with Brachypodium distachyon chromosome 5, rice chromosome 4, and sorghum chromosome 6. Seven genes associated with disease

  10. Development of Molecular Markers Linked to Powdery Mildew Resistance Gene Pm4b by Combining SNP Discovery from Transcriptome Sequencing Data with Bulked Segregant Analysis (BSR-Seq in Wheat

    Directory of Open Access Journals (Sweden)

    Peipei Wu

    2018-02-01

    Full Text Available Powdery mildew resistance gene Pm4b, originating from Triticum persicum, is effective against the prevalent Blumeria graminis f. sp. tritici (Bgt isolates from certain regions of wheat production in China. The lack of tightly linked molecular markers with the target gene prevents the precise identification of Pm4b during the application of molecular marker-assisted selection (MAS. The strategy that combines the RNA-Seq technique and the bulked segregant analysis (BSR-Seq was applied in an F2:3 mapping population (237 families derived from a pair of isogenic lines VPM1/7∗Bainong 3217 F4 (carrying Pm4b and Bainong 3217 to develop more closely linked molecular markers. RNA-Seq analysis of the two phenotypically contrasting RNA bulks prepared from the representative F2:3 families generated 20,745,939 and 25,867,480 high-quality read pairs, and 82.8 and 80.2% of them were uniquely mapped to the wheat whole genome draft assembly for the resistant and susceptible RNA bulks, respectively. Variant calling identified 283,866 raw single nucleotide polymorphisms (SNPs and InDels between the two bulks. The SNPs that were closely associated with the powdery mildew resistance were concentrated on chromosome 2AL. Among the 84 variants that were potentially associated with the disease resistance trait, 46 variants were enriched in an about 25 Mb region at the distal end of chromosome arm 2AL. Four Pm4b-linked SNP markers were developed from these variants. Based on the sequences of Chinese Spring where these polymorphic SNPs were located, 98 SSR primer pairs were designed to develop distal markers flanking the Pm4b gene. Three SSR markers, Xics13, Xics43, and Xics76, were incorporated in the new genetic linkage map, which located Pm4b in a 3.0 cM genetic interval spanning a 6.7 Mb physical genomic region. This region had a collinear relationship with Brachypodium distachyon chromosome 5, rice chromosome 4, and sorghum chromosome 6. Seven genes associated with

  11. Label-free drug discovery

    Directory of Open Access Journals (Sweden)

    Ye eFang

    2014-03-01

    Full Text Available Current drug discovery is dominated by label-dependent molecular approaches, which screen drugs in the context of a predefined and target-based hypothesis in vitro. Given that target-based discovery has not transformed the industry, phenotypic screen that identifies drugs based on a specific phenotype of cells, tissues, or animals has gained renewed interest. However, owing to the intrinsic complexity in drug-target interactions, there is often a significant gap between the phenotype screened and the ultimate molecular mechanism of action sought. This paper presents a label-free strategy for early drug discovery. This strategy combines label-free cell phenotypic profiling with computational approaches, and holds promise to bridge the gap by offering a kinetic and holistic representation of the functional consequences of drugs in disease relevant cells that is amenable to mechanistic deconvolution.

  12. Deep Learning in Drug Discovery.

    Science.gov (United States)

    Gawehn, Erik; Hiss, Jan A; Schneider, Gisbert

    2016-01-01

    Artificial neural networks had their first heyday in molecular informatics and drug discovery approximately two decades ago. Currently, we are witnessing renewed interest in adapting advanced neural network architectures for pharmaceutical research by borrowing from the field of "deep learning". Compared with some of the other life sciences, their application in drug discovery is still limited. Here, we provide an overview of this emerging field of molecular informatics, present the basic concepts of prominent deep learning methods and offer motivation to explore these techniques for their usefulness in computer-assisted drug discovery and design. We specifically emphasize deep neural networks, restricted Boltzmann machine networks and convolutional networks. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Bioinformatics in translational drug discovery.

    Science.gov (United States)

    Wooller, Sarah K; Benstead-Hume, Graeme; Chen, Xiangrong; Ali, Yusuf; Pearl, Frances M G

    2017-08-31

    Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse 'big data' that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications. © 2017 The Author(s).

  14. In defence of discovery learning.

    Science.gov (United States)

    Vereijken, B; Whiting, H T

    1990-06-01

    The present paper discusses the influence of different training methods--i.e., knowledge of results, preferred frequency, and the availability of a model--on the learning of a complex motor skill, in this case the learning of slalom ski-type movements on a ski-simulator. Results of three experiments performed on this apparatus showed that, although the training methods used influence the course of learning, none of the methods used was actually superior to discovery learning. It is suggested that discovery learning forces the learner to explore the dynamics of the system in which he or she operates, in an iterative way. Possibilities for cooperative working between prescription and discovery learning are discussed.

  15. Functional genomics and cancer drug target discovery.

    Science.gov (United States)

    Moody, Susan E; Boehm, Jesse S; Barbie, David A; Hahn, William C

    2010-06-01

    The recent development of technologies for whole-genome sequencing, copy number analysis and expression profiling enables the generation of comprehensive descriptions of cancer genomes. However, although the structural analysis and expression profiling of tumors and cancer cell lines can allow the identification of candidate molecules that are altered in the malignant state, functional analyses are necessary to confirm such genes as oncogenes or tumor suppressors. Moreover, recent research suggests that tumor cells also depend on synthetic lethal targets, which are not mutated or amplified in cancer genomes; functional genomics screening can facilitate the discovery of such targets. This review provides an overview of the tools available for the study of functional genomics, and discusses recent research involving the use of these tools to identify potential novel drug targets in cancer.

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

    Science.gov (United States)

    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

  17. Advancements in Aptamer Discovery Technologies.

    Science.gov (United States)

    Gotrik, Michael R; Feagin, Trevor A; Csordas, Andrew T; Nakamoto, Margaret A; Soh, H Tom

    2016-09-20

    Affinity reagents that specifically bind to their target molecules are invaluable tools in nearly every field of modern biomedicine. Nucleic acid-based aptamers offer many advantages in this domain, because they are chemically synthesized, stable, and economical. Despite these compelling features, aptamers are currently not widely used in comparison to antibodies. This is primarily because conventional aptamer-discovery techniques such as SELEX are time-consuming and labor-intensive and often fail to produce aptamers with comparable binding performance to antibodies. This Account describes a body of work from our laboratory in developing advanced methods for consistently producing high-performance aptamers with higher efficiency, fewer resources, and, most importantly, a greater probability of success. We describe our efforts in systematically transforming each major step of the aptamer discovery process: selection, analysis, and characterization. To improve selection, we have developed microfluidic devices (M-SELEX) that enable discovery of high-affinity aptamers after a minimal number of selection rounds by precisely controlling the target concentration and washing stringency. In terms of improving aptamer pool analysis, our group was the first to use high-throughput sequencing (HTS) for the discovery of new aptamers. We showed that tracking the enrichment trajectory of individual aptamer sequences enables the identification of high-performing aptamers without requiring full convergence of the selected aptamer pool. HTS is now widely used for aptamer discovery, and open-source software has become available to facilitate analysis. To improve binding characterization, we used HTS data to design custom aptamer arrays to measure the affinity and specificity of up to ∼10(4) DNA aptamers in parallel as a means to rapidly discover high-quality aptamers. Most recently, our efforts have culminated in the invention of the "particle display" (PD) screening system, which

  18. OPEN DATA FOR DISCOVERY SCIENCE.

    Science.gov (United States)

    Payne, Philip R O; Huang, Kun; Shah, Nigam H; Tenenbaum, Jessica

    2017-01-01

    The modern healthcare and life sciences ecosystem is moving towards an increasingly open and data-centric approach to discovery science. This evolving paradigm is predicated on a complex set of information needs related to our collective ability to share, discover, reuse, integrate, and analyze open biological, clinical, and population level data resources of varying composition, granularity, and syntactic or semantic consistency. Such an evolution is further impacted by a concomitant growth in the size of data sets that can and should be employed for both hypothesis discovery and testing. When such open data can be accessed and employed for discovery purposes, a broad spectrum of high impact end-points is made possible. These span the spectrum from identification of de novo biomarker complexes that can inform precision medicine, to the repositioning or repurposing of extant agents for new and cost-effective therapies, to the assessment of population level influences on disease and wellness. Of note, these types of uses of open data can be either primary, wherein open data is the substantive basis for inquiry, or secondary, wherein open data is used to augment or enrich project-specific or proprietary data that is not open in and of itself. This workshop is concerned with the key challenges, opportunities, and methodological best practices whereby open data can be used to drive the advancement of discovery science in all of the aforementioned capacities.

  19. Hubble 15 years of discovery

    CERN Document Server

    Lindberg Christensen, Lars; Kornmesser, M

    2006-01-01

    Hubble: 15 Years of Discovery was a key element of the European Space Agency's 15th anniversary celebration activities for the 1990 launch of the NASA/ESA Hubble Space Telescope. As an observatory in space, Hubble is one of the most successful scientific projects of all time, both in terms of scientific output and its immediate public appeal.

  20. Smartphones: A Potential Discovery Tool

    Directory of Open Access Journals (Sweden)

    Wendy Starkweather

    2009-09-01

    Full Text Available The anticipated wide adoption of smartphones by researchers is viewed by the authors as a basis for developing mobile-based services. In response to the UNLV Libraries’ strategic plan’s focus on experimentation and outreach, the authors investigate the current and potential role of smartphones as a valuable discovery tool for library users.

  1. Translational medicine and drug discovery

    National Research Council Canada - National Science Library

    Littman, Bruce H; Krishna, Rajesh

    2011-01-01

    ..., and examples of their application to real-life drug discovery and development. The latest thinking is presented by researchers from many of the world's leading pharmaceutical companies, including Pfizer, Merck, Eli Lilly, Abbott, and Novartis, as well as from academic institutions and public- private partnerships that support translational research...

  2. Structural Biology Guides Antibiotic Discovery

    Science.gov (United States)

    Polyak, Steven

    2014-01-01

    Modern drug discovery programs require the contribution of researchers in a number of specialist areas. One of these areas is structural biology. Using X-ray crystallography, the molecular basis of how a drug binds to its biological target and exerts its mode of action can be defined. For example, a drug that binds into the active site of an…

  3. A Discovery Approach to Movement.

    Science.gov (United States)

    O'Hagin, Isabel B.

    1998-01-01

    Investigates the effects of the discovery approach to movement-based instruction on children's level of musicality. Finds that the students with the highest musicality were girls, demonstrated reflective movements and a personal sense of style while moving, and made sense of the music by organizing, categorizing, and developing movement ideas.…

  4. Discoveries of isotopes by fission

    Indian Academy of Sciences (India)

    activities as the potential discovery of elements heavier than uranium [5]. He drew this conclusion ... alkaline earth metals in the irradiation of uranium by neutrons) Hahn and Strassmann did. 458. Pramana – J. ... the production of active barium isotopes from uranium and thorium by neutron irradiation;. Proof of further active ...

  5. The limits of de novo DNA motif discovery.

    Directory of Open Access Journals (Sweden)

    David Simcha

    Full Text Available A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of

  6. Arthritis Genetics Analysis Aids Drug Discovery

    Science.gov (United States)

    ... NIH Research Matters January 13, 2014 Arthritis Genetics Analysis Aids Drug Discovery An international research team identified 42 new ... Edition Distracted Driving Raises Crash Risk Arthritis Genetics Analysis Aids Drug Discovery Oxytocin Affects Facial Recognition Connect with Us ...

  7. How to Improve Postgenomic Knowledge Discovery Using Imputation

    Directory of Open Access Journals (Sweden)

    2009-02-01

    Full Text Available While microarrays make it feasible to rapidly investigate many complex biological problems, their multistep fabrication has the proclivity for error at every stage. The standard tactic has been to either ignore or regard erroneous gene readings as missing values, though this assumption can exert a major influence upon postgenomic knowledge discovery methods like gene selection and gene regulatory network (GRN reconstruction. This has been the catalyst for a raft of new flexible imputation algorithms including local least square impute and the recent heuristic collateral missing value imputation, which exploit the biological transactional behaviour of functionally correlated genes to afford accurate missing value estimation. This paper examines the influence of missing value imputation techniques upon postgenomic knowledge inference methods with results for various algorithms consistently corroborating that instead of ignoring missing values, recycling microarray data by flexible and robust imputation can provide substantial performance benefits for subsequent downstream procedures.

  8. How to Improve Postgenomic Knowledge Discovery Using Imputation

    Directory of Open Access Journals (Sweden)

    Coppel Ross

    2009-01-01

    Full Text Available While microarrays make it feasible to rapidly investigate many complex biological problems, their multistep fabrication has the proclivity for error at every stage. The standard tactic has been to either ignore or regard erroneous gene readings as missing values, though this assumption can exert a major influence upon postgenomic knowledge discovery methods like gene selection and gene regulatory network (GRN reconstruction. This has been the catalyst for a raft of new flexible imputation algorithms including local least square impute and the recent heuristic collateral missing value imputation, which exploit the biological transactional behaviour of functionally correlated genes to afford accurate missing value estimation. This paper examines the influence of missing value imputation techniques upon postgenomic knowledge inference methods with results for various algorithms consistently corroborating that instead of ignoring missing values, recycling microarray data by flexible and robust imputation can provide substantial performance benefits for subsequent downstream procedures.

  9. [Artificial Intelligence in Drug Discovery].

