Science.gov

Sample records for including functional annotations

  1. Algal functional annotation tool

    SciTech Connect

    2012-07-12

    Abstract BACKGROUND: Progress in genome sequencing is proceeding at an exponential pace, and several new algal genomes are becoming available every year. One of the challenges facing the community is the association of protein sequences encoded in the genomes with biological function. While most genome assembly projects generate annotations for predicted protein sequences, they are usually limited and integrate functional terms from a limited number of databases. Another challenge is the use of annotations to interpret large lists of 'interesting' genes generated by genome-scale datasets. Previously, these gene lists had to be analyzed across several independent biological databases, often on a gene-by-gene basis. In contrast, several annotation databases, such as DAVID, integrate data from multiple functional databases and reveal underlying biological themes of large gene lists. While several such databases have been constructed for animals, none is currently available for the study of algae. Due to renewed interest in algae as potential sources of biofuels and the emergence of multiple algal genome sequences, a significant need has arisen for such a database to process the growing compendiums of algal genomic data. DESCRIPTION: The Algal Functional Annotation Tool is a web-based comprehensive analysis suite integrating annotation data from several pathway, ontology, and protein family databases. The current version provides annotation for the model alga Chlamydomonas reinhardtii, and in the future will include additional genomes. The site allows users to interpret large gene lists by identifying associated functional terms, and their enrichment. Additionally, expression data for several experimental conditions were compiled and analyzed to provide an expression-based enrichment search. A tool to search for functionally-related genes based on gene expression across these conditions is also provided. Other features include dynamic visualization of genes on KEGG

  2. Phylogenetic molecular function annotation

    NASA Astrophysics Data System (ADS)

    Engelhardt, Barbara E.; Jordan, Michael I.; Repo, Susanna T.; Brenner, Steven E.

    2009-07-01

    It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic approach for predicting molecular function (sometimes called "phylogenomics") is an effective means to predict protein molecular function. These methods incorporate functional evidence from all members of a family that have functional characterizations using the evolutionary history of the protein family to make robust predictions for the uncharacterized proteins. However, they are often difficult to apply on a genome-wide scale because of the time-consuming step of reconstructing the phylogenies of each protein to be annotated. Our automated approach for function annotation using phylogeny, the SIFTER (Statistical Inference of Function Through Evolutionary Relationships) methodology, uses a statistical graphical model to compute the probabilities of molecular functions for unannotated proteins. Our benchmark tests showed that SIFTER provides accurate functional predictions on various protein families, outperforming other available methods.

  3. Phylogenetic molecular function annotation

    PubMed Central

    Engelhardt, Barbara E; Jordan, Michael I; Repo, Susanna T; Brenner, Steven E

    2010-01-01

    It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic approach for predicting molecular function (sometimes called “phylogenomics”) is an effective means to predict protein molecular function. These methods incorporate functional evidence from all members of a family that have functional characterizations using the evolutionary history of the protein family to make robust predictions for the uncharacterized proteins. However, they are often difficult to apply on a genome-wide scale because of the time-consuming step of reconstructing the phylogenies of each protein to be annotated. Our automated approach for function annotation using phylogeny, the SIFTER (Statistical Inference of Function Through Evolutionary Relationships) methodology, uses a statistical graphical model to compute the probabilities of molecular functions for unannotated proteins. Our benchmark tests showed that SIFTER provides accurate functional predictions on various protein families, outperforming other available methods. PMID:20664722

  4. Ontology-Based Prediction and Prioritization of Gene Functional Annotations.

    PubMed

    Chicco, Davide; Masseroli, Marco

    2016-01-01

    Genes and their protein products are essential molecular units of a living organism. The knowledge of their functions is key for the understanding of physiological and pathological biological processes, as well as in the development of new drugs and therapies. The association of a gene or protein with its functions, described by controlled terms of biomolecular terminologies or ontologies, is named gene functional annotation. Very many and valuable gene annotations expressed through terminologies and ontologies are available. Nevertheless, they might include some erroneous information, since only a subset of annotations are reviewed by curators. Furthermore, they are incomplete by definition, given the rapidly evolving pace of biomolecular knowledge. In this scenario, computational methods that are able to quicken the annotation curation process and reliably suggest new annotations are very important. Here, we first propose a computational pipeline that uses different semantic and machine learning methods to predict novel ontology-based gene functional annotations; then, we introduce a new semantic prioritization rule to categorize the predicted annotations by their likelihood of being correct. Our tests and validations proved the effectiveness of our pipeline and prioritization of predicted annotations, by selecting as most likely manifold predicted annotations that were later confirmed.

  5. Structural and functional annotation of the porcine immunome

    PubMed Central

    2013-01-01

    Background The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems. Results The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated

  6. Evolutionary Trace Annotation of Protein Function in the Structural Proteome

    PubMed Central

    Erdin, Serkan; Ward, R. Matthew; Venner, Eric

    2010-01-01

    By design, structural genomics (SG) solves many structures that cannot be assigned function based on homology to known proteins. Alternative function annotation methods are therefore needed and this study focuses on function prediction with three-dimensional (3D) templates: small structural motifs built of just a few functionally critical residues. Although experimentally proven functional residues are scarce, we show here that Evolutionary Trace (ET) rankings of residue importance are sufficient to build 3D templates, match them, and then assign Gene Ontology (GO) functions in enzymes and non-enzymes alike. In a high specificity mode, this Evolutionary Trace Annotation (ETA) method covered half (53%) of the 2384 annotated SG protein controls. Three-quarters (76%) of predictions were both correct and complete. The positive predictive value for all GO depths (all-depth PPV) was 84%, and it rose to 94% over GO depths 1– 3 (depth 3 PPV). In a high sensitivity mode coverage rose significantly (84%) while accuracy fell moderately: 68% of predictions were both correct and complete, all-depth PPV was 75%, and depth 3 PPV was 86%. These data concur with prior mutational experiments showing that ET rank information identifies key functional determinants in proteins. In practice, ETA predicted functions in 42% of 3461 un-annotated SG proteins. In 529 cases—including 280 non-enzymes and 21 for metal ion ligands—the expected accuracy is 84% at any GO depth and 94% down to GO depth 3, while for the remaining 931 the expected accuracies are 60% and 71%, respectively. Thus local structural comparisons of evolutionarily important residues can help decipher protein functions to known reliability levels and without prior assumption on functional mechanisms. ETA is available at http://mammoth.bcm.tmc.edu/eta. PMID:20036248

  7. A computational interactome and functional annotation for the human proteome

    PubMed Central

    Garzón, José Ignacio; Deng, Lei; Murray, Diana; Shapira, Sagi; Petrey, Donald; Honig, Barry

    2016-01-01

    We present a database, PrePPI (Predicting Protein-Protein Interactions), of more than 1.35 million predicted protein-protein interactions (PPIs). Of these at least 127,000 are expected to constitute direct physical interactions although the actual number may be much larger (~500,000). The current PrePPI, which contains predicted interactions for about 85% of the human proteome, is related to an earlier version but is based on additional sources of interaction evidence and is far larger in scope. The use of structural relationships allows PrePPI to infer numerous previously unreported interactions. PrePPI has been subjected to a series of validation tests including reproducing known interactions, recapitulating multi-protein complexes, analysis of disease associated SNPs, and identifying functional relationships between interacting proteins. We show, using Gene Set Enrichment Analysis (GSEA), that predicted interaction partners can be used to annotate a protein’s function. We provide annotations for most human proteins, including many annotated as having unknown function. DOI: http://dx.doi.org/10.7554/eLife.18715.001 PMID:27770567

  8. Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.

    PubMed

    Gaudet, Pascale; Livstone, Michael S; Lewis, Suzanna E; Thomas, Paul D

    2011-09-01

    The goal of the Gene Ontology (GO) project is to provide a uniform way to describe the functions of gene products from organisms across all kingdoms of life and thereby enable analysis of genomic data. Protein annotations are either based on experiments or predicted from protein sequences. Since most sequences have not been experimentally characterized, most available annotations need to be based on predictions. To make as accurate inferences as possible, the GO Consortium's Reference Genome Project is using an explicit evolutionary framework to infer annotations of proteins from a broad set of genomes from experimental annotations in a semi-automated manner. Most components in the pipeline, such as selection of sequences, building multiple sequence alignments and phylogenetic trees, retrieving experimental annotations and depositing inferred annotations, are fully automated. However, the most crucial step in our pipeline relies on software-assisted curation by an expert biologist. This curation tool, Phylogenetic Annotation and INference Tool (PAINT) helps curators to infer annotations among members of a protein family. PAINT allows curators to make precise assertions as to when functions were gained and lost during evolution and record the evidence (e.g. experimentally supported GO annotations and phylogenetic information including orthology) for those assertions. In this article, we describe how we use PAINT to infer protein function in a phylogenetic context with emphasis on its strengths, limitations and guidelines. We also discuss specific examples showing how PAINT annotations compare with those generated by other highly used homology-based methods.

  9. Functional annotation of deubiquitinating enzymes using RNA interference.

    PubMed

    Dirac, Annette M G; Nijman, Sebastian M B; Brummelkamp, Thijn R; Bernards, René

    2005-01-01

    Protein ubiquitination is a dynamic process, depending on a tightly regulated balance between the activity of ubiquitin ligases and their antagonists, the ubiquitin-specific proteases or deubiquitinating enzymes. The family of ubiquitin ligases has been studied intensively and it is well established that their deregulation contributes to diverse disease processes, including cancer. Much less is known about the function and regulation of the large group of deubiquitinating enzymes. This chapter describes how RNA interference against deubiquitinating enzymes can be used to elucidate their function. The application of this technology will greatly improve the functional annotation of this family of proteases.

  10. Neurolinguistic Annotated Bibliography (Brain Research and Language Function) with Implications for Education.

    ERIC Educational Resources Information Center

    Davis, Wesley K.

    This bibliography presents annotations of 91 journal articles, books, chapters in books, and conference papers dating from 1967 to 1984 concerning neurolinguistics, language processing, and educational implications of brain research. The annotated bibliography includes eight items on neuroanatomy and language function; 20 items on neurolinguistics…

  11. Considerations to improve functional annotations in biological databases.

    PubMed

    Benítez-Páez, Alfonso

    2009-12-01

    Despite the great effort to design efficient systems allowing the electronic indexation of information concerning genes, proteins, structures, and interactions published daily in scientific journals, some problems are still observed in specific tasks such as functional annotation. The annotation of function is a critical issue for bioinformatic routines, such as for instance, in functional genomics and the further prediction of unknown protein function, which are highly dependent of the quality of existing annotations. Some information management systems evolve to efficiently incorporate information from large-scale projects, but often, annotation of single records from the literature is difficult and slow. In this short report, functional characterizations of a representative sample of the entire set of uncharacterized proteins from Escherichia coli K12 was compiled from Swiss-Prot, PubMed, and EcoCyc and demonstrate a functional annotation deficit in biological databases. Some issues are postulated as causes of the lack of annotation, and different solutions are evaluated and proposed to avoid them. The hope is that as a consequence of these observations, there will be new impetus to improve the speed and quality of functional annotation and ultimately provide updated, reliable information to the scientific community.

  12. A spectral approach integrating functional genomic annotations for coding and noncoding variants.

    PubMed

    Ionita-Laza, Iuliana; McCallum, Kenneth; Xu, Bin; Buxbaum, Joseph D

    2016-02-01

    Over the past few years, substantial effort has been put into the functional annotation of variation in human genome sequences. Such annotations can have a critical role in identifying putatively causal variants for a disease or trait among the abundant natural variation that occurs at a locus of interest. The main challenges in using these various annotations include their large numbers and their diversity. Here we develop an unsupervised approach to integrate these different annotations into one measure of functional importance (Eigen) that, unlike most existing methods, is not based on any labeled training data. We show that the resulting meta-score has better discriminatory ability using disease-associated and putatively benign variants from published studies (in both coding and noncoding regions) than the recently proposed CADD score. Across varied scenarios, the Eigen score performs generally better than any single individual annotation, representing a powerful single functional score that can be incorporated in fine-mapping studies.

  13. AutoFACT: An Automatic Functional Annotation and Classification Tool

    PubMed Central

    Koski, Liisa B; Gray, Michael W; Lang, B Franz; Burger, Gertraud

    2005-01-01

    Background Assignment of function to new molecular sequence data is an essential step in genomics projects. The usual process involves similarity searches of a given sequence against one or more databases, an arduous process for large datasets. Results We present AutoFACT, a fully automated and customizable annotation tool that assigns biologically informative functions to a sequence. Key features of this tool are that it (1) analyzes nucleotide and protein sequence data; (2) determines the most informative functional description by combining multiple BLAST reports from several user-selected databases; (3) assigns putative metabolic pathways, functional classes, enzyme classes, GeneOntology terms and locus names; and (4) generates output in HTML, text and GFF formats for the user's convenience. We have compared AutoFACT to four well-established annotation pipelines. The error rate of functional annotation is estimated to be only between 1–2%. Comparison of AutoFACT to the traditional top-BLAST-hit annotation method shows that our procedure increases the number of functionally informative annotations by approximately 50%. Conclusion AutoFACT will serve as a useful annotation tool for smaller sequencing groups lacking dedicated bioinformatics staff. It is implemented in PERL and runs on LINUX/UNIX platforms. AutoFACT is available at . PMID:15960857

  14. microRNAs Databases: Developmental Methodologies, Structural and Functional Annotations.

    PubMed

    Singh, Nagendra Kumar

    2016-03-28

    microRNA (miRNA) is an endogenous and evolutionary conserved non-coding RNA, involved in post-transcriptional process as gene repressor and mRNA cleavage through RNA-induced silencing complex (RISC) formation. In RISC, miRNA binds in complementary base pair with targeted mRNA along with Argonaut proteins complex, causes gene repression or endonucleolytic cleavage of mRNAs and results in many diseases and syndromes. After the discovery of miRNA lin-4 and let-7, subsequently large numbers of miRNAs were discovered by low-throughput and high-throughput experimental techniques along with computational process in various biological and metabolic processes. The miRNAs are important non-coding RNA for understanding the complex biological phenomena of organism because it controls the gene regulation. This paper reviews miRNA databases with structural and functional annotations developed by various researchers. These databases contain structural and functional information of animal, plant and virus miRNAs including miRNAs-associated diseases, stress resistance in plant, miRNAs take part in various biological processes, effect of miRNAs interaction on drugs and environment, effect of variance on miRNAs, miRNAs gene expression analysis, sequence of miRNAs, structure of miRNAs. This review focuses on the developmental methodology of miRNA databases such as computational tools and methods used for extraction of miRNAs annotation from different resources or through experiment. This study also discusses the efficiency of user interface design of every database along with current entry and annotations of miRNA (pathways, gene ontology, disease ontology, etc.). Here, an integrated schematic diagram of construction process for databases is also drawn along with tabular and graphical comparison of various types of entries in different databases. Aim of this paper is to present the importance of miRNAs-related resources at a single place.

  15. Functional annotation of rare gene aberration drivers of pancreatic cancer

    PubMed Central

    Tsang, Yiu Huen; Dogruluk, Turgut; Tedeschi, Philip M.; Wardwell-Ozgo, Joanna; Lu, Hengyu; Espitia, Maribel; Nair, Nikitha; Minelli, Rosalba; Chong, Zechen; Chen, Fengju; Chang, Qing Edward; Dennison, Jennifer B.; Dogruluk, Armel; Li, Min; Ying, Haoqiang; Bertino, Joseph R.; Gingras, Marie-Claude; Ittmann, Michael; Kerrigan, John; Chen, Ken; Creighton, Chad J.; Eterovic, Karina; Mills, Gordon B.; Scott, Kenneth L.

    2016-01-01

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC). This approach reveals oncogenic activity for rare gene aberrations in genes including NAD Kinase (NADK), which regulates NADP(H) homeostasis and cellular redox state. We further validate mutant NADK, whose expression provides gain-of-function enzymatic activity leading to a reduction in cellular reactive oxygen species and tumorigenesis, and show that depletion of wild-type NADK in PDAC cell lines attenuates cancer cell growth in vitro and in vivo. These data indicate that annotating rare aberrations can reveal important cancer signalling pathways representing additional therapeutic targets. PMID:26806015

  16. Protein function annotation using protein domain family resources.

    PubMed

    Das, Sayoni; Orengo, Christine A

    2016-01-15

    As a result of the genome sequencing and structural genomics initiatives, we have a wealth of protein sequence and structural data. However, only about 1% of these proteins have experimental functional annotations. As a result, computational approaches that can predict protein functions are essential in bridging this widening annotation gap. This article reviews the current approaches of protein function prediction using structure and sequence based classification of protein domain family resources with a special focus on functional families in the CATH-Gene3D resource.

  17. Algal Functional Annotation Tool: a web-based analysis suite to functionally interpret large gene lists using integrated annotation and expression data

    PubMed Central

    2011-01-01

    Background Progress in genome sequencing is proceeding at an exponential pace, and several new algal genomes are becoming available every year. One of the challenges facing the community is the association of protein sequences encoded in the genomes with biological function. While most genome assembly projects generate annotations for predicted protein sequences, they are usually limited and integrate functional terms from a limited number of databases. Another challenge is the use of annotations to interpret large lists of 'interesting' genes generated by genome-scale datasets. Previously, these gene lists had to be analyzed across several independent biological databases, often on a gene-by-gene basis. In contrast, several annotation databases, such as DAVID, integrate data from multiple functional databases and reveal underlying biological themes of large gene lists. While several such databases have been constructed for animals, none is currently available for the study of algae. Due to renewed interest in algae as potential sources of biofuels and the emergence of multiple algal genome sequences, a significant need has arisen for such a database to process the growing compendiums of algal genomic data. Description The Algal Functional Annotation Tool is a web-based comprehensive analysis suite integrating annotation data from several pathway, ontology, and protein family databases. The current version provides annotation for the model alga Chlamydomonas reinhardtii, and in the future will include additional genomes. The site allows users to interpret large gene lists by identifying associated functional terms, and their enrichment. Additionally, expression data for several experimental conditions were compiled and analyzed to provide an expression-based enrichment search. A tool to search for functionally-related genes based on gene expression across these conditions is also provided. Other features include dynamic visualization of genes on KEGG pathway maps

  18. Evaluating Functional Annotations of Enzymes Using the Gene Ontology.

    PubMed

    Holliday, Gemma L; Davidson, Rebecca; Akiva, Eyal; Babbitt, Patricia C

    2017-01-01

    The Gene Ontology (GO) (Ashburner et al., Nat Genet 25(1):25-29, 2000) is a powerful tool in the informatics arsenal of methods for evaluating annotations in a protein dataset. From identifying the nearest well annotated homologue of a protein of interest to predicting where misannotation has occurred to knowing how confident you can be in the annotations assigned to those proteins is critical. In this chapter we explore what makes an enzyme unique and how we can use GO to infer aspects of protein function based on sequence similarity. These can range from identification of misannotation or other errors in a predicted function to accurate function prediction for an enzyme of entirely unknown function. Although GO annotation applies to any gene products, we focus here a describing our approach for hierarchical classification of enzymes in the Structure-Function Linkage Database (SFLD) (Akiva et al., Nucleic Acids Res 42(Database issue):D521-530, 2014) as a guide for informed utilisation of annotation transfer based on GO terms.

  19. Functional annotation of the human retinal pigment epithelium transcriptome

    PubMed Central

    Booij, Judith C; van Soest, Simone; Swagemakers, Sigrid MA; Essing, Anke HW; Verkerk, Annemieke JMH; van der Spek, Peter J; Gorgels, Theo GMF; Bergen, Arthur AB

    2009-01-01

    Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years) were laser dissected and used for 22k microarray studies (Agilent technologies). Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194) expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776) genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194) of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM) composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the RPE, and is useful for

  20. Functional Annotations of Paralogs: A Blessing and a Curse

    PubMed Central

    Zallot, Rémi; Harrison, Katherine J.; Kolaczkowski, Bryan; de Crécy-Lagard, Valérie

    2016-01-01

    Gene duplication followed by mutation is a classic mechanism of neofunctionalization, producing gene families with functional diversity. In some cases, a single point mutation is sufficient to change the substrate specificity and/or the chemistry performed by an enzyme, making it difficult to accurately separate enzymes with identical functions from homologs with different functions. Because sequence similarity is often used as a basis for assigning functional annotations to genes, non-isofunctional gene families pose a great challenge for genome annotation pipelines. Here we describe how integrating evolutionary and functional information such as genome context, phylogeny, metabolic reconstruction and signature motifs may be required to correctly annotate multifunctional families. These integrative analyses can also lead to the discovery of novel gene functions, as hints from specific subgroups can guide the functional characterization of other members of the family. We demonstrate how careful manual curation processes using comparative genomics can disambiguate subgroups within large multifunctional families and discover their functions. We present the COG0720 protein family as a case study. We also discuss strategies to automate this process to improve the accuracy of genome functional annotation pipelines. PMID:27618105

  1. Biocuration of functional annotation at the European nucleotide archive

    PubMed Central

    Gibson, Richard; Alako, Blaise; Amid, Clara; Cerdeño-Tárraga, Ana; Cleland, Iain; Goodgame, Neil; ten Hoopen, Petra; Jayathilaka, Suran; Kay, Simon; Leinonen, Rasko; Liu, Xin; Pallreddy, Swapna; Pakseresht, Nima; Rajan, Jeena; Rosselló, Marc; Silvester, Nicole; Smirnov, Dmitriy; Toribio, Ana Luisa; Vaughan, Daniel; Zalunin, Vadim; Cochrane, Guy

    2016-01-01

    The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is a repository for the submission, maintenance and presentation of nucleotide sequence data and related sample and experimental information. In this article we report on ENA in 2015 regarding general activity, notable published data sets and major achievements. This is followed by a focus on sustainable biocuration of functional annotation, an area which has particularly felt the pressure of sequencing growth. The importance of functional annotation, how it can be submitted and the shifting role of the biocurator in the context of increasing volumes of data are all discussed. PMID:26615190

  2. Assessment of protein set coherence using functional annotations

    PubMed Central

    Chagoyen, Monica; Carazo, Jose M; Pascual-Montano, Alberto

    2008-01-01

    Background Analysis of large-scale experimental datasets frequently produces one or more sets of proteins that are subsequently mined for functional interpretation and validation. To this end, a number of computational methods have been devised that rely on the analysis of functional annotations. Although current methods provide valuable information (e.g. significantly enriched annotations, pairwise functional similarities), they do not specifically measure the degree of homogeneity of a protein set. Results In this work we present a method that scores the degree of functional homogeneity, or coherence, of a set of proteins on the basis of the global similarity of their functional annotations. The method uses statistical hypothesis testing to assess the significance of the set in the context of the functional space of a reference set. As such, it can be used as a first step in the validation of sets expected to be homogeneous prior to further functional interpretation. Conclusion We evaluate our method by analysing known biologically relevant sets as well as random ones. The known relevant sets comprise macromolecular complexes, cellular components and pathways described for Saccharomyces cerevisiae, which are mostly significantly coherent. Finally, we illustrate the usefulness of our approach for validating 'functional modules' obtained from computational analysis of protein-protein interaction networks. Matlab code and supplementary data are available at PMID:18937846

  3. Functional Region Annotation of Liver CT Image Based on Vascular Tree

    PubMed Central

    Chen, Yufei; Wang, Gang

    2016-01-01

    Anatomical analysis of liver region is critical in diagnosis and treatment of liver diseases. The reports of liver region annotation are helpful for doctors to precisely evaluate liver system. One of the challenging issues is to annotate the functional regions of liver through analyzing Computed Tomography (CT) images. In this paper, we propose a vessel-tree-based liver annotation method for CT images. The first step of the proposed annotation method is to extract the liver region including vessels and tumors from the CT scans. And then a 3-dimensional thinning algorithm is applied to obtain the spatial skeleton and geometric structure of liver vessels. With the vessel skeleton, the topology of portal veins is further formulated by a directed acyclic graph with geometrical attributes. Finally, based on the topological graph, a hierarchical vascular tree is constructed to divide the liver into eight segments according to Couinaud classification theory and thereby annotate the functional regions. Abundant experimental results demonstrate that the proposed method is effective for precise liver annotation and helpful to support liver disease diagnosis. PMID:27891516

  4. Evolutionary Trace Annotation Server: automated enzyme function prediction in protein structures using 3D templates

    PubMed Central

    Matthew Ward, R.; Venner, Eric; Daines, Bryce; Murray, Stephen; Erdin, Serkan; Kristensen, David M.; Lichtarge, Olivier

    2009-01-01

    Summary:The Evolutionary Trace Annotation (ETA) Server predicts enzymatic activity. ETA starts with a structure of unknown function, such as those from structural genomics, and with no prior knowledge of its mechanism uses the phylogenetic Evolutionary Trace (ET) method to extract key functional residues and propose a function-associated 3D motif, called a 3D template. ETA then searches previously annotated structures for geometric template matches that suggest molecular and thus functional mimicry. In order to maximize the predictive value of these matches, ETA next applies distinctive specificity filters—evolutionary similarity, function plurality and match reciprocity. In large scale controls on enzymes, prediction coverage is 43% but the positive predictive value rises to 92%, thus minimizing false annotations. Users may modify any search parameter, including the template. ETA thus expands the ET suite for protein structure annotation, and can contribute to the annotation efforts of metaservers. Availability:The ETA Server is a web application available at http://mammoth.bcm.tmc.edu/eta/. Contact: lichtarge@bcm.edu PMID:19307237

  5. Optimizing high performance computing workflow for protein functional annotation.

    PubMed

    Stanberry, Larissa; Rekepalli, Bhanu; Liu, Yuan; Giblock, Paul; Higdon, Roger; Montague, Elizabeth; Broomall, William; Kolker, Natali; Kolker, Eugene

    2014-09-10

    Functional annotation of newly sequenced genomes is one of the major challenges in modern biology. With modern sequencing technologies, the protein sequence universe is rapidly expanding. Newly sequenced bacterial genomes alone contain over 7.5 million proteins. The rate of data generation has far surpassed that of protein annotation. The volume of protein data makes manual curation infeasible, whereas a high compute cost limits the utility of existing automated approaches. In this work, we present an improved and optmized automated workflow to enable large-scale protein annotation. The workflow uses high performance computing architectures and a low complexity classification algorithm to assign proteins into existing clusters of orthologous groups of proteins. On the basis of the Position-Specific Iterative Basic Local Alignment Search Tool the algorithm ensures at least 80% specificity and sensitivity of the resulting classifications. The workflow utilizes highly scalable parallel applications for classification and sequence alignment. Using Extreme Science and Engineering Discovery Environment supercomputers, the workflow processed 1,200,000 newly sequenced bacterial proteins. With the rapid expansion of the protein sequence universe, the proposed workflow will enable scientists to annotate big genome data.

  6. proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes

    PubMed Central

    Mende, Daniel R.; Letunic, Ivica; Huerta-Cepas, Jaime; Li, Simone S.; Forslund, Kristoffer; Sunagawa, Shinichi; Bork, Peer

    2017-01-01

    The availability of microbial genomes has opened many new avenues of research within microbiology. This has been driven primarily by comparative genomics approaches, which rely on accurate and consistent characterization of genomic sequences. It is nevertheless difficult to obtain consistent taxonomic and integrated functional annotations for defined prokaryotic clades. Thus, we developed proGenomes, a resource that provides user-friendly access to currently 25 038 high-quality genomes whose sequences and consistent annotations can be retrieved individually or by taxonomic clade. These genomes are assigned to 5306 consistent and accurate taxonomic species clusters based on previously established methodology. proGenomes also contains functional information for almost 80 million protein-coding genes, including a comprehensive set of general annotations and more focused annotations for carbohydrate-active enzymes and antibiotic resistance genes. Additionally, broad habitat information is provided for many genomes. All genomes and associated information can be downloaded by user-selected clade or multiple habitat-specific sets of representative genomes. We expect that the availability of high-quality genomes with comprehensive functional annotations will promote advances in clinical microbial genomics, functional evolution and other subfields of microbiology. proGenomes is available at http://progenomes.embl.de. PMID:28053165

  7. proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes.

    PubMed

    Mende, Daniel R; Letunic, Ivica; Huerta-Cepas, Jaime; Li, Simone S; Forslund, Kristoffer; Sunagawa, Shinichi; Bork, Peer

    2017-01-04

    The availability of microbial genomes has opened many new avenues of research within microbiology. This has been driven primarily by comparative genomics approaches, which rely on accurate and consistent characterization of genomic sequences. It is nevertheless difficult to obtain consistent taxonomic and integrated functional annotations for defined prokaryotic clades. Thus, we developed proGenomes, a resource that provides user-friendly access to currently 25 038 high-quality genomes whose sequences and consistent annotations can be retrieved individually or by taxonomic clade. These genomes are assigned to 5306 consistent and accurate taxonomic species clusters based on previously established methodology. proGenomes also contains functional information for almost 80 million protein-coding genes, including a comprehensive set of general annotations and more focused annotations for carbohydrate-active enzymes and antibiotic resistance genes. Additionally, broad habitat information is provided for many genomes. All genomes and associated information can be downloaded by user-selected clade or multiple habitat-specific sets of representative genomes. We expect that the availability of high-quality genomes with comprehensive functional annotations will promote advances in clinical microbial genomics, functional evolution and other subfields of microbiology. proGenomes is available at http://progenomes.embl.de.

  8. Eliciting the Functional Taxonomy from protein annotations and taxa

    PubMed Central

    Falda, Marco; Lavezzo, Enrico; Fontana, Paolo; Bianco, Luca; Berselli, Michele; Formentin, Elide; Toppo, Stefano

    2016-01-01

    The advances of omics technologies have triggered the production of an enormous volume of data coming from thousands of species. Meanwhile, joint international efforts like the Gene Ontology (GO) consortium have worked to provide functional information for a vast amount of proteins. With these data available, we have developed FunTaxIS, a tool that is the first attempt to infer functional taxonomy (i.e. how functions are distributed over taxa) combining functional and taxonomic information. FunTaxIS is able to define a taxon specific functional space by exploiting annotation frequencies in order to establish if a function can or cannot be used to annotate a certain species. The tool generates constraints between GO terms and taxa and then propagates these relations over the taxonomic tree and the GO graph. Since these constraints nearly cover the whole taxonomy, it is possible to obtain the mapping of a function over the taxonomy. FunTaxIS can be used to make functional comparative analyses among taxa, to detect improper associations between taxa and functions, and to discover how functional knowledge is either distributed or missing. A benchmark test set based on six different model species has been devised to get useful insights on the generated taxonomic rules. PMID:27534507

  9. Eliciting the Functional Taxonomy from protein annotations and taxa.

    PubMed

    Falda, Marco; Lavezzo, Enrico; Fontana, Paolo; Bianco, Luca; Berselli, Michele; Formentin, Elide; Toppo, Stefano

    2016-08-18

    The advances of omics technologies have triggered the production of an enormous volume of data coming from thousands of species. Meanwhile, joint international efforts like the Gene Ontology (GO) consortium have worked to provide functional information for a vast amount of proteins. With these data available, we have developed FunTaxIS, a tool that is the first attempt to infer functional taxonomy (i.e. how functions are distributed over taxa) combining functional and taxonomic information. FunTaxIS is able to define a taxon specific functional space by exploiting annotation frequencies in order to establish if a function can or cannot be used to annotate a certain species. The tool generates constraints between GO terms and taxa and then propagates these relations over the taxonomic tree and the GO graph. Since these constraints nearly cover the whole taxonomy, it is possible to obtain the mapping of a function over the taxonomy. FunTaxIS can be used to make functional comparative analyses among taxa, to detect improper associations between taxa and functions, and to discover how functional knowledge is either distributed or missing. A benchmark test set based on six different model species has been devised to get useful insights on the generated taxonomic rules.

  10. Bio301: A Web-Based EST Annotation Pipeline That Facilitates Functional Comparison Studies.

    PubMed

    Chen, Yen-Chen; Chen, Yun-Ching; Lin, Wen-Dar; Hsiao, Chung-Der; Chiu, Hung-Wen; Ho, Jan-Ming

    2012-01-01

    In this postgenomic era, a huge volume of information derived from expressed sequence tags (ESTs) has been constructed for functional description of gene expression profiles. Comparative studies have become more and more important to researchers of biology. In order to facilitate these comparative studies, we have constructed a user-friendly EST annotation pipeline with comparison tools on an integrated EST service website, Bio301. Bio301 includes regular EST preprocessing, BLAST similarity search, gene ontology (GO) annotation, statistics reporting, a graphical GO browsing interface, and microarray probe selection tools. In addition, Bio301 is equipped with statistical library comparison functions using multiple EST libraries based on GO annotations for mining meaningful biological information.

  11. Comprehensive functional annotation of 77 prostate cancer risk loci.

    PubMed

    Hazelett, Dennis J; Rhie, Suhn Kyong; Gaddis, Malaina; Yan, Chunli; Lakeland, Daniel L; Coetzee, Simon G; Henderson, Brian E; Noushmehr, Houtan; Cozen, Wendy; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F; Haiman, Christopher A; Lu, Wange; Farnham, Peggy J; Coetzee, Gerhard A

    2014-01-01

    Genome-wide association studies (GWAS) have revolutionized the field of cancer genetics, but the causal links between increased genetic risk and onset/progression of disease processes remain to be identified. Here we report the first step in such an endeavor for prostate cancer. We provide a comprehensive annotation of the 77 known risk loci, based upon highly correlated variants in biologically relevant chromatin annotations--we identified 727 such potentially functional SNPs. We also provide a detailed account of possible protein disruption, microRNA target sequence disruption and regulatory response element disruption of all correlated SNPs at r(2) ≥ 0.88%. 88% of the 727 SNPs fall within putative enhancers, and many alter critical residues in the response elements of transcription factors known to be involved in prostate biology. We define as risk enhancers those regions with enhancer chromatin biofeatures in prostate-derived cell lines with prostate-cancer correlated SNPs. To aid the identification of these enhancers, we performed genomewide ChIP-seq for H3K27-acetylation, a mark of actively engaged enhancers, as well as the transcription factor TCF7L2. We analyzed in depth three variants in risk enhancers, two of which show significantly altered androgen sensitivity in LNCaP cells. This includes rs4907792, that is in linkage disequilibrium (r(2) = 0.91) with an eQTL for NUDT11 (on the X chromosome) in prostate tissue, and rs10486567, the index SNP in intron 3 of the JAZF1 gene on chromosome 7. Rs4907792 is within a critical residue of a strong consensus androgen response element that is interrupted in the protective allele, resulting in a 56% decrease in its androgen sensitivity, whereas rs10486567 affects both NKX3-1 and FOXA-AR motifs where the risk allele results in a 39% increase in basal activity and a 28% fold-increase in androgen stimulated enhancer activity. Identification of such enhancer variants and their potential target genes represents a

  12. Visual annotation display (VLAD): a tool for finding functional themes in lists of genes.

    PubMed

    Richardson, Joel E; Bult, Carol J

    2015-10-01

    Experiments that employ genome scale technology platforms frequently result in lists of tens to thousands of genes with potential significance to a specific biological process or disease. Searching for biologically relevant connections among the genes or gene products in these lists is a common data analysis task. We have implemented a software application for uncovering functional themes in sets of genes based on their annotations to bio-ontologies, such as the gene ontology and the mammalian phenotype ontology. The application, called VisuaL Annotation Display (VLAD), performs a statistical analysis to test for the enrichment of ontology terms in a set of genes submitted by a researcher. The results for each analysis using VLAD includes a table of ontology terms, sorted in decreasing order of significance. Each row contains the term, statistics such as the number of annotated terms, the p value, etc., and the symbols of annotated genes. An accompanying graphical display shows portions of the ontology hierarchy, where node sizes are scaled based on p values. Although numerous ontology term enrichment programs already exist, VLAD is unique in that it allows users to upload their own annotation files and ontologies for customized term enrichment analyses, supports the analysis of multiple gene sets at once, provides interfaces to customize graphical output, and is tightly integrated with functional and biological details about mouse genes in the Mouse Genome Informatics (MGI) database. VLAD is available as a web-based application from the MGI web site (http://proto.informatics.jax.org/prototypes/vlad/).

  13. Protein function annotation by local binding site surface similarity.

    PubMed

    Spitzer, Russell; Cleves, Ann E; Varela, Rocco; Jain, Ajay N

    2014-04-01

    Hundreds of protein crystal structures exist for proteins whose function cannot be confidently determined from sequence similarity. Surflex-PSIM, a previously reported surface-based protein similarity algorithm, provides an alternative method for hypothesizing function for such proteins. The method now supports fully automatic binding site detection and is fast enough to screen comprehensive databases of protein binding sites. The binding site detection methodology was validated on apo/holo cognate protein pairs, correctly identifying 91% of ligand binding sites in holo structures and 88% in apo structures where corresponding sites existed. For correctly detected apo binding sites, the cognate holo site was the most similar binding site 87% of the time. PSIM was used to screen a set of proteins that had poorly characterized functions at the time of crystallization, but were later biochemically annotated. Using a fully automated protocol, this set of 8 proteins was screened against ∼60,000 ligand binding sites from the PDB. PSIM correctly identified functional matches that predated query protein biochemical annotation for five out of the eight query proteins. A panel of 12 currently unannotated proteins was also screened, resulting in a large number of statistically significant binding site matches, some of which suggest likely functions for the poorly characterized proteins.

  14. Exploring inconsistencies in genome-wide protein function annotations: a machine learning approach

    PubMed Central

    Andorf, Carson; Dobbs, Drena; Honavar, Vasant

    2007-01-01

    Background Incorrectly annotated sequence data are becoming more commonplace as databases increasingly rely on automated techniques for annotation. Hence, there is an urgent need for computational methods for checking consistency of such annotations against independent sources of evidence and detecting potential annotation errors. We show how a machine learning approach designed to automatically predict a protein's Gene Ontology (GO) functional class can be employed to identify potential gene annotation errors. Results In a set of 211 previously annotated mouse protein kinases, we found that 201 of the GO annotations returned by AmiGO appear to be inconsistent with the UniProt functions assigned to their human counterparts. In contrast, 97% of the predicted annotations generated using a machine learning approach were consistent with the UniProt annotations of the human counterparts, as well as with available annotations for these mouse protein kinases in the Mouse Kinome database. Conclusion We conjecture that most of our predicted annotations are, therefore, correct and suggest that the machine learning approach developed here could be routinely used to detect potential errors in GO annotations generated by high-throughput gene annotation projects. Editors Note : Authors from the original publication (Okazaki et al.: Nature 2002, 420:563–73) have provided their response to Andorf et al, directly following the correspondence. PMID:17683567

  15. Guidelines for the functional annotation of microRNAs using the Gene Ontology

    PubMed Central

    D'Eustachio, Peter; Smith, Jennifer R.; Zampetaki, Anna

    2016-01-01

    MicroRNA regulation of developmental and cellular processes is a relatively new field of study, and the available research data have not been organized to enable its inclusion in pathway and network analysis tools. The association of gene products with terms from the Gene Ontology is an effective method to analyze functional data, but until recently there has been no substantial effort dedicated to applying Gene Ontology terms to microRNAs. Consequently, when performing functional analysis of microRNA data sets, researchers have had to rely instead on the functional annotations associated with the genes encoding microRNA targets. In consultation with experts in the field of microRNA research, we have created comprehensive recommendations for the Gene Ontology curation of microRNAs. This curation manual will enable provision of a high-quality, reliable set of functional annotations for the advancement of microRNA research. Here we describe the key aspects of the work, including development of the Gene Ontology to represent this data, standards for describing the data, and guidelines to support curators making these annotations. The full microRNA curation guidelines are available on the GO Consortium wiki (http://wiki.geneontology.org/index.php/MicroRNA_GO_annotation_manual). PMID:26917558

  16. Combining heterogeneous data sources for accurate functional annotation of proteins

    PubMed Central

    2013-01-01

    Combining heterogeneous sources of data is essential for accurate prediction of protein function. The task is complicated by the fact that while sequence-based features can be readily compared across species, most other data are species-specific. In this paper, we present a multi-view extension to GOstruct, a structured-output framework for function annotation of proteins. The extended framework can learn from disparate data sources, with each data source provided to the framework in the form of a kernel. Our empirical results demonstrate that the multi-view framework is able to utilize all available information, yielding better performance than sequence-based models trained across species and models trained from collections of data within a given species. This version of GOstruct participated in the recent Critical Assessment of Functional Annotations (CAFA) challenge; since then we have significantly improved the natural language processing component of the method, which now provides performance that is on par with that provided by sequence information. The GOstruct framework is available for download at http://strut.sourceforge.net. PMID:23514123

  17. Annotation of Proteins of Unknown Function: Initial Enzyme Results

    PubMed Central

    McKay, Talia; Hart, Kaitlin; Horn, Alison; Kessler, Haeja; Dodge, Greg; Bardhi, Keti; Bardhi, Kostandina; Mills, Jeffrey L.; Bernstein, Herbert J.; Craig, Paul A.

    2015-01-01

    Working with a combination of ProMOL (a plugin for PyMOL that searches a library of enzymatic motifs for local structural homologs), BLAST and Pfam (servers that identify global sequence homologs), and Dali (a server that identifies global structural homologs), we have begun the process of assigning functional annotations to the approximately 3,500 structures in the Protein Data Bank that are currently classified as having “unknown function”. Using a limited template library of 388 motifs, over 500 promising in silico matches have been identified by ProMOL, among which 65 exceptionally good matches have been identified. The characteristics of the exceptionally good matches are discussed. PMID:25630330

  18. miRDB: an online resource for microRNA target prediction and functional annotations.

    PubMed

    Wong, Nathan; Wang, Xiaowei

    2015-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are extensively involved in many physiological and disease processes. One major challenge in miRNA studies is the identification of genes regulated by miRNAs. To this end, we have developed an online resource, miRDB (http://mirdb.org), for miRNA target prediction and functional annotations. Here, we describe recently updated features of miRDB, including 2.1 million predicted gene targets regulated by 6709 miRNAs. In addition to presenting precompiled prediction data, a new feature is the web server interface that allows submission of user-provided sequences for miRNA target prediction. In this way, users have the flexibility to study any custom miRNAs or target genes of interest. Another major update of miRDB is related to functional miRNA annotations. Although thousands of miRNAs have been identified, many of the reported miRNAs are not likely to play active functional roles or may even have been falsely identified as miRNAs from high-throughput studies. To address this issue, we have performed combined computational analyses and literature mining, and identified 568 and 452 functional miRNAs in humans and mice, respectively. These miRNAs, as well as associated functional annotations, are presented in the FuncMir Collection in miRDB.

  19. The Saccharomyces Genome Database: Gene Product Annotation of Function, Process, and Component.

    PubMed

    Cherry, J Michael

    2015-12-02

    An ontology is a highly structured form of controlled vocabulary. Each entry in the ontology is commonly called a term. These terms are used when talking about an annotation. However, each term has a definition that, like the definition of a word found within a dictionary, provides the complete usage and detailed explanation of the term. It is critical to consult a term's definition because the distinction between terms can be subtle. The use of ontologies in biology started as a way of unifying communication between scientific communities and to provide a standard dictionary for different topics, including molecular functions, biological processes, mutant phenotypes, chemical properties and structures. The creation of ontology terms and their definitions often requires debate to reach agreement but the result has been a unified descriptive language used to communicate knowledge. In addition to terms and definitions, ontologies require a relationship used to define the type of connection between terms. In an ontology, a term can have more than one parent term, the term above it in an ontology, as well as more than one child, the term below it in the ontology. Many ontologies are used to construct annotations in the Saccharomyces Genome Database (SGD), as in all modern biological databases; however, Gene Ontology (GO), a descriptive system used to categorize gene function, is the most extensively used ontology in SGD annotations. Examples included in this protocol illustrate the structure and features of this ontology.

  20. The Protein Information Resource: an integrated public resource of functional annotation of proteins

    PubMed Central

    Wu, Cathy H.; Huang, Hongzhan; Arminski, Leslie; Castro-Alvear, Jorge; Chen, Yongxing; Hu, Zhang-Zhi; Ledley, Robert S.; Lewis, Kali C.; Mewes, Hans-Werner; Orcutt, Bruce C.; Suzek, Baris E.; Tsugita, Akira; Vinayaka, C. R.; Yeh, Lai-Su L.; Zhang, Jian; Barker, Winona C.

    2002-01-01

    The Protein Information Resource (PIR) serves as an integrated public resource of functional annotation of protein data to support genomic/proteomic research and scientific discovery. The PIR, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Information Database (JIPID), produces the PIR-International Protein Sequence Database (PSD), the major annotated protein sequence database in the public domain, containing about 250 000 proteins. To improve protein annotation and the coverage of experimentally validated data, a bibliography submission system is developed for scientists to submit, categorize and retrieve literature information. Comprehensive protein information is available from iProClass, which includes family classification at the superfamily, domain and motif levels, structural and functional features of proteins, as well as cross-references to over 40 biological databases. To provide timely and comprehensive protein data with source attribution, we have introduced a non-redundant reference protein database, PIR-NREF. The database consists of about 800 000 proteins collected from PIR-PSD, SWISS-PROT, TrEMBL, GenPept, RefSeq and PDB, with composite protein names and literature data. To promote database interoperability, we provide XML data distribution and open database schema, and adopt common ontologies. The PIR web site (http://pir.georgetown.edu/) features data mining and sequence analysis tools for information retrieval and functional identification of proteins based on both sequence and annotation information. The PIR databases and other files are also available by FTP (ftp://nbrfa.georgetown.edu/pir_databases). PMID:11752247

  1. Improving functional annotation for industrial microbes: a case study with Pichia pastoris

    PubMed Central

    Dikicioglu, Duygu; Wood, Valerie; Rutherford, Kim M.; McDowall, Mark D.; Oliver, Stephen G.

    2014-01-01

    The research communities studying microbial model organisms, such as Escherichia coli or Saccharomyces cerevisiae, are well served by model organism databases that have extensive functional annotation. However, this is not true of many industrial microbes that are used widely in biotechnology. In this Opinion piece, we use Pichia (Komagataella) pastoris to illustrate the limitations of the available annotation. We consider the resources that can be implemented in the short term both to improve Gene Ontology (GO) annotation coverage based on annotation transfer, and to establish curation pipelines for the literature corpus of this organism. PMID:24929579

  2. Incorporating Functional Annotations for Fine-Mapping Causal Variants in a Bayesian Framework Using Summary Statistics.

    PubMed

    Chen, Wenan; McDonnell, Shannon K; Thibodeau, Stephen N; Tillmans, Lori S; Schaid, Daniel J

    2016-11-01

    Functional annotations have been shown to improve both the discovery power and fine-mapping accuracy in genome-wide association studies. However, the optimal strategy to incorporate the large number of existing annotations is still not clear. In this study, we propose a Bayesian framework to incorporate functional annotations in a systematic manner. We compute the maximum a posteriori solution and use cross validation to find the optimal penalty parameters. By extending our previous fine-mapping method CAVIARBF into this framework, we require only summary statistics as input. We also derived an exact calculation of Bayes factors using summary statistics for quantitative traits, which is necessary when a large proportion of trait variance is explained by the variants of interest, such as in fine mapping expression quantitative trait loci (eQTL). We compared the proposed method with PAINTOR using different strategies to combine annotations. Simulation results show that the proposed method achieves the best accuracy in identifying causal variants among the different strategies and methods compared. We also find that for annotations with moderate effects from a large annotation pool, screening annotations individually and then combining the top annotations can produce overly optimistic results. We applied these methods on two real data sets: a meta-analysis result of lipid traits and a cis-eQTL study of normal prostate tissues. For the eQTL data, incorporating annotations significantly increased the number of potential causal variants with high probabilities.

  3. CATH FunFHMMer web server: protein functional annotations using functional family assignments.

    PubMed

    Das, Sayoni; Sillitoe, Ian; Lee, David; Lees, Jonathan G; Dawson, Natalie L; Ward, John; Orengo, Christine A

    2015-07-01

    The widening function annotation gap in protein databases and the increasing number and diversity of the proteins being sequenced presents new challenges to protein function prediction methods. Multidomain proteins complicate the protein sequence-structure-function relationship further as new combinations of domains can expand the functional repertoire, creating new proteins and functions. Here, we present the FunFHMMer web server, which provides Gene Ontology (GO) annotations for query protein sequences based on the functional classification of the domain-based CATH-Gene3D resource. Our server also provides valuable information for the prediction of functional sites. The predictive power of FunFHMMer has been validated on a set of 95 proteins where FunFHMMer performs better than BLAST, Pfam and CDD. Recent validation by an independent international competition ranks FunFHMMer as one of the top function prediction methods in predicting GO annotations for both the Biological Process and Molecular Function Ontology. The FunFHMMer web server is available at http://www.cathdb.info/search/by_funfhmmer.

  4. Protein function prediction and annotation in an integrated environment powered by web services (AFAWE).

    PubMed

    Jöcker, Anika; Hoffmann, Fabian; Groscurth, Andreas; Schoof, Heiko

    2008-10-15

    Many sequenced genes are mainly annotated through automatic transfer of annotation from similar sequences. Manual comparison of results or intermediate results from different tools can help avoid wrong annotations and give hints to the function of a gene even if none of the automated tools could return any result. AFAWE simplifies the task of manual functional annotation by running different tools and workflows for automatic function prediction and displaying the results in a way that facilitates comparison. Because all programs are executed as web services, AFAWE is easily extensible and can directly query primary databases, thereby always using the most up-to-date data sources. Visual filters help to distinguish trustworthy results from non-significant results. Furthermore, an interface to add detailed manual annotation to each gene is provided, which can be displayed to other users.

  5. GO-FAANG meeting: A gathering on functional annotation of animal genomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The FAANG (Functional Annotation of Animal Genomes) Consortium recently held a Gathering On FAANG (GO-FAANG) Workshop in Washington, DC on October 7-8, 2015. This consortium is a grass-roots organization formed to advance the annotation of newly assembled genomes of non-model organisms (www.faang.or...

  6. Identifying functionally important cis-peptide containing segments in proteins and their utility in molecular function annotation.

    PubMed

    Das, Sreetama; Ramakumar, Suryanarayanarao; Pal, Debnath

    2014-12-01

    Cis-peptide embedded segments are rare in proteins but often highlight their important role in molecular function when they do occur. The high evolutionary conservation of these segments illustrates this observation almost universally, although no attempt has been made to systematically use this information for the purpose of function annotation. In the present study, we demonstrate how geometric clustering and level-specific Gene Ontology molecular-function terms (also known as annotations) can be used in a statistically significant manner to identify cis-embedded segments in a protein linked to its molecular function. The present study identifies novel cis-peptide fragments, which are subsequently used for fragment-based function annotation. Annotation recall benchmarks interpreted using the receiver-operator characteristic plot returned an area-under-curve > 0.9, corroborating the utility of the annotation method. In addition, we identified cis-peptide fragments occurring in conjunction with functionally important trans-peptide fragments, providing additional insights into molecular function. We further illustrate the applicability of our method in function annotation where homology-based annotation transfer is not possible. The findings of the present study add to the repertoire of function annotation approaches and also facilitate engineering, design and allied studies around the cis-peptide neighborhood of proteins.

  7. Recurrent use of evolutionary importance for functional annotation of proteins based on local structural similarity.

    PubMed

    Kristensen, David M; Chen, Brian Y; Fofanov, Viacheslav Y; Ward, R Matthew; Lisewski, Andreas Martin; Kimmel, Marek; Kavraki, Lydia E; Lichtarge, Olivier

    2006-06-01

    The annotation of protein function has not kept pace with the exponential growth of raw sequence and structure data. An emerging solution to this problem is to identify 3D motifs or templates in protein structures that are necessary and sufficient determinants of function. Here, we demonstrate the recurrent use of evolutionary trace information to construct such 3D templates for enzymes, search for them in other structures, and distinguish true from spurious matches. Serine protease templates built from evolutionarily important residues distinguish between proteases and other proteins nearly as well as the classic Ser-His-Asp catalytic triad. In 53 enzymes spanning 33 distinct functions, an automated pipeline identifies functionally related proteins with an average positive predictive power of 62%, including correct matches to proteins with the same function but with low sequence identity (the average identity for some templates is only 17%). Although these template building, searching, and match classification strategies are not yet optimized, their sequential implementation demonstrates a functional annotation pipeline which does not require experimental information, but only local molecular mimicry among a small number of evolutionarily important residues.

  8. Expression profiling and functional annotation of noncoding genes across 11 distinct organs in rat development

    PubMed Central

    Wen, Zhuo; Chen, Geng; Zhu, Sibo; Zhu, Jinhang; Li, Bin; Song, Yunjie; Li, Suqing; Shi, Leming; Zheng, Yuanting; Li, Menglong

    2016-01-01

    Accumulating evidence suggests that noncoding RNAs (ncRNAs) have important regulatory functions. However, lacking of functional annotations for ncRNAs hampered us from carrying out the subsequent functional or predictive research. Here we dissected the expression profiles of 3,458 rat noncoding genes using rat bodymap RNA-sequencing data consisting of 11 solid organs over four developmental stages (juvenile, adolescent, adult and aged) from both sexes, and conducted a comprehensive analysis of differentially expressed noncoding genes (DEnGs) between various conditions. We then constructed a co-expression network between protein-coding and noncoding genes to infer biological functions of noncoding genes. Modules of interest were linked to online databases including DAVID for functional annotation and pathway analysis. Our results indicated that noncoding genes are functionally enriched through pathways similar to those of protein-coding genes. Terms about development of the immune system were enriched with genes from age-related modules, whereas terms about sexual reproduction were enriched with genes in sex-related modules. We also built connection networks on some significant modules to visualize the interactions and regulatory relationship between protein-coding and noncoding genes. Our study could improve our understanding and facilitate a deeper investigation on organ/age/sex-related regulatory events of noncoding genes, which may lead to a superior preclinical model for drug development and translational medicine. PMID:27934932

  9. Assigning biological functions to rice genes by genome annotation, expression analysis and mutagenesis.

    PubMed

    Jiang, Shu-Ye; Ramachandran, Srinivasan

    2010-12-01

    Rice is the first cereal genome to be completely sequenced. Since the completion of its genome sequencing, considerable progress has been made in multiple areas including the whole genome annotation, gene expression profiling, mutant collection, etc. Here, we summarize the current status of rice genome annotation and review the methodology of assigning biological functions to hundreds of thousands of rice genes as well as discuss the major limitations and the future perspective in rice functional genomics. Available data analysis shows that the rice genome encodes around 32,000 protein-coding genes. Expression analysis revealed at least 31,000 genes with expression evidence from full-length cDNA/EST collection or other transcript profiling. In addition, we have summarized various strategies to generate mutant population including natural, physical, chemical, T-DNA, transposon/retrotransposon or gene silencing based mutagenesis. Currently, more than 1 million of mutants have been generated and 27,551 of them have their flanking sequence tags. To assign biological functions to hundreds of thousands of rice genes, global co-operations are required, various genetic resources should be more easily accessible and diverse data from transcriptomics, proteomics, epigenetics, comparative genomics and bioinformatics should be integrated to better understand the functions of these genes and their regulatory mechanisms.

  10. Annotating the Function of the Human Genome with Gene Ontology and Disease Ontology

    PubMed Central

    Hu, Yang; Zhou, Wenyang; Ren, Jun; Dong, Lixiang

    2016-01-01

    Increasing evidences indicated that function annotation of human genome in molecular level and phenotype level is very important for systematic analysis of genes. In this study, we presented a framework named Gene2Function to annotate Gene Reference into Functions (GeneRIFs), in which each functional description of GeneRIFs could be annotated by a text mining tool Open Biomedical Annotator (OBA), and each Entrez gene could be mapped to Human Genome Organisation Gene Nomenclature Committee (HGNC) gene symbol. After annotating all the records about human genes of GeneRIFs, 288,869 associations between 13,148 mRNAs and 7,182 terms, 9,496 associations between 948 microRNAs and 533 terms, and 901 associations between 139 long noncoding RNAs (lncRNAs) and 297 terms were obtained as a comprehensive annotation resource of human genome. High consistency of term frequency of individual gene (Pearson correlation = 0.6401, p = 2.2e − 16) and gene frequency of individual term (Pearson correlation = 0.1298, p = 3.686e − 14) in GeneRIFs and GOA shows our annotation resource is very reliable. PMID:27635398

  11. Annotating the Function of the Human Genome with Gene Ontology and Disease Ontology.

    PubMed

    Hu, Yang; Zhou, Wenyang; Ren, Jun; Dong, Lixiang; Wang, Yadong; Jin, Shuilin; Cheng, Liang

    2016-01-01

    Increasing evidences indicated that function annotation of human genome in molecular level and phenotype level is very important for systematic analysis of genes. In this study, we presented a framework named Gene2Function to annotate Gene Reference into Functions (GeneRIFs), in which each functional description of GeneRIFs could be annotated by a text mining tool Open Biomedical Annotator (OBA), and each Entrez gene could be mapped to Human Genome Organisation Gene Nomenclature Committee (HGNC) gene symbol. After annotating all the records about human genes of GeneRIFs, 288,869 associations between 13,148 mRNAs and 7,182 terms, 9,496 associations between 948 microRNAs and 533 terms, and 901 associations between 139 long noncoding RNAs (lncRNAs) and 297 terms were obtained as a comprehensive annotation resource of human genome. High consistency of term frequency of individual gene (Pearson correlation = 0.6401, p = 2.2e - 16) and gene frequency of individual term (Pearson correlation = 0.1298, p = 3.686e - 14) in GeneRIFs and GOA shows our annotation resource is very reliable.

  12. High-throughput functional annotation and data mining with the Blast2GO suite

    PubMed Central

    Götz, Stefan; García-Gómez, Juan Miguel; Terol, Javier; Williams, Tim D.; Nagaraj, Shivashankar H.; Nueda, María José; Robles, Montserrat; Talón, Manuel; Dopazo, Joaquín; Conesa, Ana

    2008-01-01

    Functional genomics technologies have been widely adopted in the biological research of both model and non-model species. An efficient functional annotation of DNA or protein sequences is a major requirement for the successful application of these approaches as functional information on gene products is often the key to the interpretation of experimental results. Therefore, there is an increasing need for bioinformatics resources which are able to cope with large amount of sequence data, produce valuable annotation results and are easily accessible to laboratories where functional genomics projects are being undertaken. We present the Blast2GO suite as an integrated and biologist-oriented solution for the high-throughput and automatic functional annotation of DNA or protein sequences based on the Gene Ontology vocabulary. The most outstanding Blast2GO features are: (i) the combination of various annotation strategies and tools controlling type and intensity of annotation, (ii) the numerous graphical features such as the interactive GO-graph visualization for gene-set function profiling or descriptive charts, (iii) the general sequence management features and (iv) high-throughput capabilities. We used the Blast2GO framework to carry out a detailed analysis of annotation behaviour through homology transfer and its impact in functional genomics research. Our aim is to offer biologists useful information to take into account when addressing the task of functionally characterizing their sequence data. PMID:18445632

  13. Information theory applied to the sparse gene ontology annotation network to predict novel gene function

    PubMed Central

    Tao, Ying; Li, Jianrong

    2010-01-01

    Motivation Despite advances in the gene annotation process, the functions of a large portion of the gene products remain insufficiently characterized. In addition, the “in silico” prediction of novel Gene Ontology (GO) annotations for partially characterized gene functions or processes is highly dependent on reverse genetic or function genomics approaches. Results We propose a novel approach, Information Theory-based Semantic Similarity (ITSS), to automatically predict molecular functions of genes based on Gene Ontology annotations. We have demonstrated using a 10-fold cross-validation that the ITSS algorithm obtains prediction accuracies (Precision 97%, Recall 77%) comparable to other machine learning algorithms when applied to similarly dense annotated portions of the GO datasets. In addition, such method can generate highly accurate predictions in sparsely annotated portions of GO, in which previous algorithm failed to do so. As a result, our technique generates an order of magnitude more gene function predictions than previous methods. Further, this paper presents the first historical rollback validation for the predicted GO annotations, which may represent more realistic conditions for an evaluation than generally used cross-validations type of evaluations. By manually assessing a random sample of 100 predictions conducted in a historical roll-back evaluation, we estimate that a minimum precision of 51% (95% confidence interval: 43%–58%) can be achieved for the human GO Annotation file dated 2003. Availability The program is available on request. The 97,732 positive predictions of novel gene annotations from the 2005 GO Annotation dataset are available at http://phenos.bsd.uchicago.edu/mphenogo/prediction_result_2005.txt. PMID:17646340

  14. Measuring semantic similarities by combining gene ontology annotations and gene co-function networks

    DOE PAGES

    Peng, Jiajie; Uygun, Sahra; Kim, Taehyong; ...

    2015-02-14

    Background: Gene Ontology (GO) has been used widely to study functional relationships between genes. The current semantic similarity measures rely only on GO annotations and GO structure. This limits the power of GO-based similarity because of the limited proportion of genes that are annotated to GO in most organisms. Results: We introduce a novel approach called NETSIM (network-based similarity measure) that incorporates information from gene co-function networks in addition to using the GO structure and annotations. Using metabolic reaction maps of yeast, Arabidopsis, and human, we demonstrate that NETSIM can improve the accuracy of GO term similarities. We also demonstratemore » that NETSIM works well even for genomes with sparser gene annotation data. We applied NETSIM on large Arabidopsis gene families such as cytochrome P450 monooxygenases to group the members functionally and show that this grouping could facilitate functional characterization of genes in these families. Conclusions: Using NETSIM as an example, we demonstrated that the performance of a semantic similarity measure could be significantly improved after incorporating genome-specific information. NETSIM incorporates both GO annotations and gene co-function network data as a priori knowledge in the model. Therefore, functional similarities of GO terms that are not explicitly encoded in GO but are relevant in a taxon-specific manner become measurable when GO annotations are limited.« less

  15. Measuring semantic similarities by combining gene ontology annotations and gene co-function networks

    SciTech Connect

    Peng, Jiajie; Uygun, Sahra; Kim, Taehyong; Wang, Yadong; Rhee, Seung Y.; Chen, Jin

    2015-02-14

    Background: Gene Ontology (GO) has been used widely to study functional relationships between genes. The current semantic similarity measures rely only on GO annotations and GO structure. This limits the power of GO-based similarity because of the limited proportion of genes that are annotated to GO in most organisms. Results: We introduce a novel approach called NETSIM (network-based similarity measure) that incorporates information from gene co-function networks in addition to using the GO structure and annotations. Using metabolic reaction maps of yeast, Arabidopsis, and human, we demonstrate that NETSIM can improve the accuracy of GO term similarities. We also demonstrate that NETSIM works well even for genomes with sparser gene annotation data. We applied NETSIM on large Arabidopsis gene families such as cytochrome P450 monooxygenases to group the members functionally and show that this grouping could facilitate functional characterization of genes in these families. Conclusions: Using NETSIM as an example, we demonstrated that the performance of a semantic similarity measure could be significantly improved after incorporating genome-specific information. NETSIM incorporates both GO annotations and gene co-function network data as a priori knowledge in the model. Therefore, functional similarities of GO terms that are not explicitly encoded in GO but are relevant in a taxon-specific manner become measurable when GO annotations are limited.

  16. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation.

    PubMed

    O'Leary, Nuala A; Wright, Mathew W; Brister, J Rodney; Ciufo, Stacy; Haddad, Diana; McVeigh, Rich; Rajput, Bhanu; Robbertse, Barbara; Smith-White, Brian; Ako-Adjei, Danso; Astashyn, Alexander; Badretdin, Azat; Bao, Yiming; Blinkova, Olga; Brover, Vyacheslav; Chetvernin, Vyacheslav; Choi, Jinna; Cox, Eric; Ermolaeva, Olga; Farrell, Catherine M; Goldfarb, Tamara; Gupta, Tripti; Haft, Daniel; Hatcher, Eneida; Hlavina, Wratko; Joardar, Vinita S; Kodali, Vamsi K; Li, Wenjun; Maglott, Donna; Masterson, Patrick; McGarvey, Kelly M; Murphy, Michael R; O'Neill, Kathleen; Pujar, Shashikant; Rangwala, Sanjida H; Rausch, Daniel; Riddick, Lillian D; Schoch, Conrad; Shkeda, Andrei; Storz, Susan S; Sun, Hanzhen; Thibaud-Nissen, Francoise; Tolstoy, Igor; Tully, Raymond E; Vatsan, Anjana R; Wallin, Craig; Webb, David; Wu, Wendy; Landrum, Melissa J; Kimchi, Avi; Tatusova, Tatiana; DiCuccio, Michael; Kitts, Paul; Murphy, Terence D; Pruitt, Kim D

    2016-01-04

    The RefSeq project at the National Center for Biotechnology Information (NCBI) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The RefSeq project leverages the data submitted to the International Nucleotide Sequence Database Collaboration (INSDC) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non-redundant reference sequences. The RefSeq project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55,000 organisms (>4800 viruses, >40,000 prokaryotes and >10,000 eukaryotes; RefSeq release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the RefSeq project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of RefSeq data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available RNA-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management.

  17. Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation

    PubMed Central

    O'Leary, Nuala A.; Wright, Mathew W.; Brister, J. Rodney; Ciufo, Stacy; Haddad, Diana; McVeigh, Rich; Rajput, Bhanu; Robbertse, Barbara; Smith-White, Brian; Ako-Adjei, Danso; Astashyn, Alexander; Badretdin, Azat; Bao, Yiming; Blinkova, Olga; Brover, Vyacheslav; Chetvernin, Vyacheslav; Choi, Jinna; Cox, Eric; Ermolaeva, Olga; Farrell, Catherine M.; Goldfarb, Tamara; Gupta, Tripti; Haft, Daniel; Hatcher, Eneida; Hlavina, Wratko; Joardar, Vinita S.; Kodali, Vamsi K.; Li, Wenjun; Maglott, Donna; Masterson, Patrick; McGarvey, Kelly M.; Murphy, Michael R.; O'Neill, Kathleen; Pujar, Shashikant; Rangwala, Sanjida H.; Rausch, Daniel; Riddick, Lillian D.; Schoch, Conrad; Shkeda, Andrei; Storz, Susan S.; Sun, Hanzhen; Thibaud-Nissen, Francoise; Tolstoy, Igor; Tully, Raymond E.; Vatsan, Anjana R.; Wallin, Craig; Webb, David; Wu, Wendy; Landrum, Melissa J.; Kimchi, Avi; Tatusova, Tatiana; DiCuccio, Michael; Kitts, Paul; Murphy, Terence D.; Pruitt, Kim D.

    2016-01-01

    The RefSeq project at the National Center for Biotechnology Information (NCBI) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The RefSeq project leverages the data submitted to the International Nucleotide Sequence Database Collaboration (INSDC) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non-redundant reference sequences. The RefSeq project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55 000 organisms (>4800 viruses, >40 000 prokaryotes and >10 000 eukaryotes; RefSeq release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the RefSeq project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of RefSeq data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available RNA-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management. PMID:26553804

  18. New in protein structure and function annotation: hotspots, single nucleotide polymorphisms and the 'Deep Web'.

    PubMed

    Bromberg, Yana; Yachdav, Guy; Ofran, Yanay; Schneider, Reinhard; Rost, Burkhard

    2009-05-01

    The rapidly increasing quantity of protein sequence data continues to widen the gap between available sequences and annotations. Comparative modeling suggests some aspects of the 3D structures of approximately half of all known proteins; homology- and network-based inferences annotate some aspect of function for a similar fraction of the proteome. For most known protein sequences, however, there is detailed knowledge about neither their function nor their structure. Comprehensive efforts towards the expert curation of sequence annotations have failed to meet the demand of the rapidly increasing number of available sequences. Only the automated prediction of protein function in the absence of homology can close the gap between available sequences and annotations in the foreseeable future. This review focuses on two novel methods for automated annotation, and briefly presents an outlook on how modern web software may revolutionize the field of protein sequence annotation. First, predictions of protein binding sites and functional hotspots, and the evolution of these into the most successful type of prediction of protein function from sequence will be discussed. Second, a new tool, comprehensive in silico mutagenesis, which contributes important novel predictions of function and at the same time prepares for the onset of the next sequencing revolution, will be described. While these two new sub-fields of protein prediction represent the breakthroughs that have been achieved methodologically, it will then be argued that a different development might further change the way biomedical researchers benefit from annotations: modern web software can connect the worldwide web in any browser with the 'Deep Web' (ie, proprietary data resources). The availability of this direct connection, and the resulting access to a wealth of data, may impact drug discovery and development more than any existing method that contributes to protein annotation.

  19. Mercator: a fast and simple web server for genome scale functional annotation of plant sequence data.

    PubMed

    Lohse, Marc; Nagel, Axel; Herter, Thomas; May, Patrick; Schroda, Michael; Zrenner, Rita; Tohge, Takayuki; Fernie, Alisdair R; Stitt, Mark; Usadel, Björn

    2014-05-01

    Next-generation technologies generate an overwhelming amount of gene sequence data. Efficient annotation tools are required to make these data amenable to functional genomics analyses. The Mercator pipeline automatically assigns functional terms to protein or nucleotide sequences. It uses the MapMan 'BIN' ontology, which is tailored for functional annotation of plant 'omics' data. The classification procedure performs parallel sequence searches against reference databases, compiles the results and computes the most likely MapMan BINs for each query. In the current version, the pipeline relies on manually curated reference classifications originating from the three reference organisms (Arabidopsis, Chlamydomonas, rice), various other plant species that have a reviewed SwissProt annotation, and more than 2000 protein domain and family profiles at InterPro, CDD and KOG. Functional annotations predicted by Mercator achieve accuracies above 90% when benchmarked against manual annotation. In addition to mapping files for direct use in the visualization software MapMan, Mercator provides graphical overview charts, detailed annotation information in a convenient web browser interface and a MapMan-to-GO translation table to export results as GO terms. Mercator is available free of charge via http://mapman.gabipd.org/web/guest/app/Mercator.

  20. ORCAN-a web-based meta-server for real-time detection and functional annotation of orthologs.

    PubMed

    Zielezinski, Andrzej; Dziubek, Michal; Sliski, Jan; Karlowski, Wojciech M

    2017-01-05

    ORCAN (ORtholog sCANner) is a web-based meta-server for one-click evolutionary and functional annotation of protein sequences. The server combines information from the most popular orthology-prediction resources, including four tools and four online databases. Functional annotation utilizes five additional comparisons between the query and identified homologs, including: sequence similarity, protein domain architectures, functional motifs, Gene Ontology term assignments and a list of associated articles. Furthermore, the server uses a plurality-based rating system to evaluate the orthology relationships and to rank the reference proteins by their evolutionary and functional relevance to the query. Using a dataset of ∼1 million true yeast orthologs as a sample reference set, we show that combining multiple orthology-prediction tools in ORCAN increases the sensitivity and precision by 1-2 percent points.

  1. Integrative Tissue-Specific Functional Annotations in the Human Genome Provide Novel Insights on Many Complex Traits and Improve Signal Prioritization in Genome Wide Association Studies.

    PubMed

    Lu, Qiongshi; Powles, Ryan Lee; Wang, Qian; He, Beixin Julie; Zhao, Hongyu

    2016-04-01

    Extensive efforts have been made to understand genomic function through both experimental and computational approaches, yet proper annotation still remains challenging, especially in non-coding regions. In this manuscript, we introduce GenoSkyline, an unsupervised learning framework to predict tissue-specific functional regions through integrating high-throughput epigenetic annotations. GenoSkyline successfully identified a variety of non-coding regulatory machinery including enhancers, regulatory miRNA, and hypomethylated transposable elements in extensive case studies. Integrative analysis of GenoSkyline annotations and results from genome-wide association studies (GWAS) led to novel biological insights on the etiologies of a number of human complex traits. We also explored using tissue-specific functional annotations to prioritize GWAS signals and predict relevant tissue types for each risk locus. Brain and blood-specific annotations led to better prioritization performance for schizophrenia than standard GWAS p-values and non-tissue-specific annotations. As for coronary artery disease, heart-specific functional regions was highly enriched of GWAS signals, but previously identified risk loci were found to be most functional in other tissues, suggesting a substantial proportion of still undetected heart-related loci. In summary, GenoSkyline annotations can guide genetic studies at multiple resolutions and provide valuable insights in understanding complex diseases. GenoSkyline is available at http://genocanyon.med.yale.edu/GenoSkyline.

  2. Integrative Tissue-Specific Functional Annotations in the Human Genome Provide Novel Insights on Many Complex Traits and Improve Signal Prioritization in Genome Wide Association Studies

    PubMed Central

    Wang, Qian; He, Beixin Julie; Zhao, Hongyu

    2016-01-01

    Extensive efforts have been made to understand genomic function through both experimental and computational approaches, yet proper annotation still remains challenging, especially in non-coding regions. In this manuscript, we introduce GenoSkyline, an unsupervised learning framework to predict tissue-specific functional regions through integrating high-throughput epigenetic annotations. GenoSkyline successfully identified a variety of non-coding regulatory machinery including enhancers, regulatory miRNA, and hypomethylated transposable elements in extensive case studies. Integrative analysis of GenoSkyline annotations and results from genome-wide association studies (GWAS) led to novel biological insights on the etiologies of a number of human complex traits. We also explored using tissue-specific functional annotations to prioritize GWAS signals and predict relevant tissue types for each risk locus. Brain and blood-specific annotations led to better prioritization performance for schizophrenia than standard GWAS p-values and non-tissue-specific annotations. As for coronary artery disease, heart-specific functional regions was highly enriched of GWAS signals, but previously identified risk loci were found to be most functional in other tissues, suggesting a substantial proportion of still undetected heart-related loci. In summary, GenoSkyline annotations can guide genetic studies at multiple resolutions and provide valuable insights in understanding complex diseases. GenoSkyline is available at http://genocanyon.med.yale.edu/GenoSkyline. PMID:27058395

  3. eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences.

    PubMed

    Huerta-Cepas, Jaime; Szklarczyk, Damian; Forslund, Kristoffer; Cook, Helen; Heller, Davide; Walter, Mathias C; Rattei, Thomas; Mende, Daniel R; Sunagawa, Shinichi; Kuhn, Michael; Jensen, Lars Juhl; von Mering, Christian; Bork, Peer

    2016-01-04

    eggNOG is a public resource that provides Orthologous Groups (OGs) of proteins at different taxonomic levels, each with integrated and summarized functional annotations. Developments since the latest public release include changes to the algorithm for creating OGs across taxonomic levels, making nested groups hierarchically consistent. This allows for a better propagation of functional terms across nested OGs and led to the novel annotation of 95 890 previously uncharacterized OGs, increasing overall annotation coverage from 67% to 72%. The functional annotations of OGs have been expanded to also provide Gene Ontology terms, KEGG pathways and SMART/Pfam domains for each group. Moreover, eggNOG now provides pairwise orthology relationships within OGs based on analysis of phylogenetic trees. We have also incorporated a framework for quickly mapping novel sequences to OGs based on precomputed HMM profiles. Finally, eggNOG version 4.5 incorporates a novel data set spanning 2605 viral OGs, covering 5228 proteins from 352 viral proteomes. All data are accessible for bulk downloading, as a web-service, and through a completely redesigned web interface. The new access points provide faster searches and a number of new browsing and visualization capabilities, facilitating the needs of both experts and less experienced users. eggNOG v4.5 is available at http://eggnog.embl.de.

  4. Expression profiling of hypothetical genes in Desulfovibrio vulgaris leads to improved functional annotation

    PubMed Central

    Elias, Dwayne A.; Mukhopadhyay, Aindrila; Joachimiak, Marcin P.; Drury, Elliott C.; Redding, Alyssa M.; Yen, Huei-Che B.; Fields, Matthew W.; Hazen, Terry C.; Arkin, Adam P.; Keasling, Jay D.; Wall, Judy D.

    2009-01-01

    Hypothetical (HyP) and conserved HyP genes account for >30% of sequenced bacterial genomes. For the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough, 347 of the 3634 genes were annotated as conserved HyP (9.5%) along with 887 HyP genes (24.4%). Given the large fraction of the genome, it is plausible that some of these genes serve critical cellular roles. The study goals were to determine which genes were expressed and provide a more functionally based annotation. To accomplish this, expression profiles of 1234 HyP and conserved genes were used from transcriptomic datasets of 11 environmental stresses, complemented with shotgun LC–MS/MS and AMT tag proteomic data. Genes were divided into putatively polycistronic operons and those predicted to be monocistronic, then classified by basal expression levels and grouped according to changes in expression for one or multiple stresses. One thousand two hundred and twelve of these genes were transcribed with 786 producing detectable proteins. There was no evidence for expression of 17 predicted genes. Except for the latter, monocistronic gene annotation was expanded using the above criteria along with matching Clusters of Orthologous Groups. Polycistronic genes were annotated in the same manner with inferences from their proximity to more confidently annotated genes. Two targeted deletion mutants were used as test cases to determine the relevance of the inferred functional annotations. PMID:19293273

  5. Expression profiling of hypothetical genes in Desulfovibrio vulgaris leads to improved functional annotation

    SciTech Connect

    Elias, Dwayne A.; Mukhopadhyay, Aindrila; Joachimiak, Marcin P.; Drury, Elliott C.; Redding, Alyssa M.; Yen, Huei-Che B.; Fields, Matthew W.; Hazen, Terry C.; Arkin, Adam P.; Keasling, Jay D.; Wall, Judy D.

    2008-10-27

    Hypothetical and conserved hypothetical genes account for>30percent of sequenced bacterial genomes. For the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough, 347 of the 3634 genes were annotated as conserved hypothetical (9.5percent) along with 887 hypothetical genes (24.4percent). Given the large fraction of the genome, it is plausible that some of these genes serve critical cellular roles. The study goals were to determine which genes were expressed and provide a more functionally based annotation. To accomplish this, expression profiles of 1234 hypothetical and conserved genes were used from transcriptomic datasets of 11 environmental stresses, complemented with shotgun LC-MS/MS and AMT tag proteomic data. Genes were divided into putatively polycistronic operons and those predicted to be monocistronic, then classified by basal expression levels and grouped according to changes in expression for one or multiple stresses. 1212 of these genes were transcribed with 786 producing detectable proteins. There was no evidence for expression of 17 predicted genes. Except for the latter, monocistronic gene annotation was expanded using the above criteria along with matching Clusters of Orthologous Groups. Polycistronic genes were annotated in the same manner with inferences from their proximity to more confidently annotated genes. Two targeted deletion mutants were used as test cases to determine the relevance of the inferred functional annotations.

  6. Structure and functional annotation of hypothetical proteins having putative Rubisco activase function from Vitis vinifera.

    PubMed

    Kumar, Suresh

    2015-01-01

    Rubisco is a very large, complex and one of the most abundant proteins in the world and comprises up to 50% of all soluble protein in plants. The activity of Rubisco, the enzyme that catalyzes CO2 assimilation in photosynthesis, is regulated by Rubisco activase (Rca). In the present study, we searched for hypothetical protein of Vitis vinifera which has putative Rubisco activase function. The Arabidopsis and tobacco Rubisco activase protein sequences were used as seed sequences to search against Vitis vinifera in UniprotKB database. The selected hypothetical proteins of Vitis vinifera were subjected to sequence, structural and functional annotation. Subcellular localization predictions suggested it to be cytoplasmic protein. Homology modelling was used to define the three-dimensional (3D) structure of selected hypothetical proteins of Vitis vinifera. Template search revealed that all the hypothetical proteins share more than 80% sequence identity with structure of green-type Rubisco activase from tobacco, indicating proteins are evolutionary conserved. The homology modelling was generated using SWISS-MODEL. Several quality assessment and validation parameters computed indicated that homology models are reliable. Further, functional annotation through PFAM, CATH, SUPERFAMILY, CDART suggested that selected hypothetical proteins of Vitis vinifera contain ATPase family associated with various cellular activities (AAA) and belong to the AAA+ super family of ring-shaped P-loop containing nucleoside triphosphate hydrolases. This study will lead to research in the optimization of the functionality of Rubisco which has large implication in the improvement of plant productivity and resource use efficiency.

  7. Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis

    PubMed Central

    Du, Yushen; Wu, Nicholas C.; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting

    2016-01-01

    ABSTRACT Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. PMID:27803181

  8. Assessing functional annotation transfers with inter-species conserved coexpression: application to Plasmodium falciparum

    PubMed Central

    2010-01-01

    Background Plasmodium falciparum is the main causative agent of malaria. Of the 5 484 predicted genes of P. falciparum, about 57% do not have sufficient sequence similarity to characterized genes in other species to warrant functional assignments. Non-homology methods are thus needed to obtain functional clues for these uncharacterized genes. Gene expression data have been widely used in the recent years to help functional annotation in an intra-species way via the so-called Guilt By Association (GBA) principle. Results We propose a new method that uses gene expression data to assess inter-species annotation transfers. Our approach starts from a set of likely orthologs between a reference species (here S. cerevisiae and D. melanogaster) and a query species (P. falciparum). It aims at identifying clusters of coexpressed genes in the query species whose coexpression has been conserved in the reference species. These conserved clusters of coexpressed genes are then used to assess annotation transfers between genes with low sequence similarity, enabling reliable transfers of annotations from the reference to the query species. The approach was used with transcriptomic data sets of P. falciparum, S. cerevisiae and D. melanogaster, and enabled us to propose with high confidence new/refined annotations for several dozens hypothetical/putative P. falciparum genes. Notably, we revised the annotation of genes involved in ribosomal proteins and ribosome biogenesis and assembly, thus highlighting several potential drug targets. Conclusions Our approach uses both sequence similarity and gene expression data to help inter-species gene annotation transfers. Experiments show that this strategy improves the accuracy achieved when using solely sequence similarity and outperforms the accuracy of the GBA approach. In addition, our experiments with P. falciparum show that it can infer a function for numerous hypothetical genes. PMID:20078859

  9. A statistical framework to predict functional non-coding regions in the human genome through integrated analysis of annotation data.

    PubMed

    Lu, Qiongshi; Hu, Yiming; Sun, Jiehuan; Cheng, Yuwei; Cheung, Kei-Hoi; Zhao, Hongyu

    2015-05-27

    Identifying functional regions in the human genome is a major goal in human genetics. Great efforts have been made to functionally annotate the human genome either through computational predictions, such as genomic conservation, or high-throughput experiments, such as the ENCODE project. These efforts have resulted in a rich collection of functional annotation data of diverse types that need to be jointly analyzed for integrated interpretation and annotation. Here we present GenoCanyon, a whole-genome annotation method that performs unsupervised statistical learning using 22 computational and experimental annotations thereby inferring the functional potential of each position in the human genome. With GenoCanyon, we are able to predict many of the known functional regions. The ability of predicting functional regions as well as its generalizable statistical framework makes GenoCanyon a unique and powerful tool for whole-genome annotation. The GenoCanyon web server is available at http://genocanyon.med.yale.edu.

  10. BioBuilder as a database development and functional annotation platform for proteins

    PubMed Central

    Navarro, J Daniel; Talreja, Naveen; Peri, Suraj; Vrushabendra, BM; Rashmi, BP; Padma, N; Surendranath, Vineeth; Jonnalagadda, Chandra Kiran; Kousthub, PS; Deshpande, Nandan; Shanker, K; Pandey, Akhilesh

    2004-01-01

    Background The explosion in biological information creates the need for databases that are easy to develop, easy to maintain and can be easily manipulated by annotators who are most likely to be biologists. However, deployment of scalable and extensible databases is not an easy task and generally requires substantial expertise in database development. Results BioBuilder is a Zope-based software tool that was developed to facilitate intuitive creation of protein databases. Protein data can be entered and annotated through web forms along with the flexibility to add customized annotation features to protein entries. A built-in review system permits a global team of scientists to coordinate their annotation efforts. We have already used BioBuilder to develop Human Protein Reference Database , a comprehensive annotated repository of the human proteome. The data can be exported in the extensible markup language (XML) format, which is rapidly becoming as the standard format for data exchange. Conclusions As the proteomic data for several organisms begins to accumulate, BioBuilder will prove to be an invaluable platform for functional annotation and development of customizable protein centric databases. BioBuilder is open source and is available under the terms of LGPL. PMID:15099404

  11. Effects of circadian rhythm phase alteration on physiological and psychological variables: Implications to pilot performance (including a partially annotated bibliography)

    NASA Technical Reports Server (NTRS)

    Holley, D. C.; Winger, C. M.; Deroshia, C. W.; Heinold, M. P.; Edgar, D. M.; Kinney, N. E.; Langston, S. E.; Markley, C. L.; Anthony, J. A.

    1981-01-01

    The effects of environmental synchronizers upon circadian rhythmic stability in man and the deleterious alterations in performance and which result from changes in this stability are points of interest in a review of selected literature published between 1972 and 1980. A total of 2,084 references relevant to pilot performance and circadian phase alteration are cited and arranged in the following categories: (1) human performance, with focus on the effects of sleep loss or disturbance and fatigue; (2) phase shift in which ground based light/dark alteration and transmeridian flight studies are discussed; (3) shiftwork; (4)internal desynchronization which includes the effect of evironmental factors on rhythmic stability, and of rhythm disturbances on sleep and psychopathology; (5) chronotherapy, the application of methods to ameliorate desynchronization symptomatology; and (6) biorythm theory, in which the birthdate based biorythm method for predicting aircraft accident susceptability is critically analyzed. Annotations are provided for most citations.

  12. Biases in the experimental annotations of protein function and their effect on our understanding of protein function space.

    PubMed

    Schnoes, Alexandra M; Ream, David C; Thorman, Alexander W; Babbitt, Patricia C; Friedberg, Iddo

    2013-01-01

    The ongoing functional annotation of proteins relies upon the work of curators to capture experimental findings from scientific literature and apply them to protein sequence and structure data. However, with the increasing use of high-throughput experimental assays, a small number of experimental studies dominate the functional protein annotations collected in databases. Here, we investigate just how prevalent is the "few articles - many proteins" phenomenon. We examine the experimentally validated annotation of proteins provided by several groups in the GO Consortium, and show that the distribution of proteins per published study is exponential, with 0.14% of articles providing the source of annotations for 25% of the proteins in the UniProt-GOA compilation. Since each of the dominant articles describes the use of an assay that can find only one function or a small group of functions, this leads to substantial biases in what we know about the function of many proteins. Mass-spectrometry, microscopy and RNAi experiments dominate high throughput experiments. Consequently, the functional information derived from these experiments is mostly of the subcellular location of proteins, and of the participation of proteins in embryonic developmental pathways. For some organisms, the information provided by different studies overlap by a large amount. We also show that the information provided by high throughput experiments is less specific than those provided by low throughput experiments. Given the experimental techniques available, certain biases in protein function annotation due to high-throughput experiments are unavoidable. Knowing that these biases exist and understanding their characteristics and extent is important for database curators, developers of function annotation programs, and anyone who uses protein function annotation data to plan experiments.

  13. RNA-seq analysis of Quercus pubescens Leaves: de novo transcriptome assembly, annotation and functional markers development.

    PubMed

    Torre, Sara; Tattini, Massimiliano; Brunetti, Cecilia; Fineschi, Silvia; Fini, Alessio; Ferrini, Francesco; Sebastiani, Federico

    2014-01-01

    Quercus pubescens Willd., a species distributed from Spain to southwest Asia, ranks high for drought tolerance among European oaks. Q. pubescens performs a role of outstanding significance in most Mediterranean forest ecosystems, but few mechanistic studies have been conducted to explore its response to environmental constrains, due to the lack of genomic resources. In our study, we performed a deep transcriptomic sequencing in Q. pubescens leaves, including de novo assembly, functional annotation and the identification of new molecular markers. Our results are a pre-requisite for undertaking molecular functional studies, and may give support in population and association genetic studies. 254,265,700 clean reads were generated by the Illumina HiSeq 2000 platform, with an average length of 98 bp. De novo assembly, using CLC Genomics, produced 96,006 contigs, having a mean length of 618 bp. Sequence similarity analyses against seven public databases (Uniprot, NR, RefSeq and KOGs at NCBI, Pfam, InterPro and KEGG) resulted in 83,065 transcripts annotated with gene descriptions, conserved protein domains, or gene ontology terms. These annotations and local BLAST allowed identify genes specifically associated with mechanisms of drought avoidance. Finally, 14,202 microsatellite markers and 18,425 single nucleotide polymorphisms (SNPs) were, in silico, discovered in assembled and annotated sequences. We completed a successful global analysis of the Q. pubescens leaf transcriptome using RNA-seq. The assembled and annotated sequences together with newly discovered molecular markers provide genomic information for functional genomic studies in Q. pubescens, with special emphasis to response mechanisms to severe constrain of the Mediterranean climate. Our tools enable comparative genomics studies on other Quercus species taking advantage of large intra-specific ecophysiological differences.

  14. SNPnexus: a web database for functional annotation of newly discovered and public domain single nucleotide polymorphisms

    PubMed Central

    Chelala, Claude; Khan, Arshad; Lemoine, Nicholas R

    2009-01-01

    Motivation: Design a new computational tool allowing scientists to functionally annotate newly discovered and public domain single nucleotide polymorphisms in order to help in prioritizing targets in further disease studies and large-scale genotyping projects. Summary: SNPnexus database provides functional annotation for both novel and public SNPs. Possible effects on the transcriptome and proteome levels are characterized and reported from five major annotation systems providing the most extensive information on alternative splicing. Additional information on HapMap genotype and allele frequency, overlaps with potential regulatory elements or structural variations as well as related genetic diseases can be also retrieved. The SNPnexus database has a user-friendly web interface, providing single or batch query options using SNP identifiers from dbSNP as well as genomic location on clones, contigs or chromosomes. Therefore, SNPnexus is the only database currently providing a complete set of functional annotations of SNPs in public databases and newly detected from sequencing projects. Hence, we describe SNPnexus, provide details of the query options, the annotation categories as well as biological examples of use. Availability: The SNPnexus database is freely available at http://www.snp-nexus.org. Contact: claude.chelala@cancer.org.uk PMID:19098027

  15. Approaching the Functional Annotation of Fungal Virulence Factors Using Cross-Species Genetic Interaction Profiling

    PubMed Central

    Brown, Jessica C. S.; Madhani, Hiten D.

    2012-01-01

    In many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. We tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen Cryptococcus neoformans. This approach involves expression of C. neoformans genes of interest in each member of the Saccharomyces cerevisiae gene deletion library, quantification of their impact on growth, and calculation of the cross-species genetic interaction profiles. To develop functional predictions, we computed and analyzed the correlations of these profiles with existing genetic interaction profiles of S. cerevisiae deletion mutants. For C. neoformans LIV7, which has no S. cerevisiae ortholog, this profiling approach predicted an unanticipated role in the Golgi apparatus. Validation studies in C. neoformans demonstrated that Liv7 is a functional Golgi factor where it promotes the suppression of the exposure of a specific immunostimulatory molecule, mannose, on the cell surface, thereby inhibiting phagocytosis. The genetic interaction profile of another pathogenicity gene that lacks an S. cerevisiae ortholog, LIV6, strongly predicted a role in endosome function. This prediction was also supported by studies of the corresponding C. neoformans null mutant. Our results demonstrate the utility of quantitative cross-species genetic interaction profiling for the functional annotation of fungal pathogenicity proteins of unknown function including, surprisingly, those that are not conserved in sequence across fungi. PMID:23300468

  16. Approaching the functional annotation of fungal virulence factors using cross-species genetic interaction profiling.

    PubMed

    Brown, Jessica C S; Madhani, Hiten D

    2012-01-01

    In many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. We tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen Cryptococcus neoformans. This approach involves expression of C. neoformans genes of interest in each member of the Saccharomyces cerevisiae gene deletion library, quantification of their impact on growth, and calculation of the cross-species genetic interaction profiles. To develop functional predictions, we computed and analyzed the correlations of these profiles with existing genetic interaction profiles of S. cerevisiae deletion mutants. For C. neoformans LIV7, which has no S. cerevisiae ortholog, this profiling approach predicted an unanticipated role in the Golgi apparatus. Validation studies in C. neoformans demonstrated that Liv7 is a functional Golgi factor where it promotes the suppression of the exposure of a specific immunostimulatory molecule, mannose, on the cell surface, thereby inhibiting phagocytosis. The genetic interaction profile of another pathogenicity gene that lacks an S. cerevisiae ortholog, LIV6, strongly predicted a role in endosome function. This prediction was also supported by studies of the corresponding C. neoformans null mutant. Our results demonstrate the utility of quantitative cross-species genetic interaction profiling for the functional annotation of fungal pathogenicity proteins of unknown function including, surprisingly, those that are not conserved in sequence across fungi.

  17. Rice DB: an Oryza Information Portal linking annotation, subcellular location, function, expression, regulation, and evolutionary information for rice and Arabidopsis.

    PubMed

    Narsai, Reena; Devenish, James; Castleden, Ian; Narsai, Kabir; Xu, Lin; Shou, Huixia; Whelan, James

    2013-12-01

    Omics research in Oryza sativa (rice) relies on the use of multiple databases to obtain different types of information to define gene function. We present Rice DB, an Oryza information portal that is a functional genomics database, linking gene loci to comprehensive annotations, expression data and the subcellular location of encoded proteins. Rice DB has been designed to integrate the direct comparison of rice with Arabidopsis (Arabidopsis thaliana), based on orthology or 'expressology', thus using and combining available information from two pre-eminent plant models. To establish Rice DB, gene identifiers (more than 40 types) and annotations from a variety of sources were compiled, functional information based on large-scale and individual studies was manually collated, hundreds of microarrays were analysed to generate expression annotations, and the occurrences of potential functional regulatory motifs in promoter regions were calculated. A range of computational subcellular localization predictions were also run for all putative proteins encoded in the rice genome, and experimentally confirmed protein localizations have been collated, curated and linked to functional studies in rice. A single search box allows anything from gene identifiers (for rice and/or Arabidopsis), motif sequences, subcellular location, to keyword searches to be entered, with the capability of Boolean searches (such as AND/OR). To demonstrate the utility of Rice DB, several examples are presented including a rice mitochondrial proteome, which draws on a variety of sources for subcellular location data within Rice DB. Comparisons of subcellular location, functional annotations, as well as transcript expression in parallel with Arabidopsis reveals examples of conservation between rice and Arabidopsis, using Rice DB (http://ricedb.plantenergy.uwa.edu.au).

  18. Rice DB: an Oryza Information Portal linking annotation, subcellular location, function, expression, regulation, and evolutionary information for rice and Arabidopsis

    PubMed Central

    Narsai, Reena; Devenish, James; Castleden, Ian; Narsai, Kabir; Xu, Lin; Shou, Huixia; Whelan, James

    2013-01-01

    Omics research in Oryza sativa (rice) relies on the use of multiple databases to obtain different types of information to define gene function. We present Rice DB, an Oryza information portal that is a functional genomics database, linking gene loci to comprehensive annotations, expression data and the subcellular location of encoded proteins. Rice DB has been designed to integrate the direct comparison of rice with Arabidopsis (Arabidopsis thaliana), based on orthology or ‘expressology’, thus using and combining available information from two pre-eminent plant models. To establish Rice DB, gene identifiers (more than 40 types) and annotations from a variety of sources were compiled, functional information based on large-scale and individual studies was manually collated, hundreds of microarrays were analysed to generate expression annotations, and the occurrences of potential functional regulatory motifs in promoter regions were calculated. A range of computational subcellular localization predictions were also run for all putative proteins encoded in the rice genome, and experimentally confirmed protein localizations have been collated, curated and linked to functional studies in rice. A single search box allows anything from gene identifiers (for rice and/or Arabidopsis), motif sequences, subcellular location, to keyword searches to be entered, with the capability of Boolean searches (such as AND/OR). To demonstrate the utility of Rice DB, several examples are presented including a rice mitochondrial proteome, which draws on a variety of sources for subcellular location data within Rice DB. Comparisons of subcellular location, functional annotations, as well as transcript expression in parallel with Arabidopsis reveals examples of conservation between rice and Arabidopsis, using Rice DB (http://ricedb.plantenergy.uwa.edu.au). PMID:24147765

  19. TheViral MetaGenome Annotation Pipeline(VMGAP):an automated tool for the functional annotation of viral Metagenomic shotgun sequencing data

    PubMed Central

    Lorenzi, Hernan A.; Hoover, Jeff; Inman, Jason; Safford, Todd; Murphy, Sean; Kagan, Leonid; Williamson, Shannon J.

    2011-01-01

    In the past few years, the field of metagenomics has been growing at an accelerated pace, particularly in response to advancements in new sequencing technologies. The large volume of sequence data from novel organisms generated by metagenomic projects has triggered the development of specialized databases and tools focused on particular groups of organisms or data types. Here we describe a pipeline for the functional annotation of viral metagenomic sequence data. The Viral MetaGenome Annotation Pipeline (VMGAP) pipeline takes advantage of a number of specialized databases, such as collections of mobile genetic elements and environmental metagenomes to improve the classification and functional prediction of viral gene products. The pipeline assigns a functional term to each predicted protein sequence following a suite of comprehensive analyses whose results are ranked according to a priority rules hierarchy. Additional annotation is provided in the form of enzyme commission (EC) numbers, GO/MeGO terms and Hidden Markov Models together with supporting evidence. PMID:21886867

  20. Functional modelling of an equine bronchoalveolar lavage fluid proteome provides experimental confirmation and functional annotation of equine genome sequences.

    PubMed

    Bright, L A; Mujahid, N; Nanduri, B; McCarthy, F M; Costa, L R R; Burgess, S C; Swiderski, C E

    2011-08-01

    The equine genome sequence enables the use of high-throughput genomic technologies in equine research, but accurate identification of expressed gene products and interpreting their biological relevance require additional structural and functional genome annotation. Here, we employ the equine genome sequence to identify predicted and known proteins using proteomics and model these proteins into biological pathways, identifying 582 proteins in normal cell-free equine bronchoalveolar lavage fluid (BALF). We improved structural and functional annotation by directly confirming the in vivo expression of 558 (96%) proteins, which were computationally predicted previously, and adding Gene Ontology (GO) annotations for 174 proteins, 108 of which lacked functional annotation. Bronchoalveolar lavage is commonly used to investigate equine respiratory disease, leading us to model the associated proteome and its biological functions. Modelling of protein functions using Ingenuity Pathway Analysis identified carbohydrate metabolism, cell-to-cell signalling, cellular function, inflammatory response, organ morphology, lipid metabolism and cellular movement as key biological processes in normal equine BALF. Comparative modelling of protein functions in normal cell-free bronchoalveolar lavage proteomes from horse, human, and mouse, performed by grouping GO terms sharing common ancestor terms, confirms conservation of functions across species. Ninety-one of 92 human GO categories and 105 of 109 mouse GO categories were conserved in the horse. Our approach confirms the utility of the equine genome sequence to characterize protein networks without antibodies or mRNA quantification, highlights the need for continued structural and functional annotation of the equine genome and provides a framework for equine researchers to aid in the annotation effort.

  1. Genome-wide functional annotation of Phomopsis longicolla isolate MSPL 10-6.

    PubMed

    Darwish, Omar; Li, Shuxian; Matthews, Benjamin; Alkharouf, Nadim

    2016-06-01

    Phomopsis seed decay of soybean is caused primarily by the seed-borne fungal pathogen Phomopsis longicolla (syn. Diaporthe longicolla). This disease severely decreases soybean seed quality, reduces seedling vigor and stand establishment, and suppresses yield. It is one of the most economically important soybean diseases. In this study we annotated the entire genome of P. longicolla isolate MSPL 10-6, which was isolated from field-grown soybean seed in Mississippi, USA. This study represents the first reported genome-wide functional annotation of a seed borne fungal pathogen in the Diaporthe-Phomopsis complex. The P. longicolla genome annotation will enable research into the genetic basis of fungal infection of soybean seed and provide information for the study of soybean-fungal interactions. The genome annotation will also be a valuable resource for the research and agricultural communities. It will aid in the development of new control strategies for this pathogen. The annotations can be found from: http://bioinformatics.towson.edu/phomopsis_longicolla/download.html. NCBI accession number is: AYRD00000000.

  2. AIGO: Towards a unified framework for the Analysis and the Inter-comparison of GO functional annotations

    PubMed Central

    2011-01-01

    Background In response to the rapid growth of available genome sequences, efforts have been made to develop automatic inference methods to functionally characterize them. Pipelines that infer functional annotation are now routinely used to produce new annotations at a genome scale and for a broad variety of species. These pipelines differ widely in their inference algorithms, confidence thresholds and data sources for reasoning. This heterogeneity makes a comparison of the relative merits of each approach extremely complex. The evaluation of the quality of the resultant annotations is also challenging given there is often no existing gold-standard against which to evaluate precision and recall. Results In this paper, we present a pragmatic approach to the study of functional annotations. An ensemble of 12 metrics, describing various aspects of functional annotations, is defined and implemented in a unified framework, which facilitates their systematic analysis and inter-comparison. The use of this framework is demonstrated on three illustrative examples: analysing the outputs of state-of-the-art inference pipelines, comparing electronic versus manual annotation methods, and monitoring the evolution of publicly available functional annotations. The framework is part of the AIGO library (http://code.google.com/p/aigo) for the Analysis and the Inter-comparison of the products of Gene Ontology (GO) annotation pipelines. The AIGO library also provides functionalities to easily load, analyse, manipulate and compare functional annotations and also to plot and export the results of the analysis in various formats. Conclusions This work is a step toward developing a unified framework for the systematic study of GO functional annotations. This framework has been designed so that new metrics on GO functional annotations can be added in a very straightforward way. PMID:22054122

  3. Functional annotation from the genome sequence of the giant panda.

    PubMed

    Huo, Tong; Zhang, Yinjie; Lin, Jianping

    2012-08-01

    The giant panda is one of the most critically endangered species due to the fragmentation and loss of its habitat. Studying the functions of proteins in this animal, especially specific trait-related proteins, is therefore necessary to protect the species. In this work, the functions of these proteins were investigated using the genome sequence of the giant panda. Data on 21,001 proteins and their functions were stored in the Giant Panda Protein Database, in which the proteins were divided into two groups: 20,179 proteins whose functions can be predicted by GeneScan formed the known-function group, whereas 822 proteins whose functions cannot be predicted by GeneScan comprised the unknown-function group. For the known-function group, we further classified the proteins by molecular function, biological process, cellular component, and tissue specificity. For the unknown-function group, we developed a strategy in which the proteins were filtered by cross-Blast to identify panda-specific proteins under the assumption that proteins related to the panda-specific traits in the unknown-function group exist. After this filtering procedure, we identified 32 proteins (2 of which are membrane proteins) specific to the giant panda genome as compared against the dog and horse genomes. Based on their amino acid sequences, these 32 proteins were further analyzed by functional classification using SVM-Prot, motif prediction using MyHits, and interacting protein prediction using the Database of Interacting Proteins. Nineteen proteins were predicted to be zinc-binding proteins, thus affecting the activities of nucleic acids. The 32 panda-specific proteins will be further investigated by structural and functional analysis.

  4. Disentangling the Effects of Colocalizing Genomic Annotations to Functionally Prioritize Non-coding Variants within Complex-Trait Loci.

    PubMed

    Trynka, Gosia; Westra, Harm-Jan; Slowikowski, Kamil; Hu, Xinli; Xu, Han; Stranger, Barbara E; Klein, Robert J; Han, Buhm; Raychaudhuri, Soumya

    2015-07-02

    Identifying genomic annotations that differentiate causal from trait-associated variants is essential to fine mapping disease loci. Although many studies have identified non-coding functional annotations that overlap disease-associated variants, these annotations often colocalize, complicating the ability to use these annotations for fine mapping causal variation. We developed a statistical approach (Genomic Annotation Shifter [GoShifter]) to assess whether enriched annotations are able to prioritize causal variation. GoShifter defines the null distribution of an annotation overlapping an allele by locally shifting annotations; this approach is less sensitive to biases arising from local genomic structure than commonly used enrichment methods that depend on SNP matching. Local shifting also allows GoShifter to identify independent causal effects from colocalizing annotations. Using GoShifter, we confirmed that variants in expression quantitative trail loci drive gene-expression changes though DNase-I hypersensitive sites (DHSs) near transcription start sites and independently through 3' UTR regulation. We also showed that (1) 15%-36% of trait-associated loci map to DHSs independently of other annotations; (2) loci associated with breast cancer and rheumatoid arthritis harbor potentially causal variants near the summits of histone marks rather than full peak bodies; (3) variants associated with height are highly enriched in embryonic stem cell DHSs; and (4) we can effectively prioritize causal variation at specific loci.

  5. Structural and Functional Annotation of the Porcine Immunome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. H...

  6. The De Novo Transcriptome and Its Functional Annotation in the Seed Beetle Callosobruchus maculatus

    PubMed Central

    Sayadi, Ahmed; Immonen, Elina; Bayram, Helen

    2016-01-01

    Despite their unparalleled biodiversity, the genomic resources available for beetles (Coleoptera) remain relatively scarce. We present an integrative and high quality annotated transcriptome of the beetle Callosobruchus maculatus, an important and cosmopolitan agricultural pest as well as an emerging model species in ecology and evolutionary biology. Using Illumina sequencing technology, we sequenced 492 million read pairs generated from 51 samples of different developmental stages (larvae, pupae and adults) of C. maculatus. Reads were de novo assembled using the Trinity software, into a single combined assembly as well as into three separate assemblies based on data from the different developmental stages. The combined assembly generated 218,192 transcripts and 145,883 putative genes. Putative genes were annotated with the Blast2GO software and the Trinotate pipeline. In total, 33,216 putative genes were successfully annotated using Blastx against the Nr (non-redundant) database and 13,382 were assigned to 34,100 Gene Ontology (GO) terms. We classified 5,475 putative genes into Clusters of Orthologous Groups (COG) and 116 metabolic pathways maps were predicted based on the annotation. Our analyses suggested that the transcriptional specificity increases with ontogeny. For example, out of 33,216 annotated putative genes, 51 were only expressed in larvae, 63 only in pupae and 171 only in adults. Our study illustrates the importance of including samples from several developmental stages when the aim is to provide an integrative and high quality annotated transcriptome. Our results will represent an invaluable resource for those working with the ecology, evolution and pest control of C. maculatus, as well for comparative studies of the transcriptomics and genomics of beetles more generally. PMID:27442123

  7. The De Novo Transcriptome and Its Functional Annotation in the Seed Beetle Callosobruchus maculatus.

    PubMed

    Sayadi, Ahmed; Immonen, Elina; Bayram, Helen; Arnqvist, Göran

    2016-01-01

    Despite their unparalleled biodiversity, the genomic resources available for beetles (Coleoptera) remain relatively scarce. We present an integrative and high quality annotated transcriptome of the beetle Callosobruchus maculatus, an important and cosmopolitan agricultural pest as well as an emerging model species in ecology and evolutionary biology. Using Illumina sequencing technology, we sequenced 492 million read pairs generated from 51 samples of different developmental stages (larvae, pupae and adults) of C. maculatus. Reads were de novo assembled using the Trinity software, into a single combined assembly as well as into three separate assemblies based on data from the different developmental stages. The combined assembly generated 218,192 transcripts and 145,883 putative genes. Putative genes were annotated with the Blast2GO software and the Trinotate pipeline. In total, 33,216 putative genes were successfully annotated using Blastx against the Nr (non-redundant) database and 13,382 were assigned to 34,100 Gene Ontology (GO) terms. We classified 5,475 putative genes into Clusters of Orthologous Groups (COG) and 116 metabolic pathways maps were predicted based on the annotation. Our analyses suggested that the transcriptional specificity increases with ontogeny. For example, out of 33,216 annotated putative genes, 51 were only expressed in larvae, 63 only in pupae and 171 only in adults. Our study illustrates the importance of including samples from several developmental stages when the aim is to provide an integrative and high quality annotated transcriptome. Our results will represent an invaluable resource for those working with the ecology, evolution and pest control of C. maculatus, as well for comparative studies of the transcriptomics and genomics of beetles more generally.