    Science.gov (United States)

    Fujiwara, Takeshi; Kamada, Mayumi; Okuno, Yasushi

    2018-04-01

    According to the increase of data generated from analytical instruments, application of artificial intelligence(AI)technology in medical field is indispensable. In particular, practical application of AI technology is strongly required in "genomic medicine" and "genomic drug discovery" that conduct medical practice and novel drug development based on individual genomic information. In our laboratory, we have been developing a database to integrate genome data and clinical information obtained by clinical genome analysis and a computational support system for clinical interpretation of variants using AI. In addition, with the aim of creating new therapeutic targets in genomic drug discovery, we have been also working on the development of a binding affinity prediction system for mutated proteins and drugs by molecular dynamics simulation using supercomputer "Kei". We also have tackled for problems in a drug virtual screening. Our developed AI technology has successfully generated virtual compound library, and deep learning method has enabled us to predict interaction between compound and target protein.

  10. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

    Serenus Hua1,2 & Hyun Joo An1,2,*

    2012-06-01

    Full Text Available The glycome consists of all glycans (or carbohydrates within abiological system, and modulates a wide range of important biologicalactivities, from protein folding to cellular communications.The mining of the glycome for disease markers representsa new paradigm for biomarker discovery; however, this effortis severely complicated by the vast complexity and structuraldiversity of glycans. This review summarizes recent developmentsin analytical technology and methodology as applied tothe fields of glycomics and glycoproteomics. Mass spectrometricstrategies for glycan compositional profiling are described, as arepotential refinements which allow structure-specific profiling.Analytical methods that can discern protein glycosylation at aspecific site of modification are also discussed in detail.Biomarker discovery applications are shown at each level ofanalysis, highlighting the key role that glycoscience can play inhelping scientists understand disease biology.

  11. Enteric Neurobiology: Discoveries and Directions.

    Science.gov (United States)

    Wood, Jackie D

    Discovery and documentation of noncholinergic-nonadrenergic neurotransmission in the enteric nervous system started a revolution in mechanisms of neural control of the digestive tract that continues into a twenty-first century era of translational gastroenterology, which is now firmly embedded in the term, neurogastroenterology. This chapter, on Enteric Neurobiology: Discoveries and Directions, tracks the step-by-step advances in enteric neuronal electrophysiology and synaptic behavior and progresses to the higher order functions of central pattern generators, hard wired synaptic circuits and libraries of neural programs in the brain-in-the-gut that underlie the several different patterns of motility and secretory behaviors that occur in the specialized, serially-connected compartments extending from the esophagus to the anus.

  12. A quantum causal discovery algorithm

    Science.gov (United States)

    Giarmatzi, Christina; Costa, Fabio

    2018-03-01

    Finding a causal model for a set of classical variables is now a well-established task—but what about the quantum equivalent? Even the notion of a quantum causal model is controversial. Here, we present a causal discovery algorithm for quantum systems. The input to the algorithm is a process matrix describing correlations between quantum events. Its output consists of different levels of information about the underlying causal model. Our algorithm determines whether the process is causally ordered by grouping the events into causally ordered non-signaling sets. It detects if all relevant common causes are included in the process, which we label Markovian, or alternatively if some causal relations are mediated through some external memory. For a Markovian process, it outputs a causal model, namely the causal relations and the corresponding mechanisms, represented as quantum states and channels. Our algorithm opens the route to more general quantum causal discovery methods.

  13. The discovery of immunoglobulin E.

    Science.gov (United States)

    Ribatti, Domenico

    2016-03-01

    The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Androgenetic alopecia: stress of discovery.

    Science.gov (United States)

    Passchier, Jan; Erdman, Jeroen; Hammiche, Fatima; Erdman, Ruud A M

    2006-02-01

    The psychological problems of men in the initial stages of alopecia androgenetica (hereditary male hair loss) have seldom been studied. We evaluated two groups of 80 men with alopecia androgenetica in Stages II to IV, indicating the amount of hair loss (overall N=160; for Group I: M=48 yr., SD=18.2; for Group II: M=50 yr., SD=18.0) who visited a dermatology clinic for benign dermatological complaints but not for hair loss, by questionnaires and interview, retrospectively. As predicted, hair problems were reported to be significantly greater overall at the moment of discovery of hair loss than later. About half of the men reported feeling annoyed to very annoyed about the discovery of hair loss. For those patients, provision of information by internet might facilitate a visit to the dermatologist.

  15. Cyber-Enabled Scientific Discovery

    International Nuclear Information System (INIS)

    Chan, Tony; Jameson, Leland

    2007-01-01

    It is often said that numerical simulation is third in the group of three ways to explore modern science: theory, experiment and simulation. Carefully executed modern numerical simulations can, however, be considered at least as relevant as experiment and theory. In comparison to physical experimentation, with numerical simulation one has the numerically simulated values of every field variable at every grid point in space and time. In comparison to theory, with numerical simulation one can explore sets of very complex non-linear equations such as the Einstein equations that are very difficult to investigate theoretically. Cyber-enabled scientific discovery is not just about numerical simulation but about every possible issue related to scientific discovery by utilizing cyberinfrastructure such as the analysis and storage of large data sets, the creation of tools that can be used by broad classes of researchers and, above all, the education and training of a cyber-literate workforce

  16. 12 CFR 308.107 - Document discovery.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Document discovery. 308.107 Section 308.107... PRACTICE AND PROCEDURE General Rules of Procedure § 308.107 Document discovery. (a) Parties to proceedings... only through the production of documents. No other form of discovery shall be allowed. (b) Any...

  17. 34 CFR 81.16 - Discovery.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Discovery. 81.16 Section 81.16 Education Office of the... voluntarily. (b) The ALJ, at a party's request, may order compulsory discovery described in paragraph (c) of... respect to an issue in the case; (3) The discovery request was not made primarily for the purposes of...

  18. 42 CFR 426.532 - Discovery.

    Science.gov (United States)

    2010-10-01

    ... purpose of this section, the term documents includes relevant information, reports, answers, records... § 426.532 Discovery. (a) General rule. If the Board orders discovery, the Board must establish a... or burdensome; or (iii) Will unduly delay the proceeding. (c) Types of discovery available. A party...

  19. The discovery of the antiproton

    International Nuclear Information System (INIS)

    Chamberlain, Owen

    1989-01-01

    A number of groups of particle physicists competed to provide track evidence of the existence of Dirac's postulated antiproton in the mid-1950s. The work of the several teams is described briefly. The author describes the work of his own group on the Bevatron in more detail, and how they finally observed the antiproton. The article finishes with an assessment of the importance of this discovery. (UK)

  20. Model organisms and target discovery.

    Science.gov (United States)

    Muda, Marco; McKenna, Sean

    2004-09-01

    The wealth of information harvested from full genomic sequencing projects has not generated a parallel increase in the number of novel targets for therapeutic intervention. Several pharmaceutical companies have realized that novel drug targets can be identified and validated using simple model organisms. After decades of service in basic research laboratories, yeasts, worms, flies, fishes, and mice are now the cornerstones of modern drug discovery programs.: © 2004 Elsevier Ltd . All rights reserved.

  1. Gas reserves, discoveries and production

    International Nuclear Information System (INIS)

    Saniere, A.

    2006-01-01

    Between 2000 and 2004, new discoveries, located mostly in the Asia/Pacific region, permitted a 71% produced reserve replacement rate. The Middle East and the offshore sector represent a growing proportion of world gas production Non-conventional gas resources are substantial but are not exploited to any significant extent, except in the United States, where they account for 30% of U.S. gas production. (author)

  2. Sea Level Rise Data Discovery

    Science.gov (United States)

    Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

    2016-12-01

    Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

  3. Discovery of a Makemakean Moon

    Science.gov (United States)

    Parker, Alex H.; Buie, Marc W.; Grundy, Will M.; Noll, Keith S.

    2016-01-01

    We describe the discovery of a satellite in orbit about the dwarf planet (136472) Makemake. This satellite, provisionally designated S/2015 (136472) 1, was detected in imaging data collected with the Hubble Space Telescope's Wide Field Camera 3 on UTC 2015 April 27 at 7.80 +/- 0.04 mag fainter than Makemake and at a separation of 0farcs57. It likely evaded detection in previous satellite searches due to a nearly edge-on orbital configuration, placing it deep within the glare of Makemake during a substantial fraction of its orbital period. This configuration would place Makemake and its satellite near a mutual event season. Insufficient orbital motion was detected to make a detailed characterization of its orbital properties, prohibiting a measurement of the system mass with the discovery data alone. Preliminary analysis indicates that if the orbit is circular, its orbital period must be longer than 12.4 days and must have a semimajor axis > or approx. = 21,000 km. We find that the properties of Makemake's moon suggest that the majority of the dark material detected in the system by thermal observations may not reside on the surface of Makemake, but may instead be attributable to S/2015 (136472) 1 having a uniform dark surface. This dark moon hypothesis can be directly tested with future James Webb Space Telescope observations. We discuss the implications of this discovery for the spin state, figure, and thermal properties of Makemake and the apparent ubiquity of trans-Neptunian dwarf planet satellites.

  4. A New Universe of Discoveries

    Science.gov (United States)

    Córdova, France A.

    2016-01-01

    The convergence of emerging advances in astronomical instruments, computational capabilities and talented practitioners (both professional and civilian) is creating an extraordinary new environment for making numerous fundamental discoveries in astronomy, ranging from the nature of exoplanets to understanding the evolution of solar systems and galaxies. The National Science Foundation is playing a critical role in supporting, stimulating, and shaping these advances. NSF is more than an agency of government or a funding mechanism for the infrastructure of science. The work of NSF is a sacred trust that every generation of Americans makes to those of the next generation, that we will build on the body of knowledge we inherit and continue to push forward the frontiers of science. We never lose sight of NSF's obligation to "explore the unexplored" and inspire all of humanity with the wonders of discovery. As the only Federal agency dedicated to the support of basic research and education in all fields of science and engineering, NSF has empowered discoveries across a broad spectrum of scientific inquiry for more than six decades. The result is fundamental scientific research that has had a profound impact on our nation's innovation ecosystem and kept our nation at the very forefront of the world's science-and-engineering enterprise.

  5. Culture-independent discovery of natural products from soil metagenomes.

    Science.gov (United States)

    Katz, Micah; Hover, Bradley M; Brady, Sean F

    2016-03-01

    Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately, traditional culture-based methods for natural product discovery have been deemphasized by pharmaceutical companies due in large part to high rediscovery rates. Culture-independent, or "metagenomic," methods, which rely on the heterologous expression of DNA extracted directly from environmental samples (eDNA), have the potential to provide access to metabolites encoded by a large fraction of the earth's microbial biosynthetic diversity. As soil is both ubiquitous and rich in bacterial diversity, it is an appealing starting point for culture-independent natural product discovery efforts. This review provides an overview of the history of soil metagenome-driven natural product discovery studies and elaborates on the recent development of new tools for sequence-based, high-throughput profiling of environmental samples used in discovering novel natural product biosynthetic gene clusters. We conclude with several examples of these new tools being employed to facilitate the recovery of novel secondary metabolite encoding gene clusters from soil metagenomes and the subsequent heterologous expression of these clusters to produce bioactive small molecules.

  6. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  7. Polar Domain Discovery with Sparkler

    Science.gov (United States)

    Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

    2017-12-01

    The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

  8. DISCOVERY OF A MAKEMAKEAN MOON

    Energy Technology Data Exchange (ETDEWEB)

    Parker, Alex H.; Buie, Marc W. [Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Grundy, Will M. [Lowell Observatory, Flagstaff, AZ (United States); Noll, Keith S., E-mail: aparker@boulder.swri.edu [NASA Goddard Space Flight Center, Greenbelt, MD (United States)

    2016-07-01

    We describe the discovery of a satellite in orbit about the dwarf planet (136472) Makemake. This satellite, provisionally designated S/2015 (136472) 1, was detected in imaging data collected with the Hubble Space Telescope ’s Wide Field Camera 3 on UTC 2015 April 27 at 7.80 ± 0.04 mag fainter than Makemake and at a separation of 0.″57. It likely evaded detection in previous satellite searches due to a nearly edge-on orbital configuration, placing it deep within the glare of Makemake during a substantial fraction of its orbital period. This configuration would place Makemake and its satellite near a mutual event season. Insufficient orbital motion was detected to make a detailed characterization of its orbital properties, prohibiting a measurement of the system mass with the discovery data alone. Preliminary analysis indicates that if the orbit is circular, its orbital period must be longer than 12.4 days and must have a semimajor axis ≳21,000 km. We find that the properties of Makemake’s moon suggest that the majority of the dark material detected in the system by thermal observations may not reside on the surface of Makemake, but may instead be attributable to S/2015 (136472) 1 having a uniform dark surface. This “dark moon hypothesis” can be directly tested with future James Webb Space Telescope observations. We discuss the implications of this discovery for the spin state, figure, and thermal properties of Makemake and the apparent ubiquity of trans-Neptunian dwarf planet satellites.

  9. New vaccines: challenges of discovery.

    Science.gov (United States)

    Mahmoud, Adel

    2016-09-01

    Vaccines have been a major component of preventing and controlling infectious diseases. The basis for discovery of what protects is reviewed as well as new attempts in utilizing Reverse Vaccinology, RNA-RNA methods and proteome analysis are adding significantly to our knowledge. The challenge of how to define protective and defined components of microbes is still hampering efforts to discover new vaccines. Recent excitement about immunotherapy of cancer opens the way to develop vaccines against multiple malignancies. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  10. Scientific discovery using genetic programming

    DEFF Research Database (Denmark)

    Keijzer, Maarten

    2001-01-01

    in this work can be summarized as: The symbolic expressions produced by genetic programming can be made suitable for analysis and interpretation by using units of measurements to guide or restrict the search. To achieve this, the following has been accomplished: A standard genetic programming system...... that are numerically stable and correct. A case study using four real-world problems in the induction of dimensionally correct empirical equations on data using the two different methods is presented to illustrate to use and limitations of these methods in a framework of scientific discovery....