  8. PFP: Automated prediction of gene ontology functional annotations with confidence scores using protein sequence data.

    PubMed

    Hawkins, Troy; Chitale, Meghana; Luban, Stanislav; Kihara, Daisuke

    2009-02-15

    Protein function prediction is a central problem in bioinformatics, increasing in importance recently due to the rapid accumulation of biological data awaiting interpretation. Sequence data represents the bulk of this new stock and is the obvious target for consideration as input, as newly sequenced organisms often lack any other type of biological characterization. We have previously introduced PFP (Protein Function Prediction) as our sequence-based predictor of Gene Ontology (GO) functional terms. PFP interprets the results of a PSI-BLAST search by extracting and scoring individual functional attributes, searching a wide range of E-value sequence matches, and utilizing conventional data mining techniques to fill in missing information. We have shown it to be effective in predicting both specific and low-resolution functional attributes when sufficient data is unavailable. Here we describe (1) significant improvements to the PFP infrastructure, including the addition of prediction significance and confidence scores, (2) a thorough benchmark of performance and comparisons to other related prediction methods, and (3) applications of PFP predictions to genome-scale data. We applied PFP predictions to uncharacterized protein sequences from 15 organisms. Among these sequences, 60-90% could be annotated with a GO molecular function term at high confidence (>or=80%). We also applied our predictions to the protein-protein interaction network of the Malaria plasmodium (Plasmodium falciparum). High confidence GO biological process predictions (>or=90%) from PFP increased the number of fully enriched interactions in this dataset from 23% of interactions to 94%. Our benchmark comparison shows significant performance improvement of PFP relative to GOtcha, InterProScan, and PSI-BLAST predictions. This is consistent with the performance of PFP as the overall best predictor in both the AFP-SIG '05 and CASP7 function (FN) assessments. PFP is available as a web service at http://dragon.bio.purdue.edu/pfp/.

  9. Curation of the genome annotation of Pichia pastoris (Komagataella phaffii) CBS7435 from gene level to protein function.

    PubMed

    Valli, Minoska; Tatto, Nadine E; Peymann, Armin; Gruber, Clemens; Landes, Nils; Ekker, Heinz; Thallinger, Gerhard G; Mattanovich, Diethard; Gasser, Brigitte; Graf, Alexandra B

    2016-09-01

    As manually curated and non-automated BLAST analysis of the published Pichia pastoris genome sequences revealed many differences between the gene annotations of the strains GS115 and CBS7435, RNA-Seq analysis, supported by proteomics, was performed to improve the genome annotation. Detailed analysis of sequence alignment and protein domain predictions were made to extend the functional genome annotation to all P. pastoris sequences. This allowed the identification of 492 new ORFs, 4916 hypothetical UTRs and the correction of 341 incorrect ORF predictions, which were mainly due to the presence of upstream ATG or erroneous intron predictions. Moreover, 175 previously erroneously annotated ORFs need to be removed from the annotation. In total, we have annotated 5325 ORFs. Regarding the functionality of those genes, we improved all gene and protein descriptions. Thereby, the percentage of ORFs with functional annotation was increased from 48% to 73%. Furthermore, we defined functional groups, covering 25 biological cellular processes of interest, by grouping all genes that are part of the defined process. All data are presented in the newly launched genome browser and database available at www.pichiagenome.org In summary, we present a wide spectrum of curation of the P. pastoris genome annotation from gene level to protein function.

  10. SARA: a server for function annotation of RNA structures.

    PubMed

    Capriotti, Emidio; Marti-Renom, Marc A

    2009-07-01

    Recent interest in non-coding RNA transcripts has resulted in a rapid increase of deposited RNA structures in the Protein Data Bank. However, a characterization and functional classification of the RNA structure and function space have only been partially addressed. Here, we introduce the SARA program for pair-wise alignment of RNA structures as a web server for structure-based RNA function assignment. The SARA server relies on the SARA program, which aligns two RNA structures based on a unit-vector root-mean-square approach. The likely accuracy of the SARA alignments is assessed by three different P-values estimating the statistical significance of the sequence, secondary structure and tertiary structure identity scores, respectively. Our benchmarks, which relied on a set of 419 RNA structures with known SCOR structural class, indicate that at a negative logarithm of mean P-value higher or equal than 2.5, SARA can assign the correct or a similar SCOR class to 81.4% and 95.3% of the benchmark set, respectively. The SARA server is freely accessible via the World Wide Web at http://sgu.bioinfo.cipf.es/services/SARA/.

  11. The development of PIPA: an integrated and automated pipeline for genome-wide protein function annotation

    PubMed Central

    Yu, Chenggang; Zavaljevski, Nela; Desai, Valmik; Johnson, Seth; Stevens, Fred J; Reifman, Jaques

    2008-01-01

    Background Automated protein function prediction methods are needed to keep pace with high-throughput sequencing. With the existence of many programs and databases for inferring different protein functions, a pipeline that properly integrates these resources will benefit from the advantages of each method. However, integrated systems usually do not provide mechanisms to generate customized databases to predict particular protein functions. Here, we describe a tool termed PIPA (Pipeline for Protein Annotation) that has these capabilities. Results PIPA annotates protein functions by combining the results of multiple programs and databases, such as InterPro and the Conserved Domains Database, into common Gene Ontology (GO) terms. The major algorithms implemented in PIPA are: (1) a profile database generation algorithm, which generates customized profile databases to predict particular protein functions, (2) an automated ontology mapping generation algorithm, which maps various classification schemes into GO, and (3) a consensus algorithm to reconcile annotations from the integrated programs and databases. PIPA's profile generation algorithm is employed to construct the enzyme profile database CatFam, which predicts catalytic functions described by Enzyme Commission (EC) numbers. Validation tests show that CatFam yields average recall and precision larger than 95.0%. CatFam is integrated with PIPA. We use an association rule mining algorithm to automatically generate mappings between terms of two ontologies from annotated sample proteins. Incorporating the ontologies' hierarchical topology into the algorithm increases the number of generated mappings. In particular, it generates 40.0% additional mappings from the Clusters of Orthologous Groups (COG) to EC numbers and a six-fold increase in mappings from COG to GO terms. The mappings to EC numbers show a very high precision (99.8%) and recall (96.6%), while the mappings to GO terms show moderate precision (80.0%) and

  12. Algal Functional Annotation Tool from the DOE-UCLA Institute for Genomics and Proteomics

    DOE Data Explorer

    Lopez, David

    The Algal Functional Annotation Tool is a bioinformatics resource to visualize pathway maps, identify enriched biological terms, or convert gene identifiers to elucidate biological function in silico. These types of analysis have been catered to support lists of gene identifiers, such as those coming from transcriptome gene expression analysis. By analyzing the functional annotation of an interesting set of genes, common biological motifs may be elucidated and a first-pass analysis can point further research in the right direction. Currently, the following databases have been parsed, processed, and added to the tool: 1( Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways Database, 2) MetaCyc Encyclopedia of Metabolic Pathways, 3) Panther Pathways Database, 4) Reactome Pathways Database, 5) Gene Ontology, 6) MapMan Ontology, 7) KOG (Eukaryotic Clusters of Orthologous Groups), 5)Pfam, 6) InterPro.

  13. Coordinated international action to accelerate genome-to-phenome with FAANG, The Functional Annotation of Animal Genomes project

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We describe the organization of a nascent international effort - the "Functional Annotation of ANimal Genomes" project - whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species....

  14. Protein intrinsic disorder within the Potyvirus genus: from proteome-wide analysis to functional annotation.

    PubMed

    Charon, Justine; Theil, Sébastien; Nicaise, Valérie; Michon, Thierry

    2016-02-01

    Within proteins, intrinsically disordered regions (IDRs) are devoid of stable secondary and tertiary structures under physiological conditions and rather exist as dynamic ensembles of inter-converting conformers. Although ubiquitous in all domains of life, the intrinsic disorder content is highly variable in viral genomes. Over the years, functional annotations of disordered regions at the scale of the whole proteome have been conducted for several animal viruses. But to date, similar studies applied to plant viruses are still missing. Based on disorder prediction tools combined with annotation programs and evolutionary studies, we analyzed the intrinsic disorder content in Potyvirus, using a 10-species dataset representative of this genus diversity. In this paper, we revealed that: (i) the Potyvirus proteome displays high disorder content, (ii) disorder is conserved during Potyvirus evolution, suggesting a functional advantage of IDRs, (iii) IDRs evolve faster than ordered regions, and (iv) IDRs may be associated with major biological functions required for the Potyvirus cycle. Notably, the proteins P1, Coat protein (CP) and Viral genome-linked protein (VPg) display a high content of conserved disorder, enriched in specific motifs mimicking eukaryotic functional modules and suggesting strategies of host machinery hijacking. In these three proteins, IDRs are particularly conserved despite their high amino acid polymorphism, indicating a link to adaptive processes. Through this comprehensive study, we further investigate the biological relevance of intrinsic disorder in Potyvirus biology and we propose a functional annotation of potyviral proteome IDRs.

  15. Annotation of Protein Domains Reveals Remarkable Conservation in the Functional Make up of Proteomes Across Superkingdoms.

    PubMed

    Nasir, Arshan; Naeem, Aisha; Khan, Muhammad Jawad; Nicora, Horacio D Lopez; Caetano-Anollés, Gustavo

    2011-11-08

    The functional repertoire of a cell is largely embodied in its proteome, the collection of proteins encoded in the genome of an organism. The molecular functions of proteins are the direct consequence of their structure and structure can be inferred from sequence using hidden Markov models of structural recognition. Here we analyze the functional annotation of protein domain structures in almost a thousand sequenced genomes, exploring the functional and structural diversity of proteomes. We find there is a remarkable conservation in the distribution of domains with respect to the molecular functions they perform in the three superkingdoms of life. In general, most of the protein repertoire is spent in functions related to metabolic processes but there are significant differences in the usage of domains for regulatory and extra-cellular processes both within and between superkingdoms. Our results support the hypotheses that the proteomes of superkingdom Eukarya evolved via genome expansion mechanisms that were directed towards innovating new domain architectures for regulatory and extra/intracellular process functions needed for example to maintain the integrity of multicellular structure or to interact with environmental biotic and abiotic factors (e.g., cell signaling and adhesion, immune responses, and toxin production). Proteomes of microbial superkingdoms Archaea and Bacteria retained fewer numbers of domains and maintained simple and smaller protein repertoires. Viruses appear to play an important role in the evolution of superkingdoms. We finally identify few genomic outliers that deviate significantly from the conserved functional design. These include Nanoarchaeum equitans, proteobacterial symbionts of insects with extremely reduced genomes, Tenericutes and Guillardia theta. These organisms spend most of their domains on information functions, including translation and transcription, rather than on metabolism and harbor a domain repertoire characteristic of

  16. Annotation of Protein Domains Reveals Remarkable Conservation in the Functional Make up of Proteomes Across Superkingdoms

    PubMed Central

    Nasir, Arshan; Naeem, Aisha; Khan, Muhammad Jawad; Lopez-Nicora, Horacio D.; Caetano-Anollés, Gustavo

    2011-01-01

    The functional repertoire of a cell is largely embodied in its proteome, the collection of proteins encoded in the genome of an organism. The molecular functions of proteins are the direct consequence of their structure and structure can be inferred from sequence using hidden Markov models of structural recognition. Here we analyze the functional annotation of protein domain structures in almost a thousand sequenced genomes, exploring the functional and structural diversity of proteomes. We find there is a remarkable conservation in the distribution of domains with respect to the molecular functions they perform in the three superkingdoms of life. In general, most of the protein repertoire is spent in functions related to metabolic processes but there are significant differences in the usage of domains for regulatory and extra-cellular processes both within and between superkingdoms. Our results support the hypotheses that the proteomes of superkingdom Eukarya evolved via genome expansion mechanisms that were directed towards innovating new domain architectures for regulatory and extra/intracellular process functions needed for example to maintain the integrity of multicellular structure or to interact with environmental biotic and abiotic factors (e.g., cell signaling and adhesion, immune responses, and toxin production). Proteomes of microbial superkingdoms Archaea and Bacteria retained fewer numbers of domains and maintained simple and smaller protein repertoires. Viruses appear to play an important role in the evolution of superkingdoms. We finally identify few genomic outliers that deviate significantly from the conserved functional design. These include Nanoarchaeum equitans, proteobacterial symbionts of insects with extremely reduced genomes, Tenericutes and Guillardia theta. These organisms spend most of their domains on information functions, including translation and transcription, rather than on metabolism and harbor a domain repertoire characteristic of

  17. In Silico Functional Pathway Annotation of 86 Established Prostate Cancer Risk Variants

    PubMed Central

    Loo, Lenora W. M.; Fong, Aaron Y. W.; Cheng, Iona; Le Marchand, Loïc

    2015-01-01

    Heritability is one of the strongest risk factors of prostate cancer, emphasizing the importance of the genetic contribution towards prostate cancer risk. To date, 86 established prostate cancer risk variants have been identified by genome-wide association studies (GWAS). To determine if these risk variants are located near genes that interact together in biological networks or pathways contributing to prostate cancer initiation or progression, we generated gene sets based on proximity to the 86 prostate cancer risk variants. We took two approaches to generate gene lists. The first strategy included all immediate flanking genes, up- and downstream of the risk variant, regardless of distance from the index variant, and the second strategy included genes closest to the index GWAS marker and to variants in high LD (r2 ≥0.8 in Europeans) with the index variant, within a 100 kb window up- and downstream. Pathway mapping of the two gene sets supported the importance of the androgen receptor-mediated signaling in prostate cancer biology. In addition, the hedgehog and Wnt/β-catenin signaling pathways were identified in pathway mapping for the flanking gene set. We also used the HaploReg resource to examine the 86 risk loci and variants high LD (r2 ≥0.8) for functional elements. We found that there was a 12.8 fold (p = 2.9 x 10-4) enrichment for enhancer motifs in a stem cell line and a 4.4 fold (p = 1.1 x 10-3) enrichment of DNase hypersensitivity in a prostate adenocarcinoma cell line, indicating that the risk and correlated variants are enriched for transcriptional regulatory motifs. Our pathway-based functional annotation of the prostate cancer risk variants highlights the potential regulatory function that GWAS risk markers, and their highly correlated variants, exert on genes. Our study also shows that these genes may function cooperatively in key signaling pathways in prostate cancer biology. PMID:25658610

  18. Functional phylogenomics analysis of bacteria and archaea using consistent genome annotation with UniFam

    SciTech Connect

    Chai, Juanjuan; Kora, Guruprasad; Ahn, Tae-Hyuk; Hyatt, Doug; Pan, Chongle

    2014-01-01

    To supply some background, phylogenetic studies have provided detailed knowledge on the evolutionary mechanisms of genes and species in Bacteria and Archaea. However, the evolution of cellular functions, represented by metabolic pathways and biological processes, has not been systematically characterized. Many clades in the prokaryotic tree of life have now been covered by sequenced genomes in GenBank. This enables a large-scale functional phylogenomics study of many computationally inferred cellular functions across all sequenced prokaryotes. Our results show a total of 14,727 GenBank prokaryotic genomes were re-annotated using a new protein family database, UniFam, to obtain consistent functional annotations for accurate comparison. The functional profile of a genome was represented by the biological process Gene Ontology (GO) terms in its annotation. The GO term enrichment analysis differentiated the functional profiles between selected archaeal taxa. 706 prokaryotic metabolic pathways were inferred from these genomes using Pathway Tools and MetaCyc. The consistency between the distribution of metabolic pathways in the genomes and the phylogenetic tree of the genomes was measured using parsimony scores and retention indices. The ancestral functional profiles at the internal nodes of the phylogenetic tree were reconstructed to track the gains and losses of metabolic pathways in evolutionary history. In conclusion, our functional phylogenomics analysis shows divergent functional profiles of taxa and clades. Such function-phylogeny correlation stems from a set of clade-specific cellular functions with low parsimony scores. On the other hand, many cellular functions are sparsely dispersed across many clades with high parsimony scores. These different types of cellular functions have distinct evolutionary patterns reconstructed from the prokaryotic tree.

  19. Functional phylogenomics analysis of bacteria and archaea using consistent genome annotation with UniFam

    DOE PAGES

    Chai, Juanjuan; Kora, Guruprasad; Ahn, Tae-Hyuk; ...

    2014-01-01

    To supply some background, phylogenetic studies have provided detailed knowledge on the evolutionary mechanisms of genes and species in Bacteria and Archaea. However, the evolution of cellular functions, represented by metabolic pathways and biological processes, has not been systematically characterized. Many clades in the prokaryotic tree of life have now been covered by sequenced genomes in GenBank. This enables a large-scale functional phylogenomics study of many computationally inferred cellular functions across all sequenced prokaryotes. Our results show a total of 14,727 GenBank prokaryotic genomes were re-annotated using a new protein family database, UniFam, to obtain consistent functional annotations for accuratemore » comparison. The functional profile of a genome was represented by the biological process Gene Ontology (GO) terms in its annotation. The GO term enrichment analysis differentiated the functional profiles between selected archaeal taxa. 706 prokaryotic metabolic pathways were inferred from these genomes using Pathway Tools and MetaCyc. The consistency between the distribution of metabolic pathways in the genomes and the phylogenetic tree of the genomes was measured using parsimony scores and retention indices. The ancestral functional profiles at the internal nodes of the phylogenetic tree were reconstructed to track the gains and losses of metabolic pathways in evolutionary history. In conclusion, our functional phylogenomics analysis shows divergent functional profiles of taxa and clades. Such function-phylogeny correlation stems from a set of clade-specific cellular functions with low parsimony scores. On the other hand, many cellular functions are sparsely dispersed across many clades with high parsimony scores. These different types of cellular functions have distinct evolutionary patterns reconstructed from the prokaryotic tree.« less

  20. De Novo Assembly and Functional Annotation of the Olive (Olea europaea) Transcriptome

    PubMed Central

    Muñoz-Mérida, Antonio; González-Plaza, Juan José; Cañada, Andrés; Blanco, Ana María; García-López, Maria del Carmen; Rodríguez, José Manuel; Pedrola, Laia; Sicardo, M. Dolores; Hernández, M. Luisa; De la Rosa, Raúl; Belaj, Angjelina; Gil-Borja, Mayte; Luque, Francisco; Martínez-Rivas, José Manuel; Pisano, David G.; Trelles, Oswaldo; Valpuesta, Victoriano; Beuzón, Carmen R.

    2013-01-01

    Olive breeding programmes are focused on selecting for traits as short juvenile period, plant architecture suited for mechanical harvest, or oil characteristics, including fatty acid composition, phenolic, and volatile compounds to suit new markets. Understanding the molecular basis of these characteristics and improving the efficiency of such breeding programmes require the development of genomic information and tools. However, despite its economic relevance, genomic information on olive or closely related species is still scarce. We have applied Sanger and 454 pyrosequencing technologies to generate close to 2 million reads from 12 cDNA libraries obtained from the Picual, Arbequina, and Lechin de Sevilla cultivars and seedlings from a segregating progeny of a Picual × Arbequina cross. The libraries include fruit mesocarp and seeds at three relevant developmental stages, young stems and leaves, active juvenile and adult buds as well as dormant buds, and juvenile and adult roots. The reads were assembled by library or tissue and then assembled together into 81 020 unigenes with an average size of 496 bases. Here, we report their assembly and their functional annotation. PMID:23297299

  1. Report on the 2011 Critical Assessment of Function Annotation (CAFA) meeting

    SciTech Connect

    Friedberg, Iddo

    2015-01-21

    The Critical Assessment of Function Annotation meeting was held July 14-15, 2011 at the Austria Conference Center in Vienna, Austria. There were 73 registered delegates at the meeting. We thank the DOE for this award. It helped us organize and support a scientific meeting AFP 2011 as a special interest group (SIG) meeting associated with the ISMB 2011 conference. The conference was held in Vienna, Austria, in July 2011. The AFP SIG was held on July 15-16, 2011 (immediately preceding the conference). The meeting consisted of two components, the first being a series of talks (invited and contributed) and discussion sections dedicated to protein function research, with an emphasis on the theory and practice of computational methods utilized in functional annotation. The second component provided a large-scale assessment of computational methods through participation in the Critical Assessment of Functional Annotation (CAFA). The meeting was exciting and, based on feedback, quite successful. There were 73 registered participants. The schedule was only slightly different from the one proposed, due to two cancellations. Dr. Olga Troyanskaya has canceled and we invited Dr. David Jones instead. Similarly, instead of Dr. Richard Roberts, Dr. Simon Kasif gave a closing keynote. The remaining invited speakers were Janet Thornton (EBI) and Amos Bairoch (University of Geneva).

  2. Assessing the impact of comparative genomic sequence data on the functional annotation of the Drosophila genome

    PubMed Central

    Bergman, Casey M; Pfeiffer, Barret D; Rincón-Limas, Diego E; Hoskins, Roger A; Gnirke, Andreas; Mungall, Chris J; Wang, Adrienne M; Kronmiller, Brent; Pacleb, Joanne; Park, Soo; Stapleton, Mark; Wan, Kenneth; George, Reed A; de Jong, Pieter J; Botas, Juan; Rubin, Gerald M; Celniker, Susan E

    2002-01-01

    Background It is widely accepted that comparative sequence data can aid the functional annotation of genome sequences; however, the most informative species and features of genome evolution for comparison remain to be determined. Results We analyzed conservation in eight genomic regions (apterous, even-skipped, fushi tarazu, twist, and Rhodopsins 1, 2, 3 and 4) from four Drosophila species (D. erecta, D. pseudoobscura, D. willistoni, and D. littoralis) covering more than 500 kb of the D. melanogaster genome. All D. melanogaster genes (and 78-82% of coding exons) identified in divergent species such as D. pseudoobscura show evidence of functional constraint. Addition of a third species can reveal functional constraint in otherwise non-significant pairwise exon comparisons. Microsynteny is largely conserved, with rearrangement breakpoints, novel transposable element insertions, and gene transpositions occurring in similar numbers. Rates of amino-acid substitution are higher in uncharacterized genes relative to genes that have previously been studied. Conserved non-coding sequences (CNCSs) tend to be spatially clustered with conserved spacing between CNCSs, and clusters of CNCSs can be used to predict enhancer sequences. Conclusions Our results provide the basis for choosing species whose genome sequences would be most useful in aiding the functional annotation of coding and cis-regulatory sequences in Drosophila. Furthermore, this work shows how decoding the spatial organization of conserved sequences, such as the clustering of CNCSs, can complement efforts to annotate eukaryotic genomes on the basis of sequence conservation alone. PMID:12537575

  3. Functional annotations for the Saccharomyces cerevisiae genome: the knowns and the known unknowns

    PubMed Central

    Christie, Karen R.; Hong, Eurie L.; Cherry, J. Michael

    2011-01-01

    The quest to characterize each of the genes of the yeast Saccharomyces cerevisiae has propelled the development and application of novel high-throughput (HTP) experimental techniques. To handle the enormous amount of information generated by these techniques, new bioinformatics tools and resources are needed. Gene Ontology (GO) annotations curated by the Saccharomyces Genome Database (SGD) have facilitated the development of algorithms that analyze HTP data and help predict functions for poorly characterized genes in S. cerevisiae and other organisms. Here, we describe how published results are incorporated into GO annotations at SGD and why researchers can benefit from using these resources wisely to analyze their HTP data and predict gene functions. PMID:19577472

  4. Functional annotation and kinetic characterization of PhnO from Salmonella enterica.

    PubMed Central

    Errey, James C.; Blanchard, John S.

    2008-01-01

    Phosphorus is an essential nutrient for all living organisms. Under conditions of inorganic phosphate starvation, genes from the Pho regulon are induced allowing microorganisms to use phosphonates as a source of phosphorus. The phnO gene was previously annotated as a transcriptional regulator of unknown function due to sequence homology with members of the GCN5-related N-acyltransferase family (GNAT). PhnO can now be functionally annotated as an aminoalkylphosphonic acid N-acetyltransferase which is able to acetylate a range of aminoalkylphosphonic acids. Studies revealed that PhnO proceeds via an ordered, sequential kinetic mechanism with acetyl-CoA binding first followed by aminoalkylphosphonate. Attack by the amine on the thioester of AcCoA generates the tetrahedral intermediate that collapses to generate the products. The enzyme also requires a divalent metal ion for activity, which is the first example of this requirement for a GNAT family member. PMID:16503658

  5. Genome-scale phylogenetic function annotation of large and diverse protein families.

    PubMed

    Engelhardt, Barbara E; Jordan, Michael I; Srouji, John R; Brenner, Steven E

    2011-11-01

    The Statistical Inference of Function Through Evolutionary Relationships (SIFTER) framework uses a statistical graphical model that applies phylogenetic principles to automate precise protein function prediction. Here we present a revised approach (SIFTER version 2.0) that enables annotations on a genomic scale. SIFTER 2.0 produces equivalently precise predictions compared to the earlier version on a carefully studied family and on a collection of 100 protein families. We have added an approximation method to SIFTER 2.0 and show a 500-fold improvement in speed with minimal impact on prediction results in the functionally diverse sulfotransferase protein family. On the Nudix protein family, previously inaccessible to the SIFTER framework because of the 66 possible molecular functions, SIFTER achieved 47.4% accuracy on experimental data (where BLAST achieved 34.0%). Finally, we used SIFTER to annotate all of the Schizosaccharomyces pombe proteins with experimental functional characterizations, based on annotations from proteins in 46 fungal genomes. SIFTER precisely predicted molecular function for 45.5% of the characterized proteins in this genome, as compared with four current function prediction methods that precisely predicted function for 62.6%, 30.6%, 6.0%, and 5.7% of these proteins. We use both precision-recall curves and ROC analyses to compare these genome-scale predictions across the different methods and to assess performance on different types of applications. SIFTER 2.0 is capable of predicting protein molecular function for large and functionally diverse protein families using an approximate statistical model, enabling phylogenetics-based protein function prediction for genome-wide analyses. The code for SIFTER and protein family data are available at http://sifter.berkeley.edu.

  6. Annotation of plant gene function via combined genomics, metabolomics and informatics.

    PubMed

    Tohge, Takayuki; Fernie, Alisdair R

    2012-06-17

    Given the ever expanding number of model plant species for which complete genome sequences are available and the abundance of bio-resources such as knockout mutants, wild accessions and advanced breeding populations, there is a rising burden for gene functional annotation. In this protocol, annotation of plant gene function using combined co-expression gene analysis, metabolomics and informatics is provided (Figure 1). This approach is based on the theory of using target genes of known function to allow the identification of non-annotated genes likely to be involved in a certain metabolic process, with the identification of target compounds via metabolomics. Strategies are put forward for applying this information on populations generated by both forward and reverse genetics approaches in spite of none of these are effortless. By corollary this approach can also be used as an approach to characterise unknown peaks representing new or specific secondary metabolites in the limited tissues, plant species or stress treatment, which is currently the important trial to understanding plant metabolism.

  7. Functional Analysis of Frequent Lung Cancer Amplicons Under Current Genome Annotation

    DTIC Science & Technology

    2015-12-01

    Exemplary groups of such genes include many non-protein-coding genes like long non-coding RNAs and microRNAs (miRNAs). In study, we examined the PVT1...lung tumorigenesis. The implication is that future studies of the 8q24 amplicon should concentrate on characterizing the PVT1 RNA transcript. 15...SUBJECT TERMS Noncoding RNA , microRNA, lung cancer, Genome annotation 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT 18. NUMBER OF

  8. Annotation of cis-regulatory elements by identification, subclassification, and functional assessment of multispecies conserved sequences

    PubMed Central

    Hughes, Jim R.; Cheng, Jan-Fang; Ventress, Nicki; Prabhakar, Shyam; Clark, Kevin; Anguita, Eduardo; De Gobbi, Marco; de Jong, Pieter; Rubin, Eddy; Higgs, Douglas R.

    2005-01-01

    An important step toward improving the annotation of the human genome is to identify cis-acting regulatory elements from primary DNA sequence. One approach is to compare sequences from multiple, divergent species. This approach distinguishes multispecies conserved sequences (MCS) in noncoding regions from more rapidly evolving neutral DNA. Here, we have analyzed a region of ≈238kb containing the human α globin cluster that was sequenced and/or annotated across the syntenic region in 22 species spanning 500 million years of evolution. Using a variety of bioinformatic approaches and correlating the results with many aspects of chromosome structure and function in this region, we were able to identify and evaluate the importance of 24 individual MCSs. This approach sensitively and accurately identified previously characterized regulatory elements but also discovered unidentified promoters, exons, splicing, and transcriptional regulatory elements. Together, these studies demonstrate an integrated approach by which to identify, subclassify, and predict the potential importance of MCSs. PMID:15998734

  9. Human cell adhesion molecules: annotated functional subtypes and overrepresentation of addiction-associated genes

    PubMed Central

    Zhong, Xiaoming; Drgonova, Jana; Li, Chuan-Yun; Uhl, George R.

    2015-01-01

    Human cell adhesion molecules (CAMs) are essential both for a) proper development, modulation and maintenance of interactions between cells and for b) cell-to-cell (and matrix-to-cell) communication about these interactions. CAMs are thus key to proper development and plasticity of organs and tissues that include the brain. Despite recognition of the existence of these dual CAM roles and appreciation of the differential functional significance of these roles, there have been surprisingly few systematic studies that have carefully enumerated the universe of CAMs, identified the preferred roles for specific CAMs in distinct types of cellular connections and communication, or related these issues to specific brain disorders or brain circuits. In this paper, we substantially update and review the set of human genes that are likely to encode CAMs based on searches of databases, literature reviews and annotations. We describe the likely CAMs and the functional CAM subclasses into which they fall. These include “iCAMs”, whose contacts largely mediate cell to cell communication, those involved in focal adhesions, CAM genes whose products are preferentially involved with stereotyped and morphologically-identifiable connections between cells (adherens junctions, gap junctions) and smaller numbers of genes in other classes. We discuss a novel proposed mechanism involving selective anchoring of the constituents of iCAM-containing lipid rafts in zones of close neuronal apposition to membranes expressing binding partners of these iCAMs. CAM data from genetic and genomic studies of addiction in humans and mouse models provide examples of the ways in which CAM variation is likely to contribute to a specific brain-based disorder. We discuss how differences in CAM splicing mediated by differences in the addiction-associated splicing regulator RBFOX1/A2BP1 could enrich this picture. CAM expression in dopamine neurons provides one of the ways in which variations in cell adhesion

  10. Accurate protein structure annotation through competitive diffusion of enzymatic functions over a network of local evolutionary similarities.

    PubMed

    Venner, Eric; Lisewski, Andreas Martin; Erdin, Serkan; Ward, R Matthew; Amin, Shivas R; Lichtarge, Olivier

    2010-12-13

    High-throughput Structural Genomics yields many new protein structures without known molecular function. This study aims to uncover these missing annotations by globally comparing select functional residues across the structural proteome. First, Evolutionary Trace Annotation, or ETA, identifies which proteins have local evolutionary and structural features in common; next, these proteins are linked together into a proteomic network of ETA similarities; then, starting from proteins with known functions, competing functional labels diffuse link-by-link over the entire network. Every node is thus assigned a likelihood z-score for every function, and the most significant one at each node wins and defines its annotation. In high-throughput controls, this competitive diffusion process recovered enzyme activity annotations with 99% and 97% accuracy at half-coverage for the third and fourth Enzyme Commission (EC) levels, respectively. This corresponds to false positive rates 4-fold lower than nearest-neighbor and 5-fold lower than sequence-based annotations. In practice, experimental validation of the predicted carboxylesterase activity in a protein from Staphylococcus aureus illustrated the effectiveness of this approach in the context of an increasingly drug-resistant microbe. This study further links molecular function to a small number of evolutionarily important residues recognizable by Evolutionary Tracing and it points to the specificity and sensitivity of functional annotation by competitive global network diffusion. A web server is at http://mammoth.bcm.tmc.edu/networks.

  11. Bacterial genome annotation.

    PubMed

    Beckloff, Nicholas; Starkenburg, Shawn; Freitas, Tracey; Chain, Patrick

    2012-01-01

    Annotation of prokaryotic sequences can be separated into structural and functional annotation. Structural annotation is dependent on algorithmic interrogation of experimental evidence to discover the physical characteristics of a gene. This is done in an effort to construct accurate gene models, so understanding function or evolution of genes among organisms is not impeded. Functional annotation is dependent on sequence similarity to other known genes or proteins in an effort to assess the function of the gene. Combining structural and functional annotation across genomes in a comparative manner promotes higher levels of accurate annotation as well as an advanced understanding of genome evolution. As the availability of bacterial sequences increases and annotation methods improve, the value of comparative annotation will increase.

  12. Annotation inconsistencies beyond sequence similarity-based function prediction - phylogeny and genome structure.

    PubMed

    Promponas, Vasilis J; Iliopoulos, Ioannis; Ouzounis, Christos A

    2015-01-01

    The function annotation process in computational biology has increasingly shifted from the traditional characterization of individual biochemical roles of protein molecules to the system-wide detection of entire metabolic pathways and genomic structures. The so-called genome-aware methods broaden misannotation inconsistencies in genome sequences beyond protein function assignments, encompassing phylogenetic anomalies and artifactual genomic regions. We outline three categories of error propagation in databases by providing striking examples - at various levels of appreciation by the community from traditional to emerging, thus raising awareness for future solutions.

  13. Functional characterization of two M42 aminopeptidases erroneously annotated as cellulases.

    PubMed

    Dutoit, Raphaël; Brandt, Nathalie; Legrain, Christianne; Bauvois, Cédric

    2012-01-01

    Several aminopeptidases of the M42 family have been described as tetrahedral-shaped dodecameric (TET) aminopeptidases. A current hypothesis suggests that these enzymes are involved, along with the tricorn peptidase, in degrading peptides produced by the proteasome. Yet the M42 family remains ill defined, as some members have been annotated as cellulases because of their homology with CelM, formerly described as an endoglucanase of Clostridium thermocellum. Here we describe the catalytic functions and substrate profiles CelM and of TmPep1050, the latter having been annotated as an endoglucanase of Thermotoga maritima. Both enzymes were shown to catalyze hydrolysis of nonpolar aliphatic L-amino acid-pNA substrates, the L-leucine derivative appearing as the best substrate. No significant endoglucanase activity was measured, either for TmPep1050 or CelM. Addition of cobalt ions enhanced the activity of both enzymes significantly, while both the chelating agent EDTA and bestatin, a specific inhibitor of metalloaminopeptidases, proved inhibitory. Our results strongly suggest that one should avoid annotating members of the M42 aminopeptidase family as cellulases. In an updated assessment of the distribution of M42 aminopeptidases, we found TET aminopeptidases to be distributed widely amongst archaea and bacteria. We additionally observed that several phyla lack both TET and tricorn. This suggests that other complexes may act downstream from the proteasome.

  14. Generation, functional annotation and comparative analysis of black spruce (Picea mariana) ESTs: an important conifer genomic resource

    PubMed Central

    2013-01-01

    Background EST (expressed sequence tag) sequences and their annotation provide a highly valuable resource for gene discovery, genome sequence annotation, and other genomics studies that can be applied in genetics, breeding and conservation programs for non-model organisms. Conifers are long-lived plants that are ecologically and economically important globally, and have a large genome size. Black spruce (Picea mariana), is a transcontinental species of the North American boreal and temperate forests. However, there are limited transcriptomic and genomic resources for this species. The primary objective of our study was to develop a black spruce transcriptomic resource to facilitate on-going functional genomics projects related to growth and adaptation to climate change. Results We conducted bidirectional sequencing of cDNA clones from a standard cDNA library constructed from black spruce needle tissues. We obtained 4,594 high quality (2,455 5' end and 2,139 3' end) sequence reads, with an average read-length of 532 bp. Clustering and assembly of ESTs resulted in 2,731 unique sequences, consisting of 2,234 singletons and 497 contigs. Approximately two-thirds (63%) of unique sequences were functionally annotated. Genes involved in 36 molecular functions and 90 biological processes were discovered, including 24 putative transcription factors and 232 genes involved in photosynthesis. Most abundantly expressed transcripts were associated with photosynthesis, growth factors, stress and disease response, and transcription factors. A total of 216 full-length genes were identified. About 18% (493) of the transcripts were novel, representing an important addition to the Genbank EST database (dbEST). Fifty-seven di-, tri-, tetra- and penta-nucleotide simple sequence repeats were identified. Conclusions We have developed the first high quality EST resource for black spruce and identified 493 novel transcripts, which may be species-specific related to life history and

  15. High-throughput comparison, functional annotation, and metabolic modeling of plant genomes using the PlantSEED resource.

    PubMed

    Seaver, Samuel M D; Gerdes, Svetlana; Frelin, Océane; Lerma-Ortiz, Claudia; Bradbury, Louis M T; Zallot, Rémi; Hasnain, Ghulam; Niehaus, Thomas D; El Yacoubi, Basma; Pasternak, Shiran; Olson, Robert; Pusch, Gordon; Overbeek, Ross; Stevens, Rick; de Crécy-Lagard, Valérie; Ware, Doreen; Hanson, Andrew D; Henry, Christopher S

    2014-07-01

    The increasing number of sequenced plant genomes is placing new demands on the methods applied to analyze, annotate, and model these genomes. Today's annotation pipelines result in inconsistent gene assignments that complicate comparative analyses and prevent efficient construction of metabolic models. To overcome these problems, we have developed the PlantSEED, an integrated, metabolism-centric database to support subsystems-based annotation and metabolic model reconstruction for plant genomes. PlantSEED combines SEED subsystems technology, first developed for microbial genomes, with refined protein families and biochemical data to assign fully consistent functional annotations to orthologous genes, particularly those encoding primary metabolic pathways. Seamless integration with its parent, the prokaryotic SEED database, makes PlantSEED a unique environment for cross-kingdom comparative analysis of plant and bacterial genomes. The consistent annotations imposed by PlantSEED permit rapid reconstruction and modeling of primary metabolism for all plant genomes in the database. This feature opens the unique possibility of model-based assessment of the completeness and accuracy of gene annotation and thus allows computational identification of genes and pathways that are restricted to certain genomes or need better curation. We demonstrate the PlantSEED system by producing consistent annotations for 10 reference genomes. We also produce a functioning metabolic model for each genome, gapfilling to identify missing annotations and proposing gene candidates for missing annotations. Models are built around an extended biomass composition representing the most comprehensive published to date. To our knowledge, our models are the first to be published for seven of the genomes analyzed.

  16. BambooGDB: a bamboo genome database with functional annotation and an analysis platform

    PubMed Central

    Zhao, Hansheng; Peng, Zhenhua; Fei, Benhua; Li, Lubin; Hu, Tao; Gao, Zhimin; Jiang, Zehui

    2014-01-01

    Bamboo, as one of the most important non-timber forest products and fastest-growing plants in the world, represents the only major lineage of grasses that is native to forests. Recent success on the first high-quality draft genome sequence of moso bamboo (Phyllostachys edulis) provides new insights on bamboo genetics and evolution. To further extend our understanding on bamboo genome and facilitate future studies on the basis of previous achievements, here we have developed BambooGDB, a bamboo genome database with functional annotation and analysis platform. The de novo sequencing data, together with the full-length complementary DNA and RNA-seq data of moso bamboo composed the main contents of this database. Based on these sequence data, a comprehensively functional annotation for bamboo genome was made. Besides, an analytical platform composed of comparative genomic analysis, protein–protein interactions network, pathway analysis and visualization of genomic data was also constructed. As discovery tools to understand and identify biological mechanisms of bamboo, the platform can be used as a systematic framework for helping and designing experiments for further validation. Moreover, diverse and powerful search tools and a convenient browser were incorporated to facilitate the navigation of these data. As far as we know, this is the first genome database for bamboo. Through integrating high-throughput sequencing data, a full functional annotation and several analysis modules, BambooGDB aims to provide worldwide researchers with a central genomic resource and an extensible analysis platform for bamboo genome. BambooGDB is freely available at http://www.bamboogdb.org/. Database URL: http://www.bamboogdb.org PMID:24602877

  17. The SOFG Anatomy Entry List (SAEL): An Annotation Tool for Functional Genomics Data

    PubMed Central

    Parkinson, Helen; Aitken, Stuart; Baldock, Richard A.; Bard, Jonathan B. L.; Burger, Albert; Hayamizu, Terry F.; Rector, Alan; Ringwald, Martin; Rogers, Jeremy; Rosse, Cornelius; Stoeckert, Christian J.

    2004-01-01

    A great deal of data in functional genomics studies needs to be annotated with low-resolution anatomical terms. For example, gene expression assays based on manually dissected samples (microarray, SAGE, etc.) need high-level anatomical terms to describe sample origin. First-pass annotation in high-throughput assays (e.g. large-scale in situ gene expression screens or phenotype screens) and bibliographic applications, such as selection of keywords, would also benefit from a minimum set of standard anatomical terms. Although only simple terms are required, the researcher faces serious practical problems of inconsistency and confusion, given the different aims and the range of complexity of existing anatomy ontologies. A Standards and Ontologies for Functional Genomics (SOFG) group therefore initiated discussions between several of the major anatomical ontologies for higher vertebrates. As we report here, one result of these discussions is a simple, accessible, controlled vocabulary of gross anatomical terms, the SOFG Anatomy Entry List (SAEL). The SAEL is available from http://www.sofg.org and is intended as a resource for biologists, curators, bioinformaticians and developers of software supporting functional genomics. It can be used directly for annotation in the contexts described above. Importantly, each term is linked to the corresponding term in each of the major anatomy ontologies. Where the simple list does not provide enough detail or sophistication, therefore, the researcher can use the SAEL to choose the appropriate ontology and move directly to the relevant term as an entry point. The SAEL links will also be used to support computational access to the respective ontologies. PMID:18629134

  18. BambooGDB: a bamboo genome database with functional annotation and an analysis platform.

    PubMed

    Zhao, Hansheng; Peng, Zhenhua; Fei, Benhua; Li, Lubin; Hu, Tao; Gao, Zhimin; Jiang, Zehui

    2014-01-01

    Bamboo, as one of the most important non-timber forest products and fastest-growing plants in the world, represents the only major lineage of grasses that is native to forests. Recent success on the first high-quality draft genome sequence of moso bamboo (Phyllostachys edulis) provides new insights on bamboo genetics and evolution. To further extend our understanding on bamboo genome and facilitate future studies on the basis of previous achievements, here we have developed BambooGDB, a bamboo genome database with functional annotation and analysis platform. The de novo sequencing data, together with the full-length complementary DNA and RNA-seq data of moso bamboo composed the main contents of this database. Based on these sequence data, a comprehensively functional annotation for bamboo genome was made. Besides, an analytical platform composed of comparative genomic analysis, protein-protein interactions network, pathway analysis and visualization of genomic data was also constructed. As discovery tools to understand and identify biological mechanisms of bamboo, the platform can be used as a systematic framework for helping and designing experiments for further validation. Moreover, diverse and powerful search tools and a convenient browser were incorporated to facilitate the navigation of these data. As far as we know, this is the first genome database for bamboo. Through integrating high-throughput sequencing data, a full functional annotation and several analysis modules, BambooGDB aims to provide worldwide researchers with a central genomic resource and an extensible analysis platform for bamboo genome. BambooGDB is freely available at http://www.bamboogdb.org/. Database URL: http://www.bamboogdb.org.

  19. Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga Nannochloropsis oceanica CCMP1779

    PubMed Central

    Tsai, Chia-Hong; Bullard, Blair; Cornish, Adam J.; Harvey, Christopher; Reca, Ida-Barbara; Thornburg, Chelsea; Achawanantakun, Rujira; Buehl, Christopher J.; Campbell, Michael S.; Cavalier, David; Childs, Kevin L.; Clark, Teresa J.; Deshpande, Rahul; Erickson, Erika; Armenia Ferguson, Ann; Handee, Witawas; Kong, Que; Li, Xiaobo; Liu, Bensheng; Lundback, Steven; Peng, Cheng; Roston, Rebecca L.; Sanjaya; Simpson, Jeffrey P.; TerBush, Allan; Warakanont, Jaruswan; Zäuner, Simone; Farre, Eva M.; Hegg, Eric L.; Jiang, Ning; Kuo, Min-Hao; Lu, Yan; Niyogi, Krishna K.; Ohlrogge, John; Osteryoung, Katherine W.; Shachar-Hill, Yair; Sears, Barbara B.; Sun, Yanni; Takahashi, Hideki; Yandell, Mark; Shiu, Shin-Han; Benning, Christoph

    2012-01-01

    Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks, although no single species has emerged as a preferred organism. Moreover, adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candidate species. Heterokonts of the genus Nannochloropsis naturally have high cellular oil content and are already in use for industrial production of high-value lipid products. First success in applying reverse genetics by targeted gene replacement makes Nannochloropsis oceanica an attractive model to investigate the cell and molecular biology and biochemistry of this fascinating organism group. Here we present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA sequencing data from nitrogen-replete and nitrogen-depleted growth conditions support a total of 11,973 genes, of which in addition to automatic annotation some were manually inspected to predict the biochemical repertoire for this organism. Among others, more than 100 genes putatively related to lipid metabolism, 114 predicted transcription factors, and 109 transcriptional regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire with the recently published N. gaditana genome identified 2,649 genes likely specific to N. oceanica CCMP1779. Many of these N. oceanica–specific genes have putative orthologs in other species or are supported by transcriptional evidence. However, because similarity-based annotations are limited, functions of most of these species-specific genes remain unknown. Aside from the genome sequence and its analysis, protocols for the transformation of N. oceanica CCMP1779 are provided. The availability of genomic and transcriptomic data for Nannochloropsis oceanica CCMP1779, along with efficient transformation protocols, provides a blueprint for future detailed gene functional analysis and genetic engineering of Nannochloropsis species by a growing

  20. Genome, functional gene annotation, and nuclear transformation of the heterokont oleaginous alga Nannochloropsis oceanica CCMP1779.

    PubMed

    Vieler, Astrid; Wu, Guangxi; Tsai, Chia-Hong; Bullard, Blair; Cornish, Adam J; Harvey, Christopher; Reca, Ida-Barbara; Thornburg, Chelsea; Achawanantakun, Rujira; Buehl, Christopher J; Campbell, Michael S; Cavalier, David; Childs, Kevin L; Clark, Teresa J; Deshpande, Rahul; Erickson, Erika; Armenia Ferguson, Ann; Handee, Witawas; Kong, Que; Li, Xiaobo; Liu, Bensheng; Lundback, Steven; Peng, Cheng; Roston, Rebecca L; Sanjaya; Simpson, Jeffrey P; Terbush, Allan; Warakanont, Jaruswan; Zäuner, Simone; Farre, Eva M; Hegg, Eric L; Jiang, Ning; Kuo, Min-Hao; Lu, Yan; Niyogi, Krishna K; Ohlrogge, John; Osteryoung, Katherine W; Shachar-Hill, Yair; Sears, Barbara B; Sun, Yanni; Takahashi, Hideki; Yandell, Mark; Shiu, Shin-Han; Benning, Christoph

    2012-01-01

    Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks, although no single species has emerged as a preferred organism. Moreover, adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candidate species. Heterokonts of the genus Nannochloropsis naturally have high cellular oil content and are already in use for industrial production of high-value lipid products. First success in applying reverse genetics by targeted gene replacement makes Nannochloropsis oceanica an attractive model to investigate the cell and molecular biology and biochemistry of this fascinating organism group. Here we present the assembly of the 28.7 Mb genome of N. oceanica CCMP1779. RNA sequencing data from nitrogen-replete and nitrogen-depleted growth conditions support a total of 11,973 genes, of which in addition to automatic annotation some were manually inspected to predict the biochemical repertoire for this organism. Among others, more than 100 genes putatively related to lipid metabolism, 114 predicted transcription factors, and 109 transcriptional regulators were annotated. Comparison of the N. oceanica CCMP1779 gene repertoire with the recently published N. gaditana genome identified 2,649 genes likely specific to N. oceanica CCMP1779. Many of these N. oceanica-specific genes have putative orthologs in other species or are supported by transcriptional evidence. However, because similarity-based annotations are limited, functions of most of these species-specific genes remain unknown. Aside from the genome sequence and its analysis, protocols for the transformation of N. oceanica CCMP1779 are provided. The availability of genomic and transcriptomic data for Nannochloropsis oceanica CCMP1779, along with efficient transformation protocols, provides a blueprint for future detailed gene functional analysis and genetic engineering of Nannochloropsis species by a growing

  1. Annotation extension through protein family annotation coherence metrics

    PubMed Central

    Bastos, Hugo P.; Clarke, Luka A.; Couto, Francisco M.

    2013-01-01

    Protein functional annotation consists in associating proteins with textual descriptors elucidating their biological roles. The bulk of annotation is done via automated procedures that ultimately rely on annotation transfer. Despite a large number of existing protein annotation procedures the ever growing protein space is never completely annotated. One of the facets of annotation incompleteness derives from annotation uncertainty. Often when protein function cannot be predicted with enough specificity it is instead conservatively annotated with more generic terms. In a scenario of protein families or functionally related (or even dissimilar) sets this leads to a more difficult task of using annotations to compare the extent of functional relatedness among all family or set members. However, we postulate that identifying sub-sets of functionally coherent proteins annotated at a very specific level, can help the annotation extension of other incompletely annotated proteins within the same family or functionally related set. As an example we analyse the status of annotation of a set of CAZy families belonging to the Polysaccharide Lyase class. We show that through the use of visualization methods and semantic similarity based metrics it is possible to identify families and respective annotation terms within them that are suitable for possible annotation extension. Based on our analysis we then propose a semi-automatic methodology leading to the extension of single annotation terms within these partially annotated protein sets or families. PMID:24130572

  2. Proteomics and transcriptomics of the BABA-induced resistance response in potato using a novel functional annotation approach

    PubMed Central

    2014-01-01

    Background Induced resistance (IR) can be part of a sustainable plant protection strategy against important plant diseases. β-aminobutyric acid (BABA) can induce resistance in a wide range of plants against several types of pathogens, including potato infected with Phytophthora infestans. However, the molecular mechanisms behind this are unclear and seem to be dependent on the system studied. To elucidate the defence responses activated by BABA in potato, a genome-wide transcript microarray analysis in combination with label-free quantitative proteomics analysis of the apoplast secretome were performed two days after treatment of the leaf canopy with BABA at two concentrations, 1 and 10 mM. Results Over 5000 transcripts were differentially expressed and over 90 secretome proteins changed in abundance indicating a massive activation of defence mechanisms with 10 mM BABA, the concentration effective against late blight disease. To aid analysis, we present a more comprehensive functional annotation of the microarray probes and gene models by retrieving information from orthologous gene families across 26 sequenced plant genomes. The new annotation provided GO terms to 8616 previously un-annotated probes. Conclusions BABA at 10 mM affected several processes related to plant hormones and amino acid metabolism. A major accumulation of PR proteins was also evident, and in the mevalonate pathway, genes involved in sterol biosynthesis were down-regulated, whereas several enzymes involved in the sesquiterpene phytoalexin biosynthesis were up-regulated. Interestingly, abscisic acid (ABA) responsive genes were not as clearly regulated by BABA in potato as previously reported in Arabidopsis. Together these findings provide candidates and markers for improved resistance in potato, one of the most important crops in the world. PMID:24773703

  3. Integrating biological knowledge based on functional annotations for biclustering of gene expression data.

    PubMed

    Nepomuceno, Juan A; Troncoso, Alicia; Nepomuceno-Chamorro, Isabel A; Aguilar-Ruiz, Jesús S

    2015-05-01

    Gene expression data analysis is based on the assumption that co-expressed genes imply co-regulated genes. This assumption is being reformulated because the co-expression of a group of genes may be the result of an independent activation with respect to the same experimental condition and not due to the same regulatory regime. For this reason, traditional techniques are recently being improved with the use of prior biological knowledge from open-access repositories together with gene expression data. Biclustering is an unsupervised machine learning technique that searches patterns in gene expression data matrices. A scatter search-based biclustering algorithm that integrates biological information is proposed in this paper. In addition to the gene expression data matrix, the input of the algorithm is only a direct annotation file that relates each gene to a set of terms from a biological repository where genes are annotated. Two different biological measures, FracGO and SimNTO, are proposed to integrate this information by means of its addition to-be-optimized fitness function in the scatter search scheme. The measure FracGO is based on the biological enrichment and SimNTO is based on the overlapping among GO annotations of pairs of genes. Experimental results evaluate the proposed algorithm for two datasets and show the algorithm performs better when biological knowledge is integrated. Moreover, the analysis and comparison between the two different biological measures is presented and it is concluded that the differences depend on both the data source and how the annotation file has been built in the case GO is used. It is also shown that the proposed algorithm obtains a greater number of enriched biclusters than other classical biclustering algorithms typically used as benchmark and an analysis of the overlapping among biclusters reveals that the biclusters obtained present a low overlapping. The proposed methodology is a general-purpose algorithm which allows

  4. Insyght: navigating amongst abundant homologues, syntenies and gene functional annotations in bacteria, it's that symbol!

    PubMed Central

    Lacroix, Thomas; Loux, Valentin; Gendrault, Annie; Hoebeke, Mark; Gibrat, Jean-François

    2014-01-01

    High-throughput techniques have considerably increased the potential of comparative genomics whilst simultaneously posing many new challenges. One of those challenges involves efficiently mining the large amount of data produced and exploring the landscape of both conserved and idiosyncratic genomic regions across multiple genomes. Domains of application of these analyses are diverse: identification of evolutionary events, inference of gene functions, detection of niche-specific genes or phylogenetic profiling. Insyght is a comparative genomic visualization tool that combines three complementary displays: (i) a table for thoroughly browsing amongst homologues, (ii) a comparator of orthologue functional annotations and (iii) a genomic organization view designed to improve the legibility of rearrangements and distinctive loci. The latter display combines symbolic and proportional graphical paradigms. Synchronized navigation across multiple species and interoperability between the views are core features of Insyght. A gene filter mechanism is provided that helps the user to build a biologically relevant gene set according to multiple criteria such as presence/absence of homologues and/or various annotations. We illustrate the use of Insyght with scenarios. Currently, only Bacteria and Archaea are supported. A public instance is available at http://genome.jouy.inra.fr/Insyght. The tool is freely downloadable for private data set analysis. PMID:25249626

  5. Annotated Videography.

    ERIC Educational Resources Information Center

    United States Holocaust Memorial Museum, Washington, DC.