  11. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...... to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how...

  12. BioPlat: a software for human cancer biomarker discovery.

    Science.gov (United States)

    Butti, Matias D; Chanfreau, Hernan; Martinez, Diego; García, Diego; Lacunza, Ezequiel; Abba, Martin C

    2014-06-15

    Development of effective tools such as oligo-microarrays and next-generation sequencing methods for monitoring gene expression on a large scale has resulted in the discovery of gene signatures with prognostic/predictive value in various malignant neoplastic diseases. However, with the exponential growth of gene expression databases, biologists are faced with the challenge of extracting useful information from these repositories. Here, we present a software package, BioPlat (Biomarkers Platform), which allows biologists to identify novel prognostic and predictive cancer biomarkers based on the data mining of gene expression signatures and gene expression profiling databases. BioPlat has been designed as an easy-to-use and flexible desktop software application, which provides a set of analytical tools related to data extraction, preprocessing, filtering, gene expression signature calculation, in silico validation, feature selection and annotation that leverage the integration and reuse of gene expression signatures in the context of follow-up data. BioPlat is a platform-independent software implemented in Java and supported on GNU/Linux and MS Windows, which is freely available for download at http://www.cancergenomics.net. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Metagenomic discovery of polybrominated diphenyl ether biosynthesis by marine sponges

    Science.gov (United States)

    Podell, Sheila; Taton, Arnaud; Schorn, Michelle A.; Busch, Julia; Lin, Zhenjian; Schmidt, Eric W.; Jensen, Paul R.; Paul, Valerie J.; Biggs, Jason S.; Golden, James W.; Allen, Eric E.; Moore, Bradley S.

    2017-01-01

    Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most prolific sources, marine sponges of the order Dysideidae, remains unidentified. Here, we report the discovery of PBDE biosynthetic gene clusters within sponge microbiome-associated cyanobacterial endosymbionts by employing an unbiased metagenome mining approach. By expression of PBDE biosynthetic genes in heterologous cyanobacterial hosts, we correlate the structural diversity of naturally produced PBDEs to modifications within PBDE biosynthetic gene clusters in multiple sponge holobionts. Our results establish the genetic and molecular foundation for the production of PBDEs in one of the most abundant natural sources of these molecules, further setting the stage for a metagenomic-based inventory of other PBDE sources in the marine environment. PMID:28319100

  14. Accelerating scientific discovery : 2007 annual report.

    Energy Technology Data Exchange (ETDEWEB)

    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

  15. The Discovery of Artificial Radioactivity

    Science.gov (United States)

    Guerra, Francesco; Leone, Matteo; Robotti, Nadia

    2012-03-01

    We reconstruct Frédéric Joliot and Irène Curie's discovery of artificial radioactivity in January 1934 based in part on documents preserved in the Joliot-Curie Archives in Paris, France. We argue that their discovery followed from the convergence of two parallel lines of research, on the neutron and on the positron, that were focused on a well-defined experimental problem, the nuclear transmutation of aluminum and other light elements. We suggest that a key role was played by a suggestion that Francis Perrin made at the seventh Solvay Conference at the end of October 1933, that the alpha-particle bombardment of aluminum produces an intermediate unstable isotope of phosphorus, which then decays by positron emission. We also suggest that a further idea that Perrin published in December 1933, and the pioneering theory of beta decay that Enrico Fermi also first published in December 1933, established a new theoretical framework that stimulated Joliot to resume the researches that he and Curie had interrupted after the Solvay Conference, now for the first time using a Geiger-Müller counter to detect the positrons emitted when he bombarded aluminum with polonium alpha particles.

  16. High-Throughput SNP Discovery And Genetic Mapping In Perennial Ryegrass

    DEFF Research Database (Denmark)

    Asp, Torben; Studer, Bruno; Lübberstedt, Thomas

    to establish the VrnA F2 mapping population. The sequences were assembled and used for in-silico SNP discovery. SNPs supported by a minimum number of eight reads, within candidate genes for important agronomic traits, were selected for Illumina GoldenGate genotyping and used to map 768 expressed genes...... in the VrnA mapping population. Here we report on large-scale SNP discovery, and the construction of a genetic map enabling QTL fine mapping, map-based cloning, and comparative genomics in perennial ryegrass....

  17. Discovery of posttranscriptional regulatory RNAs using next generation sequencing technologies.

    Science.gov (United States)

    Gelderman, Grant; Contreras, Lydia M

    2013-01-01

    Next generation sequencing (NGS) has revolutionized the way by which we engineer metabolism by radically altering the path to genome-wide inquiries. This is due to the fact that NGS approaches offer several powerful advantages over traditional methods that include the ability to fully sequence hundreds to thousands of genes in a single experiment and simultaneously detect homozygous and heterozygous deletions, alterations in gene copy number, insertions, translocations, and exome-wide substitutions that include "hot-spot mutations." This chapter describes the use of these technologies as a sequencing technique for transcriptome analysis and discovery of regulatory RNA elements in the context of three main platforms: Illumina HiSeq, 454 pyrosequencing, and SOLiD sequencing. Specifically, this chapter focuses on the use of Illumina HiSeq, since it is the most widely used platform for RNA discovery and transcriptome analysis. Regulatory RNAs have now been found in all branches of life. In bacteria, noncoding small RNAs (sRNAs) are involved in highly sophisticated regulatory circuits that include quorum sensing, carbon metabolism, stress responses, and virulence (Gorke and Vogel, Gene Dev 22:2914-2925, 2008; Gottesman, Trends Genet 21:399-404, 2005; Romby et al., Curr Opin Microbiol 9:229-236, 2006). Further characterization of the underlying regulation of gene expression remains poorly understood given that it is estimated that over 60% of all predicted genes remain hypothetical and the 5' and 3' untranslated regions are unknown for more than 90% of the genes (Siegel et al., Trends Parasitol 27:434-441, 2011). Importantly, manipulation of the posttranscriptional regulation that occurs at the level of RNA stability and export, trans-splicing, polyadenylation, protein translation, and protein stability via untranslated regions (Clayton, EMBO J 21:1881-1888, 2002; Haile and Papadopoulou, Curr Opin Microbiol 10:569-577, 2007) could be highly beneficial to metabolic

  18. The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.

    Science.gov (United States)

    Chong, Jessica X; Buckingham, Kati J; Jhangiani, Shalini N; Boehm, Corinne; Sobreira, Nara; Smith, Joshua D; Harrell, Tanya M; McMillin, Margaret J; Wiszniewski, Wojciech; Gambin, Tomasz; Coban Akdemir, Zeynep H; Doheny, Kimberly; Scott, Alan F; Avramopoulos, Dimitri; Chakravarti, Aravinda; Hoover-Fong, Julie; Mathews, Debra; Witmer, P Dane; Ling, Hua; Hetrick, Kurt; Watkins, Lee; Patterson, Karynne E; Reinier, Frederic; Blue, Elizabeth; Muzny, Donna; Kircher, Martin; Bilguvar, Kaya; López-Giráldez, Francesc; Sutton, V Reid; Tabor, Holly K; Leal, Suzanne M; Gunel, Murat; Mane, Shrikant; Gibbs, Richard A; Boerwinkle, Eric; Hamosh, Ada; Shendure, Jay; Lupski, James R; Lifton, Richard P; Valle, David; Nickerson, Deborah A; Bamshad, Michael J

    2015-08-06

    Discovering the genetic basis of a Mendelian phenotype establishes a causal link between genotype and phenotype, making possible carrier and population screening and direct diagnosis. Such discoveries also contribute to our knowledge of gene function, gene regulation, development, and biological mechanisms that can be used for developing new therapeutics. As of February 2015, 2,937 genes underlying 4,163 Mendelian phenotypes have been discovered, but the genes underlying ∼50% (i.e., 3,152) of all known Mendelian phenotypes are still unknown, and many more Mendelian conditions have yet to be recognized. This is a formidable gap in biomedical knowledge. Accordingly, in December 2011, the NIH established the Centers for Mendelian Genomics (CMGs) to provide the collaborative framework and infrastructure necessary for undertaking large-scale whole-exome sequencing and discovery of the genetic variants responsible for Mendelian phenotypes. In partnership with 529 investigators from 261 institutions in 36 countries, the CMGs assessed 18,863 samples from 8,838 families representing 579 known and 470 novel Mendelian phenotypes as of January 2015. This collaborative effort has identified 956 genes, including 375 not previously associated with human health, that underlie a Mendelian phenotype. These results provide insight into study design and analytical strategies, identify novel mechanisms of disease, and reveal the extensive clinical variability of Mendelian phenotypes. Discovering the gene underlying every Mendelian phenotype will require tackling challenges such as worldwide ascertainment and phenotypic characterization of families affected by Mendelian conditions, improvement in sequencing and analytical techniques, and pervasive sharing of phenotypic and genomic data among researchers, clinicians, and families. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. Discovery of Allostery in PKA Signaling.

    Science.gov (United States)

    Zhang, Ping; Kornev, Alexandr P; Wu, Jian; Taylor, Susan S

    2015-06-01

    cAMP-dependent protein kinase (PKA) was the second protein kinase to be discovered and the PKA catalytic (C) subunit serves as a prototype for the large protein kinase superfamily that contains over 500 gene products. The protein kinases regulate much of biology in eukaryotic cells and they are now also a major therapeutic target. Although PKA was discovered nearly 50 years ago and the subsequent discovery of the regulatory subunits that bind cAMP and release the catalytic activity from the holoenzyme followed quickly. Thus in PKA we see the convergence of two major signaling mechanisms - protein phosphorylation and second messenger signaling through cAMP. Crystallography provides a foundation for understanding function, and the structure of the isolated regulatory (R) and C-subunits have been extremely informative. Yet it is the R 2 C 2 holoenzyme that predominates in cells, and one can only appreciate the allosteric features of PKA signaling by seeing the full length protein. The symmetry and the quaternary constraints that one R:C hetero-dimer exerts on the other in the holoenzyme simply are not present in the isolated subunits or even in the R:C hetero-dimer.

  20. Scientific Discovery with the Blue Gene/L

    International Nuclear Information System (INIS)

    Negele, John W.

    2011-01-01

    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.

  1. Barbara McClintock and the Discovery of Jumping Genes

    Indian Academy of Sciences (India)

    milind1

    One fact after another started emerging regarding their behaviour; it was demonstrated that comparable elements are involved in the transfer of resistance to antibiotics, in the generation of the immune response and in the spread of certain cancers by viruses. By the end of the 1970's the story of genetic instability, when set.

  2. Chromosome substitution strains: gene discovery, functional analysis, and systems studies

    Czech Academy of Sciences Publication Activity Database

    Nadeau, J. H.; Forejt, Jiří; Takada, T.; Shiroishi, T.

    2012-01-01

    Roč. 23, 9-10 (2012), s. 693-705 ISSN 0938-8990 Grant - others:AV ČR(CZ) Praemium Academiae Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : consomic strains * QTL mapping * transgenerational effects Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.419, year: 2012

  3. Discovery and utilization of sorghum genes (Ma5/Ma6)

    Science.gov (United States)

    Mullet, John E; Rooney, William L; Klein, Patricia E; Morishige, Daryl; Murphy, Rebecca; Brady, Jeff A

    2012-11-13

    Methods and composition for the production of non-flowering or late flowering sorghum hybrid. For example, in certain aspects methods for use of molecular markers that constitute the Ma5/Ma6 pathway to modulate photoperiod sensitivity are described. The invention allows the production of plants having improved productivity and biomass generation.

  4. Barbara McClintock and the Discovery of Jumping Genes

    Indian Academy of Sciences (India)

    1822-1884). Mendel found that when hereditary traits were followed through successive generations of hybrid is a - tion, the numbers of offspring that resembled parental types were in simple numerical ratios relative to one another - 1: 1, or.

  5. Barbara McClintock and the Discovery of Jumping Genes

    Indian Academy of Sciences (India)

    milind1

    1822-1884). Mendel found that when hereditary traits were followed through successive generations of hybridisa- tion, the numbers of offspring that resembled parental types were in simple numerical ratios relative to one another – 1:1, or.

  6. Traditional exploitation of edible freshwater oyster Etheria elliptica ...

    African Journals Online (AJOL)

    ... they also targeted each year the same sites regardless rotation planning. Finally, oyster`s shell, a main substrate for larval settlement and bed restoration, were left on riverbanks after exploitation, reducing stocks reconstitution potential. Appropriate measures were suggested to Reserve staff for sustainable management.

  7. mHealth Visual Discovery Dashboard.

    Science.gov (United States)

    Fang, Dezhi; Hohman, Fred; Polack, Peter; Sarker, Hillol; Kahng, Minsuk; Sharmin, Moushumi; al'Absi, Mustafa; Chau, Duen Horng

    2017-09-01

    We present Discovery Dashboard, a visual analytics system for exploring large volumes of time series data from mobile medical field studies. Discovery Dashboard offers interactive exploration tools and a data mining motif discovery algorithm to help researchers formulate hypotheses, discover trends and patterns, and ultimately gain a deeper understanding of their data. Discovery Dashboard emphasizes user freedom and flexibility during the data exploration process and enables researchers to do things previously challenging or impossible to do - in the web-browser and in real time. We demonstrate our system visualizing data from a mobile sensor study conducted at the University of Minnesota that included 52 participants who were trying to quit smoking.

  8. Recent discoveries of anticancer flavonoids.

    Science.gov (United States)

    Raffa, Demetrio; Maggio, Benedetta; Raimondi, Maria Valeria; Plescia, Fabiana; Daidone, Giuseppe

    2017-12-15

    In this review we report the recent advances in anticancer activity of the family of natural occurring flavonoids, covering the time span of the last five years. The bibliographic data will be grouped, on the basis of biological information, in two great categories: reports in which the extract plants bioactivity is reported and the identification of each flavonoid is present or not, and reports in which the anticancer activity is attributable to purified and identified flavonoids from plants. Wherever possible, the targets and mechanisms of action as well as the structure-activity relationships of the molecules will be reported. Also, in the review it was thoroughly investigated the recent discovery on flavonoids containing the 2-phenyl-4H-chromen-4-one system even if some examples of unusual flavonoids, bearing a non-aromatic B-ring or other ring condensed to the base structure are reported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Discovery Approaches for Novel Dyslipidemia Drugs.

    Science.gov (United States)

    Maqbool, Faheem; Safavi, Malihe; Bahadar, Haji; Rahimifard, Mahban; Niaz, Kamal; Abdollahi, Mohammad

    2015-01-01

    Dyslipidemia is increased fasting level of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG), along with decreased levels of HDL cholesterol (HDL-C). Owing to effect on the cardiovascular system and increased chances of metabolic diseases, it is needed to review novel under development drugs and new approaches in drug discovery for dyslipidemia. This article reviews all phases I to IV clinical trials and preclinical trials with results associated with novel treatment of dyslipidemia. Drug discovery for dyslipidemia, toward newer targets has been addressed. Statins are, currently available, best choice of drugs for treating dyslipidemia and coronary diseases. In addition to this, lipid lowering drugs support treatment to a great extent, either as monotherapy or in combinations with other groups. Pravastatin used in combination with cholesteryl ester, transfers protein inhibitors (CETP) to produce efficient results. Peroxisome proliferator-activated receptor agonists (PPAR) like muraglitazar, aleglitazar and tesaglitazar are PPAR α/γ receptor agonist, dual in action performs better in phase 3 clinical study and reduces renal and cardiovascular events. By targeting both receptors, a better treatment for cardiovascular and diabetic problems can be achieved. Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors like humanized monoclonal antibodies, are newly discovered inhibitors that reduce the risk of cardiovascular diseases. During the past few years, nucleic acid-based therapies targeting lipid and lipoprotein metabolism, such as microsomal TG transfer protein (MTP) may be a promising therapeutic approach to treat vascular diseases. Gene regulating transcription factors involved in bile acids and cholesterol metabolism can be controlled by FXR agonists in dyslipidemia. To overcome these drawbacks, many thyroid hormone analogues have been developed to lower down cholesterol level by targeting specifically thyroid hormone

  10. Exploring new gene integration sites for gene knock-in by gene-trapping strategy.

    Science.gov (United States)

    Nanchi, Isamu; Yoshimura, Yuki; Nakamura, Kazuomi; Masago, Yusaku; Ohbayashi, Tetsuya; Okuda, Tomohiko

    2015-06-01

    The knock-in mouse is a powerful tool for biological research, but the stability of expression of an integrated gene strongly depends on where it is integrated in the mouse genome. At present, there are an insufficient number of loci suitable for gene knock-in, such as the Rosa26 locus. Therefore, in this study, we developed an efficient strategy for identifying genome loci suitable for gene knock-in and characterized the properties of such loci for gene integration. For efficient discovery and characterization, we constructed a new gene-trapping vector that enables monitoring of the expression of both trapped and integrated genes using fluorescence. We successfully obtained fluorescent-positive mouse embryonic stem cell (mESC) clones with the vector. Thorough analysis of the expression of fluorescent proteins in chimera embryos generated with the obtained mESC clones, some of the gene-trapped chimera embryos showed stable and ubiquitous expression of the integrated gene. Furthermore, adult mice derived from one of the gene-trapped mESC clones showed ubiquitous expression of the integrated gene in various tissues without any unusual phenotype. This indicated that the identified locus possesses high potential for foreign gene integration. Our strategy allows for efficient discovery and characterization of mouse genome loci for gene integration.

  11. A Tale of Two Discoveries: Comparing the Usability of Summon and EBSCO Discovery Service

    Science.gov (United States)

    Foster, Anita K.; MacDonald, Jean B.

    2013-01-01

    Web-scale discovery systems are gaining momentum among academic libraries as libraries seek a means to provide their users with a one-stop searching experience. Illinois State University's Milner Library found itself in the unique position of having access to two distinct discovery products, EBSCO Discovery Service and Serials Solutions' Summon.…

  12. Orphan nuclear receptors, excellent targets of drug discovery.

    Science.gov (United States)

    Shi, Yanhong

    2006-11-01

    To date, the pharmaceutical industry has placed a considerable amount of interest in the discovery of drug targets and diagnostics. One of the most challenging areas of drug discovery today is the search for novel receptor-ligand pairs. Nuclear receptors comprise a large superfamily of ligand-dependent transcription factors that regulate the expression of genes critical for a variety of biological processes, including development, growth, differentiation, and homeostasis. Orphan nuclear receptors, for which the ligands are not yet identified, represent the most ancient component of the nuclear receptor superfamily. Orphan nuclear receptors not only offer a unique system to uncover novel signaling pathways that impact human health, but also provide excellent targets of drug discoveries for a variety of human diseases. This review highlights advances made on ligand identification for orphan nuclear receptors using transgenic mouse models, cell-based screening, direct binding, structure-based assays, and computer-aided virtual screening. With rapid advances in combinatorial chemistry and high throughput screening, along with other modern technologies, this field promises a bountiful harvest.

  13. Optical imaging for the new grammar of drug discovery.

    Science.gov (United States)

    Krucker, Thomas; Sandanaraj, Britto S

    2011-11-28

    Optical technologies used in biomedical research have undergone tremendous development in the last decade and enabled important insight into biochemical, cellular and physiological phenomena at the microscopic and macroscopic level. Historically in drug discovery, to increase throughput in screening, or increase efficiency through automation of image acquisition and analysis in pathology, efforts in imaging were focused on the reengineering of established microscopy solutions. However, with the emergence of the new grammar for drug discovery, other requirements and expectations have created unique opportunities for optical imaging. The new grammar of drug discovery provides rules for translating the wealth of genomic and proteomic information into targeted medicines with a focus on complex interactions of proteins. This paradigm shift requires highly specific and quantitative imaging at the molecular level with tools that can be used in cellular assays, animals and finally translated into patients. The development of fluorescent targeted and activatable 'smart' probes, fluorescent proteins and new reporter gene systems as functional and dynamic markers of molecular events in vitro and in vivo is therefore playing a pivotal role. An enabling optical imaging platform will combine optical hardware refinement with a strong emphasis on creating and validating highly specific chemical and biological tools.

  14. In silico discoveries for biomedical sciences

    NARCIS (Netherlands)

    Haagen, Herman van

    2011-01-01

    Text-mining is a challenging field of research initially meant for reading large text collections with a computer. Text-mining is useful in summarizing text, searching for the informative documents, and most important to do knowledge discovery. Knowledge discovery is the main subject of this thesis.

  15. Discovery and Innovation: About this journal

    African Journals Online (AJOL)

    Discovery and Innovation: About this journal. Journal Home > Discovery and Innovation: About this journal. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. People. » Contact ...

  16. 15 CFR 785.8 - Discovery.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Discovery. 785.8 Section 785.8 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE ADDITIONAL PROTOCOL REGULATIONS ENFORCEMENT § 785.8 Discovery...

  17. Accounting for discovery bias in genomic prediction

    Science.gov (United States)

    Our objective was to evaluate an approach to mitigating discovery bias in genomic prediction. Accuracy may be improved by placing greater emphasis on regions of the genome expected to be more influential on a trait. Methods emphasizing regions result in a phenomenon known as “discovery bias” if info...

  18. 31 CFR 10.71 - Discovery.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 10.71 Section 10.71 Money and Finance: Treasury Office of the Secretary of the Treasury PRACTICE BEFORE THE INTERNAL REVENUE... seeking the discovery through another source. (e) Failure to comply. Where a party fails to comply with an...

  19. False Discovery Rates and Multiple Testing

    Indian Academy of Sciences (India)

    IAS Admin

    RESONANCE | December 2013. GENERAL | ARTICLE. False Discovery Rates and Multiple Testing. Soumen Dey and Mohan Delampady. Keywords. False discovery rate, FDR,. pFDR, multiple testing, empiri- cal Bayes, hierarchical Bayes, high-dimensional problems. Soumen Dey is a research scholar at ISI, Bangalore.

  20. On Consistency Maintenance In Service Discovery

    NARCIS (Netherlands)

    Sundramoorthy, V.; Hartel, Pieter H.; Scholten, Johan

    2005-01-01

    Communication and node failures degrade the ability of a service discovery protocol to ensure Users receive the correct service information when the service changes. We propose that service discovery protocols employ a set of recovery techniques to recover from failures and regain consistency. We

  1. 42 CFR 3.516 - Discovery.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Discovery. 3.516 Section 3.516 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS PATIENT SAFETY ORGANIZATIONS AND PATIENT SAFETY WORK PRODUCT Enforcement Program § 3.516 Discovery. (a) A party may make a request...

  2. 31 CFR 16.21 - Discovery.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Discovery. 16.21 Section 16.21 Money and Finance: Treasury Office of the Secretary of the Treasury REGULATIONS IMPLEMENTING THE PROGRAM... to require the creation of a document. (c) Unless mutually agreed to by the parties, discovery is...

  3. Service discovery in heterogeneous wireless networks

    NARCIS (Netherlands)

    Blangé, M.J.; Karkowski, I.P.; Vermeulen, B.C.B.

    2005-01-01

    In this paper we describe a possible solution to the problem of service discovery in heterogeneous wireless networks. This solution involves introduction of a network independent service discovery layer, with as main goal the improved robustness of applications running on top of it. A possible

  4. 12 CFR 908.46 - Discovery.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Discovery. 908.46 Section 908.46 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOUSING FINANCE BOARD ORGANIZATION AND OPERATIONS RULES OF... Congress, or the principles of common law. (e) Time limits. All discovery, including all responses to...

  5. The discovery of the periodic table as a case of simultaneous discovery.

    Science.gov (United States)

    Scerri, Eric

    2015-03-13

    The article examines the question of priority and simultaneous discovery in the context of the discovery of the periodic system. It is argued that rather than being anomalous, simultaneous discovery is the rule. Moreover, I argue that the discovery of the periodic system by at least six authors in over a period of 7 years represents one of the best examples of a multiple discovery. This notion is supported by a new view of the evolutionary development of science through a mechanism that is dubbed Sci-Gaia by analogy with Lovelock's Gaia hypothesis. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  6. Knowledge Discovery from Vibration Measurements

    Directory of Open Access Journals (Sweden)

    Jun Deng

    2014-01-01

    Full Text Available The framework as well as the particular algorithms of pattern recognition process is widely adopted in structural health monitoring (SHM. However, as a part of the overall process of knowledge discovery from data bases (KDD, the results of pattern recognition are only changes and patterns of changes of data features. In this paper, based on the similarity between KDD and SHM and considering the particularity of SHM problems, a four-step framework of SHM is proposed which extends the final goal of SHM from detecting damages to extracting knowledge to facilitate decision making. The purposes and proper methods of each step of this framework are discussed. To demonstrate the proposed SHM framework, a specific SHM method which is composed by the second order structural parameter identification, statistical control chart analysis, and system reliability analysis is then presented. To examine the performance of this SHM method, real sensor data measured from a lab size steel bridge model structure are used. The developed four-step framework of SHM has the potential to clarify the process of SHM to facilitate the further development of SHM techniques.

  7. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    W. Hayes McDonald

    2002-01-01

    Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

  8. Mathematical models in biological discovery

    CERN Document Server

    Walter, Charles

    1977-01-01

    When I was asked to help organize an American Association for the Advancement of Science symposium about how mathematical models have con­ tributed to biology, I agreed immediately. The subject is of immense importance and wide-spread interest. However, too often it is discussed in biologically sterile environments by "mutual admiration society" groups of "theoreticians", many of whom have never seen, and most of whom have never done, an original scientific experiment with the biolog­ ical materials they attempt to describe in abstract (and often prejudiced) terms. The opportunity to address the topic during an annual meeting of the AAAS was irresistable. In order to try to maintain the integrity ;,f the original intent of the symposium, it was entitled, "Contributions of Mathematical Models to Biological Discovery". This symposium was organized by Daniel Solomon and myself, held during the 141st annual meeting of the AAAS in New York during January, 1975, sponsored by sections G and N (Biological and Medic...

  9. NIF Discovery Science Eagle Nebula

    Science.gov (United States)

    Kane, Jave; Martinez, David; Pound, Marc; Heeter, Robert; Casner, Alexis; Villette, Bruno; Mancini, Roberto

    2017-10-01

    The University of Maryland and and LLNL are investigating the origin and dynamics of the famous Pillars of the Eagle Nebula and similar parsec-scale structures at the boundaries of HII regions in molecular hydrogen clouds. The National Ignition Facility (NIF) Discovery Science program Eagle Nebula has performed NIF shots to study models of pillar formation. The shots feature a new long-duration x-ray source, in which multiple hohlraums mimicking a cluster of stars are driven with UV light in series for 10 to 15 ns each to create a 30 to 60 ns output x-ray pulse. The source generates deeply nonlinear hydrodynamics in the Eagle science package, a structure of dense plastic and foam mocking up a molecular cloud containing a dense core. Omega EP and NIF shots have validated the source concept, showing that earlier hohlraums do not compromise later ones by preheat or by ejecting ablated plumes that deflect later beams. The NIF shots generated radiographs of shadowing-model pillars, and also showed evidence that cometary structures can be generated. The velocity and column density profiles of the NIF shadowing and cometary pillars have been compared with observations of the Eagle Pillars made at the millimeter-wave BIMA and CARMA observatories. Prepared by LLNL under Contract DE-AC52-07NA27344.