    This annotated list of 43 videotapes recommended for classroom use addresses various themes for teaching about the Holocaust, including: (1) overviews of the Holocaust; (2) life before the Holocaust; (3) propaganda; (4) racism, anti-Semitism; (5) "enemies of the state"; (6) ghettos; (7) camps; (8) genocide; (9) rescue; (10) resistance;…

  6. BIOFILTER AS A FUNCTIONAL ANNOTATION PIPELINE FOR COMMON AND RARE COPY NUMBER BURDEN

    PubMed Central

    KIM, DOKYOON; LUCAS, ANASTASIA; GLESSNER, JOSEPH; VERMA, SHEFALI S.; BRADFORD, YUKI; LI, RUOWANG; FRASE, ALEX T.; HAKONARSON, HAKON; PEISSIG, PEGGY; BRILLIANT, MURRAY; RITCHIE, MARYLYN D.

    2015-01-01

    Recent studies on copy number variation (CNV) have suggested that an increasing burden of CNVs is associated with susceptibility or resistance to disease. A large number of genes or genomic loci contribute to complex diseases such as autism. Thus, total genomic copy number burden, as an accumulation of copy number change, is a meaningful measure of genomic instability to identify the association between global genetic effects and phenotypes of interest. However, no systematic annotation pipeline has been developed to interpret biological meaning based on the accumulation of copy number change across the genome associated with a phenotype of interest. In this study, we develop a comprehensive and systematic pipeline for annotating copy number variants into genes/genomic regions and subsequently pathways and other gene groups using Biofilter – a bioinformatics tool that aggregates over a dozen publicly available databases of prior biological knowledge. Next we conduct enrichment tests of biologically defined groupings of CNVs including genes, pathways, Gene Ontology, or protein families. We applied the proposed pipeline to a CNV dataset from the Marshfield Clinic Personalized Medicine Research Project (PMRP) in a quantitative trait phenotype derived from the electronic health record – total cholesterol. We identified several significant pathways such as toll-like receptor signaling pathway and hepatitis C pathway, gene ontologies (GOs) of nucleoside triphosphatase activity (NTPase) and response to virus, and protein families such as cell morphogenesis that are associated with the total cholesterol phenotype based on CNV profiles (permutation p-value < 0.01). Based on the copy number burden analysis, it follows that the more and larger the copy number changes, the more likely that one or more target genes that influence disease risk and phenotypic severity will be affected. Thus, our study suggests the proposed enrichment pipeline could improve the

  7. BIOFILTER AS A FUNCTIONAL ANNOTATION PIPELINE FOR COMMON AND RARE COPY NUMBER BURDEN.

    PubMed

    Kim, Dokyoon; Lucas, Anastasia; Glessner, Joseph; Verma, Shefali S; Bradford, Yuki; Li, Ruowang; Frase, Alex T; Hakonarson, Hakon; Peissig, Peggy; Brilliant, Murray; Ritchie, Marylyn D

    2016-01-01

    Recent studies on copy number variation (CNV) have suggested that an increasing burden of CNVs is associated with susceptibility or resistance to disease. A large number of genes or genomic loci contribute to complex diseases such as autism. Thus, total genomic copy number burden, as an accumulation of copy number change, is a meaningful measure of genomic instability to identify the association between global genetic effects and phenotypes of interest. However, no systematic annotation pipeline has been developed to interpret biological meaning based on the accumulation of copy number change across the genome associated with a phenotype of interest. In this study, we develop a comprehensive and systematic pipeline for annotating copy number variants into genes/genomic regions and subsequently pathways and other gene groups using Biofilter - a bioinformatics tool that aggregates over a dozen publicly available databases of prior biological knowledge. Next we conduct enrichment tests of biologically defined groupings of CNVs including genes, pathways, Gene Ontology, or protein families. We applied the proposed pipeline to a CNV dataset from the Marshfield Clinic Personalized Medicine Research Project (PMRP) in a quantitative trait phenotype derived from the electronic health record - total cholesterol. We identified several significant pathways such as toll-like receptor signaling pathway and hepatitis C pathway, gene ontologies (GOs) of nucleoside triphosphatase activity (NTPase) and response to virus, and protein families such as cell morphogenesis that are associated with the total cholesterol phenotype based on CNV profiles (permutation p-value < 0.01). Based on the copy number burden analysis, it follows that the more and larger the copy number changes, the more likely that one or more target genes that influence disease risk and phenotypic severity will be affected. Thus, our study suggests the proposed enrichment pipeline could improve the interpretability of

  8. Experimental Strategies for Functional Annotation and Metabolism Discovery: Targeted Screening of Solute Binding Proteins and Unbiased Panning of Metabolomes

    PubMed Central

    2015-01-01

    The rate at which genome sequencing data is accruing demands enhanced methods for functional annotation and metabolism discovery. Solute binding proteins (SBPs) facilitate the transport of the first reactant in a metabolic pathway, thereby constraining the regions of chemical space and the chemistries that must be considered for pathway reconstruction. We describe high-throughput protein production and differential scanning fluorimetry platforms, which enabled the screening of 158 SBPs against a 189 component library specifically tailored for this class of proteins. Like all screening efforts, this approach is limited by the practical constraints imposed by construction of the library, i.e., we can study only those metabolites that are known to exist and which can be made in sufficient quantities for experimentation. To move beyond these inherent limitations, we illustrate the promise of crystallographic- and mass spectrometric-based approaches for the unbiased use of entire metabolomes as screening libraries. Together, our approaches identified 40 new SBP ligands, generated experiment-based annotations for 2084 SBPs in 71 isofunctional clusters, and defined numerous metabolic pathways, including novel catabolic pathways for the utilization of ethanolamine as sole nitrogen source and the use of d-Ala-d-Ala as sole carbon source. These efforts begin to define an integrated strategy for realizing the full value of amassing genome sequence data. PMID:25540822

  9. A Novel Method for Functional Annotation Prediction Based on Combination of Classification Methods

    PubMed Central

    Jung, Jaehee; Lee, Heung Ki

    2014-01-01

    Automated protein function prediction defines the designation of functions of unknown protein functions by using computational methods. This technique is useful to automatically assign gene functional annotations for undefined sequences in next generation genome analysis (NGS). NGS is a popular research method since high-throughput technologies such as DNA sequencing and microarrays have created large sets of genes. These huge sequences have greatly increased the need for analysis. Previous research has been based on the similarities of sequences as this is strongly related to the functional homology. However, this study aimed to designate protein functions by automatically predicting the function of the genome by utilizing InterPro (IPR), which can represent the properties of the protein family and groups of the protein function. Moreover, we used gene ontology (GO), which is the controlled vocabulary used to comprehensively describe the protein function. To define the relationship between IPR and GO terms, three pattern recognition techniques have been employed under different conditions, such as feature selection and weighted value, instead of a binary one. PMID:25133242

  10. On the Use of Gene Ontology Annotations to Assess Functional Similarity among Orthologs and Paralogs: A Short Report.

    PubMed

    Thomas, Paul D; Wood, Valerie; Mungall, Christopher J; Lewis, Suzanna E; Blake, Judith A

    2012-01-01

    A recent paper (Nehrt et al., PLoS Comput. Biol. 7:e1002073, 2011) has proposed a metric for the "functional similarity" between two genes that uses only the Gene Ontology (GO) annotations directly derived from published experimental results. Applying this metric, the authors concluded that paralogous genes within the mouse genome or the human genome are more functionally similar on average than orthologous genes between these genomes, an unexpected result with broad implications if true. We suggest, based on both theoretical and empirical considerations, that this proposed metric should not be interpreted as a functional similarity, and therefore cannot be used to support any conclusions about the "ortholog conjecture" (or, more properly, the "ortholog functional conservation hypothesis"). First, we reexamine the case studies presented by Nehrt et al. as examples of orthologs with divergent functions, and come to a very different conclusion: they actually exemplify how GO annotations for orthologous genes provide complementary information about conserved biological functions. We then show that there is a global ascertainment bias in the experiment-based GO annotations for human and mouse genes: particular types of experiments tend to be performed in different model organisms. We conclude that the reported statistical differences in annotations between pairs of orthologous genes do not reflect differences in biological function, but rather complementarity in experimental approaches. Our results underscore two general considerations for researchers proposing novel types of analysis based on the GO: 1) that GO annotations are often incomplete, potentially in a biased manner, and subject to an "open world assumption" (absence of an annotation does not imply absence of a function), and 2) that conclusions drawn from a novel, large-scale GO analysis should whenever possible be supported by careful, in-depth examination of examples, to help ensure the conclusions have a

  11. Expression profiling of hypothetical genes in Desulfovibrio vulgaris leads to improved functional annotation

    SciTech Connect

    Elias, Dwayne A.; Mukhopadhyay, Aindrila; Joachimiak, Marcine P.; Drury, Elliott C.; Redding, Alyssa M.; Yen, Huei-Che B.; Fields, Matthew; Hazen, Terry C.; Arkin, Adam P.; Keasling, Jay D.; Wall, Judy D.

    2009-03-17

    Hypothetical (HyP) and conserved HyP genes account for >30% of sequenced bacterial genomes. For the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough, 347 of the 3634 genes were annotated as conserved HyP (9.5%) along with 887 HyP genes (24.4%). Given the large fraction of the genome, it is plausible that some of these genes serve critical cellular roles. The study goals were to determine which genes were expressed and provide a more functionally based annotation. To accomplish this, expression profiles of 1234 HyP and conserved genes were used from transcriptomic datasets of 11 environmental stresses, complemented with shotgun LC–MS/MS and AMT tag proteomic data. Genes were divided into putatively polycistronic operons and those predicted to be monocistronic, then classified by basal expression levels and grouped according to changes in expression for one or multiple stresses. One thousand two hundred and twelve of these genes were transcribed with 786 producing detectable proteins. There was no evidence for expression of 17 predicted genes.

  12. GO-FAANG meeting: a Gathering On Functional Annotation of Animal Genomes.

    PubMed

    Tuggle, Christopher K; Giuffra, Elisabetta; White, Stephen N; Clarke, Laura; Zhou, Huaijun; Ross, Pablo J; Acloque, Hervé; Reecy, James M; Archibald, Alan; Bellone, Rebecca R; Boichard, Michèle; Chamberlain, Amanda; Cheng, Hans; Crooijmans, Richard P M A; Delany, Mary E; Finno, Carrie J; Groenen, Martien A M; Hayes, Ben; Lunney, Joan K; Petersen, Jessica L; Plastow, Graham S; Schmidt, Carl J; Song, Jiuzhou; Watson, Mick

    2016-10-01

    The Functional Annotation of Animal Genomes (FAANG) Consortium recently held a Gathering On FAANG (GO-FAANG) Workshop in Washington, DC on October 7-8, 2015. This consortium is a grass-roots organization formed to advance the annotation of newly assembled genomes of domesticated and non-model organisms (www.faang.org). The workshop gathered together from around the world a group of 100+ genome scientists, administrators, representatives of funding agencies and commodity groups to discuss the latest advancements of the consortium, new perspectives, next steps and implementation plans. The workshop was streamed live and recorded, and all talks, along with speaker slide presentations, are available at www.faang.org. In this report, we describe the major activities and outcomes of this meeting. We also provide updates on ongoing efforts to implement discussions and decisions taken at GO-FAANG to guide future FAANG activities. In summary, reference datasets are being established under pilot projects; plans for tissue sets, morphological classification and methods of sample collection for different tissues were organized; and core assays and data and meta-data analysis standards were established.

  13. WS-SNPs&GO: a web server for predicting the deleterious effect of human protein variants using functional annotation

    PubMed Central

    2013-01-01

    Background SNPs&GO is a method for the prediction of deleterious Single Amino acid Polymorphisms (SAPs) using protein functional annotation. In this work, we present the web server implementation of SNPs&GO (WS-SNPs&GO). The server is based on Support Vector Machines (SVM) and for a given protein, its input comprises: the sequence and/or its three-dimensional structure (when available), a set of target variations and its functional Gene Ontology (GO) terms. The output of the server provides, for each protein variation, the probabilities to be associated to human diseases. Results The server consists of two main components, including updated versions of the sequence-based SNPs&GO (recently scored as one of the best algorithms for predicting deleterious SAPs) and of the structure-based SNPs&GO3d programs. Sequence and structure based algorithms are extensively tested on a large set of annotated variations extracted from the SwissVar database. Selecting a balanced dataset with more than 38,000 SAPs, the sequence-based approach achieves 81% overall accuracy, 0.61 correlation coefficient and an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.88. For the subset of ~6,600 variations mapped on protein structures available at the Protein Data Bank (PDB), the structure-based method scores with 84% overall accuracy, 0.68 correlation coefficient, and 0.91 AUC. When tested on a new blind set of variations, the results of the server are 79% and 83% overall accuracy for the sequence-based and structure-based inputs, respectively. Conclusions WS-SNPs&GO is a valuable tool that includes in a unique framework information derived from protein sequence, structure, evolutionary profile, and protein function. WS-SNPs&GO is freely available at http://snps.biofold.org/snps-and-go. PMID:23819482

  14. Mining GO annotations for improving annotation consistency.

    PubMed

    Faria, Daniel; Schlicker, Andreas; Pesquita, Catia; Bastos, Hugo; Ferreira, António E N; Albrecht, Mario; Falcão, André O

    2012-01-01

    Despite the structure and objectivity provided by the Gene Ontology (GO), the annotation of proteins is a complex task that is subject to errors and inconsistencies. Electronically inferred annotations in particular are widely considered unreliable. However, given that manual curation of all GO annotations is unfeasible, it is imperative to improve the quality of electronically inferred annotations. In this work, we analyze the full GO molecular function annotation of UniProtKB proteins, and discuss some of the issues that affect their quality, focusing particularly on the lack of annotation consistency. Based on our analysis, we estimate that 64% of the UniProtKB proteins are incompletely annotated, and that inconsistent annotations affect 83% of the protein functions and at least 23% of the proteins. Additionally, we present and evaluate a data mining algorithm, based on the association rule learning methodology, for identifying implicit relationships between molecular function terms. The goal of this algorithm is to assist GO curators in updating GO and correcting and preventing inconsistent annotations. Our algorithm predicted 501 relationships with an estimated precision of 94%, whereas the basic association rule learning methodology predicted 12,352 relationships with a precision below 9%.

  15. Functional Annotation of Conserved Hypothetical Proteins from Haemophilus influenzae Rd KW20

    PubMed Central

    Shahbaaz, Mohd; Md. ImtaiyazHassan; Ahmad, Faizan

    2013-01-01

    Haemophilus influenzae is a Gram negative bacterium that belongs to the family Pasteurellaceae, causes bacteremia, pneumonia and acute bacterial meningitis in infants. The emergence of multi-drug resistance H. influenzae strain in clinical isolates demands the development of better/new drugs against this pathogen. Our study combines a number of bioinformatics tools for function predictions of previously not assigned proteins in the genome of H. influenzae. This genome was extensively analyzed and found 1,657 functional proteins in which function of 429 proteins are unknown, termed as hypothetical proteins (HPs). Amino acid sequences of all 429 HPs were extensively annotated and we successfully assigned the function to 296 HPs with high confidence. We also characterized the function of 124 HPs precisely, but with less confidence. We believed that sequence of a protein can be used as a framework to explain known functional properties. Here we have combined the latest versions of protein family databases, protein motifs, intrinsic features from the amino acid sequence, pathway and genome context methods to assign a precise function to hypothetical proteins for which no experimental information is available. We found these HPs belong to various classes of proteins such as enzymes, transporters, carriers, receptors, signal transducers, binding proteins, virulence and other proteins. The outcome of this work will be helpful for a better understanding of the mechanism of pathogenesis and in finding novel therapeutic targets for H. influenzae. PMID:24391926

  16. WNP: A Novel Algorithm for Gene Products Annotation from Weighted Functional Networks

    PubMed Central

    Magi, Alberto; Tattini, Lorenzo; Benelli, Matteo; Giusti, Betti; Abbate, Rosanna; Ruffo, Stefano

    2012-01-01

    Predicting the biological function of all the genes of an organism is one of the fundamental goals of computational system biology. In the last decade, high-throughput experimental methods for studying the functional interactions between gene products (GPs) have been combined with computational approaches based on Bayesian networks for data integration. The result of these computational approaches is an interaction network with weighted links representing connectivity likelihood between two functionally related GPs. The weighted network generated by these computational approaches can be used to predict annotations for functionally uncharacterized GPs. Here we introduce Weighted Network Predictor (WNP), a novel algorithm for function prediction of biologically uncharacterized GPs. Tests conducted on simulated data show that WNP outperforms other 5 state-of-the-art methods in terms of both specificity and sensitivity and that it is able to better exploit and propagate the functional and topological information of the network. We apply our method to Saccharomyces cerevisiae yeast and Arabidopsis thaliana networks and we predict Gene Ontology function for about 500 and 10000 uncharacterized GPs respectively. PMID:22761703

  17. Parallel-META 2.0: enhanced metagenomic data analysis with functional annotation, high performance computing and advanced visualization.

    PubMed

    Su, Xiaoquan; Pan, Weihua; Song, Baoxing; Xu, Jian; Ning, Kang

    2014-01-01

    The metagenomic method directly sequences and analyses genome information from microbial communities. The main computational tasks for metagenomic analyses include taxonomical and functional structure analysis for all genomes in a microbial community (also referred to as a metagenomic sample). With the advancement of Next Generation Sequencing (NGS) techniques, the number of metagenomic samples and the data size for each sample are increasing rapidly. Current metagenomic analysis is both data- and computation- intensive, especially when there are many species in a metagenomic sample, and each has a large number of sequences. As such, metagenomic analyses require extensive computational power. The increasing analytical requirements further augment the challenges for computation analysis. In this work, we have proposed Parallel-META 2.0, a metagenomic analysis software package, to cope with such needs for efficient and fast analyses of taxonomical and functional structures for microbial communities. Parallel-META 2.0 is an extended and improved version of Parallel-META 1.0, which enhances the taxonomical analysis using multiple databases, improves computation efficiency by optimized parallel computing, and supports interactive visualization of results in multiple views. Furthermore, it enables functional analysis for metagenomic samples including short-reads assembly, gene prediction and functional annotation. Therefore, it could provide accurate taxonomical and functional analyses of the metagenomic samples in high-throughput manner and on large scale.

  18. Functional annotation of the vlinc class of non-coding RNAs using systems biology approach

    PubMed Central

    Laurent, Georges St.; Vyatkin, Yuri; Antonets, Denis; Ri, Maxim; Qi, Yao; Saik, Olga; Shtokalo, Dmitry; de Hoon, Michiel J.L.; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Arner, Erik; Forrest, Alistair R.R.; Nicolas, Estelle; McCaffrey, Timothy A.; Carninci, Piero; Hayashizaki, Yoshihide; Wahlestedt, Claes; Kapranov, Philipp

    2016-01-01

    Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology-based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlincRNAs genes likely function in cis to activate nearby genes. This effect while most pronounced in closely spaced vlincRNA–gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlincRNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non-coding RNAs. PMID:27001520

  19. Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos

    PubMed Central

    Cui, Wei; Dai, Xiangpeng; Marcho, Chelsea; Han, Zhengbin; Zhang, Kun; Tremblay, Kimberly D.; Mager, Jesse

    2016-01-01

    With readily available transcriptome-wide data, understanding the role of each expressed gene is an essential next step. Although RNAi technologies allow for genome-wide screens in cell culture, these approaches cannot replace strategies for discovery in the embryo. Here we present, for the first time, a knockdown screen in mouse preimplantation embryos. Early mammalian development encompasses dynamic cellular, molecular and epigenetic events that are largely conserved from mouse to man. We assayed 712 genes for requirements during preimplantation. We identified 59 genes required for successful development or outgrowth and implantation. We have characterized each phenotype and revealed cellular, molecular, and lineage specific defects following knockdown of transcript. Induced network analyses demonstrate this as a valid approach to identify networks of genes that play important roles during preimplantation. Our approach provides a robust and efficient strategy towards identification of novel phenotypes during mouse preimplantation and facilitates functional annotation of the mammalian transcriptome. PMID:27869233

  20. Annotation error in public databases: misannotation of molecular function in enzyme superfamilies.

    PubMed

    Schnoes, Alexandra M; Brown, Shoshana D; Dodevski, Igor; Babbitt, Patricia C

    2009-12-01

    Due to the rapid release of new data from genome sequencing projects, the majority of protein sequences in public databases have not been experimentally characterized; rather, sequences are annotated using computational analysis. The level of misannotation and the types of misannotation in large public databases are currently unknown and have not been analyzed in depth. We have investigated the misannotation levels for molecular function in four public protein sequence databases (UniProtKB/Swiss-Prot, GenBank NR, UniProtKB/TrEMBL, and KEGG) for a model set of 37 enzyme families for which extensive experimental information is available. The manually curated database Swiss-Prot shows the lowest annotation error levels (close to 0% for most families); the two other protein sequence databases (GenBank NR and TrEMBL) and the protein sequences in the KEGG pathways database exhibit similar and surprisingly high levels of misannotation that average 5%-63% across the six superfamilies studied. For 10 of the 37 families examined, the level of misannotation in one or more of these databases is >80%. Examination of the NR database over time shows that misannotation has increased from 1993 to 2005. The types of misannotation that were found fall into several categories, most associated with "overprediction" of molecular function. These results suggest that misannotation in enzyme superfamilies containing multiple families that catalyze different reactions is a larger problem than has been recognized. Strategies are suggested for addressing some of the systematic problems contributing to these high levels of misannotation.

  1. Development and Evaluation of an Automated Annotation Pipeline and cDNA Annotation System

    PubMed Central

    Kasukawa, Takeya; Furuno, Masaaki; Nikaido, Itoshi; Bono, Hidemasa; Hume, David A.; Bult, Carol; Hill, David P.; Baldarelli, Richard; Gough, Julian; Kanapin, Alexander; Matsuda, Hideo; Schriml, Lynn M.; Hayashizaki, Yoshihide; Okazaki, Yasushi; Quackenbush, John

    2003-01-01

    Manual curation has long been held to be the “gold standard” for functional annotation of DNA sequence. Our experience with the annotation of more than 20,000 full-length cDNA sequences revealed problems with this approach, including inaccurate and inconsistent assignment of gene names, as well as many good assignments that were difficult to reproduce using only computational methods. For the FANTOM2 annotation of more than 60,000 cDNA clones, we developed a number of methods and tools to circumvent some of these problems, including an automated annotation pipeline that provides high-quality preliminary annotation for each sequence by introducing an “uninformative filter” that eliminates uninformative annotations, controlled vocabularies to accurately reflect both the functional assignments and the evidence supporting them, and a highly refined, Web-based manual annotation tool that allows users to view a wide array of sequence analyses and to assign gene names and putative functions using a consistent nomenclature. The ultimate utility of our approach is reflected in the low rate of reassignment of automated assignments by manual curation. Based on these results, we propose a new standard for large-scale annotation, in which the initial automated annotations are manually investigated and then computational methods are iteratively modified and improved based on the results of manual curation. PMID:12819153

  2. Functional Annotation Analytics of Bacillus Genomes Reveals Stress Responsive Acetate Utilization and Sulfate Uptake in the Biotechnologically Relevant Bacillus megaterium.

    PubMed

    Williams, Baraka S; Isokpehi, Raphael D; Mbah, Andreas N; Hollman, Antoinesha L; Bernard, Christina O; Simmons, Shaneka S; Ayensu, Wellington K; Garner, Bianca L

    2012-01-01

    Bacillus species form an heterogeneous group of Gram-positive bacteria that include members that are disease-causing, biotechnologically-relevant, and can serve as biological research tools. A common feature of Bacillus species is their ability to survive in harsh environmental conditions by formation of resistant endospores. Genes encoding the universal stress protein (USP) domain confer cellular and organismal survival during unfavorable conditions such as nutrient depletion. As of February 2012, the genome sequences and a variety of functional annotations for at least 123 Bacillus isolates including 45 Bacillus cereus isolates were available in public domain bioinformatics resources. Additionally, the genome sequencing status of 10 of the B. cereus isolates were annotated as finished with each genome encoded 3 USP genes. The conservation of gene neighborhood of the 140 aa universal stress protein in the B. cereus genomes led to the identification of a predicted plasmid-encoded transcriptional unit that includes a USP gene and a sulfate uptake gene in the soil-inhabiting Bacillus megaterium. Gene neighborhood analysis combined with visual analytics of chemical ligand binding sites data provided knowledge-building biological insights on possible cellular functions of B. megaterium universal stress proteins. These functions include sulfate and potassium uptake, acid extrusion, cellular energy-level sensing, survival in high oxygen conditions and acetate utilization. Of particular interest was a two-gene transcriptional unit that consisted of genes for a universal stress protein and a sirtuin Sir2 (deacetylase enzyme for NAD+-dependent acetate utilization). The predicted transcriptional units for stress responsive inorganic sulfate uptake and acetate utilization could explain biological mechanisms for survival of soil-inhabiting Bacillus species in sulfate and acetate limiting conditions. Considering the key role of sirtuins in mammalian physiology additional

  3. Functional Annotation Analytics of Bacillus Genomes Reveals Stress Responsive Acetate Utilization and Sulfate Uptake in the Biotechnologically Relevant Bacillus megaterium

    PubMed Central

    Williams, Baraka S.; Isokpehi, Raphael D.; Mbah, Andreas N.; Hollman, Antoinesha L.; Bernard, Christina O.; Simmons, Shaneka S.; Ayensu, Wellington K.; Garner, Bianca L.

    2012-01-01

    Bacillus species form an heterogeneous group of Gram-positive bacteria that include members that are disease-causing, biotechnologically-relevant, and can serve as biological research tools. A common feature of Bacillus species is their ability to survive in harsh environmental conditions by formation of resistant endospores. Genes encoding the universal stress protein (USP) domain confer cellular and organismal survival during unfavorable conditions such as nutrient depletion. As of February 2012, the genome sequences and a variety of functional annotations for at least 123 Bacillus isolates including 45 Bacillus cereus isolates were available in public domain bioinformatics resources. Additionally, the genome sequencing status of 10 of the B. cereus isolates were annotated as finished with each genome encoded 3 USP genes. The conservation of gene neighborhood of the 140 aa universal stress protein in the B. cereus genomes led to the identification of a predicted plasmid-encoded transcriptional unit that includes a USP gene and a sulfate uptake gene in the soil-inhabiting Bacillus megaterium. Gene neighborhood analysis combined with visual analytics of chemical ligand binding sites data provided knowledge-building biological insights on possible cellular functions of B. megaterium universal stress proteins. These functions include sulfate and potassium uptake, acid extrusion, cellular energy-level sensing, survival in high oxygen conditions and acetate utilization. Of particular interest was a two-gene transcriptional unit that consisted of genes for a universal stress protein and a sirtuin Sir2 (deacetylase enzyme for NAD+-dependent acetate utilization). The predicted transcriptional units for stress responsive inorganic sulfate uptake and acetate utilization could explain biological mechanisms for survival of soil-inhabiting Bacillus species in sulfate and acetate limiting conditions. Considering the key role of sirtuins in mammalian physiology additional

  4. Comparative analysis of grapevine whole-genome gene predictions, functional annotation, categorization and integration of the predicted gene sequences

    PubMed Central

    2012-01-01

    Background The first draft assembly and gene prediction of the grapevine genome (8X base coverage) was made available to the scientific community in 2007, and functional annotation was developed on this gene prediction. Since then additional Sanger sequences were added to the 8X sequences pool and a new version of the genomic sequence with superior base coverage (12X) was produced. Results In order to more efficiently annotate the function of the genes predicted in the new assembly, it is important to build on as much of the previous work as possible, by transferring 8X annotation of the genome to the 12X version. The 8X and 12X assemblies and gene predictions of the grapevine genome were compared to answer the question, “Can we uniquely map 8X predicted genes to 12X predicted genes?” The results show that while the assemblies and gene structure predictions are too different to make a complete mapping between them, most genes (18,725) showed a one-to-one relationship between 8X predicted genes and the last version of 12X predicted genes. In addition, reshuffled genomic sequence structures appeared. These highlight regions of the genome where the gene predictions need to be taken with caution. Based on the new grapevine gene functional annotation and in-depth functional categorization, twenty eight new molecular networks have been created for VitisNet while the existing networks were updated. Conclusions The outcomes of this study provide a functional annotation of the 12X genes, an update of VitisNet, the system of the grapevine molecular networks, and a new functional categorization of genes. Data are available at the VitisNet website (http://www.sdstate.edu/ps/research/vitis/pathways.cfm). PMID:22554261

  5. Homology modeling and assigned functional annotation of an uncharacterized antitoxin protein from Streptomyces xinghaiensis

    PubMed Central

    Oany, Arafat Rahman; Ahmed, Md Shahabuddin; Jahan, Nasreen; Latif, Md Abdul; Mahmud, Shahin; Hossain, Md. Ahmed; Akter, Fatema; Rakib, Hasibul Haque; Islam, Md. Shariful

    2015-01-01

    Streptomyces xinghaiensis is a Gram-positive, aerobic and non-motile bacterium. The bacterial genome is known. Therefore, it is of interest to study the uncharacterized proteins in the genome. An uncharacterized protein (gi|518540893|86 residues) in the genome was selected for a comprehensive computational sequence-structure-function analysis using available data and tools. Subcellular localization of the targeted protein with conserved residues and assigned secondary structures is documented. Sequence homology search against the protein data bank (PDB) and non-redundant GenBank proteins using BLASTp showed different homologous proteins with known antitoxin function. A homology model of the target protein was developed using a known template (PDB ID: 3CTO:A) with 62% sequence similarity in HHpred after assessment using programs PROCHECK and QMEAN6. The predicted active site using CASTp is analyzed for assigned anti-toxin function. This information finds specific utility in annotating the said uncharacterized protein in the bacterial genome. PMID:26912949

  6. Discovering gene functional relationships using FAUN (Feature Annotation Using Nonnegative matrix factorization)

    PubMed Central

    2010-01-01

    Background Searching the enormous amount of information available in biomedical literature to extract novel functional relationships among genes remains a challenge in the field of bioinformatics. While numerous (software) tools have been developed to extract and identify gene relationships from biological databases, few effectively deal with extracting new (or implied) gene relationships, a process which is useful in interpretation of discovery-oriented genome-wide experiments. Results In this study, we develop a Web-based bioinformatics software environment called FAUN or Feature Annotation Using Nonnegative matrix factorization (NMF) to facilitate both the discovery and classification of functional relationships among genes. Both the computational complexity and parameterization of NMF for processing gene sets are discussed. FAUN is tested on three manually constructed gene document collections. Its utility and performance as a knowledge discovery tool is demonstrated using a set of genes associated with Autism. Conclusions FAUN not only assists researchers to use biomedical literature efficiently, but also provides utilities for knowledge discovery. This Web-based software environment may be useful for the validation and analysis of functional associations in gene subsets identified by high-throughput experiments. PMID:20946597

  7. Heterologous expression of plasmodial proteins for structural studies and functional annotation

    PubMed Central

    Birkholtz, Lyn-Marie; Blatch, Gregory; Coetzer, Theresa L; Hoppe, Heinrich C; Human, Esmaré; Morris, Elizabeth J; Ngcete, Zoleka; Oldfield, Lyndon; Roth, Robyn; Shonhai, Addmore; Stephens, Linda; Louw, Abraham I

    2008-01-01

    Malaria remains the world's most devastating tropical infectious disease with as many as 40% of the world population living in risk areas. The widespread resistance of Plasmodium parasites to the cost-effective chloroquine and antifolates has forced the introduction of more costly drug combinations, such as Coartem®. In the absence of a vaccine in the foreseeable future, one strategy to address the growing malaria problem is to identify and characterize new and durable antimalarial drug targets, the majority of which are parasite proteins. Biochemical and structure-activity analysis of these proteins is ultimately essential in the characterization of such targets but requires large amounts of functional protein. Even though heterologous protein production has now become a relatively routine endeavour for most proteins of diverse origins, the functional expression of soluble plasmodial proteins is highly problematic and slows the progress of antimalarial drug target discovery. Here the status quo of heterologous production of plasmodial proteins is presented, constraints are highlighted and alternative strategies and hosts for functional expression and annotation of plasmodial proteins are reviewed. PMID:18828893

  8. Large-scale inference of gene function through phylogenetic annotation of Gene Ontology terms: case study of the apoptosis and autophagy cellular processes

    PubMed Central

    Feuermann, Marc; Gaudet, Pascale; Mi, Huaiyu; Lewis, Suzanna E.; Thomas, Paul D.

    2016-01-01

    We previously reported a paradigm for large-scale phylogenomic analysis of gene families that takes advantage of the large corpus of experimentally supported Gene Ontology (GO) annotations. This ‘GO Phylogenetic Annotation’ approach integrates GO annotations from evolutionarily related genes across ∼100 different organisms in the context of a gene family tree, in which curators build an explicit model of the evolution of gene functions. GO Phylogenetic Annotation models the gain and loss of functions in a gene family tree, which is used to infer the functions of uncharacterized (or incompletely characterized) gene products, even for human proteins that are relatively well studied. Here, we report our results from applying this paradigm to two well-characterized cellular processes, apoptosis and autophagy. This revealed several important observations with respect to GO annotations and how they can be used for function inference. Notably, we applied only a small fraction of the experimentally supported GO annotations to infer function in other family members. The majority of other annotations describe indirect effects, phenotypes or results from high throughput experiments. In addition, we show here how feedback from phylogenetic annotation leads to significant improvements in the PANTHER trees, the GO annotations and GO itself. Thus GO phylogenetic annotation both increases the quantity and improves the accuracy of the GO annotations provided to the research community. We expect these phylogenetically based annotations to be of broad use in gene enrichment analysis as well as other applications of GO annotations. Database URL: http://amigo.geneontology.org/amigo PMID:28025345

  9. Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study

    PubMed Central

    Raethong, Nachon; Wong-ekkabut, Jirasak; Laoteng, Kobkul; Vongsangnak, Wanwipa

    2016-01-01

    Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H+-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction. PMID:27274991

  10. ARC: automated resource classifier for agglomerative functional classification of prokaryotic proteins using annotation texts.

    PubMed

    Gnanamani, Muthiah; Kumar, Naveen; Ramachandran, Srinivasan

    2007-08-01

    Functional classification of proteins is central to comparative genomics. The need for algorithms tuned to enable integrative interpretation of analytical data is felt globally. The availability of a general,automated software with built-in flexibility will significantly aid this activity. We have prepared ARC (Automated Resource Classifier), which is an open source software meeting the user requirements of flexibility. The default classification scheme based on keyword match is agglomerative and directs entries into any of the 7 basic non-overlapping functional classes: Cell wall, Cell membrane and Transporters (C), Cell division (D), Information (I), Translocation (L), Metabolism (M), Stress(R), Signal and communication (S) and 2 ancillary classes: Others (O) and Hypothetical (H). The keyword library of ARC was built serially by first drawing keywords from Bacillus subtilis and Escherichia coli K12. In subsequent steps,this library was further enriched by collecting terms from archaeal representative Archaeoglobus fulgidus, Gene Ontology, and Gene Symbols. ARC is 94.04% successful on 6,75,663 annotated proteins from 348 prokaryotes. Three examples are provided to illuminate the current perspectives on mycobacterial physiology and costs of proteins in 333 prokaryotes. ARC is available at http://arc.igib.res.in.

  11. Comparison of Functional Gene Annotation of Toxascaris leonina and Toxocara canis using CLC Genomics Workbench

    PubMed Central

    Kim, Ki Uk; Park, Sang Kyun; Kang, Shin Ae; Park, Mi Kyung; Cho, Min Kyoung; Jung, Ho-jin; Kim, Kyung-Yun

    2013-01-01

    The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common gastrointestinal helminths encountered in dogs. In order to understand biological differences of 2 ascarids, we analyzed gene expression profiles of female adults of T. canis and T. leonina using CLC Genomics Workbench, and the results were compared with those of free-living nematode Caenorhabditis elegans. A total of 2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively. The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820 bp. Overall, our results showed that most functional gene annotations of 2 ascarids were quite similar to each other in 3 major categories, i.e., cellular component, biological process, and molecular function. Although some different transcript expression categories were found, the distance was short and it was not enough to explain their different lifestyles. However, we found distinguished transcript differences between ascarid parasites and free-living nematodes. Understanding evolutionary genetic changes might be helpful for studies of the lifestyle and evolution of parasites. PMID:24327777

  12. Comparison of functional gene annotation of Toxascaris leonina and Toxocara canis using CLC genomics workbench.

    PubMed

    Kim, Ki Uk; Park, Sang Kyun; Kang, Shin Ae; Park, Mi Kyung; Cho, Min Kyoung; Jung, Ho-Jin; Kim, Kyung-Yun; Yu, Hak Sun

    2013-10-01

    The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common gastrointestinal helminths encountered in dogs. In order to understand biological differences of 2 ascarids, we analyzed gene expression profiles of female adults of T. canis and T. leonina using CLC Genomics Workbench, and the results were compared with those of free-living nematode Caenorhabditis elegans. A total of 2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively. The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820 bp. Overall, our results showed that most functional gene annotations of 2 ascarids were quite similar to each other in 3 major categories, i.e., cellular component, biological process, and molecular function. Although some different transcript expression categories were found, the distance was short and it was not enough to explain their different lifestyles. However, we found distinguished transcript differences between ascarid parasites and free-living nematodes. Understanding evolutionary genetic changes might be helpful for studies of the lifestyle and evolution of parasites.

  13. Functional annotation of proteomic data from chicken heterophils and macrophages induced by carbon nanotube exposure.

    PubMed

    Li, Yun-Ze; Cheng, Chung-Shi; Chen, Chao-Jung; Li, Zi-Lin; Lin, Yao-Tung; Chen, Shuen-Ei; Huang, San-Yuan

    2014-05-12

    With the expanding applications of carbon nanotubes (CNT) in biomedicine and agriculture, questions about the toxicity and biocompatibility of CNT in humans and domestic animals are becoming matters of serious concern. This study used proteomic methods to profile gene expression in chicken macrophages and heterophils in response to CNT exposure. Two-dimensional gel electrophoresis identified 12 proteins in macrophages and 15 in heterophils, with differential expression patterns in response to CNT co-incubation (0, 1, 10, and 100 µg/mL of CNT for 6 h) (p < 0.05). Gene ontology analysis showed that most of the differentially expressed proteins are associated with protein interactions, cellular metabolic processes, and cell mobility, suggesting activation of innate immune functions. Western blot analysis with heat shock protein 70, high mobility group protein, and peptidylprolyl isomerase A confirmed the alterations of the profiled proteins. The functional annotations were further confirmed by effective cell migration, promoted interleukin-1β secretion, and more cell death in both macrophages and heterophils exposed to CNT (p < 0.05). In conclusion, results of this study suggest that CNT exposure affects protein expression, leading to activation of macrophages and heterophils, resulting in altered cytoskeleton remodeling, cell migration, and cytokine production, and thereby mediates tissue immune responses.

  14. Gene Expression and Functional Annotation of the Human Ciliary Body Epithelia

    PubMed Central

    Janssen, Sarah F.; Gorgels, Theo G. M. F.; Bossers, Koen; ten Brink, Jacoline B.; Essing, Anke H. W.; Nagtegaal, Martijn; van der Spek, Peter J.; Jansonius, Nomdo M.; Bergen, Arthur A. B.

    2012-01-01

    Purpose The ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma. Methods We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity. Results The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (N)PE of 35 genes previously implicated in molecular mechanisms related to glaucoma. Conclusion Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma. PMID:23028713

  15. Comprehensive functional annotation of 18 missense mutations found in suspected hemochromatosis type 4 patients.

    PubMed

    Callebaut, Isabelle; Joubrel, Rozenn; Pissard, Serge; Kannengiesser, Caroline; Gérolami, Victoria; Ged, Cécile; Cadet, Estelle; Cartault, François; Ka, Chandran; Gourlaouen, Isabelle; Gourhant, Lénaick; Oudin, Claire; Goossens, Michel; Grandchamp, Bernard; De Verneuil, Hubert; Rochette, Jacques; Férec, Claude; Le Gac, Gérald

    2014-09-01

    Hemochromatosis type 4 is a rare form of primary iron overload transmitted as an autosomal dominant trait caused by mutations in the gene encoding the iron transport protein ferroportin 1 (SLC40A1). SLC40A1 mutations fall into two functional categories (loss- versus gain-of-function) underlying two distinct clinical entities (hemochromatosis type 4A versus type 4B). However, the vast majority of SLC40A1 mutations are rare missense variations, with only a few showing strong evidence of causality. The present study reports the results of an integrated approach collecting genetic and phenotypic data from 44 suspected hemochromatosis type 4 patients, with comprehensive structural and functional annotations. Causality was demonstrated for 10 missense variants, showing a clear dichotomy between the two hemochromatosis type 4 subtypes. Two subgroups of loss-of-function mutations were distinguished: one impairing cell-surface expression and one altering only iron egress. Additionally, a new gain-of-function mutation was identified, and the degradation of ferroportin on hepcidin binding was shown to probably depend on the integrity of a large extracellular loop outside of the hepcidin-binding domain. Eight further missense variations, on the other hand, were shown to have no discernible effects at either protein or RNA level; these were found in apparently isolated patients and were associated with a less severe phenotype. The present findings illustrate the importance of combining in silico and biochemical approaches to fully distinguish pathogenic SLC40A1 mutations from benign variants. This has profound implications for patient management.

  16. First survey and functional annotation of prohormone and convertase genes in the pig

    PubMed Central

    2012-01-01

    Background The pig is a biomedical model to study human and livestock traits. Many of these traits are controlled by neuropeptides that result from the cleavage of prohormones by prohormone convertases. Only 45 prohormones have been confirmed in the pig. Sequence homology can be ineffective to annotate prohormone genes in sequenced species like the pig due to the multifactorial nature of the prohormone processing. The goal of this study is to undertake the first complete survey of prohormone and prohormone convertases genes in the pig genome. These genes were functionally annotated based on 35 gene expression microarray experiments. The cleavage sites of prohormone sequences into potentially active neuropeptides were predicted. Results We identified 95 unique prohormone genes, 2 alternative calcitonin-related sequences, 8 prohormone convertases and 1 cleavage facilitator in the pig genome 10.2 assembly and trace archives. Of these, 11 pig prohormone genes have not been reported in the UniProt, UniGene or Gene databases. These genes are intermedin, cortistatin, insulin-like 5, orexigenic neuropeptide QRFP, prokineticin 2, prolactin-releasing peptide, parathyroid hormone 2, urocortin, urocortin 2, urocortin 3, and urotensin 2-related peptide. In addition, a novel neuropeptide S was identified in the pig genome correcting the previously reported pig sequence that is identical to the rabbit sequence. Most differentially expressed prohormone genes were under-expressed in pigs experiencing immune challenge relative to the un-challenged controls, in non-pregnant relative to pregnant sows, in old relative to young embryos, and in non-neural relative to neural tissues. The cleavage prediction based on human sequences had the best performance with a correct classification rate of cleaved and non-cleaved sites of 92% suggesting that the processing of prohormones in pigs is similar to humans. The cleavage prediction models did not find conclusive evidence supporting the

  17. GOsummaries: an R Package for Visual Functional Annotation of Experimental Data.

    PubMed

    Kolde, Raivo; Vilo, Jaak

    2015-01-01

    Functional characterisation of gene lists using Gene Ontology (GO) enrichment analysis is a common approach in computational biology, since many analysis methods end up with a list of genes as a result. Often there can be hundreds of functional terms that are significantly associated with a single list of genes and proper interpretation of such results can be a challenging endeavour. There are methods to visualise and aid the interpretation of these results, but most of them are limited to the results associated with one list of genes. However, in practice the number of gene lists can be considerably higher and common tools are not effective in such situations. We introduce a novel R package, 'GOsummaries' that visualises the GO enrichment results as concise word clouds that can be combined together if the number of gene lists is larger. By also adding the graphs of corresponding raw experimental data, GOsummaries can create informative summary plots for various analyses such as differential expression or clustering. The case studies show that the GOsummaries plots allow rapid functional characterisation of complex sets of gene lists. The GOsummaries approach is particularly effective for Principal Component Analysis (PCA). By adding functional annotation to the principal components, GOsummaries improves  significantly the interpretability of PCA results. The GOsummaries layout for PCA can be effective even in situations where we cannot directly apply the GO analysis. For example, in case of metabolomics or metagenomics data it is possible to show the features with significant associations to the components instead of GO terms.   The GOsummaries package is available under GPL-2 licence at Bioconductor (http://www.bioconductor.org/packages/release/bioc/html/GOsummaries.html).

  18. Cellular functions of genetically imprinted genes in human and mouse as annotated in the gene ontology.

    PubMed

    Hamed, Mohamed; Ismael, Siba; Paulsen, Martina; Helms, Volkhard

    2012-01-01

    By analyzing the cellular functions of genetically imprinted genes as annotated in the Gene Ontology for human and mouse, we found that imprinted genes are often involved in developmental, transport and regulatory processes. In the human, paternally expressed genes are enriched in GO terms related to the development of organs and of anatomical structures. In the mouse, maternally expressed genes regulate cation transport as well as G-protein signaling processes. Furthermore, we investigated if imprinted genes are regulated by common transcription factors. We identified 25 TF families that showed an enrichment of binding sites in the set of imprinted genes in human and 40 TF families in mouse. In general, maternally and paternally expressed genes are not regulated by different transcription factors. The genes Nnat, Klf14, Blcap, Gnas and Ube3a contribute most to the enrichment of TF families. In the mouse, genes that are maternally expressed in placenta are enriched for AP1 binding sites. In the human, we found that these genes possessed binding sites for both, AP1 and SP1.

  19. Automated annotation of functional imaging experiments via multi-label classification.

    PubMed

    Turner, Matthew D; Chakrabarti, Chayan; Jones, Thomas B; Xu, Jiawei F; Fox, Peter T; Luger, George F; Laird, Angela R; Turner, Jessica A

    2013-01-01

    Identifying the experimental methods in human neuroimaging papers is important for grouping meaningfully similar experiments for meta-analyses. Currently, this can only be done by human readers. We present the performance of common machine learning (text mining) methods applied to the problem of automatically classifying or labeling this literature. Labeling terms are from the Cognitive Paradigm Ontology (CogPO), the text corpora are abstracts of published functional neuroimaging papers, and the methods use the performance of a human expert as training data. We aim to replicate the expert's annotation of multiple labels per abstract identifying the experimental stimuli, cognitive paradigms, response types, and other relevant dimensions of the experiments. We use several standard machine learning methods: naive Bayes (NB), k-nearest neighbor, and support vector machines (specifically SMO or sequential minimal optimization). Exact match performance ranged from only 15% in the worst cases to 78% in the best cases. NB methods combined with binary relevance transformations performed strongly and were robust to overfitting. This collection of results demonstrates what can be achieved with off-the-shelf software components and little to no pre-processing of raw text.

  20. Cross-Population Joint Analysis of eQTLs: Fine Mapping and Functional Annotation

    PubMed Central

    Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

    2015-01-01

    Mapping expression quantitative trait loci (eQTLs) has been shown as a powerful tool to uncover the genetic underpinnings of many complex traits at molecular level. In this paper, we present an integrative analysis approach that leverages eQTL data collected from multiple population groups. In particular, our approach effectively identifies multiple independent cis-eQTL signals that are consistent across populations, accounting for population heterogeneity in allele frequencies and linkage disequilibrium patterns. Furthermore, by integrating genomic annotations, our analysis framework enables high-resolution functional analysis of eQTLs. We applied our statistical approach to analyze the GEUVADIS data consisting of samples from five population groups. From this analysis, we concluded that i) jointly analysis across population groups greatly improves the power of eQTL discovery and the resolution of fine mapping of causal eQTL ii) many genes harbor multiple independent eQTLs in their cis regions iii) genetic variants that disrupt transcription factor binding are significantly enriched in eQTLs (p-value = 4.93 × 10-22). PMID:25906321

  1. Automated annotation of functional imaging experiments via multi-label classification

    PubMed Central

    Turner, Matthew D.; Chakrabarti, Chayan; Jones, Thomas B.; Xu, Jiawei F.; Fox, Peter T.; Luger, George F.; Laird, Angela R.; Turner, Jessica A.

    2013-01-01

    Identifying the experimental methods in human neuroimaging papers is important for grouping meaningfully similar experiments for meta-analyses. Currently, this can only be done by human readers. We present the performance of common machine learning (text mining) methods applied to the problem of automatically classifying or labeling this literature. Labeling terms are from the Cognitive Paradigm Ontology (CogPO), the text corpora are abstracts of published functional neuroimaging papers, and the methods use the performance of a human expert as training data. We aim to replicate the expert's annotation of multiple labels per abstract identifying the experimental stimuli, cognitive paradigms, response types, and other relevant dimensions of the experiments. We use several standard machine learning methods: naive Bayes (NB), k-nearest neighbor, and support vector machines (specifically SMO or sequential minimal optimization). Exact match performance ranged from only 15% in the worst cases to 78% in the best cases. NB methods combined with binary relevance transformations performed strongly and were robust to overfitting. This collection of results demonstrates what can be achieved with off-the-shelf software components and little to no pre-processing of raw text. PMID:24409112

  2. Commonality of functional annotation: a method for prioritization of candidate genes from genome-wide linkage studies†

    PubMed Central

    Shriner, Daniel; Baye, Tesfaye M.; Padilla, Miguel A.; Zhang, Shiju; Vaughan, Laura K.; Loraine, Ann E.

    2008-01-01

    Linkage studies of complex traits frequently yield multiple linkage regions covering hundreds of genes. Testing each candidate gene from every region is prohibitively expensive and computational methods that simplify this process would benefit genetic research. We present a new method based on commonality of functional annotation (CFA) that aids dissection of complex traits for which multiple causal genes act in a single pathway or process. CFA works by testing individual Gene Ontology (GO) terms for enrichment among candidate gene pools, performs multiple hypothesis testing adjustment using an estimate of independent tests based on correlation of GO terms, and then scores and ranks genes annotated with significantly-enriched terms based on the number of quantitative trait loci regions in which genes bearing those annotations appear. We evaluate CFA using simulated linkage data and show that CFA has good power despite being conservative. We apply CFA to published linkage studies investigating age-of-onset of Alzheimer's disease and body mass index and obtain previously known and new candidate genes. CFA provides a new tool for studies in which causal genes are expected to participate in a common pathway or process and can easily be extended to utilize annotation schemes in addition to the GO. PMID:18263617

  3. Genome-wide metabolic (re-) annotation of Kluyveromyces lactis

    PubMed Central

    2012-01-01

    Background Even before having its genome sequence published in 2004, Kluyveromyces lactis had long been considered a model organism for studies in genetics and physiology. Research on Kluyveromyces lactis is quite advanced and this yeast species is one of the few with which it is possible to perform formal genetic analysis. Nevertheless, until now, no complete metabolic functional annotation has been performed to the proteins encoded in the Kluyveromyces lactis genome. Results In this work, a new metabolic genome-wide functional re-annotation of the proteins encoded in the Kluyveromyces lactis genome was performed, resulting in the annotation of 1759 genes with metabolic functions, and the development of a methodology supported by merlin (software developed in-house). The new annotation includes novelties, such as the assignment of transporter superfamily numbers to genes identified as transporter proteins. Thus, the genes annotated with metabolic functions could be exclusively enzymatic (1410 genes), transporter proteins encoding genes (301 genes) or have both metabolic activities (48 genes). The new annotation produced by this work largely surpassed the Kluyveromyces lactis currently available annotations. A comparison with KEGG’s annotation revealed a match with 844 (~90%) of the genes annotated by KEGG, while adding 850 new gene annotations. Moreover, there are 32 genes with annotations different from KEGG. Conclusions The methodology developed throughout this work can be used to re-annotate any yeast or, with a little tweak of the reference organism, the proteins encoded in any sequenced genome. The new annotation provided by this study offers basic knowledge which might be useful for the scientific community working on this model yeast, because new functions have been identified for the so-called metabolic genes. Furthermore, it served as the basis for the reconstruction of a compartmentalized, genome-scale metabolic model of Kluyveromyces lactis, which is

  4. Model dielectric function for 2D semiconductors including substrate screening

    PubMed Central

    Trolle, Mads L.; Pedersen, Thomas G.; Véniard, Valerie

    2017-01-01

    Dielectric screening of excitons in 2D semiconductors is known to be a highly non-local effect, which in reciprocal space translates to a strong dependence on momentum transfer q. We present an analytical model dielectric function, including the full non-linear q-dependency, which may be used as an alternative to more numerically taxing ab initio screening functions. By verifying the good agreement between excitonic optical properties calculated using our model dielectric function, and those derived from ab initio methods, we demonstrate the versatility of this approach. Our test systems include: Monolayer hBN, monolayer MoS2, and the surface exciton of a 2 × 1 reconstructed Si(111) surface. Additionally, using our model, we easily take substrate screening effects into account. Hence, we include also a systematic study of the effects of substrate media on the excitonic optical properties of MoS2 and hBN. PMID:28117326

  5. Semantic Annotation of Mutable Data

    PubMed Central

    Morris, Robert A.; Dou, Lei; Hanken, James; Kelly, Maureen; Lowery, David B.; Ludäscher, Bertram; Macklin, James A.; Morris, Paul J.