  10. Discovery Mondays: Zoom on materials

    CERN Multimedia

    2003-01-01

    Following the success of the first Discovery Monday, which had over 100 visitors, the series of evening events in Microcosm continues. On Monday 2nd June, discover the world of materials. Find out how CERN scientists examine, manufacture and study different materials, at different scales. Did you know for example that using electrons you can observe a hair at a scale equivalent to looking at a boat with the naked eye? Also, that using ultrasound, you can measure the thickness of an object that is completely inaccessible? Find out more about these techniques, and also the high-tech machining and soldering that is carried out in CERN's central workshop. Plus, see how engineers can detect tiny leaks through solder points - essential for maintaining the vacuum in the LHC. The evening is open to all, without reservation, suggested age 12 and above. Rendez-vous in Microcosm on Monday 2nd June From 19.30 - 21.00 Free entry For more information : http://www.cern.ch/microcosm Using a scanning microscope, the head o...

  11. Materials discovery through crystal growth

    Science.gov (United States)

    zur Loye, Hans-Conrad

    2016-04-01

    The discovery of new materials and associated desirable properties has been a driving force behind chemical innovation for centuries. When we look at some of the many recent technological advances, and how widespread and significant their impact has been, we appreciate how much they have relied on new materials. The increase in hard drive storage capacity due to new giant magneto-resistive materials, the ever-shrinking cell phone due to improved microwave dielectric materials, the enhancement in lithium battery storage capacity due to new intercalation materials, or the improved capacitor due to new ferroelectric materials are all excellent examples. How were these materials discovered? While there is no single answer, in all cases there was a First-Material, the archetype in which the phenomenon was first observed, the one that led to further investigations and the subsequent preparation of improved 2nd or 3rd generation materials. It is this First-Material, the archetype, that was discovered - often via crystal growth.

  12. The Discovery of Dabigatran Etexilate

    Directory of Open Access Journals (Sweden)

    Joanne evan Ryn

    2013-02-01

    Full Text Available Thromboembolic disease is a major cause of mortality and morbidity in the developed world and is caused by an excessive stimulation of coagulation. Thrombin is a key serine protease in the coagulation cascade and numerous efforts have been made to develop safe and effective orally active direct thrombin inhibitors (DTIs. Current anticoagulant therapy includes the use of indirect thrombin inhibitors (e.g. heparins, low-molecular-weight-heparins [LMWHs] and vitamin K antagonists (VKA such as warfarin. However there are several caveats in the clinical use of these agents including narrow therapeutic window, parenteral delivery, and food- and drug-drug interactions. Dabigatran is a synthetic, reversible DTI with high affinity and specificity for its target binding both free and clot-bound thrombin, and offers a favorable pharmacokinetic profile. Large randomized clinical trials have demonstrated that dabigatran provides comparable or superior thromboprophylaxis in multiple thromboembolic disease indications compared to standard of care. This minireview will highlight the discovery and development of dabigatran, the first in a class of new oral anticoagulant (NOAC agents to be licensed worldwide for the prevention of thromboembolism in the setting of orthopedic surgery and stroke prevent in atrial fibrillation.

  13. Respiratory knowledge discovery utilising expertise

    Directory of Open Access Journals (Sweden)

    Tristan Ling

    2012-12-01

    Full Text Available BackgroundSignificant amounts of medical data are being archived, in the hope that they can be analysed and provide insight. A critical problem with analysing such data is the amount of existing knowledge required to produce effective results.AimsThis study tests a method that seeks to overcome these problems with analysis, by testing it over a large set of archived lung function test results. A knowledge base of lung function interpretation expertise has been compiled and serves as a base for analysis.MethodA user examines the dataset with the assistance of the knowledge discovery tool. Two pertinent respiratory research questions are analysed (the relative correlation between diffusing capacity and FEV1 or FVC bronchodilator response, and the effects of BMI on various parameters of lung function, and the results compared and contrasted with relevant literature.ResultsThe method finds interesting results from the lung function data supporting and questioning other published studies, while also finding correlations that suggest further areas of research.ConclusionWhile the analysis does not necessarily reveal groundbreaking information, it shows that the method can successfully discover new knowledge and is useful in a research context.

  14. Lysophospholipid receptors in drug discovery.

    Science.gov (United States)

    Kihara, Yasuyuki; Mizuno, Hirotaka; Chun, Jerold

    2015-05-01

    Lysophospholipids (LPs), including lysophosphatidic acid (LPA), sphingosine 1-phospate (S1P), lysophosphatidylinositol (LPI), and lysophosphatidylserine (LysoPS), are bioactive lipids that transduce signals through their specific cell-surface G protein-coupled receptors, LPA1-6, S1P1-5, LPI1, and LysoPS1-3, respectively. These LPs and their receptors have been implicated in both physiological and pathophysiological processes such as autoimmune diseases, neurodegenerative diseases, fibrosis, pain, cancer, inflammation, metabolic syndrome, bone formation, fertility, organismal development, and other effects on most organ systems. Advances in the LP receptor field have enabled the development of novel small molecules targeting LP receptors for several diseases. Most notably, fingolimod (FTY720, Gilenya, Novartis), an S1P receptor modulator, became the first FDA-approved medicine as an orally bioavailable drug for treating relapsing forms of multiple sclerosis. This success is currently being followed by multiple, mechanistically related compounds targeting S1P receptor subtypes, which are in various stages of clinical development. In addition, an LPA1 antagonist, BMS-986020 (Bristol-Myers Squibb), is in Phase 2 clinical development for treating idiopathic pulmonary fibrosis, as a distinct compound, SAR100842 (Sanofi) for the treatment of systemic sclerosis and related fibrotic diseases. This review summarizes the current state of drug discovery in the LP receptor field. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. West Nile Virus Drug Discovery

    Directory of Open Access Journals (Sweden)

    Siew Pheng Lim

    2013-12-01

    Full Text Available The outbreak of West Nile virus (WNV in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.

  16. A glycogene mutation map for discovery of diseases of glycosylation

    DEFF Research Database (Denmark)

    Hansen, Lars; Lind-Thomsen, Allan; Joshi, Hiren J

    2015-01-01

    homologous families. However, Genome-Wide-Association Studies (GWAS) have identified such isoenzyme genes as candidates for different diseases, but validation is not straightforward without biomarkers. Large-scale whole exome sequencing (WES) provides access to mutations in e.g. glycosyltransferase genes...... in populations, which can be used to predict and/or analyze functional deleterious mutations. Here, we constructed a draft of a Functional Mutational Map of glycogenes, GlyMAP, from WES of a rather homogenous population of 2,000 Danes. We catalogued all missense mutations and used prediction algorithms, manual...... inspection, and in case of CAZy family GT27 experimental analysis of mutations to map deleterious mutations. GlyMAP provides a first global view of the genetic stability of the glycogenome and should serve as a tool for discovery of novel CDGs....

  17. Students Excited by Stellar Discovery

    Science.gov (United States)

    2011-02-01

    In the constellation of Ophiuchus, above the disk of our Milky Way Galaxy, there lurks a stellar corpse spinning 30 times per second -- an exotic star known as a radio pulsar. This object was unknown until it was discovered last week by three high school students. These students are part of the Pulsar Search Collaboratory (PSC) project, run by the National Radio Astronomy Observatory (NRAO) in Green Bank, WV, and West Virginia University (WVU). The pulsar, which may be a rare kind of neutron star called a recycled pulsar, was discovered independently by Virginia students Alexander Snider and Casey Thompson, on January 20, and a day later by Kentucky student Hannah Mabry. "Every day, I told myself, 'I have to find a pulsar. I better find a pulsar before this class ends,'" said Mabry. When she actually made the discovery, she could barely contain her excitement. "I started screaming and jumping up and down." Thompson was similarly expressive. "After three years of searching, I hadn't found a single thing," he said, "but when I did, I threw my hands up in the air and said, 'Yes!'." Snider said, "It actually feels really neat to be the first person to ever see something like that. It's an uplifting feeling." As part of the PSC, the students analyze real data from NRAO's Robert C. Byrd Green Bank Telescope (GBT) to find pulsars. The students' teachers -- Debra Edwards of Sherando High School, Leah Lorton of James River High School, and Jennifer Carter of Rowan County Senior High School -- all introduced the PSC in their classes, and interested students formed teams to continue the work. Even before the discovery, Mabry simply enjoyed the search. "It just feels like you're actually doing something," she said. "It's a good feeling." Once the pulsar candidate was reported to NRAO, Project Director Rachel Rosen took a look and agreed with the young scientists. A followup observing session was scheduled on the GBT. Snider and Mabry traveled to West Virginia to assist in the

  18. An online conserved SSR discovery through cross-species comparison

    Directory of Open Access Journals (Sweden)

    Tun-Wen Pai

    2009-02-01

    Full Text Available Tun-Wen Pai1, Chien-Ming Chen1, Meng-Chang Hsiao1, Ronshan Cheng2, Wen-Shyong Tzou3, Chin-Hua Hu31Department of Computer Science and Engineering; 2Department of Aquaculture, 3Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, Republic of ChinaAbstract: Simple sequence repeats (SSRs play important roles in gene regulation and genome evolution. Although there exist several online resources for SSR mining, most of them only extract general SSR patterns without providing functional information. Here, an online search tool, CG-SSR (Comparative Genomics SSR discovery, has been developed for discovering potential functional SSRs from vertebrate genomes through cross-species comparison. In addition to revealing SSR candidates in conserved regions among various species, it also combines accurate coordinate and functional genomics information. CG-SSR is the first comprehensive and efficient online tool for conserved SSR discovery.Keywords: microsatellites, genome, comparative genomics, functional SSR, gene ontology, conserved region

  19. Discovery of novel bacterial toxins by genomics and computational biology.

    Science.gov (United States)

    Doxey, Andrew C; Mansfield, Michael J; Montecucco, Cesare

    2018-06-01

    Hundreds and hundreds of bacterial protein toxins are presently known. Traditionally, toxin identification begins with pathological studies of bacterial infectious disease. Following identification and cultivation of a bacterial pathogen, the protein toxin is purified from the culture medium and its pathogenic activity is studied using the methods of biochemistry and structural biology, cell biology, tissue and organ biology, and appropriate animal models, supplemented by bioimaging techniques. The ongoing and explosive development of high-throughput DNA sequencing and bioinformatic approaches have set in motion a revolution in many fields of biology, including microbiology. One consequence is that genes encoding novel bacterial toxins can be identified by bioinformatic and computational methods based on previous knowledge accumulated from studies of the biology and pathology of thousands of known bacterial protein toxins. Starting from the paradigmatic cases of diphtheria toxin, tetanus and botulinum neurotoxins, this review discusses traditional experimental approaches as well as bioinformatics and genomics-driven approaches that facilitate the discovery of novel bacterial toxins. We discuss recent work on the identification of novel botulinum-like toxins from genera such as Weissella, Chryseobacterium, and Enteroccocus, and the implications of these computationally identified toxins in the field. Finally, we discuss the promise of metagenomics in the discovery of novel toxins and their ecological niches, and present data suggesting the existence of uncharacterized, botulinum-like toxin genes in insect gut metagenomes. Copyright © 2018. Published by Elsevier Ltd.

  20. Discoveries on the Norwegian continental shelf

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-02-01

    As discussed in this document, there are 108 discoveries on the Norwegian continental shelf which so far have not been approved for development. The oil and gas resources of the Norwegian Sea and the Barents Sea are mostly found in discoveries containing large volumes of gas. Eighty-one of the discoveries which are not approved for development are located in the North Sea and more than 60% of the discoveries in this province contain less than 5 mill Sm{sup 3} oil equivalents. In the Norwegian Sea and the Barents Sea there are 27 discoveries which are not approved for development and whose total resources are estimated at 500 mill Sm{sup 3} oil equivalents. About 60% of the oil resources is expected to be comprised by development plans in 1997 or 1998. Another 20% is in new discoveries currently being evaluated or in discoveries containing large volumes of gas. Production forecasts indicate substantial vacant oil processing capacity after 2000. Vacant gas processing capacity will mainly arise after 2005. 23 figs., 3 tabs.

  1. Functional Principles of Registry-based Service Discovery

    NARCIS (Netherlands)

    Sundramoorthy, V.; Tan, C.; Hartel, Pieter H.; den Hartog, Jeremy; Scholten, Johan

    As Service Discovery Protocols (SDP) are becoming increasingly important for ubiquitous computing, they must behave according to predefined principles. We present the functional Principles of Service Discovery for robust, registry-based service discovery. A methodology to guarantee adherence to

  2. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  3. In silico discovery of transcription regulatory elements in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Le Roch Karine G

    2008-02-01

    Full Text Available Abstract Background With the sequence of the Plasmodium falciparum genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the P. falciparum genome sequence having revealed few cis-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of P. falciparum intergenic regions (~90% AT presents significant challenges to in silico cis-regulatory element discovery. Results We have developed an algorithm called Gene Enrichment Motif Searching (GEMS that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich P. falciparum genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from P. falciparum life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative cis-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the Plasmodium literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays

  4. The quality of media reports on discoveries related to human genetic diseases.

    Science.gov (United States)

    Holtzman, Neil A; Bernhardt, Barbara A; Mountcastle-Shah, Eliza; Rodgers, Joann E; Tambor, Ellen; Geller, Gail

    2005-01-01

    To examine (1) the quality of media reports (newspapers, television and public radio) of genetic discoveries with medical relevance and (2) factors related to the completeness and balance of the stories. Analysis of the accuracy, balance, and completeness of 228 media stories reporting 24 genetic discoveries between 1996 and 2000 using a previously validated instrument. Although usually accurate, the stories contained only 45.5 +/- 13.8% (mean +/- SD) of relevant items. Stories appearing on television and stories reporting discoveries of genes for rare diseases were the least complete. Stories in non-US English-speaking newspapers included more content items per word than US stories. Less balanced stories exaggerated the benefits of discoveries, ignored possible risks, and did not present a range of expert opinion. Scientists were sometimes the source of exaggeration. To increase the quality of media reports about genetic discoveries, stories should include more relevant items and be written by journalists skilled in science writing. Scientists will have to resist the tendency to exaggerate. These conclusions may apply to media stories of other discoveries as well.