    2013-01-01

    Electronic annotation of scientific data is very similar to annotation of documents. Both types of annotation amplify the original object, add related knowledge to it, and dispute or support assertions in it. In each case, annotation is a framework for discourse about the original object, and, in each case, an annotation needs to clearly identify its scope and its own terminology. However, electronic annotation of data differs from annotation of documents: the content of the annotations, including expectations and supporting evidence, is more often shared among members of networks. Any consequent actions taken by the holders of the annotated data could be shared as well. But even those current annotation systems that admit data as their subject often make it difficult or impossible to annotate at fine-enough granularity to use the results in this way for data quality control. We address these kinds of issues by offering simple extensions to an existing annotation ontology and describe how the results support an interest-based distribution of annotations. We are using the result to design and deploy a platform that supports annotation services overlaid on networks of distributed data, with particular application to data quality control. Our initial instance supports a set of natural science collection metadata services. An important application is the support for data quality control and provision of missing data. A previous proof of concept demonstrated such use based on data annotations modeled with XML-Schema. PMID:24223697

  6. Evaluating Computational Gene Ontology Annotations.

    PubMed

    Škunca, Nives; Roberts, Richard J; Steffen, Martin

    2017-01-01

    Two avenues to understanding gene function are complementary and often overlapping: experimental work and computational prediction. While experimental annotation generally produces high-quality annotations, it is low throughput. Conversely, computational annotations have broad coverage, but the quality of annotations may be variable, and therefore evaluating the quality of computational annotations is a critical concern.In this chapter, we provide an overview of strategies to evaluate the quality of computational annotations. First, we discuss why evaluating quality in this setting is not trivial. We highlight the various issues that threaten to bias the evaluation of computational annotations, most of which stem from the incompleteness of biological databases. Second, we discuss solutions that address these issues, for example, targeted selection of new experimental annotations and leveraging the existing experimental annotations.

  7. Annotating user-defined abstractions for optimization

    SciTech Connect

    Quinlan, D; Schordan, M; Vuduc, R; Yi, Q

    2005-12-05

    This paper discusses the features of an annotation language that we believe to be essential for optimizing user-defined abstractions. These features should capture semantics of function, data, and object-oriented abstractions, express abstraction equivalence (e.g., a class represents an array abstraction), and permit extension of traditional compiler optimizations to user-defined abstractions. Our future work will include developing a comprehensive annotation language for describing the semantics of general object-oriented abstractions, as well as automatically verifying and inferring the annotated semantics.

  8. A Coding System with Independent Annotations of Gesture Forms and Functions during Verbal Communication: Development of a Database of Speech and GEsture (DoSaGE).

    PubMed

    Kong, Anthony Pak-Hin; Law, Sam-Po; Kwan, Connie Ching-Yin; Lai, Christy; Lam, Vivian

    2015-03-01

    Gestures are commonly used together with spoken language in human communication. One major limitation of gesture investigations in the existing literature lies in the fact that the coding of forms and functions of gestures has not been clearly differentiated. This paper first described a recently developed Database of Speech and GEsture (DoSaGE) based on independent annotation of gesture forms and functions among 119 neurologically unimpaired right-handed native speakers of Cantonese (divided into three age and two education levels), and presented findings of an investigation examining how gesture use was related to age and linguistic performance. Consideration of these two factors, for which normative data are currently very limited or lacking in the literature, is relevant and necessary when one evaluates gesture employment among individuals with and without language impairment. Three speech tasks, including monologue of a personally important event, sequential description, and story-telling, were used for elicitation. The EUDICO Linguistic ANnotator (ELAN) software was used to independently annotate each participant's linguistic information of the transcript, forms of gestures used, and the function for each gesture. About one-third of the subjects did not use any co-verbal gestures. While the majority of gestures were non-content-carrying, which functioned mainly for reinforcing speech intonation or controlling speech flow, the content-carrying ones were used to enhance speech content. Furthermore, individuals who are younger or linguistically more proficient tended to use fewer gestures, suggesting that normal speakers gesture differently as a function of age and linguistic performance.

  9. A Coding System with Independent Annotations of Gesture Forms and Functions during Verbal Communication: Development of a Database of Speech and GEsture (DoSaGE)

    PubMed Central

    Kong, Anthony Pak-Hin; Law, Sam-Po; Kwan, Connie Ching-Yin; Lai, Christy; Lam, Vivian

    2014-01-01

    Gestures are commonly used together with spoken language in human communication. One major limitation of gesture investigations in the existing literature lies in the fact that the coding of forms and functions of gestures has not been clearly differentiated. This paper first described a recently developed Database of Speech and GEsture (DoSaGE) based on independent annotation of gesture forms and functions among 119 neurologically unimpaired right-handed native speakers of Cantonese (divided into three age and two education levels), and presented findings of an investigation examining how gesture use was related to age and linguistic performance. Consideration of these two factors, for which normative data are currently very limited or lacking in the literature, is relevant and necessary when one evaluates gesture employment among individuals with and without language impairment. Three speech tasks, including monologue of a personally important event, sequential description, and story-telling, were used for elicitation. The EUDICO Linguistic ANnotator (ELAN) software was used to independently annotate each participant’s linguistic information of the transcript, forms of gestures used, and the function for each gesture. About one-third of the subjects did not use any co-verbal gestures. While the majority of gestures were non-content-carrying, which functioned mainly for reinforcing speech intonation or controlling speech flow, the content-carrying ones were used to enhance speech content. Furthermore, individuals who are younger or linguistically more proficient tended to use fewer gestures, suggesting that normal speakers gesture differently as a function of age and linguistic performance. PMID:25667563

  10. Annotated Humanities Programs.

    ERIC Educational Resources Information Center

    Adler, Richard R.; Applebee, Arthur

    The humanities programs offered in 1968 by 227 United States secondary schools are listed alphabetically by state, including almost 100 new programs not annotated in the 1967 listing (see TE 000 224). Each annotation presents a brief description of the approach to study used in the particular humanities course (e.g., American Studies, Culture…

  11. An Annotated Bibliography of Resources on Educational Linking Agents: Roles, Functions, and Training Materials.

    ERIC Educational Resources Information Center

    Barth, Rodney J., Comp.

    The resources cited in this selected annotated bibliography are intended for linking agents, trainers of linking agents, managers of linking agents and their support systems, and educational policy makers. These resources, which date from 1975 to the present, variously refer to linking agents, change agents, extension agents, field agents, field…

  12. The Development of PIPA: An Integrated and Automated Pipeline for Genome-Wide Protein Function Annotation

    DTIC Science & Technology

    2008-01-25

    bacterial genome annotation. Nucleic Acids Res 2005/06/28 edition. 2005, 33(Web Server issue):W455-9. 14. Meyer F, Goesmann A, McHardy AC, Bartels D...GO.evi dence.shtml] 37. Jain AK Murthy MN, Flynn PJ: Data Clustering: A Review. ACM Computing Surveys 1999, 31(3):264-323. 38. Chenna R, Sugawara H

  13. The power of EST sequence data: Relation to Acyrthosiphon pisum genome annotation and functional genomics initiatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genes important to aphid biology, survival and reproduction were successfully identified by use of a genomics approach. We created and described the Sequencing, compilation, and annotation of the approxiamtely 525Mb nuclear genome of the pea aphid, Acyrthosiphon pisum, which represents an important ...

  14. Use of Modern Chemical Protein Synthesis and Advanced Fluorescent Assay Techniques to Experimentally Validate the Functional Annotation of Microbial Genomes

    SciTech Connect

    Kent, Stephen

    2012-07-20

    The objective of this research program was to prototype methods for the chemical synthesis of predicted protein molecules in annotated microbial genomes. High throughput chemical methods were to be used to make large numbers of predicted proteins and protein domains, based on microbial genome sequences. Microscale chemical synthesis methods for the parallel preparation of peptide-thioester building blocks were developed; these peptide segments are used for the parallel chemical synthesis of proteins and protein domains. Ultimately, it is envisaged that these synthetic molecules would be ‘printed’ in spatially addressable arrays. The unique ability of total synthesis to precision label protein molecules with dyes and with chemical or biochemical ‘tags’ can be used to facilitate novel assay technologies adapted from state-of-the art single molecule fluorescence detection techniques. In the future, in conjunction with modern laboratory automation this integrated set of techniques will enable high throughput experimental validation of the functional annotation of microbial genomes.

  15. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

    PubMed

    Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa; Kabagambe, Edmond Kato; Hong, Jaeyoung; Ng, Maggie C Y; Hivert, Marie-France; Lu, Yingchang; An, Ping; Bentley, Amy R; Drolet, Anne M; Gaulton, Kyle J; Guo, Xiuqing; Armstrong, Loren L; Irvin, Marguerite R; Li, Man; Lipovich, Leonard; Rybin, Denis V; Taylor, Kent D; Agyemang, Charles; Palmer, Nicholette D; Cade, Brian E; Chen, Wei-Min; Dauriz, Marco; Delaney, Joseph A C; Edwards, Todd L; Evans, Daniel S; Evans, Michele K; Lange, Leslie A; Leong, Aaron; Liu, Jingmin; Liu, Yongmei; Nayak, Uma; Patel, Sanjay R; Porneala, Bianca C; Rasmussen-Torvik, Laura J; Snijder, Marieke B; Stallings, Sarah C; Tanaka, Toshiko; Yanek, Lisa R; Zhao, Wei; Becker, Diane M; Bielak, Lawrence F; Biggs, Mary L; Bottinger, Erwin P; Bowden, Donald W; Chen, Guanjie; Correa, Adolfo; Couper, David J; Crawford, Dana C; Cushman, Mary; Eicher, John D; Fornage, Myriam; Franceschini, Nora; Fu, Yi-Ping; Goodarzi, Mark O; Gottesman, Omri; Hara, Kazuo; Harris, Tamara B; Jensen, Richard A; Johnson, Andrew D; Jhun, Min A; Karter, Andrew J; Keller, Margaux F; Kho, Abel N; Kizer, Jorge R; Krauss, Ronald M; Langefeld, Carl D; Li, Xiaohui; Liang, Jingling; Liu, Simin; Lowe, William L; Mosley, Thomas H; North, Kari E; Pacheco, Jennifer A; Peyser, Patricia A; Patrick, Alan L; Rice, Kenneth M; Selvin, Elizabeth; Sims, Mario; Smith, Jennifer A; Tajuddin, Salman M; Vaidya, Dhananjay; Wren, Mary P; Yao, Jie; Zhu, Xiaofeng; Ziegler, Julie T; Zmuda, Joseph M; Zonderman, Alan B; Zwinderman, Aeilko H; Adeyemo, Adebowale; Boerwinkle, Eric; Ferrucci, Luigi; Hayes, M Geoffrey; Kardia, Sharon L R; Miljkovic, Iva; Pankow, James S; Rotimi, Charles N; Sale, Michele M; Wagenknecht, Lynne E; Arnett, Donna K; Chen, Yii-Der Ida; Nalls, Michael A; Province, Michael A; Kao, W H Linda; Siscovick, David S; Psaty, Bruce M; Wilson, James G; Loos, Ruth J F; Dupuis, Josée; Rich, Stephen S; Florez, Jose C; Rotter, Jerome I; Morris, Andrew P; Meigs, James B

    2016-07-07

    Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

  16. dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs.

    PubMed

    Liu, Xiaoming; Wu, Chunlei; Li, Chang; Boerwinkle, Eric

    2016-03-01

    The purpose of the dbNSFP is to provide a one-stop resource for functional predictions and annotations for human nonsynonymous single-nucleotide variants (nsSNVs) and splice-site variants (ssSNVs), and to facilitate the steps of filtering and prioritizing SNVs from a large list of SNVs discovered in an exome-sequencing study. A list of all potential nsSNVs and ssSNVs based on the human reference sequence were created and functional predictions and annotations were curated and compiled for each SNV. Here, we report a recent major update of the database to version 3.0. The SNV list has been rebuilt based on GENCODE 22 and currently the database includes 82,832,027 nsSNVs and ssSNVs. An attached database dbscSNV, which compiled all potential human SNVs within splicing consensus regions and their deleteriousness predictions, add another 15,030,459 potentially functional SNVs. Eleven prediction scores (MetaSVM, MetaLR, CADD, VEST3, PROVEAN, 4× fitCons, fathmm-MKL, and DANN) and allele frequencies from the UK10K cohorts and the Exome Aggregation Consortium (ExAC), among others, have been added. The original seven prediction scores in v2.0 (SIFT, 2× Polyphen2, LRT, MutationTaster, MutationAssessor, and FATHMM) as well as many SNV and gene functional annotations have been updated. dbNSFP v3.0 is freely available at http://sites.google.com/site/jpopgen/dbNSFP.

  17. Smoking Gun or Circumstantial Evidence? Comparison of Statistical Learning Methods using Functional Annotations for Prioritizing Risk Variants

    PubMed Central

    Gagliano, Sarah A.; Ravji, Reena; Barnes, Michael R.; Weale, Michael E.; Knight, Jo

    2015-01-01

    Although technology has triumphed in facilitating routine genome sequencing, new challenges have been created for the data-analyst. Genome-scale surveys of human variation generate volumes of data that far exceed capabilities for laboratory characterization. By incorporating functional annotations as predictors, statistical learning has been widely investigated for prioritizing genetic variants likely to be associated with complex disease. We compared three published prioritization procedures, which use different statistical learning algorithms and different predictors with regard to the quantity, type and coding. We also explored different combinations of algorithm and annotation set. As an application, we tested which methodology performed best for prioritizing variants using data from a large schizophrenia meta-analysis by the Psychiatric Genomics Consortium. Results suggest that all methods have considerable (and similar) predictive accuracies (AUCs 0.64–0.71) in test set data, but there is more variability in the application to the schizophrenia GWAS. In conclusion, a variety of algorithms and annotations seem to have a similar potential to effectively enrich true risk variants in genome-scale datasets, however none offer more than incremental improvement in prediction. We discuss how methods might be evolved for risk variant prediction to address the impending bottleneck of the new generation of genome re-sequencing studies. PMID:26300220

  18. Smoking Gun or Circumstantial Evidence? Comparison of Statistical Learning Methods using Functional Annotations for Prioritizing Risk Variants.

    PubMed

    Gagliano, Sarah A; Ravji, Reena; Barnes, Michael R; Weale, Michael E; Knight, Jo

    2015-08-24

    Although technology has triumphed in facilitating routine genome sequencing, new challenges have been created for the data-analyst. Genome-scale surveys of human variation generate volumes of data that far exceed capabilities for laboratory characterization. By incorporating functional annotations as predictors, statistical learning has been widely investigated for prioritizing genetic variants likely to be associated with complex disease. We compared three published prioritization procedures, which use different statistical learning algorithms and different predictors with regard to the quantity, type and coding. We also explored different combinations of algorithm and annotation set. As an application, we tested which methodology performed best for prioritizing variants using data from a large schizophrenia meta-analysis by the Psychiatric Genomics Consortium. Results suggest that all methods have considerable (and similar) predictive accuracies (AUCs 0.64-0.71) in test set data, but there is more variability in the application to the schizophrenia GWAS. In conclusion, a variety of algorithms and annotations seem to have a similar potential to effectively enrich true risk variants in genome-scale datasets, however none offer more than incremental improvement in prediction. We discuss how methods might be evolved for risk variant prediction to address the impending bottleneck of the new generation of genome re-sequencing studies.

  19. Identification of novel biomass-degrading enzymes from genomic dark matter: Populating genomic sequence space with functional annotation.

    PubMed

    Piao, Hailan; Froula, Jeff; Du, Changbin; Kim, Tae-Wan; Hawley, Erik R; Bauer, Stefan; Wang, Zhong; Ivanova, Nathalia; Clark, Douglas S; Klenk, Hans-Peter; Hess, Matthias

    2014-08-01

    Although recent nucleotide sequencing technologies have significantly enhanced our understanding of microbial genomes, the function of ∼35% of genes identified in a genome currently remains unknown. To improve the understanding of microbial genomes and consequently of microbial processes it will be crucial to assign a function to this "genomic dark matter." Due to the urgent need for additional carbohydrate-active enzymes for improved production of transportation fuels from lignocellulosic biomass, we screened the genomes of more than 5,500 microorganisms for hypothetical proteins that are located in the proximity of already known cellulases. We identified, synthesized and expressed a total of 17 putative cellulase genes with insufficient sequence similarity to currently known cellulases to be identified as such using traditional sequence annotation techniques that rely on significant sequence similarity. The recombinant proteins of the newly identified putative cellulases were subjected to enzymatic activity assays to verify their hydrolytic activity towards cellulose and lignocellulosic biomass. Eleven (65%) of the tested enzymes had significant activity towards at least one of the substrates. This high success rate highlights that a gene context-based approach can be used to assign function to genes that are otherwise categorized as "genomic dark matter" and to identify biomass-degrading enzymes that have little sequence similarity to already known cellulases. The ability to assign function to genes that have no related sequence representatives with functional annotation will be important to enhance our understanding of microbial processes and to identify microbial proteins for a wide range of applications.

  20. BABELOMICS: a systems biology perspective in the functional annotation of genome-scale experiments

    PubMed Central

    Al-Shahrour, Fátima; Minguez, Pablo; Tárraga, Joaquín; Montaner, David; Alloza, Eva; Vaquerizas, Juan M.; Conde, Lucía; Blaschke, Christian; Vera, Javier; Dopazo, Joaquín

    2006-01-01

    We present a new version of Babelomics, a complete suite of web tools for functional analysis of genome-scale experiments, with new and improved tools. New functionally relevant terms have been included such as CisRed motifs or bioentities obtained by text-mining procedures. An improved indexing has considerably speeded up several of the modules. An improved version of the FatiScan method for studying the coordinate behaviour of groups of functionally related genes is presented, along with a similar tool, the Gene Set Enrichment Analysis. Babelomics is now more oriented to test systems biology inspired hypotheses. Babelomics can be found at . PMID:16845052

  1. Non-Gaussian Distributions Affect Identification of Expression Patterns, Functional Annotation, and Prospective Classification in Human Cancer Genomes

    PubMed Central

    Marko, Nicholas F.; Weil, Robert J.

    2012-01-01

    Introduction Gene expression data is often assumed to be normally-distributed, but this assumption has not been tested rigorously. We investigate the distribution of expression data in human cancer genomes and study the implications of deviations from the normal distribution for translational molecular oncology research. Methods We conducted a central moments analysis of five cancer genomes and performed empiric distribution fitting to examine the true distribution of expression data both on the complete-experiment and on the individual-gene levels. We used a variety of parametric and nonparametric methods to test the effects of deviations from normality on gene calling, functional annotation, and prospective molecular classification using a sixth cancer genome. Results Central moments analyses reveal statistically-significant deviations from normality in all of the analyzed cancer genomes. We observe as much as 37% variability in gene calling, 39% variability in functional annotation, and 30% variability in prospective, molecular tumor subclassification associated with this effect. Conclusions Cancer gene expression profiles are not normally-distributed, either on the complete-experiment or on the individual-gene level. Instead, they exhibit complex, heavy-tailed distributions characterized by statistically-significant skewness and kurtosis. The non-Gaussian distribution of this data affects identification of differentially-expressed genes, functional annotation, and prospective molecular classification. These effects may be reduced in some circumstances, although not completely eliminated, by using nonparametric analytics. This analysis highlights two unreliable assumptions of translational cancer gene expression analysis: that “small” departures from normality in the expression data distributions are analytically-insignificant and that “robust” gene-calling algorithms can fully compensate for these effects. PMID:23118863

  2. Morgan’s Legacy: Fruit Flies and the Functional Annotation of Conserved Genes

    PubMed Central

    Bellen, Hugo J.; Yamamoto, Shinya

    2016-01-01

    In 1915, “The Mechanism of Mendelian Heredity” was published by four prominent Drosophila geneticists. They discovered that genes form linkage groups on chromosomes inherited in a Mendelian fashion and laid the genetic foundation that promoted Drosophila as a model organism. Flies continue to offer great opportunities, including studies in the field of functional genomics. PMID:26406362

  3. Functional annotation of sixty-five type-2 diabetes risk SNPs and its application in risk prediction

    PubMed Central

    Wu, Yiming; Jing, Runyu; Dong, Yongcheng; Kuang, Qifan; Li, Yan; Huang, Ziyan; Gan, Wei; Xue, Yue; Li, Yizhou; Li, Menglong

    2017-01-01

    Genome-wide association studies (GWAS) have identified more than sixty single nucleotide polymorphisms (SNPs) associated with increased risk for type 2 diabetes (T2D). However, the identification of causal risk SNPs for T2D pathogenesis was complicated by the factor that each risk SNP is a surrogate for the hundreds of SNPs, most of which reside in non-coding regions. Here we provide a comprehensive annotation of 65 known T2D related SNPs and inspect putative functional SNPs probably causing protein dysfunction, response element disruptions of known transcription factors related to T2D genes and regulatory response element disruption of four histone marks in pancreas and pancreas islet. In new identified risk SNPs, some of them were reported as T2D related SNPs in recent studies. Further, we found that accumulation of modest effects of single sites markedly enhanced the risk prediction based on 1989 T2D samples and 3000 healthy controls. The AROC value increased from 0.58 to 0.62 by only using genotype score when putative risk SNPs were added. Besides, the net reclassification improvement is 10.03% on the addition of new risk SNPs. Taken together, functional annotation could provide a list of prioritized potential risk SNPs for the further estimation on the T2D susceptibility of individuals. PMID:28262806

  4. Functional Genomic Annotation of Genetic Risk Loci Highlights Inflammation and Epithelial Biology Networks in CKD

    PubMed Central

    Ledo, Nora; Ko, Yi-An; Park, Ae-Seo Deok; Kang, Hyun-Mi; Han, Sang-Youb; Choi, Peter

    2015-01-01

    Genome-wide association studies (GWASs) have identified multiple loci associated with the risk of CKD. Almost all risk variants are localized to the noncoding region of the genome; therefore, the role of these variants in CKD development is largely unknown. We hypothesized that polymorphisms alter transcription factor binding, thereby influencing the expression of nearby genes. Here, we examined the regulation of transcripts in the vicinity of CKD-associated polymorphisms in control and diseased human kidney samples and used systems biology approaches to identify potentially causal genes for prioritization. We interrogated the expression and regulation of 226 transcripts in the vicinity of 44 single nucleotide polymorphisms using RNA sequencing and gene expression arrays from 95 microdissected control and diseased tubule samples and 51 glomerular samples. Gene expression analysis from 41 tubule samples served for external validation. 92 transcripts in the tubule compartment and 34 transcripts in glomeruli showed statistically significant correlation with eGFR. Many novel genes, including ACSM2A/2B, FAM47E, and PLXDC1, were identified. We observed that the expression of multiple genes in the vicinity of any single CKD risk allele correlated with renal function, potentially indicating that genetic variants influence multiple transcripts. Network analysis of GFR-correlating transcripts highlighted two major clusters; a positive correlation with epithelial and vascular functions and an inverse correlation with inflammatory gene cluster. In summary, our functional genomics analysis highlighted novel genes and critical pathways associated with kidney function for future analysis. PMID:25231882

  5. Solving the Problem: Genome Annotation Standards before the Data Deluge

    PubMed Central

    Klimke, William; O'Donovan, Claire; White, Owen; Brister, J. Rodney; Clark, Karen; Fedorov, Boris; Mizrachi, Ilene; Pruitt, Kim D.; Tatusova, Tatiana

    2011-01-01

    The promise of genome sequencing was that the vast undiscovered country would be mapped out by comparison of the multitude of sequences available and would aid researchers in deciphering the role of each gene in every organism. Researchers recognize that there is a need for high quality data. However, different annotation procedures, numerous databases, and a diminishing percentage of experimentally determined gene functions have resulted in a spectrum of annotation quality. NCBI in collaboration with sequencing centers, archival databases, and researchers, has developed the first international annotation standards, a fundamental step in ensuring that high quality complete prokaryotic genomes are available as gold standard references. Highlights include the development of annotation assessment tools, community acceptance of protein naming standards, comparison of annotation resources to provide consistent annotation, and improved tracking of the evidence used to generate a particular annotation. The development of a set of minimal standards, including the requirement for annotated complete prokaryotic genomes to contain a full set of ribosomal RNAs, transfer RNAs, and proteins encoding core conserved functions, is an historic milestone. The use of these standards in existing genomes and future submissions will increase the quality of databases, enabling researchers to make accurate biological discoveries. PMID:22180819

  6. Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.

    PubMed

    Han, Ying; Hazelett, Dennis J; Wiklund, Fredrik; Schumacher, Fredrick R; Stram, Daniel O; Berndt, Sonja I; Wang, Zhaoming; Rand, Kristin A; Hoover, Robert N; Machiela, Mitchell J; Yeager, Merideth; Burdette, Laurie; Chung, Charles C; Hutchinson, Amy; Yu, Kai; Xu, Jianfeng; Travis, Ruth C; Key, Timothy J; Siddiq, Afshan; Canzian, Federico; Takahashi, Atsushi; Kubo, Michiaki; Stanford, Janet L; Kolb, Suzanne; Gapstur, Susan M; Diver, W Ryan; Stevens, Victoria L; Strom, Sara S; Pettaway, Curtis A; Al Olama, Ali Amin; Kote-Jarai, Zsofia; Eeles, Rosalind A; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; Isaacs, William B; Chen, Constance; Lindstrom, Sara; Le Marchand, Loic; Giovannucci, Edward L; Pomerantz, Mark; Long, Henry; Li, Fugen; Ma, Jing; Stampfer, Meir; John, Esther M; Ingles, Sue A; Kittles, Rick A; Murphy, Adam B; Blot, William J; Signorello, Lisa B; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, M Cristina; Wu, Suh-Yuh; Hennis, Anselm J M; Rybicki, Benjamin A; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Witte, John S; Casey, Graham; Riboli, Elio; Li, Qiyuan; Freedman, Matthew L; Hunter, David J; Gronberg, Henrik; Cook, Michael B; Nakagawa, Hidewaki; Kraft, Peter; Chanock, Stephen J; Easton, Douglas F; Henderson, Brian E; Coetzee, Gerhard A; Conti, David V; Haiman, Christopher A

    2015-10-01

    Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation.

  7. Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions

    PubMed Central

    Han, Ying; Hazelett, Dennis J.; Wiklund, Fredrik; Schumacher, Fredrick R.; Stram, Daniel O.; Berndt, Sonja I.; Wang, Zhaoming; Rand, Kristin A.; Hoover, Robert N.; Machiela, Mitchell J.; Yeager, Merideth; Burdette, Laurie; Chung, Charles C.; Hutchinson, Amy; Yu, Kai; Xu, Jianfeng; Travis, Ruth C.; Key, Timothy J.; Siddiq, Afshan; Canzian, Federico; Takahashi, Atsushi; Kubo, Michiaki; Stanford, Janet L.; Kolb, Suzanne; Gapstur, Susan M.; Diver, W. Ryan; Stevens, Victoria L.; Strom, Sara S.; Pettaway, Curtis A.; Al Olama, Ali Amin; Kote-Jarai, Zsofia; Eeles, Rosalind A.; Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P.; Isaacs, William B.; Chen, Constance; Lindstrom, Sara; Le Marchand, Loic; Giovannucci, Edward L.; Pomerantz, Mark; Long, Henry; Li, Fugen; Ma, Jing; Stampfer, Meir; John, Esther M.; Ingles, Sue A.; Kittles, Rick A.; Murphy, Adam B.; Blot, William J.; Signorello, Lisa B.; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, M. Cristina; Wu, Suh-Yuh; Hennis, Anselm J. M.; Rybicki, Benjamin A.; Neslund-Dudas, Christine; Hsing, Ann W.; Chu, Lisa; Goodman, Phyllis J.; Klein, Eric A.; Zheng, S. Lilly; Witte, John S.; Casey, Graham; Riboli, Elio; Li, Qiyuan; Freedman, Matthew L.; Hunter, David J.; Gronberg, Henrik; Cook, Michael B.; Nakagawa, Hidewaki; Kraft, Peter; Chanock, Stephen J.; Easton, Douglas F.; Henderson, Brian E.; Coetzee, Gerhard A.; Conti, David V.; Haiman, Christopher A.

    2015-01-01

    Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10−4–5.6 × 10−3) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10−6) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation. PMID:26162851

  8. Comparative omics-driven genome annotation refinement: application across Yersiniae.

    PubMed

    Schrimpe-Rutledge, Alexandra C; Jones, Marcus B; Chauhan, Sadhana; Purvine, Samuel O; Sanford, James A; Monroe, Matthew E; Brewer, Heather M; Payne, Samuel H; Ansong, Charles; Frank, Bryan C; Smith, Richard D; Peterson, Scott N; Motin, Vladimir L; Adkins, Joshua N

    2012-01-01

    Genome sequencing continues to be a rapidly evolving technology, yet most downstream aspects of genome annotation pipelines remain relatively stable or are even being abandoned. The annotation process is now performed almost exclusively in an automated fashion to balance the large number of sequences generated. One possible way of reducing errors inherent to automated computational annotations is to apply data from omics measurements (i.e. transcriptional and proteomic) to the un-annotated genome with a proteogenomic-based approach. Here, the concept of annotation refinement has been extended to include a comparative assessment of genomes across closely related species. Transcriptomic and proteomic data derived from highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis Pestoides F, and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive comparative omic-based annotation methodology. Peptide and oligo measurements experimentally validated the expression of nearly 40% of each strain's predicted proteome and revealed the identification of 28 novel and 68 incorrect (i.e., observed frameshifts, extended start sites, and translated pseudogenes) protein-coding sequences within the three current genome annotations. Gene loss is presumed to play a major role in Y. pestis acquiring its niche as a virulent pathogen, thus the discovery of many translated pseudogenes, including the insertion-ablated argD, underscores a need for functional analyses to investigate hypotheses related to divergence. Refinements included the discovery of a seemingly essential ribosomal protein, several virulence-associated factors, a transcriptional regulator, and many hypothetical proteins that were missed during annotation.

  9. Quality of computationally inferred gene ontology annotations.

    PubMed

    Skunca, Nives; Altenhoff, Adrian; Dessimoz, Christophe

    2012-05-01

    Gene Ontology (GO) has established itself as the undisputed standard for protein function annotation. Most annotations are inferred electronically, i.e. without individual curator supervision, but they are widely considered unreliable. At the same time, we crucially depend on those automated annotations, as most newly sequenced genomes are non-model organisms. Here, we introduce a methodology to systematically and quantitatively evaluate electronic annotations. By exploiting changes in successive releases of the UniProt Gene Ontology Annotation database, we assessed the quality of electronic annotations in terms of specificity, reliability, and coverage. Overall, we not only found that electronic annotations have significantly improved in recent years, but also that their reliability now rivals that of annotations inferred by curators when they use evidence other than experiments from primary literature. This work provides the means to identify the subset of electronic annotations that can be relied upon-an important outcome given that >98% of all annotations are inferred without direct curation.

  10. Analysis and Functional Annotation of an Expressed Sequence Tag Collection for Tropical Crop Sugarcane

    PubMed Central

    Vettore, André L.; da Silva, Felipe R.; Kemper, Edson L.; Souza, Glaucia M.; da Silva, Aline M.; Ferro, Maria Inês T.; Henrique-Silva, Flavio; Giglioti, Éder A.; Lemos, Manoel V.F.; Coutinho, Luiz L.; Nobrega, Marina P.; Carrer, Helaine; França, Suzelei C.; Bacci, Maurício; Goldman, Maria Helena S.; Gomes, Suely L.; Nunes, Luiz R.; Camargo, Luis E.A.; Siqueira, Walter J.; Van Sluys, Marie-Anne; Thiemann, Otavio H.; Kuramae, Eiko E.; Santelli, Roberto V.; Marino, Celso L.; Targon, Maria L.P.N.; Ferro, Jesus A.; Silveira, Henrique C.S.; Marini, Danyelle C.; Lemos, Eliana G.M.; Monteiro-Vitorello, Claudia B.; Tambor, José H.M.; Carraro, Dirce M.; Roberto, Patrícia G.; Martins, Vanderlei G.; Goldman, Gustavo H.; de Oliveira, Regina C.; Truffi, Daniela; Colombo, Carlos A.; Rossi, Magdalena; de Araujo, Paula G.; Sculaccio, Susana A.; Angella, Aline; Lima, Marleide M.A.; de Rosa, Vicente E.; Siviero, Fábio; Coscrato, Virginia E.; Machado, Marcos A.; Grivet, Laurent; Di Mauro, Sonia M.Z.; Nobrega, Francisco G.; Menck, Carlos F.M.; Braga, Marilia D.V.; Telles, Guilherme P.; Cara, Frank A.A.; Pedrosa, Guilherme; Meidanis, João; Arruda, Paulo

    2003-01-01

    To contribute to our understanding of the genome complexity of sugarcane, we undertook a large-scale expressed sequence tag (EST) program. More than 260,000 cDNA clones were partially sequenced from 26 standard cDNA libraries generated from different sugarcane tissues. After the processing of the sequences, 237,954 high-quality ESTs were identified. These ESTs were assembled into 43,141 putative transcripts. Of the assembled sequences, 35.6% presented no matches with existing sequences in public databases. A global analysis of the whole SUCEST data set indicated that 14,409 assembled sequences (33% of the total) contained at least one cDNA clone with a full-length insert. Annotation of the 43,141 assembled sequences associated almost 50% of the putative identified sugarcane genes with protein metabolism, cellular communication/signal transduction, bioenergetics, and stress responses. Inspection of the translated assembled sequences for conserved protein domains revealed 40,821 amino acid sequences with 1415 Pfam domains. Reassembling the consensus sequences of the 43,141 transcripts revealed a 22% redundancy in the first assembling. This indicated that possibly 33,620 unique genes had been identified and indicated that >90% of the sugarcane expressed genes were tagged. PMID:14613979

  11. Dictionary-driven protein annotation.

    PubMed

    Rigoutsos, Isidore; Huynh, Tien; Floratos, Aris; Parida, Laxmi; Platt, Daniel

    2002-09-01

    Computational methods seeking to automatically determine the properties (functional, structural, physicochemical, etc.) of a protein directly from the sequence have long been the focus of numerous research groups. With the advent of advanced sequencing methods and systems, the number of amino acid sequences that are being deposited in the public databases has been increasing steadily. This has in turn generated a renewed demand for automated approaches that can annotate individual sequences and complete genomes quickly, exhaustively and objectively. In this paper, we present one such approach that is centered around and exploits the Bio-Dictionary, a collection of amino acid patterns that completely covers the natural sequence space and can capture functional and structural signals that have been reused during evolution, within and across protein families. Our annotation approach also makes use of a weighted, position-specific scoring scheme that is unaffected by the over-representation of well-conserved proteins and protein fragments in the databases used. For a given query sequence, the method permits one to determine, in a single pass, the following: local and global similarities between the query and any protein already present in a public database; the likeness of the query to all available archaeal/ bacterial/eukaryotic/viral sequences in the database as a function of amino acid position within the query; the character of secondary structure of the query as a function of amino acid position within the query; the cytoplasmic, transmembrane or extracellular behavior of the query; the nature and position of binding domains, active sites, post-translationally modified sites, signal peptides, etc. In terms of performance, the proposed method is exhaustive, objective and allows for the rapid annotation of individual sequences and full genomes. Annotation examples are presented and discussed in Results, including individual queries and complete genomes that were

  12. The standard operating procedure of the DOE-JGI Microbial Genome Annotation Pipeline (MGAP v.4)

    DOE PAGES

    Huntemann, Marcel; Ivanova, Natalia N.; Mavromatis, Konstantinos; ...

    2015-10-26

    The DOE-JGI Microbial Genome Annotation Pipeline performs structural and functional annotation of microbial genomes that are further included into the Integrated Microbial Genome comparative analysis system. MGAP is applied to assembled nucleotide sequence datasets that are provided via the IMG submission site. Dataset submission for annotation first requires project and associated metadata description in GOLD. The MGAP sequence data processing consists of feature prediction including identification of protein-coding genes, non-coding RNAs and regulatory RNA features, as well as CRISPR elements. In conclusion, structural annotation is followed by assignment of protein product names and functions.

  13. The standard operating procedure of the DOE-JGI Microbial Genome Annotation Pipeline (MGAP v.4).

    PubMed

    Huntemann, Marcel; Ivanova, Natalia N; Mavromatis, Konstantinos; Tripp, H James; Paez-Espino, David; Palaniappan, Krishnaveni; Szeto, Ernest; Pillay, Manoj; Chen, I-Min A; Pati, Amrita; Nielsen, Torben; Markowitz, Victor M; Kyrpides, Nikos C

    2015-01-01

    The DOE-JGI Microbial Genome Annotation Pipeline performs structural and functional annotation of microbial genomes that are further included into the Integrated Microbial Genome comparative analysis system. MGAP is applied to assembled nucleotide sequence datasets that are provided via the IMG submission site. Dataset submission for annotation first requires project and associated metadata description in GOLD. The MGAP sequence data processing consists of feature prediction including identification of protein-coding genes, non-coding RNAs and regulatory RNA features, as well as CRISPR elements. Structural annotation is followed by assignment of protein product names and functions.

  14. A scattering function of star polymers including excluded volume effects

    SciTech Connect

    Li, Xin; Do, Changwoo; Liu, Yun; Sánchez-Diáz, Luis; Smith, Gregory; Chen, Wei-Ren

    2014-11-04

    In this work we present a new model for the form factor of a star polymer consisting of self-avoiding branches. This new model incorporates excluded volume effects and is derived from the two point correlation function for a star polymer.. We compare this model to small angle neutron scattering (SANS) measurements from polystyrene (PS) stars immersed in a good solvent, tetrahydrofuran (THF). It is shown that this model provides a good description of the scattering signature originating from the excluded volume effect and it explicitly elucidates the connection between the global conformation of a star polymer and the local stiffness of its constituent branch.

  15. A scattering function of star polymers including excluded volume effects

    DOE PAGES

    Li, Xin; Do, Changwoo; Liu, Yun; ...

    2014-11-04

    In this work we present a new model for the form factor of a star polymer consisting of self-avoiding branches. This new model incorporates excluded volume effects and is derived from the two point correlation function for a star polymer.. We compare this model to small angle neutron scattering (SANS) measurements from polystyrene (PS) stars immersed in a good solvent, tetrahydrofuran (THF). It is shown that this model provides a good description of the scattering signature originating from the excluded volume effect and it explicitly elucidates the connection between the global conformation of a star polymer and the local stiffnessmore » of its constituent branch.« less

  16. Taxonomic Precision of Different Hypervariable Regions of 16S rRNA Gene and Annotation Methods for Functional Bacterial Groups in Biological Wastewater Treatment

    PubMed Central

    Guo, Feng; Ju, Feng; Cai, Lin; Zhang, Tong

    2013-01-01

    High throughput sequencing of 16S rRNA gene leads us into a deeper understanding on bacterial diversity for complex environmental samples, but introduces blurring due to the relatively low taxonomic capability of short read. For wastewater treatment plant, only those functional bacterial genera categorized as nutrient remediators, bulk/foaming species, and potential pathogens are significant to biological wastewater treatment and environmental impacts. Precise taxonomic assignment of these bacteria at least at genus level is important for microbial ecological research and routine wastewater treatment monitoring. Therefore, the focus of this study was to evaluate the taxonomic precisions of different ribosomal RNA (rRNA) gene hypervariable regions generated from a mix activated sludge sample. In addition, three commonly used classification methods including RDP Classifier, BLAST-based best-hit annotation, and the lowest common ancestor annotation by MEGAN were evaluated by comparing their consistency. Under an unsupervised way, analysis of consistency among different classification methods suggests there are no hypervariable regions with good taxonomic coverage for all genera. Taxonomic assignment based on certain regions of the 16S rRNA genes, e.g. the V1&V2 regions – provide fairly consistent taxonomic assignment for a relatively wide range of genera. Hence, it is recommended to use these regions for studying functional groups in activated sludge. Moreover, the inconsistency among methods also demonstrated that a specific method might not be suitable for identification of some bacterial genera using certain 16S rRNA gene regions. As a general rule, drawing conclusions based only on one sequencing region and one classification method should be avoided due to the potential false negative results. PMID:24146837

  17. RATT: Rapid Annotation Transfer Tool

    PubMed Central

    Otto, Thomas D.; Dillon, Gary P.; Degrave, Wim S.; Berriman, Matthew

    2011-01-01

    Second-generation sequencing technologies have made large-scale sequencing projects commonplace. However, making use of these datasets often requires gene function to be ascribed genome wide. Although tool development has kept pace with the changes in sequence production, for tasks such as mapping, de novo assembly or visualization, genome annotation remains a challenge. We have developed a method to rapidly provide accurate annotation for new genomes using previously annotated genomes as a reference. The method, implemented in a tool called RATT (Rapid Annotation Transfer Tool), transfers annotations from a high-quality reference to a new genome on the basis of conserved synteny. We demonstrate that a Mycobacterium tuberculosis genome or a single 2.5 Mb chromosome from a malaria parasite can be annotated in less than five minutes with only modest computational resources. RATT is available at http://ratt.sourceforge.net. PMID:21306991

  18. Valuing preferences over stormwater management outcomes including improved hydrologic function

    NASA Astrophysics Data System (ADS)

    LondoñO Cadavid, Catalina; Ando, Amy W.

    2013-07-01

    Stormwater runoff causes environmental problems such as flooding, soil erosion, and water pollution. Conventional stormwater management has focused primarily on flood reduction, while a new generation of decentralized stormwater solutions yields ancillary benefits such as healthier aquatic habitat, improved surface water quality, and increased water table recharge. Previous research has estimated values for flood reduction from stormwater management, but no estimates exist for the willingness to pay (WTP) for some of the other environmental benefits of alternative approaches to stormwater control. This paper uses a choice experiment survey of households in Champaign-Urbana, Illinois, to estimate the values of several attributes of stormwater management outcomes. We analyzed data from 131 surveyed households in randomly selected neighborhoods. We find that people value reduced basement flooding more than reductions in yard or street flooding, but WTP for basement flood reduction in the area only exists if individuals are currently experiencing significant flooding themselves. Citizens value both improved water quality and improved hydrologic function and aquatic habitat from runoff reduction. Thus, widespread investment in low impact development stormwater solutions could have very large total benefits, and stormwater managers should be wary of policies and infrastructure plans that reduce flooding at the expense of water quality and aquatic habitat.

  19. High-throughput comparison, functional annotation, and metabolic modeling of plant genomes using the PlantSEED resource

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The increasing number of sequenced plant genomes is placing new demands on the methods applied to analyze, annotate, and model these genomes. Today's annotation pipelines result in inconsistent gene assignments that complicate comparative analyses and prevent efficient construction of metabolic mode...

  20. Functional Annotation, Genome Organization and Phylogeny of the Grapevine (Vitis vinifera) Terpene Synthase Gene Family Based on Genome Assembly, FLcDNA Cloning, and Enzyme Assays

    PubMed Central

    2010-01-01

    Background Terpenoids are among the most important constituents of grape flavour and wine bouquet, and serve as useful metabolite markers in viticulture and enology. Based on the initial 8-fold sequencing of a nearly homozygous Pinot noir inbred line, 89 putative terpenoid synthase genes (VvTPS) were predicted by in silico analysis of the grapevine (Vitis vinifera) genome assembly [1]. The finding of this very large VvTPS family, combined with the importance of terpenoid metabolism for the organoleptic properties of grapevine berries and finished wines, prompted a detailed examination of this gene family at the genomic level as well as an investigation into VvTPS biochemical functions. Results We present findings from the analysis of the up-dated 12-fold sequencing and assembly of the grapevine genome that place the number of predicted VvTPS genes at 69 putatively functional VvTPS, 20 partial VvTPS, and 63 VvTPS probable pseudogenes. Gene discovery and annotation included information about gene architecture and chromosomal location. A dense cluster of 45 VvTPS is localized on chromosome 18. Extensive FLcDNA cloning, gene synthesis, and protein expression enabled functional characterization of 39 VvTPS; this is the largest number of functionally characterized TPS for any species reported to date. Of these enzymes, 23 have unique functions and/or phylogenetic locations within the plant TPS gene family. Phylogenetic analyses of the TPS gene family showed that while most VvTPS form species-specific gene clusters, there are several examples of gene orthology with TPS of other plant species, representing perhaps more ancient VvTPS, which have maintained functions independent of speciation. Conclusions The highly expanded VvTPS gene family underpins the prominence of terpenoid metabolism in grapevine. We provide a detailed experimental functional annotation of 39 members of this important gene family in grapevine and comprehensive information about gene structure and

  1. The Ensembl gene annotation system

    PubMed Central

    Aken, Bronwen L.; Ayling, Sarah; Barrell, Daniel; Clarke, Laura; Curwen, Valery; Fairley, Susan; Fernandez Banet, Julio; Billis, Konstantinos; García Girón, Carlos; Hourlier, Thibaut; Howe, Kevin; Kähäri, Andreas; Kokocinski, Felix; Martin, Fergal J.; Murphy, Daniel N.; Nag, Rishi; Ruffier, Magali; Schuster, Michael; Tang, Y. Amy; Vogel, Jan-Hinnerk; White, Simon; Zadissa, Amonida; Flicek, Paul

    2016-01-01

    The Ensembl gene annotation system has been used to annotate over 70 different vertebrate species across a wide range of genome projects. Furthermore, it generates the automatic alignment-based annotation for the human and mouse GENCODE gene sets. The system is based on the alignment of biological sequences, including cDNAs, proteins and RNA-seq reads, to the target genome in order to construct candidate transcript models. Careful assessment and filtering of these candidate transcripts ultimately leads to the final gene set, which is made available on the Ensembl website. Here, we describe the annotation process in detail. Database URL: http://www.ensembl.org/index.html PMID:27337980

  2. Functional annotation of proteomic sequences based on consensus of sequence and structural analysis.

    PubMed

    Kitson, David H; Badretdinov, Azat; Zhu, Zhan-yang; Velikanov, Mikhail; Edwards, David J; Olszewski, Krzysztof; Szalma, Sándor; Yan, Lisa

    2002-03-01

    To maximise the assignment of function of the proteins encoded by a genome and to aid the search for novel drug targets, there is an emerging need for sensitive methods of predicting protein function on a genome-wide basis. GeneAtlas is an automated, high-throughput pipeline for the prediction of protein structure and function using sequence similarity detection, homology modelling and fold recognition methods. GeneAtlas is described in detail here. To test GeneAtlas, a 'virtual' genome was used, a subset of PDB structures from the SCOP database, in which the functional relationships are known. GeneAtlas detects additional relationships by building 3D models in comparison with the sequence searching method PSI-BLAST. Functionally related proteins with sequence identity below the twilight zone can be recognised correctly.

  3. Next-Generation High-Throughput Functional Annotation of Microbial Genomes

    PubMed Central

    Baric, Ralph S.; Damania, Blossom; Miller, Samuel I.; Rubin, Eric J.

    2016-01-01

    ABSTRACT Host infection by microbial pathogens cues global changes in microbial and host cell biology that facilitate microbial replication and disease. The complete maps of thousands of bacterial and viral genomes have recently been defined; however, the rate at which physiological or biochemical functions have been assigned to genes has greatly lagged. The National Institute of Allergy and Infectious Diseases (NIAID) addressed this gap by creating functional genomics centers dedicated to developing high-throughput approaches to assign gene function. These centers require broad-based and collaborative research programs to generate and integrate diverse data to achieve a comprehensive understanding of microbial pathogenesis. High-throughput functional genomics can lead to new therapeutics and better understanding of the next generation of emerging pathogens by rapidly defining new general mechanisms by which organisms cause disease and replicate in host tissues and by facilitating the rate at which functional data reach the scientific community. PMID:27703071

  4. The DOE-JGI Standard Operating Procedure for the Annotations of the Microbial Genomes

    SciTech Connect

    Mavromatis, Konstantinos; Ivanova, Natalia; Chen, I-Min A.; Szeto, Ernest; Markowitz, Victor; Kyrpides, Nikos C.

    2009-05-20

    The DOE-JGI Microbial Annotation Pipeline (DOE-JGI MAP) supports gene prediction and/or functional annotation of microbial genomes towards comparative analysis with the Integrated Microbial Genome (IMG) system. DOE-JGI MAP annotation is applied on nucleotide sequence datasets included in the IMG-ER (Expert Review) version of IMG via the IMG ER submission site. Users can submit the sequence datasets consisting of one or more contigs in a multi-fasta file. DOE-JGI MAP annotation includes prediction of protein coding and RNA genes, as well as repeats and assignment of product names to these genes.

  5. Injectors and Annotations

    NASA Technical Reports Server (NTRS)

    Filman, Robert E.

    2004-01-01

    In a previous paper, we presented the Object Infrastructure Framework. The goal of that system is to simplify the creation of distributed applications. The primary claim of that work is that non-functional 'ilities' could be achieved by controlling and manipulating the communications between components, thereby simplifying the development of distributed systems. A secondary element of that paper is to argue for extending the conventional distributed objects model in two important ways: 1) The ability to insert injectors (filters, wrappers) into the communication path between components; 2) The ability to annotate communications with additional information, and to propagate these annotations through an application. Here we express the descriptions of that paper.

  6. Transcriptomic Analysis of the Endangered Neritid Species Clithon retropictus: De Novo Assembly, Functional Annotation, and Marker Discovery

    PubMed Central

    Park, So Young; Patnaik, Bharat Bhusan; Kang, Se Won; Hwang, Hee-Ju; Chung, Jong Min; Song, Dae Kwon; Sang, Min Kyu; Patnaik, Hongray Howrelia; Lee, Jae Bong; Noh, Mi Young; Kim, Changmu; Kim, Soonok; Park, Hong Seog; Lee, Jun Sang; Han, Yeon Soo; Lee, Yong Seok

    2016-01-01

    An aquatic gastropod belonging to the family Neritidae, Clithon retropictus is listed as an endangered class II species in South Korea. The lack of information on its genomic background limits the ability to obtain functional data resources and inhibits informed conservation planning for this species. In the present study, the transcriptomic sequencing and de novo assembly of C. retropictus generated a total of 241,696,750 high-quality reads. These assembled to 282,838 unigenes with mean and N50 lengths of 736.9 and 1201 base pairs, respectively. Of these, 125,616 unigenes were subjected to annotation analysis with known proteins in Protostome DB, COG, GO, and KEGG protein databases (BLASTX; E ≤ 0.00001) and with known nucleotides in the Unigene database (BLASTN; E ≤ 0.00001). The GO analysis indicated that cellular process, cell, and catalytic activity are the predominant GO terms in the biological process, cellular component, and molecular function categories, respectively. In addition, 2093 unigenes were distributed in 107 different KEGG pathways. Furthermore, 49,280 simple sequence repeats were identified in the unigenes (>1 kilobase sequences). This is the first report on the identification of transcriptomic and microsatellite resources for C. retropictus, which opens up the possibility of exploring traits related to the adaptation and acclimatization of this species. PMID:27455329

  7. Transcript Annotation in FANTOM3: Mouse Gene Catalog Based on Physical cDNAs

    PubMed Central

    Maeda, Norihiro; Kasukawa, Takeya; Oyama, Rieko; Gough, Julian; Frith, Martin; Engström, Pär G; Lenhard, Boris; Aturaliya, Rajith N; Batalov, Serge; Beisel, Kirk W; Bult, Carol J; Fletcher, Colin F; Forrest, Alistair R. R; Furuno, Masaaki; Hill, David; Itoh, Masayoshi; Kanamori-Katayama, Mutsumi; Katayama, Shintaro; Katoh, Masaru; Kawashima, Tsugumi; Quackenbush, John; Ravasi, Timothy; Ring, Brian Z; Shibata, Kazuhiro; Sugiura, Koji; Takenaka, Yoichi; Teasdale, Rohan D; Wells, Christine A; Zhu, Yunxia; Kai, Chikatoshi; Kawai, Jun; Hume, David A; Carninci, Piero; Hayashizaki, Yoshihide

    2006-01-01

    The international FANTOM consortium aims to produce a comprehensive picture of the mammalian transcriptome, based upon an extensive cDNA collection and functional annotation of full-length enriched cDNAs. The previous dataset, FANTOM2, comprised 60,770 full-length enriched cDNAs. Functional annotation revealed that this cDNA dataset contained only about half of the estimated number of mouse protein-coding genes, indicating that a number of cDNAs still remained to be collected and identified. To pursue the complete gene catalog that covers all predicted mouse genes, cloning and sequencing of full-length enriched cDNAs has been continued since FANTOM2. In FANTOM3, 42,031 newly isolated cDNAs were subjected to functional annotation, and the annotation of 4,347 FANTOM2 cDNAs was updated. To accomplish accurate functional annotation, we improved our automated annotation pipeline by introducing new coding sequence prediction programs and developed a Web-based annotation interface for simplifying the annotation procedures to reduce manual annotation errors. Automated coding sequence and function prediction was followed with manual curation and review by expert curators. A total of 102,801 full-length enriched mouse cDNAs were annotated. Out of 102,801 transcripts, 56,722 were functionally annotated as protein coding (including partial or truncated transcripts), providing to our knowledge the greatest current coverage of the mouse proteome by full-length cDNAs. The total number of distinct non-protein-coding transcripts increased to 34,030. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and final expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species. PMID:16683036

  8. Functional annotation of rare gene aberration drivers of pancreatic cancer | Office of Cancer Genomics

    Cancer.gov

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC).

  9. An atlas of tissue-specific conserved coexpression for functional annotation and disease gene prediction.

    PubMed

    Piro, Rosario Michael; Ala, Ugo; Molineris, Ivan; Grassi, Elena; Bracco, Chiara; Perego, Gian Paolo; Provero, Paolo; Di Cunto, Ferdinando

    2011-11-01

    Gene coexpression relationships that are phylogenetically conserved between human and mouse have been shown to provide important clues about gene function that can be efficiently used to identify promising candidate genes for human hereditary disorders. In the past, such approaches have considered mostly generic gene expression profiles that cover multiple tissues and organs. The individual genes of multicellular organisms, however, can participate in different transcriptional programs, operating at scales as different as single-cell types, tissues, organs, body regions or the entire organism. Therefore, systematic analysis of tissue-specific coexpression could be, in principle, a very powerful strategy to dissect those functional relationships among genes that emerge only in particular tissues or organs. In this report, we show that, in fact, conserved coexpression as determined from tissue-specific and condition-specific data sets can predict many functional relationships that are not detected by analyzing heterogeneous microarray data sets. More importantly, we find that, when combined with disease networks, the simultaneous use of both generic (multi-tissue) and tissue-specific conserved coexpression allows a more efficient prediction of human disease genes than the use of generic conserved coexpression alone. Using this strategy, we were able to identify high-probability candidates for 238 orphan disease loci. We provide proof of concept that this combined use of generic and tissue-specific conserved coexpression can be very useful to prioritize the mutational candidates obtained from deep-sequencing projects, even in the case of genetic disorders as heterogeneous as XLMR.