  5. Biomarkers: in medicine, drug discovery, and environmental health

    National Research Council Canada - National Science Library

    Vaidya, Vishal S; Bonventre, Joseph V

    2010-01-01

    ... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

  6. Queen's discovery lauded by top scientific journal

    CERN Multimedia

    McGrady, S

    2002-01-01

    A scientific breakthrough at Queen's University's Sudbury Neutrino Observatory has received major international recognition. The journal Science ranked the discovery that cracked the "neutrino problem" second, in the journal's top 10 scientific achievements of 2002 (1/2 page).

  7. Literature-Related Discovery: A Review

    National Research Council Canada - National Science Library

    Kostoff, Ronald N; Block, Joel A; Solka, Jeffrey L; Briggs, Michael B; Rushenberg, Robert L; Stump, Jesse A; Johnson, Dustin; Lyons, Terence J; Wyatt, Jeffrey R

    2007-01-01

    .... Literature-related discovery (LRD) is the linking of two or more literature concepts that have heretofore not been linked to produce novel interesting, plausible, and intelligible knowledge (i.e...

  8. Specification Editing and Discovery Assistant Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The project will prototype a specification editing and discovery tool (SPEEDY) for C/C++ that will assist software developers with modular formal verification tasks...

  9. An introduction to web scale discovery systems.

    Science.gov (United States)

    Hoy, Matthew B

    2012-01-01

    This article explores the basic principles of web-scale discovery systems and how they are being implemented in libraries. "Web scale discovery" refers to a class of products that index a vast number of resources in a wide variety formats and allow users to search for content in the physical collection, print and electronic journal collections, and other resources from a single search box. Search results are displayed in a manner similar to Internet searches, in a relevance ranked list with links to online content. The advantages and disadvantages of these systems are discussed, and a list of popular discovery products is provided. A list of library websites with discovery systems currently implemented is also provided.

  10. Advances in synthetic peptides reagent discovery

    Science.gov (United States)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Stratis-Cullum, Dimitra N.

    2013-05-01

    Bacterial display technology offers a number of advantages over competing display technologies (e.g, phage) for the rapid discovery and development of peptides with interaction targeted to materials ranging from biological hazards through inorganic metals. We have previously shown that discovery of synthetic peptide reagents utilizing bacterial display technology is relatively simple and rapid to make laboratory automation possible. This included extensive study of the protective antigen system of Bacillus anthracis, including development of discovery, characterization, and computational biology capabilities for in-silico optimization. Although the benefits towards CBD goals are evident, the impact is far-reaching due to our ability to understand and harness peptide interactions that are ultimately extendable to the hybrid biomaterials of the future. In this paper, we describe advances in peptide discovery including, new target systems (e.g. non-biological materials), advanced library development and clone analysis including integrated reporting.

  11. Discovery of Cyclic Peptide Estrogens and Antiestrogens

    National Research Council Canada - National Science Library

    Clark, Daniel

    2004-01-01

    The identification of proteins involved in the initiation of disease and the identification of small molecules that modulate these proteins are of great importance for the discovery of improved therapeutics...

  12. Discovery of Cyclic Peptide Estrogens and Antiestrogens

    National Research Council Canada - National Science Library

    Clark, Daniel

    2003-01-01

    Identification of proteins involved in the initiation of disease and the identification of small molecules that can modulate these proteins are of great importance towards the discovery of treatments...

  13. 42 CFR 1005.7 - Discovery.

    Science.gov (United States)

    2010-10-01

    ... OF EXCLUSIONS, CIVIL MONEY PENALTIES AND ASSESSMENTS § 1005.7 Discovery. (a) A party may make a... contained in this section will be interpreted to require the creation of a document, except that requested...

  14. Taxonomy Enabled Discovery (TED), Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposal addresses the NASA's need to enable scientific discovery and the topic's requirements for: processing large volumes of data, commonly available on the...

  15. Applying genetics in inflammatory disease drug discovery

    DEFF Research Database (Denmark)

    Folkersen, Lasse; Biswas, Shameek; Frederiksen, Klaus Stensgaard

    2015-01-01

    , with several notable exceptions, the journey from a small-effect genetic variant to a functional drug has proven arduous, and few examples of actual contributions to drug discovery exist. Here, we discuss novel approaches of overcoming this hurdle by using instead public genetics resources as a pragmatic guide...... alongside existing drug discovery methods. Our aim is to evaluate human genetic confidence as a rationale for drug target selection....

  16. The discovery of the structure of DNA

    Science.gov (United States)

    Squires, G. L.

    2003-04-01

    On 25 April 1953, Nature published a letter by Francis Crick and James Watson, at the Cavendish Laboratory, Cambridge, proposing a structure for DNA. This letter marked the beginning of a revolution in biology. Besides Crick and Watson, two other scientists, Rosalind Franklin and Maurice Wilkins, played key roles in the discovery. After sketching the early careers of the four scientists, the present article gives an account of the physics and chemistry involved in the discovery, and the events leading up to it.

  17. The Gozo discovery bus : a successful experiment

    OpenAIRE

    Vella, Maryrose

    2008-01-01

    The introduction of a tourist discovery bus in Gozo came about as a result of an EU Project which is part of the Interreg III B Archimed programmes in which the Islands and Small States Institute of the University of Malta participated. Other countries participating in this programme besides Malta, represented by the Islands and Small States Institute, are Italy, Cyprus and Greece. The discovery bus service was aimed at encouraging more tourists to come to Gozo and enabling them to visit stra...

  18. Compound Data Mining for Drug Discovery.

    Science.gov (United States)

    Bajorath, Jürgen

    2017-01-01

    In recent years, there has been unprecedented growth in compound activity data in the public domain. These compound data provide an indispensable resource for drug discovery in academic environments as well as in the pharmaceutical industry. To handle large volumes of heterogeneous and complex compound data and extract discovery-relevant knowledge from these data, advanced computational mining approaches are required. Herein, major public compound data repositories are introduced, data confidence criteria reviewed, and selected data mining approaches discussed.

  19. Literature-Related Discovery: A Review

    Science.gov (United States)

    2007-11-05

    disaggregation; Guar Gum for decrease in plasma fibrinogen and viscosity; Cell hydration to improve cell deformity and increase arm blood flow. This...discoveries to insure that they were indeed unique. Some potential discoveries include: The use of plasmin to deter cell adhesion for use in non...2006] have generated a semantic space approach that bears some similarities to LSI. It is based on the Hyperspace Analogue to Language (HAL

  20. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    cancer immunotherapies has yet to be fulfilled. The insufficient efficacy of existing treatments can be attributed to a number of biological and technical issues. In this review, we detail the current limitations of immunotherapy target selection and design, and review computational methods to streamline...... therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

  1. Challenges of the information age: the impact of false discovery on pathway identification.

    Science.gov (United States)

    Rog, Colin J; Chekuri, Srinivasa C; Edgerton, Mary E

    2012-11-21

    Pathways with members that have known relevance to a disease are used to support hypotheses generated from analyses of gene expression and proteomic studies. Using cancer as an example, the pitfalls of searching pathways databases as support for genes and proteins that could represent false discoveries are explored. The frequency with which networks could be generated from 100 instances each of randomly selected five and ten genes sets as input to MetaCore, a commercial pathways database, was measured. A PubMed search enumerated cancer-related literature published for any gene in the networks. Using three, two, and one maximum intervening step between input genes to populate the network, networks were generated with frequencies of 97%, 77%, and 7% using ten gene sets and 73%, 27%, and 1% using five gene sets. PubMed reported an average of 4225 cancer-related articles per network gene. This can be attributed to the richly populated pathways databases and the interest in the molecular basis of cancer. As information sources become enriched, they are more likely to generate plausible mechanisms for false discoveries.

  2. Challenges of the information age: the impact of false discovery on pathway identification

    Directory of Open Access Journals (Sweden)

    Rog Colin J

    2012-11-01

    Full Text Available Abstract Background Pathways with members that have known relevance to a disease are used to support hypotheses generated from analyses of gene expression and proteomic studies. Using cancer as an example, the pitfalls of searching pathways databases as support for genes and proteins that could represent false discoveries are explored. Findings The frequency with which networks could be generated from 100 instances each of randomly selected five and ten genes sets as input to MetaCore, a commercial pathways database, was measured. A PubMed search enumerated cancer-related literature published for any gene in the networks. Using three, two, and one maximum intervening step between input genes to populate the network, networks were generated with frequencies of 97%, 77%, and 7% using ten gene sets and 73%, 27%, and 1% using five gene sets. PubMed reported an average of 4225 cancer-related articles per network gene. Discussion This can be attributed to the richly populated pathways databases and the interest in the molecular basis of cancer. As information sources become enriched, they are more likely to generate plausible mechanisms for false discoveries.

  3. Discovery of stress responsive DNA regulatory motifs in Arabidopsis.

    Science.gov (United States)

    Ma, Shisong; Bachan, Shawn; Porto, Matthew; Bohnert, Hans J; Snyder, Michael; Dinesh-Kumar, Savithramma P

    2012-01-01

    The discovery of DNA regulatory motifs in the sequenced genomes using computational methods remains challenging. Here, we present MotifIndexer--a comprehensive strategy for de novo identification of DNA regulatory motifs at a genome level. Using word-counting methods, we indexed the existence of every 8-mer oligo composed of bases A, C, G, T, r, y, s, w, m, k, n or 12-mer oligo composed of A, C, G, T, n, in the promoters of all predicted genes of Arabidopsis thaliana genome and of selected stress-induced co-expressed genes. From this analysis, we identified number of over-represented motifs. Among these, major critical motifs were identified using a position filter. We used a model based on uniform distribution and the z-scores derived from this model to describe position bias. Interestingly, many motifs showed position bias towards the transcription start site. We extended this model to show biased distribution of motifs in the genomes of both A. thaliana and rice. We also used MotifIndexer to identify conserved motifs in co-expressed gene groups from two Arabidopsis species, A. thaliana and A. lyrata. This new comparative genomics method does not depend on alignments of homologous gene promoter sequences.

  4. Insecticide discovery: an evaluation and analysis.

    Science.gov (United States)

    Sparks, Thomas C

    2013-09-01

    There is an on-going need for the discovery and development of new insecticides due to the loss of existing products through the development of resistance, the desire for products with more favorable environmental and toxicological profiles, shifting pest spectrums, and changing agricultural practices. Since 1960, the number of research-based companies in the US and Europe involved in the discovery of new insecticidal chemistries has been declining. In part this is a reflection of the increasing costs of the discovery and development of new pesticides. Likewise, the number of compounds that need to be screened for every product developed has, until recently, been climbing. In the past two decades the agrochemical industry has been able to develop a range of new products that have more favorable mammalian vs. insect selectivity. This review provides an analysis of the time required for the discovery, or more correctly the building process, for a wide range of insecticides developed during the last 60 years. An examination of the data around the time requirements for the discovery of products based on external patents, prior internal products, or entirely new chemistry provides some unexpected observations. In light of the increasing costs of discovery and development, coupled with fewer companies willing or able to make the investment, insecticide resistance management takes on greater importance as a means to preserve existing and new insecticides. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Shuttle Discovery Landing at Edwards

    Science.gov (United States)

    1989-01-01

    The STS-29 Space Shuttle Discovery mission lands at NASA's then Ames-Dryden Flight Research Facility, Edwards AFB, California, early Saturday morning, 18 March 1989. Touchdown was at 6:35:49 a.m. PST and wheel stop was at 6:36:40 a.m. on runway 22. Controllers chose the concrete runway for the landing in order to make tests of braking and nosewheel steering. The STS-29 mission was very successful, completing the launch of a Tracking and Data Relay communications satellite, as well as a range of scientific experiments. Discovery's five-man crew was led by Commander Michael L. Coats, and included pilot John E. Blaha and mission specialists James P. Bagian, Robert C. Springer, and James F. Buchli. Space Shuttles are the main element of America's Space Transportation System and are used for space research and other space applications. The shuttles are the first vehicles capable of being launched into space and returning to Earth on a routine basis. Space Shuttles are used as orbiting laboratories in which scientists and mission specialists conduct a wide variety of scientific experiments. Crews aboard shuttles place satellites in orbit, rendezvous with satellites to carry out repair missions and return them to space, and retrieve satellites and return them to Earth for refurbishment and reuse. Space Shuttles are true aerospace vehicles. They leave Earth and its atmosphere under rocket power provided by three liquid-propellant main engines with two solid-propellant boosters attached plus an external liquid-fuel tank. After their orbital missions, they streak back through the atmosphere and land like airplanes. The returning shuttles, however, land like gliders, without power and on runways. Other rockets can place heavy payloads into orbit, but, they can only be used once. Space Shuttles are designed to be continually reused. When Space Shuttles are used to transport complete scientific laboratories into space, the laboratories remain inside the payload bay throughout

  6. Large-scale discovery of promoter motifs in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Thomas A Down

    2007-01-01

    Full Text Available A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes.

  7. Extracting replicable associations across multiple studies: Empirical Bayes algorithms for controlling the false discovery rate.

    Directory of Open Access Journals (Sweden)

    David Amar

    2017-08-01

    Full Text Available In almost every field in genomics, large-scale biomedical datasets are used to report associations. Extracting associations that recur across multiple studies while controlling the false discovery rate is a fundamental challenge. Here, we propose a new method to allow joint analysis of multiple studies. Given a set of p-values obtained from each study, the goal is to identify associations that recur in at least k > 1 studies while controlling the false discovery rate. We propose several new algorithms that differ in how the study dependencies are modeled, and compare them and extant methods under various simulated scenarios. The top algorithm, SCREEN (Scalable Cluster-based REplicability ENhancement, is our new algorithm that works in three stages: (1 clustering an estimated correlation network of the studies, (2 learning replicability (e.g., of genes within clusters, and (3 merging the results across the clusters. When we applied SCREEN to two real datasets it greatly outperformed the results obtained via standard meta-analysis. First, on a collection of 29 case-control gene expression cancer studies, we detected a large set of consistently up-regulated genes related to proliferation and cell cycle regulation. These genes are both consistently up-regulated across many cancer studies, and are well connected in known gene networks. Second, on a recent pan-cancer study that examined the expression profiles of patients with and without mutations in the HLA complex, we detected a large active module of up-regulated genes that are both related to immune responses and are well connected in known gene networks. This module covers thrice more genes as compared to the original study at a similar false discovery rate, demonstrating the high power of SCREEN. An implementation of SCREEN is available in the supplement.

  8. Sexual and vegetative compatibility genes in the aspergilli

    NARCIS (Netherlands)

    Pal, K.; Diepeningen, van A.D.; Varga, J.; Hoekstra, R.F.; Dyer, P.S.; Debets, A.J.M.

    2007-01-01

    Gene flow within populations can occur by sexual and/or parasexual means. Analyses of experimental and in silico work are presented relevant to possible gene flow within the aspergilli. First, the discovery of mating-type (MAT) genes within certain species of Aspergillus is described. The

  9. Internet Naming and Discovery Architecture and Economics

    CERN Document Server

    Khoury, Joud S

    2013-01-01

    Naming is an integral building block within data networks and systems and is becoming ever more important as complex data-centric usage models emerge. Internet Naming and Discovery is timely in developing a unified model for studying the topic of naming and discovery. It details the architectural and economic tools needed for designing naming and discovery schemes within the broader context of internetwork architecture.   Readers will find in this book a historic overview of the Internet and a comprehensive survey of the literature, followed by and an in-depth examination of naming and discovery. Specific topics covered include: ·         formal definitions of name, address, identifier, locator, binding, routing, discovery, mapping, and resolution; ·         a discussion of the properties of names and bindings, along with illustrative case studies; ·         taxonomy that helps in organizing the solution space, and more importantly in identifying new avenues for contributing to the...

  10. The Discovery of Subatomic Particles Revised Edition

    Science.gov (United States)

    Weinberg, Steven

    2003-09-01

    This commentary on the discovery of the atom's constituents provides an historical account of key events in the physics of the twentieth century that led to the discoveries of the electron, proton and neutron. Steven Weinberg introduces the fundamentals of classical physics that played crucial roles in these discoveries. Connections are shown throughout the book between the historic discoveries of subatomic particles and contemporary research at the frontiers of physics, including the most current discoveries of new elementary particles. Steven Weinberg was Higgins Professor of Physics at Harvard before moving to The University of Texas at Austin, where he founded its Theory Group. At Texas he holds the Josey Regental Chair of Science and is a member of the Physics and Astronomy Departments. His research has spanned a broad range of topics in quantum field theory, elementary particle physics, and cosmology, and has been honored with numerous awards, including the Nobel Prize in Physics, the National Medal of Science, the Heinemann Prize in Mathematical Physics, the Cresson Medal of the Franklin Institute, the Madison Medal of Princeton University, and the Oppenheimer Prize. In addition to the well-known treatise, Gravitation and Cosmololgy, he has written several books for general readers, including the prize-winning The First Three Minutes (now translated into 22 foreign languages), and most recently Dreams of a Final Theory (Pantheon Books, 1993). He has also written a textbook The Quantum Theory of Fields, Vol.I, Vol. II, and Vol. III (Cambridge).

  11. Lifeomics leads the age of grand discoveries.

    Science.gov (United States)

    He, Fuchu

    2013-03-01

    When our knowledge of a field accumulates to a certain level, we are bound to see the rise of one or more great scientists. They will make a series of grand discoveries/breakthroughs and push the discipline into an 'age of grand discoveries'. Mathematics, geography, physics and chemistry have all experienced their ages of grand discoveries; and in life sciences, the age of grand discoveries has appeared countless times since the 16th century. Thanks to the ever-changing development of molecular biology over the past 50 years, contemporary life science is once again approaching its breaking point and the trigger for this is most likely to be 'lifeomics'. At the end of the 20th century, genomics wrote out the 'script of life'; proteomics decoded the script; and RNAomics, glycomics and metabolomics came into bloom. These 'omics', with their unique epistemology and methodology, quickly became the thrust of life sciences, pushing the discipline to new high. Lifeomics, which encompasses all omics, has taken shape and is now signalling the dawn of a new era, the age of grand discoveries.

  12. New genes linked to lung cancer susceptibility in Asian women

    Science.gov (United States)

    An international group of scientists has identified three genes that predispose Asian women who have never smoked to lung cancer. The discovery of specific genetic variations, which have not previously been associated with lung cancer risk in other popul

  13. Gene Linked to Excess Male Hormones in Female Infertility Disorder

    Science.gov (United States)

    ... April 15, 2014 Gene linked to excess male hormones in female infertility disorder Discovery by NIH-supported ... may lead to the overproduction of androgens — male hormones similar to testosterone — occurring in women with polycystic ...

  14. Biased agonism: An emerging paradigm in GPCR drug discovery.

    Science.gov (United States)

    Rankovic, Zoran; Brust, Tarsis F; Bohn, Laura M

    2016-01-15

    G protein coupled receptors have historically been one of the most druggable classes of cellular proteins. The members of this large receptor gene family couple to primary effectors, G proteins, that have built in mechanisms for regeneration and amplification of signaling with each engagement of receptor and ligand, a kinetic event in itself. In recent years GPCRs, have been found to interact with arrestin proteins to initiate signal propagation in the absence of G protein interactions. This pinnacle observation has changed a previously held notion of the linear spectrum of GPCR efficacy and uncovered a new paradigm in GPCR research and drug discovery that relies on multidimensionality of GPCR signaling. Ligands were found that selectively confer activity in one pathway over another, and this phenomenon has been referred to as 'biased agonism' or 'functional selectivity'. While great strides in the understanding of this phenomenon have been made in recent years, two critical questions still dominate the field: How can we rationally design biased GPCR ligands, and ultimately, which physiological responses are due to G protein versus arrestin interactions? This review will discuss the current understanding of some of the key aspects of biased signaling that are related to these questions, including mechanistic insights in the nature of biased signaling and methods for measuring ligand bias, as well as relevant examples of drug discovery applications and medicinal chemistry strategies that highlight the challenges and opportunities in this rapidly evolving field. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Discovery of nutritional biomarkers: future directions based on omics technologies.

    Science.gov (United States)

    Odriozola, Leticia; Corrales, Fernado J

    2015-07-01

    Understanding the interactions between food and human biology is of utmost importance to facilitate the development of more efficient nutritional interventions that might improve our wellness status and future health outcomes by reducing risk factors for non-transmittable chronic diseases, such as cardiovascular diseases, cancer, obesity and metabolic syndrome. Dissection of the molecular mechanisms that mediate the physiological effects of diets and bioactive compounds is one of the main goals of current nutritional investigation and the food industry as might lead to the discovery of novel biomarkers. It is widely recognized that the availability of robust nutritional biomarkers represents a bottleneck that delays the innovation process of the food industry. In this regard, omics sciences have opened up new avenues of research and opportunities in nutrition. Advances in mass spectrometry, nuclear magnetic resonance, next generation sequencing and microarray technologies allow massive genome, gene expression, proteomic and metabolomic profiling, obtaining a global and in-depth analysis of physiological/pathological scenarios. For this reason, omics platforms are most suitable for the discovery and characterization of novel nutritional markers that will define the nutritional status of both individuals and populations in the near future, and to identify the nutritional bioactive compounds responsible for the health outcomes.

  16. The impact of genetics on future drug discovery in schizophrenia.

    Science.gov (United States)

    Matsumoto, Mitsuyuki; Walton, Noah M; Yamada, Hiroshi; Kondo, Yuji; Marek, Gerard J; Tajinda, Katsunori

    2017-07-01

    Failures of investigational new drugs (INDs) for schizophrenia have left huge unmet medical needs for patients. Given the recent lackluster results, it is imperative that new drug discovery approaches (and resultant drug candidates) target pathophysiological alterations that are shared in specific, stratified patient populations that are selected based on pre-identified biological signatures. One path to implementing this paradigm is achievable by leveraging recent advances in genetic information and technologies. Genome-wide exome sequencing and meta-analysis of single nucleotide polymorphism (SNP)-based association studies have already revealed rare deleterious variants and SNPs in patient populations. Areas covered: Herein, the authors review the impact that genetics have on the future of schizophrenia drug discovery. The high polygenicity of schizophrenia strongly indicates that this disease is biologically heterogeneous so the identification of unique subgroups (by patient stratification) is becoming increasingly necessary for future investigational new drugs. Expert opinion: The authors propose a pathophysiology-based stratification of genetically-defined subgroups that share deficits in particular biological pathways. Existing tools, including lower-cost genomic sequencing and advanced gene-editing technology render this strategy ever more feasible. Genetically complex psychiatric disorders such as schizophrenia may also benefit from synergistic research with simpler monogenic disorders that share perturbations in similar biological pathways.

  17. Proteomics for discovery of candidate colorectal cancer biomarkers

    Science.gov (United States)

    Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

  18. 'Big data' approaches for novel anti-cancer drug discovery.

    Science.gov (United States)

    Benstead-Hume, Graeme; Wooller, Sarah K; Pearl, Frances M G

    2017-06-01

    The development of improved cancer therapies is frequently cited as an urgent unmet medical need. Recent advances in platform technologies and the increasing availability of biological 'big data' are providing an unparalleled opportunity to systematically identify the key genes and pathways involved in tumorigenesis. The discoveries made using these new technologies may lead to novel therapeutic interventions. Areas covered: The authors discuss the current approaches that use 'big data' to identify cancer drivers. These approaches include the analysis of genomic sequencing data, pathway data, multi-platform data, identifying genetic interactions such as synthetic lethality and using cell line data. They review how big data is being used to identify novel drug targets. The authors then provide an overview of the available data repositories and tools being used at the forefront of cancer drug discovery. Expert opinion: Targeted therapies based on the genomic events driving the tumour will eventually inform treatment protocols. However, using a tailored approach to treat all tumour patients may require developing a large repertoire of targeted drugs.

  19. Application of “omics” to Prion Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Rhiannon L. C. H. Huzarewich

    2010-01-01

    Full Text Available The advent of genomics and proteomics has been a catalyst for the discovery of biomarkers able to discriminate biological processes such as the pathogenesis of complex diseases. Prompt detection of prion diseases is particularly desirable given their transmissibility, which is responsible for a number of human health risks stemming from exogenous sources of prion protein. Diagnosis relies on the ability to detect the biomarker PrPSc, a pathological isoform of the host protein PrPC, which is an essential component of the infectious prion. Immunochemical detection of PrPSc is specific and sensitive enough for antemortem testing of brain tissue, however, this is not the case in accessible biological fluids or for the detection of recently identified novel prions with unique biochemical properties. A complementary approach to the detection of PrPSc itself is to identify alternative, “surrogate” gene or protein biomarkers indicative of disease. Biomarkers are also useful to track the progress of disease, especially important in the assessment of therapies, or to identify individuals “at risk”. In this review we provide perspective on current progress and pitfalls in the use of “omics” technologies to screen body fluids and tissues for biomarker discovery in prion diseases.

  20. Drug discovery and development for rare genetic disorders.

    Science.gov (United States)

    Sun, Wei; Zheng, Wei; Simeonov, Anton

    2017-09-01

    Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated. © 2017 Wiley Periodicals, Inc.

  1. Context-sensitive service discovery experimental prototype and evaluation

    DEFF Research Database (Denmark)

    Balken, Robin; Haukrogh, Jesper; L. Jensen, Jens

    2007-01-01

    the network in domains that handle the complex distributed service discovery, which is based on dynamically changing context information. In the prototype, a method for performing context-sensitive service discovery has been realised. The service discovery part utilizes UPnP, which has been expanded in order...... to increase network scalability. The experimental analysis of service discovery times for different scenarios is used to optimize parameter settings of the service discovery system in order to achieve short response times....

  2. A perfect launch of Space Shuttle Discovery

    Science.gov (United States)

    2000-01-01

    Space Shuttle Discovery lifts off Launch Pad 39A against a backdrop of xenon lights (just above the orbiter' nose and at left). On the Mobile Launcher Platform beneath, water begins flooding the area for flame and sound control. The perfect on- time liftoff occurred at 7:17 p.m. EDT, sending a crew of seven on the 100th launch in the history of the Shuttle program. Discovery 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.