  10. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.

    PubMed

    Okazaki, Y; Furuno, M; Kasukawa, T; Adachi, J; Bono, H; Kondo, S; Nikaido, I; Osato, N; Saito, R; Suzuki, H; Yamanaka, I; Kiyosawa, H; Yagi, K; Tomaru, Y; Hasegawa, Y; Nogami, A; Schönbach, C; Gojobori, T; Baldarelli, R; Hill, D P; Bult, C; Hume, D A; Quackenbush, J; Schriml, L M; Kanapin, A; Matsuda, H; Batalov, S; Beisel, K W; Blake, J A; Bradt, D; Brusic, V; Chothia, C; Corbani, L E; Cousins, S; Dalla, E; Dragani, T A; Fletcher, C F; Forrest, A; Frazer, K S; Gaasterland, T; Gariboldi, M; Gissi, C; Godzik, A; Gough, J; Grimmond, S; Gustincich, S; Hirokawa, N; Jackson, I J; Jarvis, E D; Kanai, A; Kawaji, H; Kawasawa, Y; Kedzierski, R M; King, B L; Konagaya, A; Kurochkin, I V; Lee, Y; Lenhard, B; Lyons, P A; Maglott, D R; Maltais, L; Marchionni, L; McKenzie, L; Miki, H; Nagashima, T; Numata, K; Okido, T; Pavan, W J; Pertea, G; Pesole, G; Petrovsky, N; Pillai, R; Pontius, J U; Qi, D; Ramachandran, S; Ravasi, T; Reed, J C; Reed, D J; Reid, J; Ring, B Z; Ringwald, M; Sandelin, A; Schneider, C; Semple, C A M; Setou, M; Shimada, K; Sultana, R; Takenaka, Y; Taylor, M S; Teasdale, R D; Tomita, M; Verardo, R; Wagner, L; Wahlestedt, C; Wang, Y; Watanabe, Y; Wells, C; Wilming, L G; Wynshaw-Boris, A; Yanagisawa, M; Yang, I; Yang, L; Yuan, Z; Zavolan, M; Zhu, Y; Zimmer, A; Carninci, P; Hayatsu, N; Hirozane-Kishikawa, T; Konno, H; Nakamura, M; Sakazume, N; Sato, K; Shiraki, T; Waki, K; Kawai, J; Aizawa, K; Arakawa, T; Fukuda, S; Hara, A; Hashizume, W; Imotani, K; Ishii, Y; Itoh, M; Kagawa, I; Miyazaki, A; Sakai, K; Sasaki, D; Shibata, K; Shinagawa, A; Yasunishi, A; Yoshino, M; Waterston, R; Lander, E S; Rogers, J; Birney, E; Hayashizaki, Y

    2002-12-05

    Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

  11. IsoSeq analysis and functional annotation of the infratentorial ependymoma tumor tissue on PacBio RSII platform.

    PubMed

    Singh, Neetu; Sahu, Dinesh Kumar; Chowdhry, Rebecca; Mishra, Archana; Goel, Madhu Mati; Faheem, Mohd; Srivastava, Chhitij; Ojha, Bal Krishna; Gupta, Devendra Kumar; Kant, Ravi

    2016-02-01

    Here, we sequenced and functionally annotated the long reads (1-2 kb) cDNAs library of an infratentorial ependymoma tumor tissue on PacBio RSII by Iso-Seq protocol using SMRT technology. 577 MB, data was generated from the brain tissues of ependymoma tumor patient, producing 1,19,313 high-quality reads assembled into 19,878 contigs using Celera assembler followed by Quiver pipelines, which produced 2952 unique protein accessions in the nr protein database and 307 KEGG pathways. Additionally, when we compared GO terms of second and third level with alternative splicing data obtained through HTA Array2.0. We identified four and twelve transcript cluster IDs in Level-2 and Level-3 scores respectively with alternative splicing index predicting mainly the major pathways of hallmarks of cancer. Out of these transcript cluster IDs only transcript cluster IDs of gene PNMT, SNN and LAMB1 showed Reads Per Kilobase of exon model per Million mapped reads (RPKM) values at gene-level expression (GE) and transcript-level (TE) track. Most importantly, brain-specific genes--PNMT, SNN and LAMB1 show their involvement in Ependymoma.

  12. IsoSeq analysis and functional annotation of the infratentorial ependymoma tumor tissue on PacBio RSII platform

    PubMed Central

    Singh, Neetu; Sahu, Dinesh Kumar; Chowdhry, Rebecca; Mishra, Archana; Goel, Madhu Mati; Faheem, Mohd; Srivastava, Chhitij; Ojha, Bal Krishna; Gupta, Devendra Kumar; Kant, Ravi

    2015-01-01

    Here, we sequenced and functionally annotated the long reads (1–2 kb) cDNAs library of an infratentorial ependymoma tumor tissue on PacBio RSII by Iso-Seq protocol using SMRT technology. 577 MB, data was generated from the brain tissues of ependymoma tumor patient, producing 1,19,313 high-quality reads assembled into 19,878 contigs using Celera assembler followed by Quiver pipelines, which produced 2952 unique protein accessions in the nr protein database and 307 KEGG pathways. Additionally, when we compared GO terms of second and third level with alternative splicing data obtained through HTA Array2.0. We identified four and twelve transcript cluster IDs in Level-2 and Level-3 scores respectively with alternative splicing index predicting mainly the major pathways of hallmarks of cancer. Out of these transcript cluster IDs only transcript cluster IDs of gene PNMT, SNN and LAMB1 showed Reads Per Kilobase of exon model per Million mapped reads (RPKM) values at gene-level expression (GE) and transcript-level (TE) track. Most importantly, brain-specific genes–—PNMT, SNN and LAMB1 show their involvement in Ependymoma. PMID:26862483

  13. TreeQ-VISTA: An Interactive Tree Visualization Tool withFunctional Annotation Query Capabilities

    SciTech Connect

    Gu, Shengyin; Anderson, Iain; Kunin, Victor; Cipriano, Michael; Minovitsky, Simon; Weber, Gunther; Amenta, Nina; Hamann, Bernd; Dubchak,Inna

    2007-05-07

    Summary: We describe a general multiplatform exploratorytool called TreeQ-Vista, designed for presenting functional annotationsin a phylogenetic context. Traits, such as phenotypic and genomicproperties, are interactively queried from a relational database with auser-friendly interface which provides a set of tools for users with orwithout SQL knowledge. The query results are projected onto aphylogenetic tree and can be displayed in multiple color groups. A richset of browsing, grouping and query tools are provided to facilitatetrait exploration, comparison and analysis.Availability: The program,detailed tutorial and examples are available online athttp://genome-test.lbl.gov/vista/TreeQVista.

  14. Functional annotation of the T-cell immunoglobulin mucin family in birds.

    PubMed

    Hu, Tuanjun; Wu, Zhiguang; Vervelde, Lonneke; Rothwell, Lisa; Hume, David A; Kaiser, Pete

    2016-07-01

    T-cell immunoglobulin and mucin (TIM) family molecules are cell membrane proteins, preferentially expressed on various immune cells and implicated in recognition and clearance of apoptotic cells. Little is known of their function outside human and mouse, and nothing outside mammals. We identified only two TIM genes (chTIM) in the chicken genome, putative orthologues of mammalian TIM1 and TIM4, and cloned the respective cDNAs. Like mammalian TIM1, chTIM1 expression was restricted to lymphoid tissues and immune cells. The gene chTIM4 encodes at least five splice variants with distinct expression profiles that also varied between strains of chicken. Expression of chTIM4 was detected in myeloid antigen-presenting cells, and in γδ T cells, whereas mammalian TIM4 is not expressed in T cells. Like the mammalian proteins, chTIM1 and chTIM4 fusion proteins bind to phosphatidylserine, and are thereby implicated in recognition of apoptotic cells. The chTIM4-immunoglobulin fusion protein also had co-stimulatory activity on chicken T cells, suggesting a function in antigen presentation.

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

    PubMed

    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.

  16. Structure and sequence based functional annotation of Zika virus NS2b protein: Computational insights.

    PubMed

    Aguilera-Pesantes, Daniel; Méndez, Miguel A

    2017-02-08

    While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition.

  17. A prioritization analysis of disease association by data-mining of functional annotation of human genes.

    PubMed

    Taniya, Takayuki; Tanaka, Susumu; Yamaguchi-Kabata, Yumi; Hanaoka, Hideki; Yamasaki, Chisato; Maekawa, Harutoshi; Barrero, Roberto A; Lenhard, Boris; Datta, Milton W; Shimoyama, Mary; Bumgarner, Roger; Chakraborty, Ranajit; Hopkinson, Ian; Jia, Libin; Hide, Winston; Auffray, Charles; Minoshima, Shinsei; Imanishi, Tadashi; Gojobori, Takashi

    2012-01-01

    Complex diseases result from contributions of multiple genes that act in concert through pathways. Here we present a method to prioritize novel candidates of disease-susceptibility genes depending on the biological similarities to the known disease-related genes. The extent of disease-susceptibility of a gene is prioritized by analyzing seven features of human genes captured in H-InvDB. Taking rheumatoid arthritis (RA) and prostate cancer (PC) as two examples, we evaluated the efficiency of our method. Highly scored genes obtained included TNFSF12 and OSM as candidate disease genes for RA and PC, respectively. Subsequent characterization of these genes based upon an extensive literature survey reinforced the validity of these highly scored genes as possible disease-susceptibility genes. Our approach, Prioritization ANalysis of Disease Association (PANDA), is an efficient and cost-effective method to narrow down a large set of genes into smaller subsets that are most likely to be involved in the disease pathogenesis.

  18. An in silico functional annotation and screening of potential drug targets derived from Leishmania spp. hypothetical proteins identified by immunoproteomics.

    PubMed

    Chávez-Fumagalli, Miguel A; Schneider, Mônica S; Lage, Daniela P; Machado-de-Ávila, Ricardo A; Coelho, Eduardo A F

    2017-05-01

    Leishmaniasis is a parasitic disease caused by the protozoan of the Leishmania genus. While no human vaccine is available, drugs such as pentavalent antimonials, pentamidine and amphotericin B are used for treat the patients. However, the high toxicity of these pharmaceutics, the emergence of parasite resistance and/or their high cost have showed to the urgent need of identify new targets to be employed in the improvement of the treatment against leishmaniasis. In a recent immunoproteomics approach performed in the Leishmania infantum species, 104 antigenic proteins were recognized by antibodies in sera of visceral leishmaniasis (VL) dogs. Some of them were later showed to be effective diagnostic markers and/or vaccine candidates against the disease. Between these proteins, 24 considered as hypothetical were identified in the promastigote and amastigote-like extracts of the parasites. The present study aimed to use bioinformatics tools to select new drug targets between these hypothetical proteins. Their cellular localization was predicted to be seven membrane proteins, as well as eight cytoplasmic, three nuclear, one mitochondrial and five proteins remained unclassified. Their functions were predicted as being two transport proteins, as well as five with metabolic activity, three as cell signaling and fourteen proteins remained unclassified. Ten hypothetical proteins were well-annotated and compared to their homology regarding to human proteins. Two proteins, a calpain-like and clavaminate synthase-like proteins were selected by using Docking analysis as being possible drug targets. In this sense, the present study showed the employ of new strategies to select possible drug candidates, according their localization and biological function in Leishmania parasites, aiming to treat against VL.

  19. Functional Annotation of Metastasis-associated MicroRNAs of Melanoma: A Meta-analysis of Expression Profiles

    PubMed Central

    Li, Jing-Yi; Zheng, Li-Li; Wang, Ting-Ting; Hu, Min

    2016-01-01

    Background: Melanoma is a type of cancer that develops from the pigment-containing cells. Until now, its pathological mechanisms remain largely unknown. The aim of this study was to identify metastasis-related microRNA (miRNAs) and gain an understanding of the biological functions in the metastasis of melanoma. Methods: We searched the PubMed and Gene Expression Omnibus database to collect miRNA expression profiling datasets about melanoma, with key words of “melanoma”, “miRNA”, “microarray”, and “gene expression profiling”. Only the original experimental works published before June 2016 for analyzing the metastasis of melanoma were retained, other nonhuman studies, reviews, and meta-analyses were removed. We performed a meta-analysis to explore the differentially expressed miRNA between metastatic and nonmetastatic samples. Moreover, we predicted target genes of the miRNAs to study their biological roles for these miRNAs. Results: We identified a total of 63 significantly differentially expressed miRNAs by meta-analysis of the melanoma expression profiling data. The regulatory network constructed by using these miRNAs and the predicted targets identified several key genes involved in the metastasis of melanoma. Functional annotation of these genes indicated that they are mainly enriched in some biological pathways such as mitogen-activated protein kinase signaling pathway, cell junction, and focal adhesion. Conclusions: By collecting the miRNA expression datasets from different platforms, multiple biological markers were identified for the metastasis of melanoma. This study provided novel insights into the molecular mechanisms underlying this disease, thereby aiding the diagnosis and treatment of the disease. PMID:27748342

  20. Functional Annotation of Two New Carboxypeptidases from the Amidohydrolase Superfamily of Enzymes

    SciTech Connect

    Xiang, D.; Xu, C; Kumaran, D; Brown, A; Sauder, M; Burley, S; Swaminathan, S; Raushel, F

    2009-01-01

    Two proteins from the amidohydrolase superfamily of enzymes were cloned, expressed, and purified to homogeneity. The first protein, Cc0300, was from Caulobacter crescentus CB-15 (Cc0300), while the second one (Sgx9355e) was derived from an environmental DNA sequence originally isolated from the Sargasso Sea (gi|44371129). The catalytic functions and the substrate profiles for the two enzymes were determined with the aid of combinatorial dipeptide libraries. Both enzymes were shown to catalyze the hydrolysis of l-Xaa-l-Xaa dipeptides in which the amino acid at the N-terminus was relatively unimportant. These enzymes were specific for hydrophobic amino acids at the C-terminus. With Cc0300, substrates terminating in isoleucine, leucine, phenylalanine, tyrosine, valine, methionine, and tryptophan were hydrolyzed. The same specificity was observed with Sgx9355e, but this protein was also able to hydrolyze peptides terminating in threonine. Both enzymes were able to hydrolyze N-acetyl and N-formyl derivatives of the hydrophobic amino acids and tripeptides. The best substrates identified for Cc0300 were l-Ala-l-Leu with kcat and kcat/Km values of 37 s-1 and 1.1 x 105 M-1 s-1, respectively, and N-formyl-l-Tyr with kcat and kcat/Km values of 33 s-1 and 3.9 x 105 M-1 s-1, respectively. The best substrate identified for Sgx9355e was l-Ala-l-Phe with kcat and kcat/Km values of 0.41 s-1 and 5.8 x 103 M-1 s-1. The three-dimensional structure of Sgx9355e was determined to a resolution of 2.33 Angstroms with l-methionine bound in the active site. The a-carboxylate of the methionine is ion-paired to His-237 and also hydrogen bonded to the backbone amide groups of Val-201 and Leu-202. The a-amino group of the bound methionine interacts with Asp-328. The structural determinants for substrate recognition were identified and compared with other enzymes in this superfamily that hydrolyze dipeptides with different specificities.

  1. Functional Annotation of Two New Carboxypeptidases from the Amidohydrolase Superfamily of Enzymes†

    PubMed Central

    Xiang, Dao Feng; Xu, Chengfu; Kumaran, Desigan; Brown, Ann C.; Sauder, J. Michael; Burley, Stephen K.; Swaminathan, Subramanyam; Raushel, Frank M.

    2009-01-01

    Two proteins from the amidohydrolase superfamily of enzymes were cloned, expressed and purified to homogeneity. The first protein, Cc0300, was from Caulobacter crescentus CB-15 (Cc0300) while the second one (Sgx9355e) was derived from an environmental DNA sequence originally isolated from the Sargasso Sea (gi| 44371129). The catalytic functions and the substrate profiles for the two enzymes were determined with the aid of combinatorial dipeptide libraries. Both enzymes were shown to catalyze the hydrolysis of L-Xaa-L-Xaa dipeptides where the amino acid at the N-terminus was relatively unimportant. These enzymes were specific for hydrophobic amino acids at the C-terminus. With Cc0300, substrates terminating in isoleucine, leucine, phenylalanine, tyrosine, valine, methionine, and tryptophan were hydrolyzed. The same specificity was observed with Sgx9355e but this protein was also able to hydrolyze peptides terminating in threonine. Both enzymes were able to hydrolyze N-acetyl and N-formyl derivatives of the hydrophobic amino acids and tripeptides. The best substrates identified for Cc0300 were L-Ala-L-Leu with values of kcat and kcat/Km of 37 s−1 and 1.1 × 105 M−1 s−1, respectively, and N-formyl-L-Tyr with values of kcat and kcat/Km of 33 s−1 and 3.9 × 105 M−1 s−1, respectively. The best substrate identified for Sgx9355e was L-Ala-L-Phe will values of kcat and kcat/Km of 0.41 s−1 and 5.8 × 103 M−1 s−1. The three-dimensional structure of Sgx9355e was determined to a resolution of 2.33 Å with L-methionine bound in the active site. The α-carboxylate of the methionine is ion-paired to His-237 and also hydrogen bonded to the backbone amide groups of Val-201 and Leu-202. The α-amino group of the bound methionine interacts with Asp-328. The structural determinants for substrate recognition were identified and compared with other enzymes in this superfamily that hydrolyze dipeptides with different specificities. PMID:19358546

  2. Ranking Biomedical Annotations with Annotator's Semantic Relevancy

    PubMed Central

    2014-01-01

    Biomedical annotation is a common and affective artifact for researchers to discuss, show opinion, and share discoveries. It becomes increasing popular in many online research communities, and implies much useful information. Ranking biomedical annotations is a critical problem for data user to efficiently get information. As the annotator's knowledge about the annotated entity normally determines quality of the annotations, we evaluate the knowledge, that is, semantic relationship between them, in two ways. The first is extracting relational information from credible websites by mining association rules between an annotator and a biomedical entity. The second way is frequent pattern mining from historical annotations, which reveals common features of biomedical entities that an annotator can annotate with high quality. We propose a weighted and concept-extended RDF model to represent an annotator, a biomedical entity, and their background attributes and merge information from the two ways as the context of an annotator. Based on that, we present a method to rank the annotations by evaluating their correctness according to user's vote and the semantic relevancy between the annotator and the annotated entity. The experimental results show that the approach is applicable and efficient even when data set is large. PMID:24899918

  3. Ranking biomedical annotations with annotator's semantic relevancy.

    PubMed

    Wu, Aihua

    2014-01-01

    Biomedical annotation is a common and affective artifact for researchers to discuss, show opinion, and share discoveries. It becomes increasing popular in many online research communities, and implies much useful information. Ranking biomedical annotations is a critical problem for data user to efficiently get information. As the annotator's knowledge about the annotated entity normally determines quality of the annotations, we evaluate the knowledge, that is, semantic relationship between them, in two ways. The first is extracting relational information from credible websites by mining association rules between an annotator and a biomedical entity. The second way is frequent pattern mining from historical annotations, which reveals common features of biomedical entities that an annotator can annotate with high quality. We propose a weighted and concept-extended RDF model to represent an annotator, a biomedical entity, and their background attributes and merge information from the two ways as the context of an annotator. Based on that, we present a method to rank the annotations by evaluating their correctness according to user's vote and the semantic relevancy between the annotator and the annotated entity. The experimental results show that the approach is applicable and efficient even when data set is large.

  4. Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma

    PubMed Central

    Allingham, R. Rand; Whigham, Benjamin T.; Havens, Shane; Garrett, Melanie E.; Qiao, Chunyan; Katsanis, Nicholas; Wiggs, Janey L.; Pasquale, Louis R.; Ashley-Koch, Allison; Oh, Edwin C.; Hauser, Michael A.

    2014-01-01

    Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified a significant association between POAG and the SIX6 locus (rs10483727, odds ratio (OR) = 1.32, p = 3.87×10−11). SIX6 plays a role in ocular development and has been associated with the morphology of the optic nerve. We sequenced the SIX6 coding and regulatory regions in 262 POAG cases and 256 controls and identified six nonsynonymous coding variants, including five rare and one common variant, Asn141His (rs33912345), which was associated significantly with POAG (OR = 1.27, p = 4.2×10−10) in the NEIGHBOR/GLAUGEN datasets. These variants were tested in an in vivo Danio rerio (zebrafish) complementation assay to evaluate ocular metrics such as eye size and optic nerve structure. Five variants, found primarily in POAG cases, were hypomorphic or null, while the sixth variant, found only in controls, was benign. One variant in the SIX6 enhancer increased expression of SIX6 and disrupted its regulation. Finally, to our knowledge for the first time, we have identified a clinical feature in POAG patients that appears to be dependent upon SIX6 genotype: patients who are homozygous for the SIX6 risk allele (His141) have a statistically thinner retinal nerve fiber layer than patients homozygous for the SIX6 non-risk allele (Asn141). Our results, in combination with previous SIX6 work, lead us to hypothesize that SIX6 risk variants disrupt the development of the neural retina, leading to a reduced number of retinal ganglion cells, thereby increasing the risk of glaucoma-associated vision loss. PMID:24875647

  5. Genix: a new online automated pipeline for bacterial genome annotation.

    PubMed

    Kremer, Frederico Schmitt; Eslabão, Marcus Redü; Dellagostin, Odir Antônio; Pinto, Luciano da Silva

    2016-12-01

    Next-generation sequencing has significantly reduced the cost of genome-sequencing projects, resulting in an expressive increase in the availability of genomic data in public databases. The cheaper and easier is to sequence new genomes, the more accurate the annotation steps have to be to avoid both the loss of information and the accumulation of erroneous features that may affect the accuracy of further analysis. In the case of bacteria genomes, a range of web annotation software has been developed; however, many applications have yet to incorporate the steps required to improve their result, including the removal of false-positive/spurious and a more complete identification of non-coding features. We present Genix, a new web-based bacterial genome annotation pipeline. A comparison of the results generated by Genix for four reference genomes against those generated by other annotation tools indicated that our pipeline is able to provide results that are closer to the reference genome annotation, with a smaller amount of false-positive proteins and missing functional annotated proteins. Additionally, the metrics obtained by Genix were slightly better than those obtained by Prokka, a state-of-art standalone annotation system. Our results indicate that Genix is a useful tool that is able to provide a more refined result, and may be a user-friendly way to obtain high-quality results.

  6. Characterizing the state of the art in the computational assignment of gene function: lessons from the first critical assessment of functional annotation (CAFA)

    PubMed Central

    2013-01-01

    The assignment of gene function remains a difficult but important task in computational biology. The establishment of the first Critical Assessment of Functional Annotation (CAFA) was aimed at increasing progress in the field. We present an independent analysis of the results of CAFA, aimed at identifying challenges in assessment and at understanding trends in prediction performance. We found that well-accepted methods based on sequence similarity (i.e., BLAST) have a dominant effect. Many of the most informative predictions turned out to be either recovering existing knowledge about sequence similarity or were "post-dictions" already documented in the literature. These results indicate that deep challenges remain in even defining the task of function assignment, with a particular difficulty posed by the problem of defining function in a way that is not dependent on either flawed gold standards or the input data itself. In particular, we suggest that using the Gene Ontology (or other similar systematizations of function) as a gold standard is unlikely to be the way forward. PMID:23630983

  7. Sequencing, De novo Assembly, Functional Annotation and Analysis of Phyllanthus amarus Leaf Transcriptome Using the Illumina Platform

    PubMed Central

    Bose Mazumdar, Aparupa; Chattopadhyay, Sharmila

    2016-01-01

    Phyllanthus amarus Schum. and Thonn., a widely distributed annual medicinal herb has a long history of use in the traditional system of medicine for over 2000 years. However, the lack of genomic data for P. amarus, a non-model organism hinders research at the molecular level. In the present study, high-throughput sequencing technology has been employed to enhance better understanding of this herb and provide comprehensive genomic information for future work. Here P. amarus leaf transcriptome was sequenced using the Illumina Miseq platform. We assembled 85,927 non-redundant (nr) “unitranscript” sequences with an average length of 1548 bp, from 18,060,997 raw reads. Sequence similarity analyses and annotation of these unitranscripts were performed against databases like green plants nr protein database, Gene Ontology (GO), Clusters of Orthologous Groups (COG), PlnTFDB, KEGG databases. As a result, 69,394 GO terms, 583 enzyme codes (EC), 134 KEGG maps, and 59 Transcription Factor (TF) families were generated. Functional and comparative analyses of assembled unitranscripts were also performed with the most closely related species like Populus trichocarpa and Ricinus communis using TRAPID. KEGG analysis showed that a number of assembled unitranscripts were involved in secondary metabolites, mainly phenylpropanoid, flavonoid, terpenoids, alkaloids, and lignan biosynthetic pathways that have significant medicinal attributes. Further, Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values of the identified secondary metabolite pathway genes were determined and Reverse Transcription PCR (RT-PCR) of a few of these genes were performed to validate the de novo assembled leaf transcriptome dataset. In addition 65,273 simple sequence repeats (SSRs) were also identified. To the best of our knowledge, this is the first transcriptomic dataset of P. amarus till date. Our study provides the largest genetic resource that will lead to drug development and pave

  8. Current and future trends in marine image annotation software

    NASA Astrophysics Data System (ADS)

    Gomes-Pereira, Jose Nuno; Auger, Vincent; Beisiegel, Kolja; Benjamin, Robert; Bergmann, Melanie; Bowden, David; Buhl-Mortensen, Pal; De Leo, Fabio C.; Dionísio, Gisela; Durden, Jennifer M.; Edwards, Luke; Friedman, Ariell; Greinert, Jens; Jacobsen-Stout, Nancy; Lerner, Steve; Leslie, Murray; Nattkemper, Tim W.; Sameoto, Jessica A.; Schoening, Timm; Schouten, Ronald; Seager, James; Singh, Hanumant; Soubigou, Olivier; Tojeira, Inês; van den Beld, Inge; Dias, Frederico; Tempera, Fernando; Santos, Ricardo S.

    2016-12-01

    Given the need to describe, analyze and index large quantities of marine imagery data for exploration and monitoring activities, a range of specialized image annotation tools have been developed worldwide. Image annotation - the process of transposing objects or events represented in a video or still image to the semantic level, may involve human interactions and computer-assisted solutions. Marine image annotation software (MIAS) have enabled over 500 publications to date. We review the functioning, application trends and developments, by comparing general and advanced features of 23 different tools utilized in underwater image analysis. MIAS requiring human input are basically a graphical user interface, with a video player or image browser that recognizes a specific time code or image code, allowing to log events in a time-stamped (and/or geo-referenced) manner. MIAS differ from similar software by the capability of integrating data associated to video collection, the most simple being the position coordinates of the video recording platform. MIAS have three main characteristics: annotating events in real time, posteriorly to annotation and interact with a database. These range from simple annotation interfaces, to full onboard data management systems, with a variety of toolboxes. Advanced packages allow to input and display data from multiple sensors or multiple annotators via intranet or internet. Posterior human-mediated annotation often include tools for data display and image analysis, e.g. length, area, image segmentation, point count; and in a few cases the possibility of browsing and editing previous dive logs or to analyze the annotations. The interaction with a database allows the automatic integration of annotations from different surveys, repeated annotation and collaborative annotation of shared datasets, browsing and querying of data. Progress in the field of automated annotation is mostly in post processing, for stable platforms or still images

  9. Comparative Omics-Driven Genome Annotation Refinement: Application across Yersiniae

    SciTech Connect

    Rutledge, Alexandra C.; Jones, Marcus B.; Chauhan, Sadhana; Purvine, Samuel O.; Sanford, James; Monroe, Matthew E.; Brewer, Heather M.; Payne, Samuel H.; Ansong, Charles; Frank, Bryan C.; Smith, Richard D.; Peterson, Scott; Motin, Vladimir L.; Adkins, Joshua N.

    2012-03-27

    the discovery of many translated pseudogenes underscores a need for functional analyses to investigate hypotheses related to divergence. Refinements included the discovery of a seemingly essential ribosomal protein, several virulence-associated factors, and a transcriptional regulator, among other proteins, most of which are annotated as hypothetical, that were missed during annotation.

  10. Patient Education: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Simmons, Jeannette

    Topics included in this annotated bibliography on patient education are (1) background on development of patient education programs, (2) patient education interventions, (3) references for health professionals, and (4) research and evaluation in patient education. (TA)

  11. MEGANTE: a web-based system for integrated plant genome annotation.

    PubMed

    Numa, Hisataka; Itoh, Takeshi

    2014-01-01

    The recent advancement of high-throughput genome sequencing technologies has resulted in a considerable increase in demands for large-scale genome annotation. While annotation is a crucial step for downstream data analyses and experimental studies, this process requires substantial expertise and knowledge of bioinformatics. Here we present MEGANTE, a web-based annotation system that makes plant genome annotation easy for researchers unfamiliar with bioinformatics. Without any complicated configuration, users can perform genomic sequence annotations simply by uploading a sequence and selecting the species to query. MEGANTE automatically runs several analysis programs and integrates the results to select the appropriate consensus exon-intron structures and to predict open reading frames (ORFs) at each locus. Functional annotation, including a similarity search against known proteins and a functional domain search, are also performed for the predicted ORFs. The resultant annotation information is visualized with a widely used genome browser, GBrowse. For ease of analysis, the results can be downloaded in Microsoft Excel format. All of the query sequences and annotation results are stored on the server side so that users can access their own data from virtually anywhere on the web. The current release of MEGANTE targets 24 plant species from the Brassicaceae, Fabaceae, Musaceae, Poaceae, Salicaceae, Solanaceae, Rosaceae and Vitaceae families, and it allows users to submit a sequence up to 10 Mb in length and to save up to 100 sequences with the annotation information on the server. The MEGANTE web service is available at https://megante.dna.affrc.go.jp/.

  12. Functional genomics tools applied to plant metabolism: a survey on plant respiration, its connections and the annotation of complex gene functions

    PubMed Central

    Araújo, Wagner L.; Nunes-Nesi, Adriano; Williams, Thomas C. R.

    2012-01-01

    The application of post-genomic techniques in plant respiration studies has greatly improved our ability to assign functions to gene products. In addition it has also revealed previously unappreciated interactions between distal elements of metabolism. Such results have reinforced the need to consider plant respiratory metabolism as part of a complex network and making sense of such interactions will ultimately require the construction of predictive and mechanistic models. Transcriptomics, proteomics, metabolomics, and the quantification of metabolic flux will be of great value in creating such models both by facilitating the annotation of complex gene function, determining their structure and by furnishing the quantitative data required to test them. In this review, we highlight how these experimental approaches have contributed to our current understanding of plant respiratory metabolism and its interplay with associated process (e.g., photosynthesis, photorespiration, and nitrogen metabolism). We also discuss how data from these techniques may be integrated, with the ultimate aim of identifying mechanisms that control and regulate plant respiration and discovering novel gene functions with potential biotechnological implications. PMID:22973288

  13. OrthoDB v9.1: cataloging evolutionary and functional annotations for animal, fungal, plant, archaeal, bacterial and viral orthologs.

    PubMed

    Zdobnov, Evgeny M; Tegenfeldt, Fredrik; Kuznetsov, Dmitry; Waterhouse, Robert M; Simão, Felipe A; Ioannidis, Panagiotis; Seppey, Mathieu; Loetscher, Alexis; Kriventseva, Evgenia V

    2017-01-04

    OrthoDB is a comprehensive catalog of orthologs, genes inherited by extant species from a single gene in their last common ancestor. In 2016 OrthoDB reached its 9th release, growing to over 22 million genes from over 5000 species, now adding plants, archaea and viruses. In this update we focused on usability of this fast-growing wealth of data: updating the user and programmatic interfaces to browse and query the data, and further enhancing the already extensive integration of available gene functional annotations. Collating functional annotations from over 100 resources, and enabled us to propose descriptive titles for 87% of ortholog groups. Additionally, OrthoDB continues to provide computed evolutionary annotations and to allow user queries by sequence homology. The OrthoDB resource now enables users to generate publication-quality comparative genomics charts, as well as to upload, analyze and interactively explore their own private data. OrthoDB is available from http://orthodb.org.

  14. OrthoDB v9.1: cataloging evolutionary and functional annotations for animal, fungal, plant, archaeal, bacterial and viral orthologs

    PubMed Central

    Zdobnov, Evgeny M.; Tegenfeldt, Fredrik; Kuznetsov, Dmitry; Waterhouse, Robert M.; Simão, Felipe A.; Ioannidis, Panagiotis; Seppey, Mathieu; Loetscher, Alexis; Kriventseva, Evgenia V.

    2017-01-01

    OrthoDB is a comprehensive catalog of orthologs, genes inherited by extant species from a single gene in their last common ancestor. In 2016 OrthoDB reached its 9th release, growing to over 22 million genes from over 5000 species, now adding plants, archaea and viruses. In this update we focused on usability of this fast-growing wealth of data: updating the user and programmatic interfaces to browse and query the data, and further enhancing the already extensive integration of available gene functional annotations. Collating functional annotations from over 100 resources, and enabled us to propose descriptive titles for 87% of ortholog groups. Additionally, OrthoDB continues to provide computed evolutionary annotations and to allow user queries by sequence homology. The OrthoDB resource now enables users to generate publication-quality comparative genomics charts, as well as to upload, analyze and interactively explore their own private data. OrthoDB is available from http://orthodb.org. PMID:27899580

  15. Annotated bibliography and index map of sulfur and pyrites deposits in the United States and Alaska (including references to July 1, 1951)

    USGS Publications Warehouse

    Espenshade, Gilbert H.; Broedel, Carl H.

    1952-01-01

    Since the end of World War II, the pattern of sulfur production and consumption in the United States and abroad has changed markedly from the pattern that existed before the war. Although production of sulfur in the United States in 1950 was more than double the average annual production for the 1935-39 period, consumption had increased at such a rate that current domestic and foreign demand for U. S. sulfur exceeds the productive capacity of the industry. Production of sulfur (including brimstone, pyrites, and all other forms) in the 1935-39 period and in 1950 are compared in the table below.

  16. 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

    PubMed Central

    Kang, Se Won; Hwang, Hee-Ju; Park, So Young; Park, Eun Bi; Chung, Jong Min; Song, Dae Kwon; Kim, Changmu; Kim, Soonok; Lee, Jun Sang; Han, Yeon Soo; Park, Hong Seog; Lee, Yong Seok

    2016-01-01

    Background 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. Results 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. Conclusions This dataset represents the first transcriptome analysis of the endangered

  17. IMG ER: A System for Microbial Genome Annotation Expert Review and Curation

    SciTech Connect

    Markowitz, Victor M.; Mavromatis, Konstantinos; Ivanova, Natalia N.; Chen, I-Min A.; Chu, Ken; Kyrpides, Nikos C.

    2009-05-25

    A rapidly increasing number of microbial genomes are sequenced by organizations worldwide and are eventually included into various public genome data resources. The quality of the annotations depends largely on the original dataset providers, with erroneous or incomplete annotations often carried over into the public resources and difficult to correct. We have developed an Expert Review (ER) version of the Integrated Microbial Genomes (IMG) system, with the goal of supporting systematic and efficient revision of microbial genome annotations. IMG ER provides tools for the review and curation of annotations of both new and publicly available microbial genomes within IMG's rich integrated genome framework. New genome datasets are included into IMG ER prior to their public release either with their native annotations or with annotations generated by IMG ER's annotation pipeline. IMG ER tools allow addressing annotation problems detected with IMG's comparative analysis tools, such as genes missed by gene prediction pipelines or genes without an associated function. Over the past year, IMG ER was used for improving the annotations of about 150 microbial genomes.

  18. Gene Ontology annotations and resources.

    PubMed

    Blake, J A; Dolan, M; Drabkin, H; Hill, D P; Li, Ni; Sitnikov, D; Bridges, S; Burgess, S; Buza, T; McCarthy, F; Peddinti, D; Pillai, L; Carbon, S; Dietze, H; Ireland, A; Lewis, S E; Mungall, C J; Gaudet, P; Chrisholm, R L; Fey, P; Kibbe, W A; Basu, S; Siegele, D A; McIntosh, B K; Renfro, D P; Zweifel, A E; Hu, J C; Brown, N H; Tweedie, S; Alam-Faruque, Y; Apweiler, R; Auchinchloss, A; Axelsen, K; Bely, B; Blatter, M -C; Bonilla, C; Bouguerleret, L; Boutet, E; Breuza, L; Bridge, A; Chan, W M; Chavali, G; Coudert, E; Dimmer, E; Estreicher, A; Famiglietti, L; Feuermann, M; Gos, A; Gruaz-Gumowski, N; Hieta, R; Hinz, C; Hulo, C; Huntley, R; James, J; Jungo, F; Keller, G; Laiho, K; Legge, D; Lemercier, P; Lieberherr, D; Magrane, M; Martin, M J; Masson, P; Mutowo-Muellenet, P; O'Donovan, C; Pedruzzi, I; Pichler, K; Poggioli, D; Porras Millán, P; Poux, S; Rivoire, C; Roechert, B; Sawford, T; Schneider, M; Stutz, A; Sundaram, S; Tognolli, M; Xenarios, I; Foulgar, R; Lomax, J; Roncaglia, P; Khodiyar, V K; Lovering, R C; Talmud, P J; Chibucos, M; Giglio, M Gwinn; Chang, H -Y; Hunter, S; McAnulla, C; Mitchell, A; Sangrador, A; Stephan, R; Harris, M A; Oliver, S G; Rutherford, K; Wood, V; Bahler, J; Lock, A; Kersey, P J; McDowall, D M; Staines, D M; Dwinell, M; Shimoyama, M; Laulederkind, S; Hayman, T; Wang, S -J; Petri, V; Lowry, T; D'Eustachio, P; Matthews, L; Balakrishnan, R; Binkley, G; Cherry, J M; Costanzo, M C; Dwight, S S; Engel, S R; Fisk, D G; Hitz, B C; Hong, E L; Karra, K; Miyasato, S R; Nash, R S; Park, J; Skrzypek, M S; Weng, S; Wong, E D; Berardini, T Z; Huala, E; Mi, H; Thomas, P D; Chan, J; Kishore, R; Sternberg, P; Van Auken, K; Howe, D; Westerfield, M

    2013-01-01

    The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources.

  19. NCBI prokaryotic genome annotation pipeline.

    PubMed

    Tatusova, Tatiana; DiCuccio, Michael; Badretdin, Azat; Chetvernin, Vyacheslav; Nawrocki, Eric P; Zaslavsky, Leonid; Lomsadze, Alexandre; Pruitt, Kim D; Borodovsky, Mark; Ostell, James

    2016-08-19

    Recent technological advances have opened unprecedented opportunities for large-scale sequencing and analysis of populations of pathogenic species in disease outbreaks, as well as for large-scale diversity studies aimed at expanding our knowledge across the whole domain of prokaryotes. To meet the challenge of timely interpretation of structure, function and meaning of this vast genetic information, a comprehensive approach to automatic genome annotation is critically needed. In collaboration with Georgia Tech, NCBI has developed a new approach to genome annotation that combines alignment based methods with methods of predicting protein-coding and RNA genes and other functional elements directly from sequence. A new gene finding tool, GeneMarkS+, uses the combined evidence of protein and RNA placement by homology as an initial map of annotation to generate and modify ab initio gene predictions across the whole genome. Thus, the new NCBI's Prokaryotic Genome Annotation Pipeline (PGAP) relies more on sequence similarity when confident comparative data are available, while it relies more on statistical predictions in the absence of external evidence. The pipeline provides a framework for generation and analysis of annotation on the full breadth of prokaryotic taxonomy. For additional information on PGAP see https://www.ncbi.nlm.nih.gov/genome/annotation_prok/ and the NCBI Handbook, https://www.ncbi.nlm.nih.gov/books/NBK174280/.

  20. Estimating the annotation error rate of curated GO database sequence annotations

    PubMed Central

    Jones, Craig E; Brown, Alfred L; Baumann, Ute

    2007-01-01

    Background Annotations that describe the function of sequences are enormously important to researchers during laboratory investigations and when making computational inferences. However, there has been little investigation into the data quality of sequence function annotations. Here we have developed a new method of estimating the error rate of curated sequence annotations, and applied this to the Gene Ontology (GO) sequence database (GOSeqLite). This method involved artificially adding errors to sequence annotations at known rates, and used regression to model the impact on the precision of annotations based on BLAST matched sequences. Results We estimated the error rate of curated GO sequence annotations in the GOSeqLite database (March 2006) at between 28% and 30%. Annotations made without use of sequence similarity based methods (non-ISS) had an estimated error rate of between 13% and 18%. Annotations made with the use of sequence similarity methodology (ISS) had an estimated error rate of 49%. Conclusion While the overall error rate is reasonably low, it would be prudent to treat all ISS annotations with caution. Electronic annotators that use ISS annotations as the basis of predictions are likely to have higher false prediction rates, and for this reason designers of these systems should consider avoiding ISS annotations where possible. Electronic annotators that use ISS annotations to make predictions should be viewed sceptically. We recommend that curators thoroughly review ISS annotations before accepting them as valid. Overall, users of curated sequence annotations from the GO database should feel assured that they are using a comparatively high quality source of information. PMID:17519041

  1. Computational algorithms to predict Gene Ontology annotations

    PubMed Central

    2015-01-01

    Background Gene function annotations, which are associations between a gene and a term of a controlled vocabulary describing gene functional features, are of paramount importance in modern biology. Datasets of these annotations, such as the ones provided by the Gene Ontology Consortium, are used to design novel biological experiments and interpret their results. Despite their importance, these sources of information have some known issues. They are incomplete, since biological knowledge is far from being definitive and it rapidly evolves, and some erroneous annotations may be present. Since the curation process of novel annotations is a costly procedure, both in economical and time terms, computational tools that can reliably predict likely annotations, and thus quicken the discovery of new gene annotations, are very useful. Methods We used a set of computational algorithms and weighting schemes to infer novel gene annotations from a set of known ones. We used the latent semantic analysis approach, implementing two popular algorithms (Latent Semantic Indexing and Probabilistic Latent Semantic Analysis) and propose a novel method, the Semantic IMproved Latent Semantic Analysis, which adds a clustering step on the set of considered genes. Furthermore, we propose the improvement of these algorithms by weighting the annotations in the input set. Results We tested our methods and their weighted variants on the Gene Ontology annotation sets of three model organism genes (Bos taurus, Danio rerio and Drosophila melanogaster ). The methods showed their ability in predicting novel gene annotations and the weighting procedures demonstrated to lead to a valuable improvement, although the obtained results vary according to the dimension of the input annotation set and the considered algorithm. Conclusions Out of the three considered methods, the Semantic IMproved Latent Semantic Analysis is the one that provides better results. In particular, when coupled with a proper

  2. Gene Ontology Annotations and Resources

    PubMed Central

    2013-01-01

    The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new ‘phylogenetic annotation’ process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources. PMID:23161678

  3. Towards Viral Genome Annotation Standards, Report from the 2010 NCBI Annotation Workshop.

    PubMed

    Brister, James Rodney; Bao, Yiming; Kuiken, Carla; Lefkowitz, Elliot J; Le Mercier, Philippe; Leplae, Raphael; Madupu, Ramana; Scheuermann, Richard H; Schobel, Seth; Seto, Donald; Shrivastava, Susmita; Sterk, Peter; Zeng, Qiandong; Klimke, William; Tatusova, Tatiana

    2010-10-01

    Improvements in DNA sequencing technologies portend a new era in virology and could possibly lead to a giant leap in our understanding of viral evolution and ecology. Yet, as viral genome sequences begin to fill the world's biological databases, it is critically important to recognize that the scientific promise of this era is dependent on consistent and comprehensive genome annotation. With this in mind, the NCBI Genome Annotation Workshop recently hosted a study group tasked with developing sequence, function, and metadata annotation standards for viral genomes. This report describes the issues involved in viral genome annotation and reviews policy recommendations presented at the NCBI Annotation Workshop.

  4. Towards Viral Genome Annotation Standards, Report from the 2010 NCBI Annotation Workshop

    PubMed Central

    Brister, James Rodney; Bao, Yiming; Kuiken, Carla; Lefkowitz, Elliot J.; Le Mercier, Philippe; Leplae, Raphael; Madupu, Ramana; Scheuermann, Richard H.; Schobel, Seth; Seto, Donald; Shrivastava, Susmita; Sterk, Peter; Zeng, Qiandong; Klimke, William; Tatusova, Tatiana

    2010-01-01

    Improvements in DNA sequencing technologies portend a new era in virology and could possibly lead to a giant leap in our understanding of viral evolution and ecology. Yet, as viral genome sequences begin to fill the world’s biological databases, it is critically important to recognize that the scientific promise of this era is dependent on consistent and comprehensive genome annotation. With this in mind, the NCBI Genome Annotation Workshop recently hosted a study group tasked with developing sequence, function, and metadata annotation standards for viral genomes. This report describes the issues involved in viral genome annotation and reviews policy recommendations presented at the NCBI Annotation Workshop. PMID:21994619

  5. The Management of Higher Education: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Schofield, Allan, Ed.

    This document provides an annotated bibliography of Commonwealth (formerly the British Commonwealth) university management functions. Selection criteria included the following: items had to be practical and designed to support institutional management, be applicable to most Commonwealth higher education systems, and wherever possible be available…

  6. Quality of Computationally Inferred Gene Ontology Annotations

    PubMed Central

    Škunca, Nives; Altenhoff, Adrian; Dessimoz, Christophe

    2012-01-01

    Gene Ontology (GO) has established itself as the undisputed standard for protein function annotation. Most annotations are inferred electronically, i.e. without individual curator supervision, but they are widely considered unreliable. At the same time, we crucially depend on those automated annotations, as most newly sequenced genomes are non-model organisms. Here, we introduce a methodology to systematically and quantitatively evaluate electronic annotations. By exploiting changes in successive releases of the UniProt Gene Ontology Annotation database, we assessed the quality of electronic annotations in terms of specificity, reliability, and coverage. Overall, we not only found that electronic annotations have significantly improved in recent years, but also that their reliability now rivals that of annotations inferred by curators when they use evidence other than experiments from primary literature. This work provides the means to identify the subset of electronic annotations that can be relied upon—an important outcome given that >98% of all annotations are inferred without direct curation. PMID:22693439

  7. UCSC Data Integrator and Variant Annotation Integrator

    PubMed Central

    Hinrichs, Angie S.; Raney, Brian J.; Speir, Matthew L.; Rhead, Brooke; Casper, Jonathan; Karolchik, Donna; Kuhn, Robert M.; Rosenbloom, Kate R.; Zweig, Ann S.; Haussler, David; Kent, W. James

    2016-01-01

    Summary: Two new tools on the UCSC Genome Browser web site provide improved ways of combining information from multiple datasets, optionally including the user's own custom track data and/or data from track hubs. The Data Integrator combines columns from multiple data tracks, showing all items from the first track along with overlapping items from the other tracks. The Variant Annotation Integrator is tailored to adding functional annotations to variant calls; it offers a more restricted set of underlying data tracks but adds predictions of each variant's consequences for any overlapping or nearby gene transcript. When available, it optionally adds additional annotations including effect prediction scores from dbNSFP for missense mutations, ENCODE regulatory summary tracks and conservation scores. Availability and implementation: The web tools are freely available at http://genome.ucsc.edu/ and the underlying database is available for download at http://hgdownload.cse.ucsc.edu/. The software (written in C and Javascript) is available from https://genome-store.ucsc.edu/ and is freely available for academic and non-profit usage; commercial users must obtain a license. Contact: angie@soe.ucsc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26740527

  8. Prediction driven functional annotation of hypothetical proteins in the major facilitator superfamily of S. aureus NCTC 8325

    PubMed Central

    Marklevitz, Jessica; Harris, Laura K.

    2016-01-01

    Antibiotic resistance Staphylococcus aureus strains cause several life threatening infections. New drug treatment options are needed, but are slow to develop because 50% of the S. aureus genome is hypothetical. The goal of this is to aid in the annotation of the S. aureus NCTC 8325 genome by identifying hypothetical proteins related to the Major Facilitator Superfamily (MFS). The MFS is a broad protein group with members involved in drug efflux mechanisms causing resistance. To do this, sequences for three MFS proteins with x-ray crystal structures in E. coli were PSI-BLASTed against the S. aureus NCTC 8325 genome to identify homologs. Eleven identified hypothetical protein homologs underwent BLASTP against the non-redundant NCBI database to fit homologs specific to each hypothetical protein. ExPASy characterized the physiochemical features, CDD-BLAST and Pfam identified domains, and the SOSUI server defined transmembrane helices of each hypothetical protein. Based on size (300 – 700 amino acids), number of transmembrane helices (>7), CD06174 and MFS domains in CDD-BLAST and Pfam, respectively, and close relation to well-defined homologs, SAOUHSC_00058, SAOUHSC_00078, SAOUHSC_00952, SAOUHSC_02435, SAOUHSC_02752, and ABD31642.1 are members of the MFS. Further multiple-alignment and phylogeny analyses show SAOUHSC_00058 to be a quinolone resistance protein (NorB), SAOUHSC_00058 a siderophore biosynthesis protein (SbnD), SAOUHSC_00952 a glycolipid permease (LtaA), SAOUHSC_02435 a macrolide MFS transporter, SAOUHSC_02752 a chloramphenicol resistance (DHA1), and ABD31642.1 is a Bcr/CflA family drug resistance efflux transporter. These findings provide better annotation for the existing genome, and identify proteins related to antibiotic resistance in S. aureus NCTC 8325. PMID:28197063

  9. Prediction driven functional annotation of hypothetical proteins in the major facilitator superfamily of S. aureus NCTC 8325.

    PubMed

    Marklevitz, Jessica; Harris, Laura K

    2016-01-01

    Antibiotic resistance Staphylococcus aureus strains cause several life threatening infections. New drug treatment options are needed, but are slow to develop because 50% of the S. aureus genome is hypothetical. The goal of this is to aid in the annotation of the S. aureus NCTC 8325 genome by identifying hypothetical proteins related to the Major Facilitator Superfamily (MFS). The MFS is a broad protein group with members involved in drug efflux mechanisms causing resistance. To do this, sequences for three MFS proteins with x-ray crystal structures in E. coli were PSI-BLASTed against the S. aureus NCTC 8325 genome to identify homologs. Eleven identified hypothetical protein homologs underwent BLASTP against the non-redundant NCBI database to fit homologs specific to each hypothetical protein. ExPASy characterized the physiochemical features, CDD-BLAST and Pfam identified domains, and the SOSUI server defined transmembrane helices of each hypothetical protein. Based on size (300 - 700 amino acids), number of transmembrane helices (>7), CD06174 and MFS domains in CDD-BLAST and Pfam, respectively, and close relation to well-defined homologs, SAOUHSC_00058, SAOUHSC_00078, SAOUHSC_00952, SAOUHSC_02435, SAOUHSC_02752, and ABD31642.1 are members of the MFS. Further multiple-alignment and phylogeny analyses show SAOUHSC_00058 to be a quinolone resistance protein (NorB), SAOUHSC_00058 a siderophore biosynthesis protein (SbnD), SAOUHSC_00952 a glycolipid permease (LtaA), SAOUHSC_02435 a macrolide MFS transporter, SAOUHSC_02752 a chloramphenicol resistance (DHA1), and ABD31642.1 is a Bcr/CflA family drug resistance efflux transporter. These findings provide better annotation for the existing genome, and identify proteins related to antibiotic resistance in S. aureus NCTC 8325.

  10. Annotated chemical patent corpus: a gold standard for text mining.

    PubMed

    Akhondi, Saber A; Klenner, Alexander G; Tyrchan, Christian; Manchala, Anil K; Boppana, Kiran; Lowe, Daniel; Zimmermann, Marc; Jagarlapudi, Sarma A R P; Sayle, Roger; Kors, Jan A; Muresan, Sorel

    2014-01-01

    Exploring the chemical and biological space covered by patent applications is crucial in early-stage medicinal chemistry activities. Patent analysis can provide understanding of compound prior art, novelty checking, validation of biological assays, and identification of new starting points for chemical exploration. Extracting chemical and biological entities from patents through manual extraction by expert curators can take substantial amount of time and resources. Text mining methods can help to ease this process. To validate the performance of such methods, a manually annotated patent corpus is essential. In this study we have produced a large gold standard chemical patent corpus. We developed annotation guidelines and selected 200 full patents from the World Intellectual Property Organization, United States Patent and Trademark Office, and European Patent Office. The patents were pre-annotated automatically and made available to four independent annotator groups each consisting of two to ten annotators. The annotators marked chemicals in different subclasses, diseases, targets, and modes of action. Spelling mistakes and spurious line break due to optical character recognition errors were also annotated. A subset of 47 patents was annotated by at least three annotator groups, from which harmonized annotations and inter-annotator agreement scores were derived. One group annotated the full set. The patent corpus includes 400,125 annotations for the full set and 36,537 annotations for the harmonized set. All patents and annotated entities are publicly available at www.biosemantics.org.

  11. Annotated Chemical Patent Corpus: A Gold Standard for Text Mining

    PubMed Central

    Akhondi, Saber A.; Klenner, Alexander G.; Tyrchan, Christian; Manchala, Anil K.; Boppana, Kiran; Lowe, Daniel; Zimmermann, Marc; Jagarlapudi, Sarma A. R. P.; Sayle, Roger; Kors, Jan A.; Muresan, Sorel

    2014-01-01

    Exploring the chemical and biological space covered by patent applications is crucial in early-stage medicinal chemistry activities. Patent analysis can provide understanding of compound prior art, novelty checking, validation of biological assays, and identification of new starting points for chemical exploration. Extracting chemical and biological entities from patents through manual extraction by expert curators can take substantial amount of time and resources. Text mining methods can help to ease this process. To validate the performance of such methods, a manually annotated patent corpus is essential. In this study we have produced a large gold standard chemical patent corpus. We developed annotation guidelines and selected 200 full patents from the World Intellectual Property Organization, United States Patent and Trademark Office, and European Patent Office. The patents were pre-annotated automatically and made available to four independent annotator groups each consisting of two to ten annotators. The annotators marked chemicals in different subclasses, diseases, targets, and modes of action. Spelling mistakes and spurious line break due to optical character recognition errors were also annotated. A subset of 47 patents was annotated by at least three annotator groups, from which harmonized annotations and inter-annotator agreement scores were derived. One group annotated the full set. The patent corpus includes 400,125 annotations for the full set and 36,537 annotations for the harmonized set. All patents and annotated entities are publicly available at www.biosemantics.org. PMID:25268232

  12. Bovine Genome Database: integrated tools for genome annotation and discovery.

    PubMed

    Childers, Christopher P; Reese, Justin T; Sundaram, Jaideep P; Vile, Donald C; Dickens, C Michael; Childs, Kevin L; Salih, Hanni; Bennett, Anna K; Hagen, Darren E; Adelson, David L; Elsik, Christine G

    2011-01-01

    The Bovine Genome Database (BGD; http://BovineGenome.org) strives to improve annotation of the bovine genome and to integrate the genome sequence with other genomics data. BGD includes GBrowse genome browsers, the Apollo Annotation Editor, a quantitative trait loci (QTL) viewer, BLAST databases and gene pages. Genome browsers, available for both scaffold and chromosome coordinate systems, display the bovine Official Gene Set (OGS), RefSeq and Ensembl gene models, non-coding RNA, repeats, pseudogenes, single-nucleotide polymorphism, markers, QTL and alignments to complementary DNAs, ESTs and protein homologs. The Bovine QTL viewer is connected to the BGD Chromosome GBrowse, allowing for the identification of candidate genes underlying QTL. The Apollo Annotation Editor connects directly to the BGD Chado database to provide researchers with remote access to gene evidence in a graphical interface that allows editing and creating new gene models. Researchers may upload their annotations to the BGD server for review and integration into the subsequent release of the OGS. Gene pages display information for individual OGS gene models, including gene structure, transcript variants, functional descriptions, gene symbols, Gene Ontology terms, annotator comments and links to National Center for Biotechnology Information and Ensembl. Each gene page is linked to a wiki page to allow input from the research community.

  13. Visualizing GO Annotations.

    PubMed

    Supek, Fran; Škunca, Nives

    2017-01-01

    Contemporary techniques in biology produce readouts for large numbers of genes simultaneously, the typical example being differential gene expression measurements. Moreover, those genes are often richly annotated using GO terms that describe gene function and that can be used to summarize the results of the genome-scale experiments. However, making sense of such GO enrichment analyses may be challenging. For instance, overrepresented GO functions in a set of differentially expressed genes are typically output as a flat list, a format not adequate to capture the complexities of the hierarchical structure of the GO annotation labels.In this chapter, we survey various methods to visualize large, difficult-to-interpret lists of GO terms. We catalog their availability-Web-based or standalone, the main principles they employ in summarizing large lists of GO terms, and the visualization styles they support. These brief commentaries on each software are intended as a helpful inventory, rather than comprehensive descriptions of the underlying algorithms. Instead, we show examples of their use and suggest that the choice of an appropriate visualization tool may be crucial to the utility of GO in biological discovery.

  14. The standard operating procedure of the DOE-JGI Metagenome Annotation Pipeline (MAP v.4).

    PubMed

    Huntemann, Marcel; Ivanova, Natalia N; Mavromatis, Konstantinos; Tripp, H James; Paez-Espino, David; Tennessen, Kristin; Palaniappan, Krishnaveni; Szeto, Ernest; Pillay, Manoj; Chen, I-Min A; Pati, Amrita; Nielsen, Torben; Markowitz, Victor M; Kyrpides, Nikos C

    2016-01-01

    The DOE-JGI Metagenome Annotation Pipeline (MAP v.4) performs structural and functional annotation for metagenomic sequences that are submitted to the Integrated Microbial Genomes with Microbiomes (IMG/M) system for comparative analysis. The pipeline runs on nucleotide sequences provided via the IMG submission site. Users must first define their analysis projects in GOLD and then submit the associated sequence datasets consisting of scaffolds/contigs with optional coverage information and/or unassembled reads in fasta and fastq file formats. The MAP processing consists of feature prediction including identification of protein-coding genes, non-coding RNAs and regulatory RNAs, as well as CRISPR elements. Structural annotation is followed by functional annotation including assignment of protein product names and connection to various protein family databases.

  15. Understanding how and why the Gene Ontology and its annotations evolve: the GO within UniProt.

    PubMed

    Huntley, Rachael P; Sawford, Tony; Martin, Maria J; O'Donovan, Claire

    2014-03-18

    The Gene Ontology Consortium (GOC) is a major bioinformatics project that provides structured controlled vocabularies to classify gene product function and location. GOC members create annotations to gene products using the Gene Ontology (GO) vocabularies, thus providing an extensive, publicly available resource. The GO and its annotations to gene products are now an integral part of functional analysis, and statistical tests using GO data are becoming routine for researchers to include when publishing functional information. While many helpful articles about the GOC are available, there are certain updates to the ontology and annotation sets that sometimes go unobserved. Here we describe some of the ways in which GO can change that should be carefully considered by all users of GO as they may have a significant impact on the resulting gene product annotations, and therefore the functional description of the gene product, or the interpretation of analyses performed on GO datasets. GO annotations for gene products change for many reasons, and while these changes generally improve the accuracy of the representation of the underlying biology, they do not necessarily imply that previous annotations were incorrect. We additionally describe the quality assurance mechanisms we employ to improve the accuracy of annotations, which necessarily changes the composition of the annotation sets we provide. We use the Universal Protein Resource (UniProt) for illustrative purposes of how the GO Consortium, as a whole, manages these changes.

  16. 24 CFR 943.120 - What programs of a PHA are included in a consortium's functions?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... in a consortium's functions? 943.120 Section 943.120 Housing and Urban Development REGULATIONS... HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING AGENCY CONSORTIA AND JOINT VENTURES Consortia § 943.120 What programs of a PHA are included in a consortium's functions? (a) A PHA may enter...

  17. 24 CFR 943.120 - What programs of a PHA are included in a consortium's functions?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... in a consortium's functions? 943.120 Section 943.120 Housing and Urban Development Regulations... HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING AGENCY CONSORTIA AND JOINT VENTURES Consortia § 943.120 What programs of a PHA are included in a consortium's functions? (a) A PHA may enter...

  18. 24 CFR 943.120 - What programs of a PHA are included in a consortium's functions?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... in a consortium's functions? 943.120 Section 943.120 Housing and Urban Development REGULATIONS... HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING AGENCY CONSORTIA AND JOINT VENTURES Consortia § 943.120 What programs of a PHA are included in a consortium's functions? (a) A PHA may enter...

  19. 24 CFR 943.120 - What programs of a PHA are included in a consortium's functions?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... in a consortium's functions? 943.120 Section 943.120 Housing and Urban Development REGULATIONS... HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING AGENCY CONSORTIA AND JOINT VENTURES Consortia § 943.120 What programs of a PHA are included in a consortium's functions? (a) A PHA may enter...

  20. 24 CFR 943.120 - What programs of a PHA are included in a consortium's functions?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... in a consortium's functions? 943.120 Section 943.120 Housing and Urban Development REGULATIONS... HOUSING, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING AGENCY CONSORTIA AND JOINT VENTURES Consortia § 943.120 What programs of a PHA are included in a consortium's functions? (a) A PHA may enter...

  1. Annotating Enzymes of Uncertain Function: The Deacylation of d-Amino Acids by Members of the Amidohydrolase Superfamily

    SciTech Connect

    Cummings, J.; Fedorov, A; Xu, C; Brown, S; Fedorov, E; Babbitt, P; Almo, S; Raushel, F

    2009-01-01

    The catalytic activities of three members of the amidohydrolase superfamily were discovered using amino acid substrate libraries. Bb3285 from Bordetella bronchiseptica, Gox1177 from Gluconobacter oxidans, and Sco4986 from Streptomyces coelicolor are currently annotated as d-aminoacylases or N-acetyl-d-glutamate deacetylases. These three enzymes are 22-34% identical to one another in amino acid sequence. Substrate libraries containing nearly all combinations of N-formyl-d-Xaa, N-acetyl-d-Xaa, N-succinyl-d-Xaa, and l-Xaa-d-Xaa were used to establish the substrate profiles for these enzymes. It was demonstrated that Bb3285 is restricted to the hydrolysis of N-acyl-substituted derivatives of d-glutamate. The best substrates for this enzyme are N-formyl-d-glutamate (k{sub cat}/K{sub m} = 5.8 x 10{sup 6} M{sup -1} s{sup -1}), N-acetyl-d-glutamate (k{sub cat}/K{sub m} = 5.2 x 10{sup 6} M{sup -1} s{sup -1}), and l-methionine-d-glutamate (k{sub cat}/K{sub m} = 3.4 x 10{sup 5} M{sup -1} s{sup -1}). Gox1177 and Sco4986 preferentially hydrolyze N-acyl-substituted derivatives of hydrophobic d-amino acids. The best substrates for Gox1177 are N-acetyl-d-leucine (k{sub cat}/K{sub m} = 3.2 x 104 M{sup -1} s-1), N-acetyl-d-tryptophan (kcat/Km = 4.1 x 104 M-1 s-1), and l-tyrosine-d-leucine (kcat/Km = 1.5 x 104 M-1 s-1). A fourth protein, Bb2785 from B. bronchiseptica, did not have d-aminoacylase activity. The best substrates for Sco4986 are N-acetyl-d-phenylalanine and N-acetyl-d-tryptophan. The three-dimensional structures of Bb3285 in the presence of the product acetate or a potent mimic of the tetrahedral intermediate were determined by X-ray diffraction methods. The side chain of the d-glutamate moiety of the inhibitor is ion-paired to Arg-295, while the {alpha}-carboxylate is ion-paired with Lys-250 and Arg-376. These results have revealed the chemical and structural determinants for substrate specificity in this protein. Bioinformatic analyses of an additional {approx}250

  2. Accumulation, functional annotation, and comparative analysis of expressed sequence tags in eggplant (Solanum melongena L.), the third pole of the genus Solanum species after tomato and potato.

    PubMed

    Fukuoka, Hiroyuki; Yamaguchi, Hirotaka; Nunome, Tsukasa; Negoro, Satomi; Miyatake, Koji; Ohyama, Akio

    2010-01-15

    Eggplant (Solanum melongena L.) is a widely grown vegetable crop that belongs to the genus Solanum, which is comprised of more than 1000 species of wide genetic and phenotypic variation. Unlike tomato and potato, Solanum crops that belong to subgenus Potatoe and have been targets for comprehensive genomic studies, eggplant is endemic to the Old World and belongs to a different subgenus, Leptostemonum, and therefore, would be a unique member for comparative molecular biology in Solanum. In this study, more than 60,000 eggplant cDNA clones from various tissues and treatments were sequenced from both the 5'- and 3'-ends, and a unigene set consisting of 16,245 unique sequences was constructed. Functional annotations based on sequence similarity to known plant reference datasets revealed a distribution of functional categories almost similar to that of tomato, while 1316 unigenes were suggested to be eggplant-specific. Sequence-based comparative analysis using putative orthologous gene groups setup by reciprocal sequence comparison among six solanaceous species suggested that eggplant and its wild ally Solanum torvum were clustered separately from subgenus Potatoe species, and then, all Solanum species were clustered separately from the genus Capsicum. Microsatellite motif distribution was different among species and likely to be coincident with the phylogenetic relationships. Furthermore, the eggplant unigene dataset exhibited its utility in transcriptome analysis by the SAGE strategy where a considerable number of short tag sequences of interest were successfully assigned to unigenes and their functional annotations. The eggplant ESTs and 16k unigene set developed in this study would be a useful resource not only for molecular genetics and breeding in eggplant itself, but for expanding the scope of comparative biology in Solanum species.

  3. Statistical algorithms for ontology-based annotation of scientific literature

    PubMed Central

    2014-01-01

    Background Ontologies encode relationships within a domain in robust data structures that can be used to annotate data objects, including scientific papers, in ways that ease tasks such as search and meta-analysis. However, the annotation process requires significant time and effort when performed by humans. Text mining algorithms can facilitate this process, but they render an analysis mainly based upon keyword, synonym and semantic matching. They do not leverage information embedded in an ontology's structure. Methods We present a probabilistic framework that facilitates the automatic annotation of literature by indirectly modeling the restrictions among the different classes in the ontology. Our research focuses on annotating human functional neuroimaging literature within the Cognitive Paradigm Ontology (CogPO). We use an approach that combines the stochastic simplicity of naïve Bayes with the formal transparency of decision trees. Our data structure is easily modifiable to reflect changing domain knowledge. Results We compare our results across naïve Bayes, Bayesian Decision Trees, and Constrained Decision Tree classifiers that keep a human expert in the loop, in terms of the quality measure of the F1-mirco score. Conclusions Unlike traditional text mining algorithms, our framework can model the knowledge encoded by the dependencies in an ontology, albeit indirectly. We successfully exploit the fact that CogPO has explicitly stated restrictions, and implicit dependencies in the form of patterns in the expert curated annotations. PMID:25093071

  4. Updating annotations with the distributed annotation system and the automated sequence annotation pipeline

    PubMed Central

    Speier, William; Ochs, Michael F.

    2012-01-01

    Summary: The integration between BioDAS ProServer and Automated Sequence Annotation Pipeline (ASAP) provides an interface for querying diverse annotation sources, chaining and linking results, and standardizing the output using the Distributed Annotation System (DAS) protocol. This interface allows pipeline plans in ASAP to be integrated into any system using HTTP and also allows the information returned by ASAP to be included in the DAS registry for use in any DAS-aware system. Three example implementations have been developed: the first accesses TRANSFAC information to automatically create gene sets for the Coordinated Gene Activity in Pattern Sets (CoGAPS) algorithm; the second integrates annotations from multiple array platforms and provides unified annotations in an R environment; and the third wraps the UniProt database for integration with the SPICE DAS client. Availability: Source code for ASAP 2.7 and the DAS 1.6 interface is available under the GNU public license. Proserver 2.20 is free software available from SourceForge. Scripts for installation and configuration on Linux are provided at our website: http://www.rits.onc.jhmi.edu/dbb/custom/A6/ Contact: Speier@mii.ucla.edu or mfo@jhu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22945787

  5. Radiocarbon Dating: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Fortine, Suellen

    This selective annotated bibliography covers various sources of information on the radiocarbon dating method, including journal articles, conference proceedings, and reports, reflecting the most important and useful sources of the last 25 years. The bibliography is divided into five parts--general background on radiocarbon, radiocarbon dating,…

  6. Annotated Videography. Part 3. [Revised].

    ERIC Educational Resources Information Center

    United States Holocaust Memorial Museum, Washington, DC.

    This annotated videography has been designed to identify videotapes addressing Holocaust history that have been used effectively in classrooms and are available readily to most communities. The guide is divided into 15 topical categories, including: life before the Holocaust; perpetrators; propaganda; racism; antisemitism; mosaic of victims;…

  7. ANNOTATED BIBLIOGRAPHY OF GEOLOGICAL EDUCATION.

    ERIC Educational Resources Information Center

    BERG, J. ROBERT; AND OTHERS

    ARTICLES ABOUT GEOLOGICAL EDUCATION WRITTEN DURING THE PERIOD 1919-62 ARE INCLUDED IN THIS ANNOTATED BIBLIOGRAPHY. RECOMMENDATIONS OF INDIVIDUAL EDUCATORS AND PROFESSIONAL GROUPS FOR THE UNDERGRADUATE AND GRADUATE PREPARATION OF GEOLOGISTS ARE CONTAINED IN MOST OF THE ITEMS. THE ARTICLES WERE ORIGINALLY PUBLISHED IN PROFESSIONAL JOURNALS OR…

  8. Vietnamese Amerasians: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Johnson, Mark C.; And Others

    This annotated bibliography on Vietnamese Amerasians includes primary and secondary sources as well as reviews of three documentary films. Sources were selected in order to provide an overview of the historical and political context of Amerasian resettlement and a review of the scant available research on coping and adaptation with this…

  9. Child Development: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Dickerson, LaVerne Thornton, Comp.

    This annotated bibliography focuses on recent publications dealing with factors that influence child growth and development, rather than the developmental processes themselves. Topics include: general sources on child development; physical and perceptual-motor development; cognitive development; social and personality development; and play.…

  10. MSDAC Resource Library Annotated Bibliography.

    ERIC Educational Resources Information Center

    Watson, Cristel; And Others

    This annotated bibliography lists books, films, filmstrips, recordings, and booklets on sex equity. Entries are arranged according to the following topics: career resources, curriculum resources, management, sex equity, sex roles, women's studies, student activities, and sex-fair fiction. Included in each entry are name of author, editor or…

  11. Migrant Education: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Palmer, Barbara C., Comp.

    Materials selected for inclusion in the annotated bibliography of 139 publications from 1970 to 1980 give a general understanding of the lives of migrant children, their educational needs and problems, and various attempts made to meet those needs. The bibliography, a valuable tool for researchers and teachers in migrant education, includes books,…

  12. Meaningful Assessment: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Thrond, Mary A.

    The annotated bibliography contains citations of nine references on alternative student assessment methods in second language programs, particularly at the secondary school level. The references include a critique of conventional reading comprehension assessment, a discussion of performance assessment, a proposal for a multi-trait, multi-method…

  13. On the necessity of dissecting sequence similarity scores into segment-specific contributions for inferring protein homology, function prediction and annotation

    PubMed Central

    2014-01-01

    Background Protein sequence similarities to any types of non-globular segments (coiled coils, low complexity regions, transmembrane regions, long loops, etc. where either positional sequence conservation is the result of a very simple, physically induced pattern or rather integral sequence properties are critical) are pertinent sources for mistaken homologies. Regretfully, these considerations regularly escape attention in large-scale annotation studies since, often, there is no substitute to manual handling of these cases. Quantitative criteria are required to suppress events of function annotation transfer as a result of false homology assignments. Results The sequence homology concept is based on the similarity comparison between the structural elements, the basic building blocks for conferring the overall fold of a protein. We propose to dissect the total similarity score into fold-critical and other, remaining contributions and suggest that, for a valid homology statement, the fold-relevant score contribution should at least be significant on its own. As part of the article, we provide the DissectHMMER software program for dissecting HMMER2/3 scores into segment-specific contributions. We show that DissectHMMER reproduces HMMER2/3 scores with sufficient accuracy and that it is useful in automated decisions about homology for instructive sequence examples. To generalize the dissection concept for cases without 3D structural information, we find that a dissection based on alignment quality is an appropriate surrogate. The approach was applied to a large-scale study of SMART and PFAM domains in the space of seed sequences and in the space of UniProt/SwissProt. Conclusions Sequence similarity core dissection with regard to fold-critical and other contributions systematically suppresses false hits and, additionally, recovers previously obscured homology relationships such as the one between aquaporins and formate/nitrite transporters that, so far, was only

  14. Determining similarity of scientific entities in annotation datasets.

    PubMed

    Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

    2015-01-01

    Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug-drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called 'AnnSim' that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1-1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/

  15. Determining similarity of scientific entities in annotation datasets

    PubMed Central

    Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

    2015-01-01

    Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug–drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called ‘AnnSim’ that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1–1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ PMID:25725057

  16. Computing human image annotation.

    PubMed

    Channin, David S; Mongkolwat, Pattanasak; Kleper, Vladimir; Rubin, Daniel L

    2009-01-01

    An image annotation is the explanatory or descriptive information about the pixel data of an image that is generated by a human (or machine) observer. An image markup is the graphical symbols placed over the image to depict an annotation. In the majority of current, clinical and research imaging practice, markup is captured in proprietary formats and annotations are referenced only in free text radiology reports. This makes these annotations difficult to query, retrieve and compute upon, hampering their integration into other data mining and analysis efforts. This paper describes the National Cancer Institute's Cancer Biomedical Informatics Grid's (caBIG) Annotation and Image Markup (AIM) project, focusing on how to use AIM to query for annotations. The AIM project delivers an information model for image annotation and markup. The model uses controlled terminologies for important concepts. All of the classes and attributes of the model have been harmonized with the other models and common data elements in use at the National Cancer Institute. The project also delivers XML schemata necessary to instantiate AIMs in XML as well as a software application for translating AIM XML into DICOM S/R and HL7 CDA. Large collections of AIM annotations can be built and then queried as Grid or Web services. Using the tools of the AIM project, image annotations and their markup can be captured and stored in human and machine readable formats. This enables the inclusion of human image observation and inference as part of larger data mining and analysis activities.

  17. Annotation of Fusarium graminearum (PH-1) Version 5.0

    PubMed Central

    Hammond-Kosack, Kim E.

    2017-01-01

    ABSTRACT Fusarium graminearum floral infections are a major risk to the global supply of safe cereal grains. We report updates to the PH-1 reference genome and significant improvements to the annotation. Changes include introduction of legacy annotation identifiers, new gene models, secretome and effectorP predictions, and inclusion of extensive untranslated region (UTR) annotations. PMID:28082505

  18. Functional gains of including non-commercial epibenthic taxa in coastal beam trawl surveys: A note

    NASA Astrophysics Data System (ADS)

    Brind'Amour, Anik; Rouyer, Armelle; Martin, Jocelyne

    2009-05-01

    The development of ecosystem-based indicators requires the broadening of a view of the community, from fish species to all the species (macrobenthic and fish) correctly captured by a given sampling gear. Many scientific surveys already have such integrated databases. The present note aims to demonstrate that existing databases, herein from dedicated coastal nursery surveys, are actually underexploited. Such databases contain information on non-commercial taxa, which could greatly improve our knowledge on the organisation and functioning of coastal ecosystems. Using two datasets, a "complete" dataset composed of commercial and not-commercial epibenthic trawled species (fish and invertebrate) and a "subset" dataset characterized by commercial and routinely surveyed species (mainly fish and cephalopods), different measures of functional diversity are compared to identify the functional gains of including epibenthic species. The results show that, when included in the analyses, epibenthic taxa provide gains of functional information, associated mainly with the community feeding traits, i.e. organisms composing the primary and secondary consumer levels of the coastal nursery food web. Failure to include some of the primary (zooplanktivores and suspension feeders) and secondary consumers (detritivores-scavengers) in coastal survey analyses may, for instance, hamper our understanding of energy flux between the benthic and water column compartments of these ecosystems. The results also suggest that the exclusion of some taxa associated with these two food web compartments, may lead to the underestimation of the functional redundancy in coastal ecosystems.

  19. Cognitive Functioning after Medial Frontal Lobe Damage Including the Anterior Cingulate Cortex: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J.; Dolan, Raymond J.; Cipolotti, Lisa

    2006-01-01

    Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was…

  20. Systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions

    DOEpatents

    Cooks, Robert Graham; Li, Anyin; Luo, Qingjie

    2017-01-24

    The invention generally relates to systems and methods for producing metal clusters; functionalized surfaces; and droplets including solvated metal ions. In certain aspects, the invention provides methods that involve providing a metal and a solvent. The methods additionally involve applying voltage to the solvated metal to thereby produce solvent droplets including ions of the metal containing compound, and directing the solvent droplets including the metal ions to a target. In certain embodiments, once at the target, the metal ions can react directly or catalyze reactions.

  1. Gene Model Annotations for Drosophila melanogaster: Impact of High-Throughput Data

    PubMed Central

    Matthews, Beverley B.; dos Santos, Gilberto; Crosby, Madeline A.; Emmert, David B.; St. Pierre, Susan E.; Gramates, L. Sian; Zhou, Pinglei; Schroeder, Andrew J.; Falls, Kathleen; Strelets, Victor; Russo, Susan M.; Gelbart, William M.

    2015-01-01

    We report the current status of the FlyBase annotated gene set for Drosophila melanogaster and highlight improvements based on high-throughput data. The FlyBase annotated gene set consists entirely of manually annotated gene models, with the exception of some classes of small non-coding RNAs. All gene models have been reviewed using evidence from high-throughput datasets, primarily from the modENCODE project. These datasets include RNA-Seq coverage data, RNA-Seq junction data, transcription start site profiles, and translation stop-codon read-through predictions. New annotation guidelines were developed to take into account the use of the high-throughput data. We describe how this flood of new data was incorporated into thousands of new and revised annotations. FlyBase has adopted a philosophy of excluding low-confidence and low-frequency data from gene model annotations; we also do not attempt to represent all possible permutations for complex and modularly organized genes. This has allowed us to produce a high-confidence, manageable gene annotation dataset that is available at FlyBase (http://flybase.org). Interesting aspects of new annotations include new genes (coding, non-coding, and antisense), many genes with alternative transcripts with very long 3′ UTRs (up to 15–18 kb), and a stunning mismatch in the number of male-specific genes (approximately 13% of all annotated gene models) vs. female-specific genes (less than 1%). The number of identified pseudogenes and mutations in the sequenced strain also increased significantly. We discuss remaining challenges, for instance, identification of functional small polypeptides and detection of alternative translation starts. PMID:26109357

  2. Gene Model Annotations for Drosophila melanogaster: Impact of High-Throughput Data.

    PubMed

    Matthews, Beverley B; Dos Santos, Gilberto; Crosby, Madeline A; Emmert, David B; St Pierre, Susan E; Gramates, L Sian; Zhou, Pinglei; Schroeder, Andrew J; Falls, Kathleen; Strelets, Victor; Russo, Susan M; Gelbart, William M

    2015-06-24

    We report the current status of the FlyBase annotated gene set for Drosophila melanogaster and highlight improvements based on high-throughput data. The FlyBase annotated gene set consists entirely of manually annotated gene models, with the exception of some classes of small non-coding RNAs. All gene models have been reviewed using evidence from high-throughput datasets, primarily from the modENCODE project. These datasets include RNA-Seq coverage data, RNA-Seq junction data, transcription start site profiles, and translation stop-codon read-through predictions. New annotation guidelines were developed to take into account the use of the high-throughput data. We describe how this flood of new data was incorporated into thousands of new and revised annotations. FlyBase has adopted a philosophy of excluding low-confidence and low-frequency data from gene model annotations; we also do not attempt to represent all possible permutations for complex and modularly organized genes. This has allowed us to produce a high-confidence, manageable gene annotation dataset that is available at FlyBase (http://flybase.org). Interesting aspects of new annotations include new genes (coding, non-coding, and antisense), many genes with alternative transcripts with very long 3' UTRs (up to 15-18 kb), and a stunning mismatch in the number of male-specific genes (approximately 13% of all annotated gene models) vs. female-specific genes (less than 1%). The number of identified pseudogenes and mutations in the sequenced strain also increased significantly. We discuss remaining challenges, for instance, identification of functional small polypeptides and detection of alternative translation starts.

  3. RASTtk: A modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes

    PubMed Central

    Brettin, Thomas; Davis, James J.; Disz, Terry; Edwards, Robert A.; Gerdes, Svetlana; Olsen, Gary J.; Olson, Robert; Overbeek, Ross; Parrello, Bruce; Pusch, Gordon D.; Shukla, Maulik; Thomason, James A.; Stevens, Rick; Vonstein, Veronika; Wattam, Alice R.; Xia, Fangfang

    2015-01-01

    The RAST (Rapid Annotation using Subsystem Technology) annotation engine was built in 2008 to annotate bacterial and archaeal genomes. It works by offering a standard software pipeline for identifying genomic features (i.e., protein-encoding genes and RNA) and annotating their functions. Recently, in order to make RAST a more useful research tool and to keep pace with advancements in bioinformatics, it has become desirable to build a version of RAST that is both customizable and extensible. In this paper, we describe the RAST tool kit (RASTtk), a modular version of RAST that enables researchers to build custom annotation pipelines. RASTtk offers a choice of software for identifying and annotating genomic features as well as the ability to add custom features to an annotation job. RASTtk also accommodates the batch submission of genomes and the ability to customize annotation protocols for batch submissions. This is the first major software restructuring of RAST since its inception. PMID:25666585

  4. RASTtk: A modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes

    SciTech Connect

    Brettin, Thomas; Davis, James J.; Disz, Terry; Edwards, Robert A.; Gerdes, Svetlana; Olsen, Gary J.; Olson, Robert; Overbeek, Ross; Parrello, Bruce; Pusch, Gordon D.; Shukla, Maulik; Thomason, III, James A.; Stevens, Rick; Vonstein, Veronika; Wattam, Alice R.; Xia, Fangfang

    2015-02-10

    The RAST (Rapid Annotation using Subsystem Technology) annotation engine was built in 2008 to annotate bacterial and archaeal genomes. It works by offering a standard software pipeline for identifying genomic features (i.e., protein-encoding genes and RNA) and annotating their functions. Recently, in order to make RAST a more useful research tool and to keep pace with advancements in bioinformatics, it has become desirable to build a version of RAST that is both customizable and extensible. In this paper, we describe the RAST tool kit (RASTtk), a modular version of RAST that enables researchers to build custom annotation pipelines. RASTtk offers a choice of software for identifying and annotating genomic features as well as the ability to add custom features to an annotation job. RASTtk also accommodates the batch submission of genomes and the ability to customize annotation protocols for batch submissions. This is the first major software restructuring of RAST since its inception.

  5. RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes.

    PubMed

    Brettin, Thomas; Davis, James J; Disz, Terry; Edwards, Robert A; Gerdes, Svetlana; Olsen, Gary J; Olson, Robert; Overbeek, Ross; Parrello, Bruce; Pusch, Gordon D; Shukla, Maulik; Thomason, James A; Stevens, Rick; Vonstein, Veronika; Wattam, Alice R; Xia, Fangfang

    2015-02-10

    The RAST (Rapid Annotation using Subsystem Technology) annotation engine was built in 2008 to annotate bacterial and archaeal genomes. It works by offering a standard software pipeline for identifying genomic features (i.e., protein-encoding genes and RNA) and annotating their functions. Recently, in order to make RAST a more useful research tool and to keep pace with advancements in bioinformatics, it has become desirable to build a version of RAST that is both customizable and extensible. In this paper, we describe the RAST tool kit (RASTtk), a modular version of RAST that enables researchers to build custom annotation pipelines. RASTtk offers a choice of software for identifying and annotating genomic features as well as the ability to add custom features to an annotation job. RASTtk also accommodates the batch submission of genomes and the ability to customize annotation protocols for batch submissions. This is the first major software restructuring of RAST since its inception.

  6. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle–brachial index

    PubMed Central

    Ferreira, Naomi Vidal; Cunha, Paulo Jannuzzi; da Costa, Danielle Irigoyen; dos Santos, Fernando; Costa, Fernando Oliveira; Consolim-Colombo, Fernanda; Irigoyen, Maria Cláudia

    2015-01-01

    Introduction Peripheral arterial disease, as measured by the ankle–brachial index (ABI), is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT). Executive cognitive function (ECF) impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI. Aim To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI. Method The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19), and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07). We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE), and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT) for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT) for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF). Results Before adjustment, the ABI group performed worse on global cognition, attention span, working memory, inhibitory control/impulsivity, semantic verbal fluency, and phonemic verbal fluency. After adjustment, the ABI group performance remained worse for working memory and semantic verbal fluency. In a simple correlation analysis including all of the subjects, the 6MWT was associated with global cognition, attention span, working memory, information processing speed, inhibitory control/impulsivity, semantic verbal fluency, and global ECF. After adjustment, all the associations remained statistically significant. Conclusion This study found an independent association between

  7. Computer systems for annotation of single molecule fragments

    DOEpatents

    Schwartz, David Charles; Severin, Jessica

    2016-07-19

    There are provided computer systems for visualizing and annotating single molecule images. Annotation systems in accordance with this disclosure allow a user to mark and annotate single molecules of interest and their restriction enzyme cut sites thereby determining the restriction fragments of single nucleic acid molecules. The markings and annotations may be automatically generated by the system in certain embodiments and they may be overlaid translucently onto the single molecule images. An image caching system may be implemented in the computer annotation systems to reduce image processing time. The annotation systems include one or more connectors connecting to one or more databases capable of storing single molecule data as well as other biomedical data. Such diverse array of data can be retrieved and used to validate the markings and annotations. The annotation systems may be implemented and deployed over a computer network. They may be ergonomically optimized to facilitate user interactions.

  8. Community annotation and bioinformatics workforce development in concert--Little Skate Genome Annotation Workshops and Jamborees.

    PubMed

    Wang, Qinghua; Arighi, Cecilia N; King, Benjamin L; Polson, Shawn W; Vincent, James; Chen, Chuming; Huang, Hongzhan; Kingham, Brewster F; Page, Shallee T; Rendino, Marc Farnum; Thomas, William Kelley; Udwary, Daniel W; Wu, Cathy H

    2012-01-01

    Recent advances in high-throughput DNA sequencing technologies have equipped biologists with a powerful new set of tools for advancing research goals. The resulting flood of sequence data has made it critically important to train the next generation of scientists to handle the inherent bioinformatic challenges. The North East Bioinformatics Collaborative (NEBC) is undertaking the genome sequencing and annotation of the little skate (Leucoraja erinacea) to promote advancement of bioinformatics infrastructure in our region, with an emphasis on practical education to create a critical mass of informatically savvy life scientists. In support of the Little Skate Genome Project, the NEBC members have developed several annotation workshops and jamborees to provide training in genome sequencing, annotation and analysis. Acting as a nexus for both curation activities and dissemination of project data, a project web portal, SkateBase (http://skatebase.org) has been developed. As a case study to illustrate effective coupling of community annotation with workforce development, we report the results of the Mitochondrial Genome Annotation Jamborees organized to annotate the first completely assembled element of the Little Skate Genome Project, as a culminating experience for participants from our three prior annotation workshops. We are applying the physical/virtual infrastructure and lessons learned from these activities to enhance and streamline the genome annotation workflow, as we look toward our continuing efforts for larger-scale functional and structural community annotation of the L. erinacea genome.

  9. Intra-species sequence comparisons for annotating genomes

    SciTech Connect

    Boffelli, Dario; Weer, Claire V.; Weng, Li; Lewis, Keith D.; Shoukry, Malak I.; Pachter, Lior; Keys, David N.; Rubin, Edward M.

    2004-07-15

    Analysis of sequence variation among members of a single species offers a potential approach to identify functional DNA elements responsible for biological features unique to that species. Due to its high rate of allelic polymorphism and ease of genetic manipulability, we chose the sea squirt, Ciona intestinalis, to explore intra-species sequence comparisons for genome annotation. A large number of C. intestinalis specimens were collected from four continents and a set of genomic intervals amplified, resequenced and analyzed to determine the mutation rates at each nucleotide in the sequence. We found that regions with low mutation rates efficiently demarcated functionally constrained sequences: these include a set of noncoding elements, which we showed in C intestinalis transgenic assays to act as tissue-specific enhancers, as well as the location of coding sequences. This illustrates that comparisons of multiple members of a species can be used for genome annotation, suggesting a path for the annotation of the sequenced genomes of organisms occupying uncharacterized phylogenetic branches of the animal kingdom and raises the possibility that the resequencing of a large number of Homo sapiens individuals might be used to annotate the human genome and identify sequences defining traits unique to our species. The sequence data from this study has been submitted to GenBank under accession nos. AY667278-AY667407.

  10. An Informally Annotated Bibliography of Sociolinguistics.

    ERIC Educational Resources Information Center

    Tannen, Deborah

    This annotated bibliography of sociolinguistics is divided into the following sections: speech events, ethnography of speaking and anthropological approaches to analysis of conversation; discourse analysis (including analysis of conversation and narrative), ethnomethodology and nonverbal communication; sociolinguistics; pragmatics (including…

  11. Cognitive functioning after medial frontal lobe damage including the anterior cingulate cortex: a preliminary investigation.

    PubMed

    Baird, Amee; Dewar, Bonnie-Kate; Critchley, Hugo; Gilbert, Sam J; Dolan, Raymond J; Cipolotti, Lisa

    2006-03-01

    Two patients with medial frontal lobe damage involving the anterior cingulate cortex (ACC) performed a range of cognitive tasks, including tests of executive function and anterior attention. Both patients lesions extended beyond the ACC, therefore caution needs to be exerted in ascribing observed deficits to the ACC alone. Patient performance was compared with age and education matched healthy controls. Both patients showed intact intellectual, memory, and language abilities. No clear-cut abnormalities were noted in visuoperceptual functions. Speed of information processing was mildly reduced only in Patient 2 (bilateral ACC lesion). The patients demonstrated weak or impaired performance only on selective executive function tests. Performance on anterior attention tasks was satisfactory. We tentatively suggest that our findings are inconsistent with anterior attention theories of ACC function based on neuroimaging findings. We propose that the data may imply that the ACC does not have a central role in cognition. We speculate that our findings may be compatible with the view that the ACC integrates cognitive processing with autonomic functioning to guide behaviour.

  12. Non-Formal Education and Radio: A Selected, Annotated Bibliography. Annotated Bibliography #14.

    ERIC Educational Resources Information Center

    Vergeldt, Vicki; And Others

    Materials concerning the use of radio and mass communications for non-formal education and development are listed in a selected annotated bibliography, intended for those actively involved in non-formal education and development. Three sections contain annotated entries (which range from 1972-1983), each of which includes source information and…

  13. AutoAnnotate: A Cytoscape app for summarizing networks with semantic annotations

    PubMed Central

    Kucera, Mike; Isserlin, Ruth; Arkhangorodsky, Arkady; Bader, Gary D.

    2016-01-01

    Networks often contain regions of tightly connected nodes, or clusters, that highlight their shared relationships. An effective way to create a visual summary of a network is to identify clusters and annotate them with an enclosing shape and a summarizing label. Cytoscape provides the ability to annotate a network with shapes and labels, however these annotations must be created manually one at a time, which can be a laborious process. AutoAnnotate is a Cytoscape 3 App that automates the process of identifying clusters and visually annotating them. It greatly reduces the time and effort required to fully annotate clusters in a network, and provides freedom to experiment with different strategies for identifying and labelling clusters. Many customization options are available that enable the user to refine the generated annotations as required. Annotated clusters may be collapsed into single nodes using the Cytoscape groups feature, which helps simplify a network by making its overall structure more visible. AutoAnnotate is applicable to any type of network, including enrichment maps, protein-protein interactions, pathways, or social networks. PMID:27830058

  14. AutoAnnotate: A Cytoscape app for summarizing networks with semantic annotations.

    PubMed

    Kucera, Mike; Isserlin, Ruth; Arkhangorodsky, Arkady; Bader, Gary D

    2016-01-01

    Networks often contain regions of tightly connected nodes, or clusters, that highlight their shared relationships. An effective way to create a visual summary of a network is to identify clusters and annotate them with an enclosing shape and a summarizing label. Cytoscape provides the ability to annotate a network with shapes and labels, however these annotations must be created manually one at a time, which can be a laborious process. AutoAnnotate is a Cytoscape 3 App that automates the process of identifying clusters and visually annotating them. It greatly reduces the time and effort required to fully annotate clusters in a network, and provides freedom to experiment with different strategies for identifying and labelling clusters. Many customization options are available that enable the user to refine the generated annotations as required. Annotated clusters may be collapsed into single nodes using the Cytoscape groups feature, which helps simplify a network by making its overall structure more visible. AutoAnnotate is applicable to any type of network, including enrichment maps, protein-protein interactions, pathways, or social networks.

  15. NoisyGOA: Noisy GO annotations prediction using taxonomic and semantic similarity.

    PubMed

    Lu, Chang; Wang, Jun; Zhang, Zili; Yang, Pengyi; Yu, Guoxian

    2016-12-01

    Gene Ontology (GO) provides GO annotations (GOA) that associate gene products with GO terms that summarize their cellular, molecular and functional aspects in the context of biological pathways. GO Consortium (GOC) resorts to various quality assurances to ensure the correctness of annotations. Due to resources limitations, only a small portion of annotations are manually added/checked by GO curators, and a large portion of available annotations are computationally inferred. While computationally inferred annotations provide greater coverage of known genes, they may also introduce annotation errors (noise) that could mislead the interpretation of the gene functions and their roles in cellular and biological processes. In this paper, we investigate how to identify noisy annotations, a rarely addressed problem, and propose a novel approach called NoisyGOA. NoisyGOA first measures taxonomic similarity between ontological terms using the GO hierarchy and semantic similarity between genes. Next, it leverages the taxonomic similarity and semantic similarity to predict noisy annotations. We compare NoisyGOA with other alternative methods on identifying noisy annotations under different simulated cases of noisy annotations, and on archived GO annotations. NoisyGOA achieved higher accuracy than other alternative methods in comparison. These results demonstrated both taxonomic similarity and semantic similarity contribute to the identification of noisy annotations. Our study shows that annotation errors are predictable and removing noisy annotations improves the performance of gene function prediction. This study can prompt the community to study methods for removing inaccurate annotations, a critical step for annotating gene and pathway functions.

  16. The Use of Annotations in Examination Marking: Opening a Window into Markers' Minds

    ERIC Educational Resources Information Center

    Crisp, Victoria; Johnson, Martin

    2007-01-01

    This study investigated the functions of annotations, the role of annotations in markers' decision-making processes, whether annotations conform to conventions, and whether these vary according to subject area. Across subjects a number of scripts were analysed to survey which annotations are subject specific and which are more general. Twelve…

  17. Genotator: A Workbench for Sequence Annotation

    SciTech Connect

    Harris, N.L.

    1997-05-01

    Sequencing centers such as the Human Genome Center at LBNL are producing an ever-increasing flood of genetic data. Annotation can greatly enhance the biological value of these sequences. Useful annotations include possible gene locations, homologies to known genes, and gene signals such as promoters and splice sites. Genotator is a workbench for automated sequence annotation and annotation browsing. The back end runs a series of sequence analysis tools on a DNA sequence, handling the various input and output formats required by the tools. Genotator currently runs five different gene finding programs, three homology searches, and searches for promoters, splice sites, and ORFs. The results of the analyses run by Genotator can be viewed with the interactive graphical browser. The browser displays color-coded sequence annotations on a canvas that can be scrolled and zoomed, allowing the annotated sequence to be explored at multiple levels of detail. The user can view the actual DNA sequence in a separate window; when a region is selected in the map display, it is automatically highlighted in the sequence display, and vice-versa. By displaying the output of all of the sequence analyses, Genotator provides an intuitive way to identify the significant regions (for example, probable exons) in a sequence. Users can interactively add personal annotations to label regions of interest. Additional capabilities of Genotator include primer design and pattern searching.

  18. The Uniqueness of Single Data Function, Multiple Model Functions, Inverse Problems Including the Rayleigh Wave Dispersion Problem

    NASA Astrophysics Data System (ADS)

    Menke, William

    2017-02-01

    We prove that the problem of inverting Rayleigh wave phase velocity functions c( k ) , where k is wavenumber, for density ρ ( z ) , rigidity μ ( z ) and Lamé parameter λ ( z ) , where z is depth, is fully non-unique, at least in the highly-idealized case where the base Earth model is an isotropic half space. The model functions completely trade off. This is one special case of a common inversion scenario in which one seeks to determine several model functions from a single data function. We explore the circumstances under which this broad class of problems is unique, starting with very simple scenarios, building up to the somewhat more complicated (and common) case where data and model functions are related by convolutions, and then finally, to scale-independent problems (which include the Rayleigh wave problem). The idealized cases that we examine analytically provide insight into the kinds of nonuniqueness that are inherent in the much more complicated problems encountered in modern geophysical imaging (though they do not necessarily provide methods for solving those problems). We also define what is meant by a Backus and Gilbert resolution kernel in this kind of inversion and show under what circumstances a unique localized average of a single model function can be constructed.

  19. AnnotCompute: annotation-based exploration and meta-analysis of genomics experiments

    PubMed Central

    Zheng, Jie; Stoyanovich, Julia; Manduchi, Elisabetta; Liu, Junmin; Stoeckert, Christian J.

    2011-01-01

    The ever-increasing scale of biological data sets, particularly those arising in the context of high-throughput technologies, requires the development of rich data exploration tools. In this article, we present AnnotCompute, an information discovery platform for repositories of functional genomics experiments such as ArrayExpress. Our system leverages semantic annotations of functional genomics experiments with controlled vocabulary and ontology terms, such as those from the MGED Ontology, to compute conceptual dissimilarities between pairs of experiments. These dissimilarities are then used to support two types of exploratory analysis—clustering and query-by-example. We show that our proposed dissimilarity measures correspond to a user's intuition about conceptual dissimilarity, and can be used to support effective query-by-example. We also evaluate the quality of clustering based on these measures. While AnnotCompute can support a richer data exploration experience, its effectiveness is limited in some cases, due to the quality of available annotations. Nonetheless, tools such as AnnotCompute may provide an incentive for richer annotations of experiments. Code is available for download at http://www.cbil.upenn.edu/downloads/AnnotCompute. Database URL: http://www.cbil.upenn.edu/annotCompute/ PMID:22190598

  20. Making web annotations persistent over time

    SciTech Connect

    Sanderson, Robert; Van De Sompel, Herbert

    2010-01-01

    As Digital Libraries (DL) become more aligned with the web architecture, their functional components need to be fundamentally rethought in terms of URIs and HTTP. Annotation, a core scholarly activity enabled by many DL solutions, exhibits a clearly unacceptable characteristic when existing models are applied to the web: due to the representations of web resources changing over time, an annotation made about a web resource today may no longer be relevant to the representation that is served from that same resource tomorrow. We assume the existence of archived versions of resources, and combine the temporal features of the emerging Open Annotation data model with the capability offered by the Memento framework that allows seamless navigation from the URI of a resource to archived versions of that resource, and arrive at a solution that provides guarantees regarding the persistence of web annotations over time. More specifically, we provide theoretical solutions and proof-of-concept experimental evaluations for two problems: reconstructing an existing annotation so that the correct archived version is displayed for all resources involved in the annotation, and retrieving all annotations that involve a given archived version of a web resource.

  1. Comprehensive functional characterization of murine infantile Batten disease including Parkinson-like behavior and dopaminergic markers

    PubMed Central

    Dearborn, Joshua T.; Harmon, Steven K.; Fowler, Stephen C.; O’Malley, Karen L.; Taylor, George T.; Sands, Mark S.; Wozniak, David F.

    2015-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL, Infantile Batten disease) is a neurodegenerative lysosomal storage disease caused by a deficiency in palmitoyl protein thioesterase-1 (PPT1). The PPT1-deficient mouse (Cln1−/−) is a useful phenocopy of human INCL. Cln1−/− mice display retinal dysfunction, seizures, motor deficits, and die at ~8 months of age. However, little is known about the cognitive and behavioral functions of Cln1−/− mice during disease progression. In the present study, younger (~1–2 months of age) Cln1−/− mice showed minor deficits in motor/sensorimotor functions while older (~5–6 months of age) Cln1−/− mice exhibited more severe impairments, including decreased locomotor activity, inferior cued water maze performance, decreased running wheel ability, and altered auditory cue conditioning. Unexpectedly, certain cognitive functions such as some learning and memory capabilities seemed intact in older Cln1−/− mice. Younger and older Cln1−/− mice presented with walking initiation defects, gait abnormalities, and slowed movements, which are analogous to some symptoms reported in INCL and parkinsonism. However, there was no evidence of alterations in dopaminergic markers in Cln1−/− mice. Results from this study demonstrate quantifiable changes in behavioral functions during progression of murine INCL and suggest that Parkinson-like motor/sensorimotor deficits in Cln1−/− mice are not mediated by dopamine deficiency. PMID:26238334

  2. Discovery and Characterization of Chromatin States for Systematic Annotation of the Human Genome

    NASA Astrophysics Data System (ADS)

    Ernst, Jason; Kellis, Manolis

    A plethora of epigenetic modifications have been described in the human genome and shown to play diverse roles in gene regulation, cellular differentiation and the onset of disease. Although individual modifications have been linked to the activity levels of various genetic functional elements, their combinatorial patterns are still unresolved and their potential for systematic de novo genome annotation remains untapped. Here, we use a multivariate Hidden Markov Model to reveal chromatin states in human T cells, based on recurrent and spatially coherent combinations of chromatin marks.We define 51 distinct chromatin states, including promoter-associated, transcription-associated, active intergenic, largescale repressed and repeat-associated states. Each chromatin state shows specific enrichments in functional annotations, sequence motifs and specific experimentally observed characteristics, suggesting distinct biological roles. This approach provides a complementary functional annotation of the human genome that reveals the genome-wide locations of diverse classes of epigenetic function.

  3. Functional Annotation of the Ophiostoma novo-ulmi Genome: Insights into the Phytopathogenicity of the Fungal Agent of Dutch Elm Disease

    PubMed Central

    Comeau, André M.; Dufour, Josée; Bouvet, Guillaume F.; Jacobi, Volker; Nigg, Martha; Henrissat, Bernard; Laroche, Jérôme; Levesque, Roger C.; Bernier, Louis

    2015-01-01

    The ascomycete fungus Ophiostoma novo-ulmi is responsible for the pandemic of Dutch elm disease that has been ravaging Europe and North America for 50 years. We proceeded to annotate the genome of the O. novo-ulmi strain H327 that was sequenced in 2012. The 31.784-Mb nuclear genome (50.1% GC) is organized into 8 chromosomes containing a total of 8,640 protein-coding genes that we validated with RNA sequencing analysis. Approximately 53% of these genes have their closest match to Grosmannia clavigera kw1407, followed by 36% in other close Sordariomycetes, 5% in other Pezizomycotina, and surprisingly few (5%) orphans. A relatively small portion (∼3.4%) of the genome is occupied by repeat sequences; however, the mechanism of repeat-induced point mutation appears active in this genome. Approximately 76% of the proteins could be assigned functions using Gene Ontology analysis; we identified 311 carbohydrate-active enzymes, 48 cytochrome P450s, and 1,731 proteins potentially involved in pathogen–host interaction, along with 7 clusters of fungal secondary metabolites. Complementary mating-type locus sequencing, mating tests, and culturing in the presence of elm terpenes were conducted. Our analysis identified a specific genetic arsenal impacting the sexual and vegetative growth, phytopathogenicity, and signaling/plant–defense–degradation relationship between O. novo-ulmi and its elm host and insect vectors. PMID:25539722

  4. PSSP-RFE: accurate prediction of protein structural class by recursive feature extraction from PSI-BLAST profile, physical-chemical property and functional annotations.

    PubMed

    Li, Liqi; Cui, Xiang; Yu, Sanjiu; Zhang, Yuan; Luo, Zhong; Yang, Hua; Zhou, Yue; Zheng, Xiaoqi

    2014-01-01

    Protein structure prediction is critical to functional annotation of the massively accumulated biological sequences, which prompts an imperative need for the development of high-throughput technologies. As a first and key step in protein structure prediction, protein structural class prediction becomes an increasingly challenging task. Amongst most homological-based approaches, the accuracies of protein structural class prediction are sufficiently high for high similarity datasets, but still far from being satisfactory for low similarity datasets, i.e., below 40% in pairwise sequence similarity. Therefore, we present a novel method for accurate and reliable protein structural class prediction for both high and low similarity datasets. This method is based on Support Vector Machine (SVM) in conjunction with integrated features from position-specific score matrix (PSSM), PROFEAT and Gene Ontology (GO). A feature selection approach, SVM-RFE, is also used to rank the integrated feature vectors through recursively removing the feature with the lowest ranking score. The definitive top features selected by SVM-RFE are input into the SVM engines to predict the structural class of a query protein. To validate our method, jackknife tests were applied to seven widely used benchmark datasets, reaching overall accuracies between 84.61% and 99.79%, which are significantly higher than those achieved by state-of-the-art tools. These results suggest that our method could serve as an accurate and cost-effective alternative to existing methods in protein structural classification, especially for low similarity datasets.

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

    PubMed

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

    2013-11-01

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

  6. Oncotator: cancer variant annotation tool.

    PubMed

    Ramos, Alex H; Lichtenstein, Lee; Gupta, Manaswi; Lawrence, Michael S; Pugh, Trevor J; Saksena, Gordon; Meyerson, Matthew; Getz, Gad

    2015-04-01

    Oncotator is a tool for annotating genomic point mutations and short nucleotide insertions/deletions (indels) with variant- and gene-centric information relevant to cancer researchers. This information is drawn from 14 different publicly available resources that have been pooled and indexed, and we provide an extensible framework to add additional data sources. Annotations linked to variants range from basic information, such as gene names and functional classification (e.g. missense), to cancer-specific data from resources such as the Catalogue of Somatic Mutations in Cancer (COSMIC), the Cancer Gene Census, and The Cancer Genome Atlas (TCGA). For local use, Oncotator is freely available as a python module hosted on Github (https://github.com/broadinstitute/oncotator). Furthermore, Oncotator is also available as a web service and web application at http://www.broadinstitute.org/oncotator/.

  7. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features.

    PubMed

    Arias, Carolina; Weisburd, Ben; Stern-Ginossar, Noam; Mercier, Alexandre; Madrid, Alexis S; Bellare, Priya; Holdorf, Meghan; Weissman, Jonathan S; Ganem, Don

    2014-01-01

    Productive herpesvirus infection requires a profound, time-controlled remodeling of the viral transcriptome and proteome. To gain insights into the genomic architecture and gene expression control in Kaposi's sarcoma-associated herpesvirus (KSHV), we performed a systematic genome-wide survey of viral transcriptional and translational activity throughout the lytic cycle. Using mRNA-sequencing and ribosome profiling, we found that transcripts encoding lytic genes are promptly bound by ribosomes upon lytic reactivation, suggesting their regulation is mainly transcriptional. Our approach also uncovered new genomic features such as ribosome occupancy of viral non-coding RNAs, numerous upstream and small open reading frames (ORFs), and unusual strategies to expand the virus coding repertoire that include alternative splicing, dynamic viral mRNA editing, and the use of alternative translation initiation codons. Furthermore, we provide a refined and expanded annotation of transcription start sites, polyadenylation sites, splice junctions, and initiation/termination codons of known and new viral features in the KSHV genomic space which we have termed KSHV 2.0. Our results represent a comprehensive genome-scale image of gene regulation during lytic KSHV infection that substantially expands our understanding of the genomic architecture and coding capacity of the virus.

  8. An annotated energy bibliography

    NASA Technical Reports Server (NTRS)

    Blow, S. J.