  3. John Herschel on the Discovery of Neptune

    Science.gov (United States)

    Kollerstrom, Nicholas

    2006-12-01

    The letters of John Herschel that concern the discovery of the planet Neptune have not been greatly discussed by historians of science. I have transcribed these in the course of archiving the British Neptune-discovery documents. Herschel tends to be depicted as a background figure in narrations of the story of Neptune's discovery, whereas the present account focuses upon his evolving view of the topic: the rival merits of the two main protagonists, and the startling manner in which an obscure branch of mathematics (perturbation theory) was able to pinpoint the position of a new sphere in the sky. As the son of the man who found Uranus, his views have a special relevance. Also, I suggest that his eloquent prose style may still be enjoyed today.

  4. Virtual drug discovery: beyond computational chemistry?

    Science.gov (United States)

    Gilardoni, Francois; Arvanites, Anthony C

    2010-02-01

    This editorial looks at how a fully integrated structure that performs all aspects in the drug discovery process, under one company, is slowly disappearing. The steps in the drug discovery paradigm have been slowly increasing toward virtuality or outsourcing at various phases of product development in a company's candidate pipeline. Each step in the process, such as target identification and validation and medicinal chemistry, can be managed by scientific teams within a 'virtual' company. Pharmaceutical companies to biotechnology start-ups have been quick in adopting this new research and development business strategy in order to gain flexibility, access the best technologies and technical expertise, and decrease product developmental costs. In today's financial climate, the term virtual drug discovery has an organizational meaning. It represents the next evolutionary step in outsourcing drug development.

  5. Discovery, Characterization, and Dynamics of Transiting Exoplanets

    DEFF Research Database (Denmark)

    Van Eylen, Vincent

    2015-01-01

    Are we alone in the Universe? So far, the question remains unanswered, but a significant leap forward was achieved two decades ago, with the discovery of the first planets orbiting stars other than our Sun. Almost 2000 exoplanets have now been detected. They are diverse in radius, mass and orbital......, in this thesis I make use of the transit method, which is based on the observed brightness drop of a star as a planet crosses in front of it. This thesis consists of two parts. The first part focuses on the discovery of new planets and the understanding of exoplanet properties. I report the discovery...... results of this study, constraining the masses and bulk compositions of three planets. The second part of this thesis focuses on dynamics of exoplanets. All the solar system planets orbit in nearly the same plane, and that plane is also aligned with the equatorial plane of the Sun. That is not true...

  6. Protein chemical synthesis in drug discovery.

    Science.gov (United States)

    Liu, Fa; Mayer, John P

    2015-01-01

    The discovery of novel therapeutics to combat human disease has traditionally been among the most important goals of research chemists. After a century of innovation, state-of-the-art chemical protein synthesis is now capable of efficiently assembling proteins of up to several hundred residues in length from individual amino acids. By virtue of its unique ability to incorporate non-native structural elements, chemical protein synthesis has been seminal in the recent development of several novel drug discovery technologies. In this chapter, we review the key advances in peptide and protein chemistry which have enabled our current synthetic capabilities. We also discuss the synthesis of D-proteins and their applications in mirror image phage-display and racemic protein crystallography, the synthesis of enzymes for structure-based drug discovery, and the direct synthesis of homogenous protein pharmaceuticals.

  7. Neutron Diffraction and Inorganic Materials Discovery

    International Nuclear Information System (INIS)

    Rosseinsky, M.J.

    2005-01-01

    Full text: The discovery of complex inorganic materials is an important academic and technological challenge because of the opportunities these systems offer for observation of new phenomena, and the questions they pose for fundamental understanding. This presentation will illustrate the key role of neutron powder diffraction in enabling the discovery of new classes of materials, and in evaluating their properties and the conditions under which they need to be processed to optimise their behaviour in devices for applications. New chemistry is illustrated by the transition metal oxide hydrides, where both structure and ionic mobility required neutron scattering characterisation. The relationship between chemistry, structure and properties will be addressed by considering the difficulties in inducing superconductivity in analogues of magnesium diboride. The role of both neutron and X-ray diffraction in evaluating the processing of microwave dielectric ceramics will be highlighted, with the discovery of new phases shown to be a useful bonus in this type of in-situ study. (author)

  8. The genetics of politics: discovery, challenges, and progress.

    Science.gov (United States)

    Hatemi, Peter K; McDermott, Rose

    2012-10-01

    For the greater part of human history, political behaviors, values, preferences, and institutions have been viewed as socially determined. Discoveries during the 1970s that identified genetic influences on political orientations remained unaddressed. However, over the past decade, an unprecedented amount of scholarship utilizing genetic models to expand the understanding of political traits has emerged. Here, we review the 'genetics of politics', focusing on the topics that have received the most attention: attitudes, ideologies, and pro-social political traits, including voting behavior and participation. The emergence of this research has sparked a broad paradigm shift in the study of political behaviors toward the inclusion of biological influences and recognition of the mutual co-dependence between genes and environment in forming political behaviors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Predictors of timing of pregnancy discovery.

    Science.gov (United States)

    McCarthy, Molly; Upadhyay, Ushma; Biggs, M Antonia; Anthony, Renaisa; Holl, Jennifer; Roberts, Sarah Cm

    2018-04-01

    Earlier pregnancy discovery is important in the context of prenatal and abortion care. We evaluated characteristics associated with later pregnancy discovery among women seeking abortion care. Data come from a survey of women seeking abortion care at four family planning facilities in Utah. The participants completed a survey during the state-mandated abortion information visit they are required to complete prior to having an abortion. The outcome in this study was pregnancy discovery before versus after 6 weeks since respondents' last menstrual period (LMP). We used logistic regression to estimate the relationship between sociodemographic and health-related independent variables of interest and pregnancy discovery before versus after 6 weeks. Among the 458 women in the sample, 28% discovered their pregnancy later than 6 weeks since LMP. Most (n=366, 80%) knew the exact date of their LMP and a significant minority estimated it (n=92, 20%). Those who estimated the date of their LMP had higher odds of later pregnancy discovery than those who knew the exact date (adjusted odds ratio (aOR)=1.81[1.07-3.07]). Those who used illicit drugs weekly, daily, or almost daily had higher odds of later pregnancy discovery (aOR=6.33[2.44, 16.40]). Women who did not track their menstrual periods and those who frequently used drugs had higher odds of discovering their pregnancies later. Women who estimated the date of their LMP and who frequently used drugs may benefit from strategies to help them recognize their pregnancies earlier and link them to care when they discover their pregnancies later. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Strain prioritization for natural product discovery by a high-throughput real-time PCR method.

    Science.gov (United States)

    Hindra; Huang, Tingting; Yang, Dong; Rudolf, Jeffrey D; Xie, Pengfei; Xie, Guangbo; Teng, Qihui; Lohman, Jeremy R; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Duan, Yanwen; Shen, Ben

    2014-10-24

    Natural products offer unmatched chemical and structural diversity compared to other small-molecule libraries, but traditional natural product discovery programs are not sustainable, demanding too much time, effort, and resources. Here we report a strain prioritization method for natural product discovery. Central to the method is the application of real-time PCR, targeting genes characteristic to the biosynthetic machinery of natural products with distinct scaffolds in a high-throughput format. The practicality and effectiveness of the method were showcased by prioritizing 1911 actinomycete strains for diterpenoid discovery. A total of 488 potential diterpenoid producers were identified, among which six were confirmed as platensimycin and platencin dual producers and one as a viguiepinol and oxaloterpin producer. While the method as described is most appropriate to prioritize strains for discovering specific natural products, variations of this method should be applicable to the discovery of other classes of natural products. Applications of genome sequencing and genome mining to the high-priority strains could essentially eliminate the chance elements from traditional discovery programs and fundamentally change how natural products are discovered.

  11. Traditional Chinese Medicine-Based Network Pharmacology Could Lead to New Multicompound Drug Discovery

    Directory of Open Access Journals (Sweden)

    Jian Li

    2012-01-01

    Full Text Available Current strategies for drug discovery have reached a bottleneck where the paradigm is generally “one gene, one drug, one disease.” However, using holistic and systemic views, network pharmacology may be the next paradigm in drug discovery. Based on network pharmacology, a combinational drug with two or more compounds could offer beneficial synergistic effects for complex diseases. Interestingly, traditional chinese medicine (TCM has been practicing holistic views for over 3,000 years, and its distinguished feature is using herbal formulas to treat diseases based on the unique pattern classification. Though TCM herbal formulas are acknowledged as a great source for drug discovery, no drug discovery strategies compatible with the multidimensional complexities of TCM herbal formulas have been developed. In this paper, we highlighted some novel paradigms in TCM-based network pharmacology and new drug discovery. A multiple compound drug can be discovered by merging herbal formula-based pharmacological networks with TCM pattern-based disease molecular networks. Herbal formulas would be a source for multiple compound drug candidates, and the TCM pattern in the disease would be an indication for a new drug.

  12. From the nucleus discovery to DWBA

    International Nuclear Information System (INIS)

    Fernandez, B.

    2007-01-01

    The author presents a brief review of the main events in the field of nuclear reactions that are acknowledged as milestones because of their importance due to either experimental setting or physical interpretation. It is shown that the pace of discoveries has been strongly dependent on the technical progress in detection means at the beginning of nuclear physics and now is linked to the development of simulation means. The discovery of the neutron, the development of the Geiger counter, the theory of the compound nucleus or the first direct reactions are among these milestones

  13. The discovery of the tau lepton

    International Nuclear Information System (INIS)

    Perl, M.L.

    1992-09-01

    The discovery of the tau lepton and the third generation of fermions came from the convergence of three physics streams in the late 1960's and early 1970's. These streams were: the failed attempts by myself and others to understand the connection between the electron and the muon, the development of electron-positron storage rings, and the development of the theory of sequential leptons. In this paper I give the history of the discovery of the tau and the measurement of its major properties-the properties which established the tau as a sequential lepton

  14. Net present value approaches for drug discovery.

    Science.gov (United States)

    Svennebring, Andreas M; Wikberg, Jarl Es

    2013-12-01

    Three dedicated approaches to the calculation of the risk-adjusted net present value (rNPV) in drug discovery projects under different assumptions are suggested. The probability of finding a candidate drug suitable for clinical development and the time to the initiation of the clinical development is assumed to be flexible in contrast to the previously used models. The rNPV of the post-discovery cash flows is calculated as the probability weighted average of the rNPV at each potential time of initiation of clinical development. Practical considerations how to set probability rates, in particular during the initiation and termination of a project is discussed.

  15. Antibacterial drug discovery in the resistance era.

    Science.gov (United States)

    Brown, Eric D; Wright, Gerard D

    2016-01-21

    The looming antibiotic-resistance crisis has penetrated the consciousness of clinicians, researchers, policymakers, politicians and the public at large. The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens has made diseases that were once easily treatable deadly again. Unfortunately, accompanying the rise in global resistance is a failure in antibacterial drug discovery. Lessons from the history of antibiotic discovery and fresh understanding of antibiotic action and the cell biology of microorganisms have the potential to deliver twenty-first century medicines that are able to control infection in the resistance era.

  16. The centenary of discovery of radium

    International Nuclear Information System (INIS)

    Mazeron, J.-J.; Gerbaulet, A.

    1998-01-01

    Henri Becquerel presented the discovery of radium by Pierre and Marie Curie at the Paris Academy of Science on 26th December 1898. One century later, radium has been abandoned, mainly for radiation protection difficulties. It is, however, likely that modern techniques of brachytherapy have inherited to those designed for radium sources, and that radium has cured thousands and thousands patients all over the world for about eighty years. The history of discovery and medical use of radium is summarised. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  17. The discovery of elements 113 to 118

    Directory of Open Access Journals (Sweden)

    Utyonkov Vladimir

    2016-01-01

    Full Text Available Discovery and investigation of the “Island of stability” of superheavy nuclei at the separator DGFRS in the 238U-249Cf+ 48Ca reactions is reviewed. The results are compared with the data obtained in chemistry experiments and at the separators SHIP, BGS, TASCA, and GARIS. The synthesis of the heaviest nuclei, their decay properties, and methods of identification are discussed and compared with the criteria that must be satisfied for claiming the discovery of a new chemical element. The role of shell effects in the stability of superheavy nuclei is demonstrated by comparison of the experimental results with empirical systematics and theoretical data.

  18. Effective Online Group Discovery in Trajectory Databases

    DEFF Research Database (Denmark)

    Li, Xiaohui; Ceikute, Vaida; Jensen, Christian S.

    2013-01-01

    GPS-enabled devices are pervasive nowadays. Finding movement patterns in trajectory data stream is gaining in importance. We propose a group discovery framework that aims to efficiently support the online discovery of moving objects that travel together. The framework adopts a sampling...... based on their cardinality and duration, and the top-$k$ groups are returned. To avoid returning similar subgroups in a result, notions of domination and similarity are introduced that enable the pruning of low-interest groups. Empirical studies on real and synthetic data sets offer insight...

  19. Using Discovery Learning to Encourage Creative Thinking

    Directory of Open Access Journals (Sweden)

    Mardia Hi. Rahman

    2017-10-01

    Full Text Available Creative thinking ability development is needed to be implemented by every educator including lecturers to their students. Therefore, they need to seriously act and design their learning process. One of the ways to develop student’s creative thinking is using discovery learning model. This research is conducted in physics education study program in 2016 with students who took learning and teaching class as research subject. From the research analysis result and discussion, it can be concluded that discovery learning model can encourage students’ creative thinking ability in learning and teaching strategy subject.

  20. History, Discovery, and Classification of lncRNAs.

    Science.gov (United States)

    Jarroux, Julien; Morillon, Antonin; Pinskaya, Marina

    2017-01-01

    The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of