    1979-01-01

    Comprehensive annotated compilation of books, journals, periodicals, and reports on energy and energy related topics, contains approximately 10,0000 tehcnical and nontechnical references from bibliographic and other sources dated January 1975 through May 1977.

  9. Genomic Data and Annotation from the SEED

    DOE Data Explorer

    Fonstein, Michael; Kogan, Yakov; Osterman, Andrei; Overbeek, Ross; Vonstein, Veronika The Fellowship for Interpretation of Genomes (FIG)

    The SEED Project is a cooperative effort to annotate ever-expanding genomic data so researchers can conduct effective comparative analyses of genomes. Launched in 2003 by the Fellowship for Interpretation of Genomes (FIG), the project is one of several initiatives in ongoing development of data curation systems. SEED is designed to be used by scientists from numerous centers and with varied research objectives. As such, several institutions have since joined FIG in a consortium, including the University of Chicago, DOE’s Argonne National Laboratory (ANL), the University of Illinois at Urbana-Champaign, and others. As one example, ANL has used SEED to develop the National Microbial Pathogen Data Resource. Other agencies and institutions have used the project to discover genome components and clarify gene functions such as metabolism. SEED also has enabled researchers to conduct comparative analyses of closely related genomes and has supported derivation of stoichiometric models to understand metabolic processes. The SEED Project has been extended to support metagenomic samples and concomitant analytical tools. Moreover, the number of genomes being introduced into SEED is growing very rapidly. Building a framework to support this growth while providing highly accurate annotations is centrally important to SEED. The project’s subsystem-based annotation strategy has become the technological foundation for addressing these challenges.(copied from Appendix 7 of Systems Biology Knowledgebase for a New Era in Biology, A Genomics:GTL Report from the May 2008 Workshop, DOE/SC-0113, Grequrick, S; Fredrickson, J.K.; Stevens, R., Pub March 1, 2009.)

  10. MixtureTree annotator: a program for automatic colorization and visual annotation of MixtureTree.

    PubMed

    Chen, Shu-Chuan; Ogata, Aaron

    2015-01-01

    The MixtureTree Annotator, written in JAVA, allows the user to automatically color any phylogenetic tree in Newick format generated from any phylogeny reconstruction program and output the Nexus file. By providing the ability to automatically color the tree by sequence name, the MixtureTree Annotator provides a unique advantage over any other programs which perform a similar function. In addition, the MixtureTree Annotator is the only package that can efficiently annotate the output produced by MixtureTree with mutation information and coalescent time information. In order to visualize the resulting output file, a modified version of FigTree is used. Certain popular methods, which lack good built-in visualization tools, for example, MEGA, Mesquite, PHY-FI, TreeView, treeGraph and Geneious, may give results with human errors due to either manually adding colors to each node or with other limitations, for example only using color based on a number, such as branch length, or by taxonomy. In addition to allowing the user to automatically color any given Newick tree by sequence name, the MixtureTree Annotator is the only method that allows the user to automatically annotate the resulting tree created by the MixtureTree program. The MixtureTree Annotator is fast and easy-to-use, while still allowing the user full control over the coloring and annotating process.

  11. An Introduction to Genome Annotation.

    PubMed

    Campbell, Michael S; Yandell, Mark

    2015-12-17

    Genome projects have evolved from large international undertakings to tractable endeavors for a single lab. Accurate genome annotation is critical for successful genomic, genetic, and molecular biology experiments. These annotations can be generated using a number of approaches and available software tools. This unit describes methods for genome annotation and a number of software tools commonly used in gene annotation.

  12. Conservation, sex-biased expression and functional annotation of microRNAs in the gonad of Amur sturgeon (Acipenser schrenckii).

    PubMed

    Zhang, Xiujuan; Yuan, Lihong; Li, Linmiao; Jiang, Haiying; Chen, Jinping

    2016-06-01

    MicroRNAs (miRNAs) are involved in post-transcriptional gene regulation and have crucial roles in regulating the expression of gametogenesis-related genes in animals. However, the mechanism of sex determination and differentiation in the sturgeon has remained unclear. Identifying miRNAs and characterizing sex-biased miRNA expression is therefore critical for understanding the role of miRNAs during sexual differentiation in sturgeon. In this study, five different tissues from sturgeon before sex differentiation and the gonads were used for miRNA expression profiling. We screened 1037 miRNAs in miRBase 20.0 and an additional 103 sturgeon miRNAs using microarray and real-time PCR. We found that the sequences of 477 miRNAs out of a total of 1140 miRNAs were highly conserved (100%) among different fish species. From a total of 663 non-redundant miRNA probes, 481 miRNAs were detected in the gonads of both sexes. Of the 148 miRNAs that were identified to have sex-biased expression patterns between the testis and the ovary (P<0.01), 21 miRNAs (14.19%) were relatively highly expressed in the testis or the ovary with fold-changes >2. The microarray expression patterns of 13 randomly selected sex-biased miRNAs were validated using real-time PCR. Target gene prediction revealed a significant enrichment of functional groups (88 GO terms) and 18 KEGG pathways (P<0.05) and suggested that there are interactions between sex-biased miRNAs and 25 putative gametogenesis-related targets. Therefore, our miRNA expression analysis in juvenile A. schrenckii establishes a foundation for understanding and further investigating the role of miRNAs in sturgeon sex differentiation.

  13. Integration of high-content screening and untargeted metabolomics for comprehensive functional annotation of natural product libraries.

    PubMed

    Kurita, Kenji L; Glassey, Emerson; Linington, Roger G

    2015-09-29

    Traditional natural products discovery using a combination of live/dead screening followed by iterative bioassay-guided fractionation affords no information about compound structure or mode of action until late in the discovery process. This leads to high rates of rediscovery and low probabilities of finding compounds with unique biological and/or chemical properties. By integrating image-based phenotypic screening in HeLa cells with high-resolution untargeted metabolomics analysis, we have developed a new platform, termed Compound Activity Mapping, that is capable of directly predicting the identities and modes of action of bioactive constituents for any complex natural product extract library. This new tool can be used to rapidly identify novel bioactive constituents and provide predictions of compound modes of action directly from primary screening data. This approach inverts the natural products discovery process from the existing "grind and find" model to a targeted, hypothesis-driven discovery model where the chemical features and biological function of bioactive metabolites are known early in the screening workflow, and lead compounds can be rationally selected based on biological and/or chemical novelty. We demonstrate the utility of the Compound Activity Mapping platform by combining 10,977 mass spectral features and 58,032 biological measurements from a library of 234 natural products extracts and integrating these two datasets to identify 13 clusters of fractions containing 11 known compound families and four new compounds. Using Compound Activity Mapping we discovered the quinocinnolinomycins, a new family of natural products with a unique carbon skeleton that cause endoplasmic reticulum stress.

  14. Functional annotation of noncoding variants and prioritization of cancer-associated lncRNAs in lung cancer

    PubMed Central

    LI, HUA; LV, XIN

    2016-01-01

    Multiple computational tools have been widely applied to the detection of coding driver mutations in cancer; however, the prioritization of pathogenic non-coding variants remains a difficult and demanding task. The present study was performed to distinguish non-coding disease-causing mutations from neutral ones, and to prioritize potential cancer-associated long non-coding RNAs (lncRNAs) with a logistic regression model in lung cancer. A logistic regression model was constructed, combining 19,153 disease-associated ClinVar and Human Gene Mutation Database pathogenic variants as the response variable and non-coding features as the predictor variable. Validation of the model was conducted with genome-wide association study (GWAS) disease- or trait-associated single nucleotide polymorphisms (SNPs) and recurrent somatic mutations. High scoring regions were characterized with respect to their distribution in various features and gene classes; potential cancer-associated lncRNA candidates were prioritized, combining the fraction of high-scoring regions and average score predicted by the logistic regression model. H3K79me2 was the most negative factor that contributed to the model, while conserved regions were most positively informative to the model. The area under the receiver operating characteristic curve of the model was 0.89. The model assigned a significantly higher score to GWAS SNPs and recurrent somatic mutations compared with neutral SNPs (mean, 5.9012 vs. 5.5238; P<0.001, Mann-Whitney U test) and non-recurrent mutations (mean, 5.4677 vs. 5.2277, P<0.001, Mann-Whitney U test), respectively. It was observed that regions, including splicing sites and untranslated regions, and gene classes, including cancer genes and cancer-associated lncRNAs, had an increased enrichment of high-scoring regions. In total, 2,679 cancer-associated lncRNAs were determined and characterized. A total of 104 of these lncRNAs were differentially expressed between lung cancer and normal

  15. De novo assembly, functional annotation, and marker development of Asian pear (Pyrus pyrifolia) fruit transcriptome through massively parallel sequencing.

    PubMed

    Li, J F; Gao, Z; Lou, Y S; Luo, M; Song, S R; Xu, W P; Wang, S P; Zhang, C X

    2015-12-28

    This study investigated the Asian pear transcriptome using the RNA-Seq normalized fruit cDNA library to create a transcriptomic resource for unigene and marker discovery. Following the removal of lowquality reads, 127,085,054 trimmed reads were assembled de novo to yield 37,649 non-redundant unigenes with an average length of 599 bp. Alternative splicing events were detected in 4121 contigs. A total of 30,560 single nucleotide polymorphisms (SNPs) and 7443 simple sequence repeat (SSR) makers were obtained. Approximately 21,449 (56.9%) unigenes were categorized into three gene ontology groups; 3682 (9.8%) were classified into 25 cluster of orthologous groups; and 10,451 (27.8%) were assigned to six Kyoto Encyclopedia of Genes and Genomes pathways. Differentially expressed genes were investigated using the reads per kilobase of the exon model per million reads methodology. A total of 546 unigenes showed significant differences in expression levels at different fruit developmental stages. Gene ontology categories associated with various aspects, including carbohydrate metabolic processes, transmembrane transport, and signal transduction, were enriched with genes with divergent expressions. These Pyrus pyrifolia transcriptome data provide a rich resource for the discovery and identification of new genes. Furthermore, the numerous putative SSRs and SNPs detected in this study will be important resources for the future development of a linkage map or of marker-assisted breeding programs for the Asian pear.

  16. Multirate Simulations of String Vibrations Including Nonlinear Fret-String Interactions Using the Functional Transformation Method

    NASA Astrophysics Data System (ADS)

    Trautmann, L.; Rabenstein, R.

    2004-12-01

    The functional transformation method (FTM) is a well-established mathematical method for accurate simulations of multidimensional physical systems from various fields of science, including optics, heat and mass transfer, electrical engineering, and acoustics. This paper applies the FTM to real-time simulations of transversal vibrating strings. First, a physical model of a transversal vibrating lossy and dispersive string is derived. Afterwards, this model is solved with the FTM for two cases: the ideally linearly vibrating string and the string interacting nonlinearly with the frets. It is shown that accurate and stable simulations can be achieved with the discretization of the continuous solution at audio rate. Both simulations can also be performed with a multirate approach with only minor degradations of the simulation accuracy but with preservation of stability. This saves almost 80% of the computational cost for the simulation of a six-string guitar and therefore it is in the range of the computational cost for digital waveguide simulations.

  17. InterPro in 2017—beyond protein family and domain annotations

    PubMed Central

    Finn, Robert D.; Attwood, Teresa K.; Babbitt, Patricia C.; Bateman, Alex; Bork, Peer; Bridge, Alan J.; Chang, Hsin-Yu; Dosztányi, Zsuzsanna; El-Gebali, Sara; Fraser, Matthew; Gough, Julian; Haft, David; Holliday, Gemma L.; Huang, Hongzhan; Huang, Xiaosong; Letunic, Ivica; Lopez, Rodrigo; Lu, Shennan; Marchler-Bauer, Aron; Mi, Huaiyu; Mistry, Jaina; Natale, Darren A.; Necci, Marco; Nuka, Gift; Orengo, Christine A.; Park, Youngmi; Pesseat, Sebastien; Piovesan, Damiano; Potter, Simon C.; Rawlings, Neil D.; Redaschi, Nicole; Richardson, Lorna; Rivoire, Catherine; Sangrador-Vegas, Amaia; Sigrist, Christian; Sillitoe, Ian; Smithers, Ben; Squizzato, Silvano; Sutton, Granger; Thanki, Narmada; Thomas, Paul D; Tosatto, Silvio C. E.; Wu, Cathy H.; Xenarios, Ioannis; Yeh, Lai-Su; Young, Siew-Yit; Mitchell, Alex L.

    2017-01-01

    InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences. PMID:27899635

  18. KEGG as a reference resource for gene and protein annotation

    PubMed Central

    Kanehisa, Minoru; Sato, Yoko; Kawashima, Masayuki; Furumichi, Miho; Tanabe, Mao

    2016-01-01

    KEGG (http://www.kegg.jp/ or http://www.genome.jp/kegg/) is an integrated database resource for biological interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 complete genomes are annotated with KOs in the KEGG GENES database, which can be used as a reference data set for KO assignment and subsequent reconstruction of KEGG pathways and other molecular networks. As an annotation resource, the following improvements have been made. First, each KO record is re-examined and associated with protein sequence data used in experiments of functional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for antimicrobial resistance and drug interaction networks. PMID:26476454

  19. Protein Sequence Annotation Tool (PSAT): A centralized web-based meta-server for high-throughput sequence annotations

    SciTech Connect

    Leung, Elo; Huang, Amy; Cadag, Eithon; Montana, Aldrin; Soliman, Jan Lorenz; Zhou, Carol L. Ecale

    2016-01-20

    In this study, we introduce the Protein Sequence Annotation Tool (PSAT), a web-based, sequence annotation meta-server for performing integrated, high-throughput, genome-wide sequence analyses. Our goals in building PSAT were to (1) create an extensible platform for integration of multiple sequence-based bioinformatics tools, (2) enable functional annotations and enzyme predictions over large input protein fasta data sets, and (3) provide a web interface for convenient execution of the tools. In this paper, we demonstrate the utility of PSAT by annotating the predicted peptide gene products of Herbaspirillum sp. strain RV1423, importing the results of PSAT into EC2KEGG, and using the resulting functional comparisons to identify a putative catabolic pathway, thereby distinguishing RV1423 from a well annotated Herbaspirillum species. This analysis demonstrates that high-throughput enzyme predictions, provided by PSAT processing, can be used to identify metabolic potential in an otherwise poorly annotated genome. Lastly, PSAT is a meta server that combines the results from several sequence-based annotation and function prediction codes, and is available at http://psat.llnl.gov/psat/. PSAT stands apart from other sequencebased genome annotation systems in providing a high-throughput platform for rapid de novo enzyme predictions and sequence annotations over large input protein sequence data sets in FASTA. PSAT is most appropriately applied in annotation of large protein FASTA sets that may or may not be associated with a single genome.

  20. Protein Sequence Annotation Tool (PSAT): A centralized web-based meta-server for high-throughput sequence annotations

    DOE PAGES

    Leung, Elo; Huang, Amy; Cadag, Eithon; ...

    2016-01-20

    In this study, we introduce the Protein Sequence Annotation Tool (PSAT), a web-based, sequence annotation meta-server for performing integrated, high-throughput, genome-wide sequence analyses. Our goals in building PSAT were to (1) create an extensible platform for integration of multiple sequence-based bioinformatics tools, (2) enable functional annotations and enzyme predictions over large input protein fasta data sets, and (3) provide a web interface for convenient execution of the tools. In this paper, we demonstrate the utility of PSAT by annotating the predicted peptide gene products of Herbaspirillum sp. strain RV1423, importing the results of PSAT into EC2KEGG, and using the resultingmore » functional comparisons to identify a putative catabolic pathway, thereby distinguishing RV1423 from a well annotated Herbaspirillum species. This analysis demonstrates that high-throughput enzyme predictions, provided by PSAT processing, can be used to identify metabolic potential in an otherwise poorly annotated genome. Lastly, PSAT is a meta server that combines the results from several sequence-based annotation and function prediction codes, and is available at http://psat.llnl.gov/psat/. PSAT stands apart from other sequencebased genome annotation systems in providing a high-throughput platform for rapid de novo enzyme predictions and sequence annotations over large input protein sequence data sets in FASTA. PSAT is most appropriately applied in annotation of large protein FASTA sets that may or may not be associated with a single genome.« less

  1. Companion: a web server for annotation and analysis of parasite genomes

    PubMed Central

    Steinbiss, Sascha; Silva-Franco, Fatima; Brunk, Brian; Foth, Bernardo; Hertz-Fowler, Christiane; Berriman, Matthew; Otto, Thomas D.

    2016-01-01

    Currently available sequencing technologies enable quick and economical sequencing of many new eukaryotic parasite (apicomplexan or kinetoplastid) species or strains. Compared to SNP calling approaches, de novo assembly of these genomes enables researchers to additionally determine insertion, deletion and recombination events as well as to detect complex sequence diversity, such as that seen in variable multigene families. However, there currently are no automated eukaryotic annotation pipelines offering the required range of results to facilitate such analyses. A suitable pipeline needs to perform evidence-supported gene finding as well as functional annotation and pseudogene detection up to the generation of output ready to be submitted to a public database. Moreover, no current tool includes quick yet informative comparative analyses and a first pass visualization of both annotation and analysis results. To overcome those needs we have developed the Companion web server (http://companion.sanger.ac.uk) providing parasite genome annotation as a service using a reference-based approach. We demonstrate the use and performance of Companion by annotating two Leishmania and Plasmodium genomes as typical parasite cases and evaluate the results compared to manually annotated references. PMID:27105845

  2. AnnotCompute: annotation-based exploration and meta-analysis of genomics experiments.

    PubMed

    Zheng, Jie; Stoyanovich, Julia; Manduchi, Elisabetta; Liu, Junmin; Stoeckert, Christian J

    2011-01-01

    The ever-increasing scale of biological data sets, particularly those arising in the context of high-throughput technologies, requires the development of rich data exploration tools. In this article, we present AnnotCompute, an information discovery platform for repositories of functional genomics experiments such as ArrayExpress. Our system leverages semantic annotations of functional genomics experiments with controlled vocabulary and ontology terms, such as those from the MGED Ontology, to compute conceptual dissimilarities between pairs of experiments. These dissimilarities are then used to support two types of exploratory analysis-clustering and query-by-example. We show that our proposed dissimilarity measures correspond to a user's intuition about conceptual dissimilarity, and can be used to support effective query-by-example. We also evaluate the quality of clustering based on these measures. While AnnotCompute can support a richer data exploration experience, its effectiveness is limited in some cases, due to the quality of available annotations. Nonetheless, tools such as AnnotCompute may provide an incentive for richer annotations of experiments. Database URL: http://www.cbil.upenn.edu/annotCompute/

  3. Functional annotation of mammalian genomic DNA sequence by chemical mutagenesis: a fine-structure genetic mutation map of a 1- to 2-cM segment of mouse chromosome 7 corresponding to human chromosome 11p14-p15.

    PubMed

    Rinchik, Eugene M; Carpenter, Donald A; Johnson, Dabney K

    2002-01-22

    Eleven independent, recessive, N-ethyl-N-nitrosourea-induced mutations that map to a approximately 1- to 2-cM region of mouse chromosome (Chr) 7 homologous to human Chr 11p14-p15 were recovered from a screen of 1,218 gametes. These mutations were initially identified in a hemizygous state opposite a large p-locus deletion and subsequently were mapped to finer genomic intervals by crosses to a panel of smaller p deletions. The 11 mutations also were classified into seven complementation groups by pairwise crosses. Four complementation groups were defined by seven prenatally lethal mutations, including a group (l7R3) comprised of two alleles of obvious differing severity. Two allelic mutations (at the psrt locus) result in a severe seizure and runting syndrome, but one mutation (at the fit2 locus) results in a more benign runting phenotype. This experiment has added seven loci, defined by phenotypes of presumed point mutations, to the genetic map of a small (1-2 cM) region of mouse Chr 7 and will facilitate the task of functional annotation of DNA sequence and transcription maps both in the mouse and the corresponding human 11p14-p15 homology region.

  4. Operational Dataset Update Functionality Included in the NCAR Research Data Archive Management System

    NASA Astrophysics Data System (ADS)

    Ji, Z.; Worley, S. J.; Schuster, D. C.

    2011-12-01

    Growing complexity, volume, and reliance on operationally created datasets poses challenges to the centers tasked with archiving and curating this information. Past tools focused on data delivered via media, such as tape, or data downloaded by single dataset customized ftp scripting. Presently nearly all data are acquired via network interactions, which can happen many times per day. Prior archive management technologies do not scale to this new paradigm. The Research Data Archive Management System (RDAMS) was developed to meet this challenge and has been implemented to support archive management within the Research Data Archive (RDA) at the National Center for Atmospheric Research (NCAR). RDAMS is driven by open source based databases and utilities, and is designed to support the complete data archive cycle by fetching, interrogating, archiving, and providing long-term research data stewardship. A good example of RDAMS functionality is found in the utility developed to specifically manage operational dataset updates, and can be applied to any dataset that requires periodic updating. The RDAMS dataset update utility (DSUPDT) accomplishes four basic tasks: 1) contact and query a remote server to see if new or modified data are available, 2) move data from a remote host to a local system and verify data transfer integrity, 3) execute any required data processing steps including metadata harvesting, 4) archive data to local disk and backup media systems. To accomplish these tasks across a diverse variety of datasets, DSUPDT incorporates a broad base of functionality. For example, it can be configured to run according to many different data set requirements, handles multiple web protocols, automatically recovers from system outages at the remote or local site, can execute 3rd party data manipulation software, and accommodates irregular data delivery schedules. Currently over 150 RDA dataset products are configured to be under DSUPDT control, with datasets being updated

  5. Human Genome Annotation

    NASA Astrophysics Data System (ADS)

    Gerstein, Mark

    A central problem for 21st century science is annotating the human genome and making this annotation useful for the interpretation of personal genomes. My talk will focus on annotating the 99% of the genome that does not code for canonical genes, concentrating on intergenic features such as structural variants (SVs), pseudogenes (protein fossils), binding sites, and novel transcribed RNAs (ncRNAs). In particular, I will describe how we identify regulatory sites and variable blocks (SVs) based on processing next-generation sequencing experiments. I will further explain how we cluster together groups of sites to create larger annotations. Next, I will discuss a comprehensive pseudogene identification pipeline, which has enabled us to identify >10K pseudogenes in the genome and analyze their distribution with respect to age, protein family, and chromosomal location. Throughout, I will try to introduce some of the computational algorithms and approaches that are required for genome annotation. Much of this work has been carried out in the framework of the ENCODE, modENCODE, and 1000 genomes projects.

  6. Analysis and functional annotation of expressed sequence tags from in vitro cell lines of elasmobranchs: Spiny dogfish shark (Squalus acanthias) and little skate (Leucoraja erinacea).

    PubMed

    Parton, Angela; Bayne, Christopher J; Barnes, David W

    2010-09-01

    Elasmobranchs are the most commonly used experimental models among the jawed, cartilaginous fish (Chondrichthyes). Previously we developed cell lines from embryos of two elasmobranchs, Squalus acanthias the spiny dogfish shark (SAE line), and Leucoraja erinacea the little skate (LEE-1 line). From these lines cDNA libraries were derived and expressed sequence tags (ESTs) generated. From the SAE cell line 4303 unique transcripts were identified, with 1848 of these representing unknown sequences (showing no BLASTX identification). From the LEE-1 cell line, 3660 unique transcripts were identified, and unknown, unique sequences totaled 1333. Gene Ontology (GO) annotation showed that GO assignments for the two cell lines were in general similar. These results suggest that the procedures used to derive the cell lines led to isolation of cell types of the same general embryonic origin from both species. The LEE-1 transcripts included GO categories "envelope" and "oxidoreductase activity" but the SAE transcripts did not. GO analysis of SAE transcripts identified the category "anatomical structure formation" that was not present in LEE-1 cells. Increased organelle compartments may exist within LEE-1 cells compared to SAE cells, and the higher oxidoreductase activity in LEE-1 cells may indicate a role for these cells in responses associated with innate immunity or in steroidogenesis. These EST libraries from elasmobranch cell lines provide information for assembly of genomic sequences and are useful in revealing gene diversity, new genes and molecular markers, as well as in providing means for elucidation of full-length cDNAs and probes for gene array analyses. This is the first study of this type with members of the Chondrichthyes.

  7. Dynamical Green's function and an exact optical potential for electron-molecule scattering including nuclear dynamics

    NASA Astrophysics Data System (ADS)

    Brand, Joachim; Cederbaum, Lorenz S.; Meyer, Hans-Dieter

    1999-10-01

    We derive a rigorous optical potential for electron-molecule scattering including the effects of nuclear dynamics by extending the common many-body Green's function approach to optical potentials beyond the fixed-nuclei limit for molecular targets. Our formalism treats the projectile electron and the nuclear motion of the target molecule on the same footing whereby the dynamical optical potential rigorously accounts for the complex many-body nature of the scattering target. One central result of the present work is that the common fixed-nuclei optical potential is a valid adiabatic approximation to the dynamical optical potential even when projectile and nuclear motion are (nonadiabatically) coupled as long as the scattering energy is well below the electronic excitation thresholds of the target. For extremely low projectile velocities, however, when the cross sections are most sensitive to the scattering potential, we expect the influences of the nuclear dynamics on the optical potential to become relevant. For these cases, a systematic way to improve the adiabatic approximation to the dynamical optical potential is presented that yields nonlocal operators with respect to the nuclear coordinates.

  8. Re-Annotator: Annotation Pipeline for Microarray Probe Sequences.

    PubMed

    Arloth, Janine; Bader, Daniel M; Röh, Simone; Altmann, Andre

    2015-01-01

    Microarray technologies are established approaches for high throughput gene expression, methylation and genotyping analysis. An accurate mapping of the array probes is essential to generate reliable biological findings. However, manufacturers of the microarray platforms typically provide incomplete and outdated annotation tables, which often rely on older genome and transcriptome versions that differ substantially from up-to-date sequence databases. Here, we present the Re-Annotator, a re-annotation pipeline for microarray probe sequences. It is primarily designed for gene expression microarrays but can also be adapted to other types of microarrays. The Re-Annotator uses a custom-built mRNA reference database to identify the positions of gene expression array probe sequences. We applied Re-Annotator to the Illumina Human-HT12 v4 microarray platform and found that about one quarter (25%) of the probes differed from the manufacturer's annotation. In further computational experiments on experimental gene expression data, we compared Re-Annotator to another probe re-annotation tool, ReMOAT, and found that Re-Annotator provided an improved re-annotation of microarray probes. A thorough re-annotation of probe information is crucial to any microarray analysis. The Re-Annotator pipeline is freely available at http://sourceforge.net/projects/reannotator along with re-annotated files for Illumina microarrays HumanHT-12 v3/v4 and MouseRef-8 v2.

  9. Draft Genome Sequence and Gene Annotation of Stemphylium lycopersici Strain CIDEFI-216.

    PubMed

    Franco, Mario E E; López, Silvina; Medina, Rocio; Saparrat, Mario C N; Balatti, Pedro

    2015-09-24

    Stemphylium lycopersici is a plant-pathogenic fungus that is widely distributed throughout the world. In tomatoes, it is one of the etiological agents of gray leaf spot disease. Here, we report the first draft genome sequence of S. lycopersici, including its gene structure and functional annotation.

  10. Draft Genome Sequence and Gene Annotation of Stemphylium lycopersici Strain CIDEFI-216

    PubMed Central

    Franco, Mario E. E.; López, Silvina; Medina, Rocio; Saparrat, Mario C. N.

    2015-01-01

    Stemphylium lycopersici is a plant-pathogenic fungus that is widely distributed throughout the world. In tomatoes, it is one of the etiological agents of gray leaf spot disease. Here, we report the first draft genome sequence of S. lycopersici, including its gene structure and functional annotation. PMID:26404600

  11. CIPRO 2.5: Ciona intestinalis protein database, a unique integrated repository of large-scale omics data, bioinformatic analyses and curated annotation, with user rating and reviewing functionality.

    PubMed

    Endo, Toshinori; Ueno, Keisuke; Yonezawa, Kouki; Mineta, Katsuhiko; Hotta, Kohji; Satou, Yutaka; Yamada, Lixy; Ogasawara, Michio; Takahashi, Hiroki; Nakajima, Ayako; Nakachi, Mia; Nomura, Mamoru; Yaguchi, Junko; Sasakura, Yasunori; Yamasaki, Chisato; Sera, Miho; Yoshizawa, Akiyasu C; Imanishi, Tadashi; Taniguchi, Hisaaki; Inaba, Kazuo

    2011-01-01

    The Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogenetic position, Ciona is suitable model for understanding vertebrate evolution; and second, the database includes original large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a favorite of developmental biologists. Therefore, large amounts of data exist on its development and morphology, along with a recent genome sequence and gene expression data. The CIPRO database is aimed at collecting those published data as well as providing unique information from unpublished experimental data, such as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale analyses at various developmental stages, curated annotation data and various bioinformatic data, to facilitate research in diverse areas, including developmental, comparative and evolutionary biology. For medical and evolutionary research, homologs in humans and major model organisms are intentionally included. The current database is based on a recently developed KH model containing 36,034 unique sequences, but for higher usability it covers 89,683 all known and predicted proteins from all gene models for this species. Of these sequences, more than 10,000 proteins have been manually annotated. Furthermore, to establish a community-supported protein database, these annotations are open to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible at http://cipro.ibio.jp/2.5.

  12. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    SciTech Connect

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI

  13. Pulmonary Function after Treatment for Embryonal Brain Tumors on SJMB03 that Included Craniospinal Irradiation

    PubMed Central

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-01-01

    Purpose Treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods Protocol XXXXX enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by spirometry, total lung capacity (TLC) by nitrogen washout or plethysmography and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin (DLCOcorr)] were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after completion of treatment (ACT) were compared using exact Wilcoxon signed rank tests and repeated measures models. Results 303 eligible patients (spine dose: ≤ 2345 cGy- 201; > 2345 cGy-102; proton beam, 20) were enrolled between June 24, 2003 and March 1, 2010, 260 of whom had at least one PFT. The median age at diagnosis was 8.9 years (range, 3.1–20.4 years). The median thoracic spinal RT dose was 23.4 Gy (Inter Quartile Range (IQR), 23.4–36.0 Gy). The median cyclophosphamide dose was 16.0 g/m2 (IQR, 15.7–16.0 g/m2). 24 and 60 months ACT, DLCOcorr was <75% predicted in 23% (27/118) and 25% (21/84), FEV1 <80% predicted in 20% (34/170) and 29% (32/109), FVC < 80% predicted in 27% (46/172) and 28% (30/108) and TLC <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCOcorr was significantly decreased 24 (median difference (MD) in % predicted, − 3.00%; p=0.028) and 60 months ACT (MD in % predicted, − 6.00%; p=0.033) compared to the end of RT. These significant decreases in DLCOcorr were also observed in repeated measures models (p=0.011 and p=0.032 at 24 and 60 months ACT, respectively). Conclusions A significant minority of EBT survivors experience PFT deficits following CSI. Continued monitoring of this cohort is planned. PMID:26279023

  14. The GOA database: Gene Ontology annotation updates for 2015

    PubMed Central

    Huntley, Rachael P.; Sawford, Tony; Mutowo-Meullenet, Prudence; Shypitsyna, Aleksandra; Bonilla, Carlos; Martin, Maria J.; O'Donovan, Claire

    2015-01-01

    The Gene Ontology Annotation (GOA) resource (http://www.ebi.ac.uk/GOA) provides evidence-based Gene Ontology (GO) annotations to proteins in the UniProt Knowledgebase (UniProtKB). Manual annotations provided by UniProt curators are supplemented by manual and automatic annotations from model organism databases and specialist annotation groups. GOA currently supplies 368 million GO annotations to almost 54 million proteins in more than 480 000 taxonomic groups. The resource now provides annotations to five times the number of proteins it did 4 years ago. As a member of the GO Consortium, we adhere to the most up-to-date Consortium-agreed annotation guidelines via the use of quality control checks that ensures that the GOA resource supplies high-quality functional information to proteins from a wide range of species. Annotations from GOA are freely available and are accessible through a powerful web browser as well as a variety of annotation file formats. PMID:25378336

  15. Omics data management and annotation.

    PubMed

    Harel, Arye; Dalah, Irina; Pietrokovski, Shmuel; Safran, Marilyn; Lancet, Doron

    2011-01-01

    Technological Omics breakthroughs, including next generation sequencing, bring avalanches of data which need to undergo effective data management to ensure integrity, security, and maximal knowledge-gleaning. Data management system requirements include flexible input formats, diverse data entry mechanisms and views, user friendliness, attention to standards, hardware and software platform definition, as well as robustness. Relevant solutions elaborated by the scientific community include Laboratory Information Management Systems (LIMS) and standardization protocols facilitating data sharing and managing. In project planning, special consideration has to be made when choosing relevant Omics annotation sources, since many of them overlap and require sophisticated integration heuristics. The data modeling step defines and categorizes the data into objects (e.g., genes, articles, disorders) and creates an application flow. A data storage/warehouse mechanism must be selected, such as file-based systems and relational databases, the latter typically used for larger projects. Omics project life cycle considerations must include the definition and deployment of new versions, incorporating either full or partial updates. Finally, quality assurance (QA) procedures must validate data and feature integrity, as well as system performance expectations. We illustrate these data management principles with examples from the life cycle of the GeneCards Omics project (http://www.genecards.org), a comprehensive, widely used compendium of annotative information about human genes. For example, the GeneCards infrastructure has recently been changed from text files to a relational database, enabling better organization and views of the growing data. Omics data handling benefits from the wealth of Web-based information, the vast amount of public domain software, increasingly affordable hardware, and effective use of data management and annotation principles as outlined in this chapter.

  16. Definition and annotation of (myco)bacterial non-coding RNA.

    PubMed

    Lamichhane, Gyanu; Arnvig, Kristine B; McDonough, Kathleen A

    2013-01-01

    RNA in bacteria may be broadly classified into coding and non-coding types. The prior, also known as messenger RNA, encode proteins as their final product. The non-coding RNA include all RNAs that are not translated into a protein. Examples of extensively studied and therefore prominent non-coding RNAs include rRNA, tRNA, tmRNA, whose designations reflect the functions performed by these RNAs. Discoveries of non-coding RNAs in mycobacteria have been reported in the recent years. At this early stage of this discipline of mycobacterial research, there is an opportunity for the scientific community to establish a consistent, systematic and objective approach to annotation of these RNAs. We are providing recommendations for this systematic annotation that we hope will be adopted by the mycobacterial research community. These may also serve as templates for annotation of non-coding RNAs in other bacteria.

  17. The SeqFEATURE library of 3D functional site models: comparison to existing methods and applications to protein function annotation.

    PubMed

    Wu, Shirley; Liang, Mike P; Altman, Russ B

    2008-01-16

    Structural genomics efforts have led to increasing numbers of novel, uncharacterized protein structures with low sequence identity to known proteins, resulting in a growing need for structure-based function recognition tools. Our method, SeqFEATURE, robustly models protein functions described by sequence motifs using a structural representation. We built a library of models that shows good performance compared to other methods. In particular, SeqFEATURE demonstrates significant improvement over other methods when sequence and structural similarity are low.

  18. Modeling loosely annotated images using both given and imagined annotations

    NASA Astrophysics Data System (ADS)

    Tang, Hong; Boujemaa, Nozha; Chen, Yunhao; Deng, Lei

    2011-12-01

    In this paper, we present an approach to learn latent semantic analysis models from loosely annotated images for automatic image annotation and indexing. The given annotation in training images is loose due to: 1. ambiguous correspondences between visual features and annotated keywords; 2. incomplete lists of annotated keywords. The second reason motivates us to enrich the incomplete annotation in a simple way before learning a topic model. In particular, some ``imagined'' keywords are poured into the incomplete annotation through measuring similarity between keywords in terms of their co-occurrence. Then, both given and imagined annotations are employed to learn probabilistic topic models for automatically annotating new images. We conduct experiments on two image databases (i.e., Corel and ESP) coupled with their loose annotations, and compare the proposed method with state-of-the-art discrete annotation methods. The proposed method improves word-driven probability latent semantic analysis (PLSA-words) up to a comparable performance with the best discrete annotation method, while a merit of PLSA-words is still kept, i.e., a wider semantic range.

  19. svmPRAT: SVM-based Protein Residue Annotation Toolkit

    PubMed Central

    2009-01-01

    Background Over the last decade several prediction methods have been developed for determining the structural and functional properties of individual protein residues using sequence and sequence-derived information. Most of these methods are based on support vector machines as they provide accurate and generalizable prediction models. Results We present a general purpose protein residue annotation toolkit (svmPRAT) to allow biologists to formulate residue-wise prediction problems. svmPRAT formulates the annotation problem as a classification or regression problem using support vector machines. One of the key features of svmPRAT is its ease of use in incorporating any user-provided information in the form of feature matrices. For every residue svmPRAT captures local information around the reside to create fixed length feature vectors. svmPRAT implements accurate and fast kernel functions, and also introduces a flexible window-based encoding scheme that accurately captures signals and pattern for training effective predictive models. Conclusions In this work we evaluate svmPRAT on several classification and regression problems including disorder prediction, residue-wise contact order estimation, DNA-binding site prediction, and local structure alphabet prediction. svmPRAT has also been used for the development of state-of-the-art transmembrane helix prediction method called TOPTMH, and secondary structure prediction method called YASSPP. This toolkit developed provides practitioners an efficient and easy-to-use tool for a wide variety of annotation problems. Availability: http://www.cs.gmu.edu/~mlbio/svmprat PMID:20028521

  20. Annotated Bibliography. First Edition.

    ERIC Educational Resources Information Center

    Haring, Norris G.

    An annotated bibliography which presents approximately 300 references from 1951 to 1973 on the education of severely/profoundly handicapped persons. Citations are grouped alphabetically by author's name within the following categories: characteristics and treatment, gross motor development, sensory and motor development, physical therapy for the…

  1. Ghostwriting: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Simmons, Donald B.

    Drawn from communication journals, historical and news magazines, business and industrial magazines, political science and world affairs journals, general interest periodicals, and literary and political review magazines, the approximately 90 entries in this annotated bibliography discuss ghostwriting as practiced through the ages and reveal the…

  2. Automated Microbial Genome Annotation

    SciTech Connect

    Land, Miriam

    2009-05-29

    Miriam Land of the DOE Joint Genome Institute at Oak Ridge National Laboratory gives a talk on the current state and future challenges of moving toward automated microbial genome annotation at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

  3. Cheating. An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Wildemuth, Barbara M., Comp.

    This 89-item, annotated bibliography was compiled to provide access to research and discussions of cheating and, specifically, cheating on tests. It is not limited to any educational level, nor is it confined to any specific curriculum area. Two data bases were searched by computer, and a library search was conducted. A computer search of the…

  4. Fungal-specific subunits of the Candida albicans mitochondrial complex I drive diverse cell functions including cell wall synthesis.

    PubMed

    She, Xiaodong; Khamooshi, Kasra; Gao, Yin; Shen, Yongnian; Lv, Yuxia; Calderone, Richard; Fonzi, William; Liu, Weida; Li, Dongmei

    2015-09-01

    Our published research has focused on the role of Goa1p, an apparent regulator of the Candida albicans mitochondrial complex I (CI). Lack of Goa1p affects optimum cell growth, CI activity and virulence. Eukaryotic CI is composed of a core of 14 alpha-proteobacterial subunit proteins and a variable number of supernumerary subunit proteins. Of the latter group of proteins, one (NUZM) is fungal specific and the other (NUXM) is found in fungi, algae and plants, but is not a mammalian CI subunit protein. We have established that NUXM is orf19.6607 and NUZM is orf19.287 in C. albicans. Herein, we validate both subunit proteins as NADH:ubiquinone oxidoreductases (NUO) and annotate their gene functions. To accomplish these objectives, we compared null mutants of each with wild type (WT) and gene-reconstituted strains. Genetic mutants of genes NUO1 (orf19.6607) and NUO2 (orf19.287), not surprisingly, each had reduced oxygen consumption, decreased mitochondrial redox potential, decreased CI activity, increased reactive oxidant species (ROS) and decreased chronological ageing in vitro. Loss of either gene results in disassembly of CI. Transcriptional profiling of both mutants indicated significant down-regulation of genes of carbon metabolism, as well as up-regulation of mitochondrial-associated gene families that may occur to compensate for the loss of CI activity. Profiling of both mutants also demonstrated a loss of cell wall β-mannosylation but not in a conserved CI subunit (ndh51Δ). The profiling data may indicate specific functions driven by the enzymatic activity of Nuo1p and Nuo2p. Of importance, each mutant is also avirulent in a murine blood-borne, invasive model of candidiasis associated with their reduced colonization of tissues. Based on their fungal specificity and roles in virulence, we suggest both as drug targets for antifungal drug discovery.

  5. Fungal-specific subunits of the Candida albicans mitochondrial complex I drive diverse cell functions including cell wall synthesis

    PubMed Central

    She, Xiaodong; Khamooshi, Kasra; Gao, Yin; Shen, Yongnian; Lv, Yuxia; Calderone, Richard; Fonzi, William; Liu, Weida; Li, Dongmei

    2015-01-01

    Summary Our published research has focused upon the role of Goa1p, an apparent regulator of the Candida albicans mitochondrial complex I (CI). Lack of Goa1p effects optimum cell growth, CI activity, and virulence. Eukaryotic CI is composed of a core of 14 alpha-proteobacterial subunit proteins and a variable number of supernumerary subunit proteins. Of the latter group of proteins, one (NUZM) is fungal-specific, and a second (NUXM) is found in fungi, algae and plants but is not a mammalian CI subunit protein. We have established that NUXM is orf19.6607 and NUZM is orf19.287 in C. albicans. Herein, we validate both subunit proteins as NADH:ubiquinone oxidoreductases (NUO) and annotate their gene functions. To accomplish these objectives, we compared null mutants of each with WT and gene-reconstituted strains. Genetic mutants of genes NUO1 (19.6607) and NUO2 (19.287), not surprisingly, each had reduced oxygen consumption, decreased mitochondrial redox potential, decreased CI activity, increased reactive oxidant species (ROS), and a decrease in chronological aging in vitro. Loss of either gene results in a disassembly of CI. Transcriptional profiling of both mutants indicated significant down regulation of genes of carbon metabolism, as well as upregulation of mitochondrial-associated gene families which may occur to compensate for the loss of CI activity. Profiling of both mutants also demonstrated a loss of cell wall β-mannosylation but not in a conserved CI subunit (ndh51Δ). The profiling data may indicate specific functions driven by the enzymatic activity of Nuo1p and Nuo2p. Of importance, each mutant is also avirulent in a murine blood-borne, invasive model of candidiasis associated with their reduced colonization of tissues. Based upon their fungal-specificity and roles in virulence, we suggest both as drug targets for antifungal drug discovery. PMID:25801605

  6. ASGARD: an open-access database of annotated transcriptomes for emerging model arthropod species.

    PubMed

    Zeng, Victor; Extavour, Cassandra G

    2012-01-01

    The increased throughput and decreased cost of next-generation sequencing (NGS) have shifted the bottleneck genomic research from sequencing to annotation, analysis and accessibility. This is particularly challenging for research communities working on organisms that lack the basic infrastructure of a sequenced genome, or an efficient way to utilize whatever sequence data may be available. Here we present a new database, the Assembled Searchable Giant Arthropod Read Database (ASGARD). This database is a repository and search engine for transcriptomic data from arthropods that are of high interest to multiple research communities but currently lack sequenced genomes. We demonstrate the functionality and utility of ASGARD using de novo assembled transcriptomes from the milkweed bug Oncopeltus fasciatus, the cricket Gryllus bimaculatus and the amphipod crustacean Parhyale hawaiensis. We have annotated these transcriptomes to assign putative orthology, coding region determination, protein domain identification and Gene Ontology (GO) term annotation to all possible assembly products. ASGARD allows users to search all assemblies by orthology annotation, GO term annotation or Basic Local Alignment Search Tool. User-friendly features of ASGARD include search term auto-completion suggestions based on database content, the ability to download assembly product sequences in FASTA format, direct links to NCBI data for predicted orthologs and graphical representation of the location of protein domains and matches to similar sequences from the NCBI non-redundant database. ASGARD will be a useful repository for transcriptome data from future NGS studies on these and other emerging model arthropods, regardless of sequencing platform, assembly or annotation status. This database thus provides easy, one-stop access to multi-species annotated transcriptome information. We anticipate that this database will be useful for members of multiple research communities, including developmental

  7. Validating Annotations for Uncharacterized Proteins in Shewanella oneidensis

    PubMed Central

    Louie, Brenton; Tarczy-Hornoch, Peter; Higdon, Roger

    2008-01-01

    Abstract Proteins of unknown function are a barrier to our understanding of molecular biology. Assigning function to these “uncharacterized” proteins is imperative, but challenging. The usual approach is similarity searches using annotation databases, which are useful for predicting function. However, since the performance of these databases on uncharacterized proteins is basically unknown, the accuracy of their predictions is suspect, making annotation difficult. To address this challenge, we developed a benchmark annotation dataset of 30 proteins in Shewanella oneidensis. The proteins in the dataset were originally uncharacterized after the initial annotation of the S. oneidensis proteome in 2002. In the intervening 5 years, the accumulation of new experimental evidence has enabled specific functions to be predicted. We utilized this benchmark dataset to evaluate several commonly utilized annotation databases. According to our criteria, six annotation databases accurately predicted functions for at least 60% of proteins in our dataset. Two of these six even had a “conditional accuracy” of 90%. Conditional accuracy is another evaluation metric we developed which excludes results from databases where no function was predicted. Also, 27 of the 30 proteins' functions were correctly predicted by at least one database. These represent one of the first performance evaluations of annotation databases on uncharacterized proteins. Our evaluation indicates that these databases readily incorporate new information and are accurate in predicting functions for uncharacterized proteins, provided that experimental function evidence exists. PMID:18687039

  8. VariantAnnotation: a Bioconductor package for exploration and annotation of genetic variants

    PubMed Central

    Obenchain, Valerie; Lawrence, Michael; Carey, Vincent; Gogarten, Stephanie; Shannon, Paul; Morgan, Martin

    2014-01-01

    Summary: VariantAnnotation is an R / Bioconductor package for the exploration and annotation of genetic variants. Capabilities exist for reading, writing and filtering variant call format (VCF) files. VariantAnnotation allows ready access to additional R / Bioconductor facilities for advanced statistical analysis, data transformation, visualization and integration with diverse genomic resources. Availability and implementation: This package is implemented in R and available for download at the Bioconductor Web site (http://bioconductor.org/packages/2.13/bioc/html/VariantAnnotation.html). The package contains extensive help pages for individual functions and a ‘vignette’ outlining typical work flows; it is made available under the open source ‘Artistic-2.0’ license. Version 1.9.38 was used in this article. Contact: vobencha@fhcrc.org PMID:24681907

  9. RNA-Seq of Guar (Cyamopsis tetragonoloba, L. Taub.) Leaves: De novo Transcriptome Assembly, Functional Annotation and Development of Genomic Resources

    PubMed Central

    Tanwar, Umesh K.; Pruthi, Vikas; Randhawa, Gursharn S.

    2017-01-01

    Genetic improvement in industrially important guar (Cyamopsis tetragonoloba, L. Taub.) crop has been hindered due to the lack of sufficient genomic or transcriptomic resources. In this study, RNA-Seq technology was employed to characterize the transcriptome of leaf tissues from two guar varieties, namely, M-83 and RGC-1066. Approximately 30 million high-quality pair-end reads of each variety generated by Illumina HiSeq platform were used for de novo assembly by Trinity program. A total of 62,146 non-redundant unigenes with an average length of 679 bp were obtained. The quality assessment of assembled unigenes revealed 87.50% of complete and 97.18% partial core eukaryotic genes (CEGs). Sequence similarity analyses and annotation of the unigenes against non-redundant protein (Nr) and Gene Ontology (GO) databases identified 175,882 GO annotations. A total of 11,308 guar unigenes were annotated with various enzyme codes (EC) and categorized in six categories with 55 subclasses. The annotation of biochemical pathways resulted in a total of 11,971 unigenes assigned with 145 KEGG maps and 1759 enzyme codes. The species distribution analysis of the unigenes showed highest similarity with Glycine max genes. A total of 5773 potential simple sequence repeats (SSRs) and 3594 high-quality single nucleotide polymorphisms (SNPs) were identified. Out of 20 randomly selected SSRs for wet laboratory validation, 13 showed consistent PCR amplification in both guar varieties. In silico studies identified 145 polymorphic SSR markers in two varieties. To the best of our knowledge, this is the first report on transcriptome analysis and SNPs identification in guar till date. PMID:28210265

  10. Computer Applications in Marketing. An Annotated Bibliography of Computer Software.

    ERIC Educational Resources Information Center

    Burrow, Jim; Schwamman, Faye

    This bibliography contains annotations of 95 items of educational and business software with applications in seven marketing and business functions. The annotations, which appear in alphabetical order by title, provide this information: category (related application), title, date, source and price, equipment, supplementary materials, description…

  11. Maize - GO annotation methods, evaluation, and review (Maize-GAMER)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Making a genome sequence accessible and useful involves three basic steps: genome assembly, structural annotation, and functional annotation. The quality of data generated at each step influences the accuracy of inferences that can be made, with high-quality analyses produce better datasets resultin...

  12. Case Studies in Reading: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Trela, Thaddeus M., Comp.; Becker, George J., Comp.

    Descriptions of individual diagnosis and remediation of reading problems experienced by students at all levels are included in this annotated bibliography. Included are books, texts having case study sections, and journal reports which together comprise useful sources of case studies of reading disabilities. An opening section lists nine "first…

  13. Greeks in Canada (an Annotated Bibliography).

    ERIC Educational Resources Information Center

    Bombas, Leonidas C.

    This bibliography on Greeks in Canada includes annotated references to both published and (mostly) unpublished works. Among the 70 entries (arranged in alphabetical order by author) are articles, reports, papers, and theses that deal either exclusively with or include a separate section on Greeks in the various Canadian provinces. (GC)

  14. FIGENIX: Intelligent automation of genomic annotation: expertise integration in a new software platform

    PubMed Central

    Gouret, Philippe; Vitiello, Vérane; Balandraud, Nathalie; Gilles, André; Pontarotti, Pierre; Danchin, Etienne GJ

    2005-01-01

    Background Two of the main objectives of the genomic and post-genomic era are to structurally and functionally annotate genomes which consists of detecting genes' position and structure, and inferring their function (as well as of other features of genomes). Structural and functional annotation both require the complex chaining of numerous different software, algorithms and methods under the supervision of a biologist. The automation of these pipelines is necessary to manage huge amounts of data released by sequencing projects. Several pipelines already automate some of these complex chaining but still necessitate an important contribution of biologists for supervising and controlling the results at various steps. Results Here we propose an innovative automated platform, FIGENIX, which includes an expert system capable to substitute to human expertise at several key steps. FIGENIX currently automates complex pipelines of structural and functional annotation under the supervision of the expert system (which allows for example to make key decisions, check intermediate results or refine the dataset). The quality of the results produced by FIGENIX is comparable to those obtained by expert biologists with a drastic gain in terms of time costs and avoidance of errors due to the human manipulation of data. Conclusion The core engine and expert system of the FIGENIX platform currently handle complex annotation processes of broad interest for the genomic community. They could be easily adapted to new, or more specialized pipelines, such as for example the annotation of miRNAs, the classification of complex multigenic families, annotation of regulatory elements and other genomic features of interest. PMID:16083500

  15. IFA - INTELLIGENT FRONT ANNOTATION PROGRAM

    NASA Technical Reports Server (NTRS)

    Burke, G. R.

    1994-01-01

    An important aspect of an ASIC (Application Specific Integrated Circuit) design process is verification. The design must not only be functionally accurate, but it must also maintain the correct timing. After a circuit has been laid out, one can utilize the Back Annotation (BA) method to simulate the design and obtain an accurate estimate of performance. However, this can lead to major design changes. It is therefore preferable to eliminate potential problems early in this process. IFA, the Intelligent Front Annotation program, assists in verifying the timing of the ASIC early in the design process. Many difficulties can arise during ASIC design. In a synchronous design, both long path and short path problems can be present. In modern ASIC technologies, the delay through a gate is very dependent on loading. This loading has two main components, the capacitance of the gates being driven and the capacitance of the metal tracks (wires). When using GaAs gate arrays, the metal line capacitance is often the dominating factor. Additionally, the RC delay through the wire itself is significant in sub-micron technologies. Since the wire lengths are unknown before place and route of the entire chip, this would seem to postpone any realistic timing verification until towards the end of the design process, obviously an undesirable situation. The IFA program estimates the delays in an ASIC before layout. Currently the program is designed for Vitesse GaAs gate arrays and, for input, requires the expansion file which is output by the program GED; however, the algorithm is appropriate for many different ASIC types and CAE platforms. IFA is especially useful for devices whose delay is extremely dependent on the interconnection wiring. It estimates the length of the interconnects using information supplied by the user and information in the netlist. The resulting wire lengths are also used to constrain the Place and Route program, ensuring reasonable results. IFA takes locality into

  16. MPEG-7 based video annotation and browsing

    NASA Astrophysics Data System (ADS)

    Hoeynck, Michael; Auweiler, Thorsten; Wellhausen, Jens

    2003-11-01

    The huge amount of multimedia data produced worldwide requires annotation in order to enable universal content access and to provide content-based search-and-retrieval functionalities. Since manual video annotation can be time consuming, automatic annotation systems are required. We review recent approaches to content-based indexing and annotation of videos for different kind of sports and describe our approach to automatic annotation of equestrian sports videos. We especially concentrate on MPEG-7 based feature extraction and content description, where we apply different visual descriptors for cut detection. Further, we extract the temporal positions of single obstacles on the course by analyzing MPEG-7 edge information. Having determined single shot positions as well as the visual highlights, the information is jointly stored with meta-textual information in an MPEG-7 description scheme. Based on this information, we generate content summaries which can be utilized in a user-interface in order to provide content-based access to the video stream, but further for media browsing on a streaming server.

  17. Gene and alternative splicing annotation with AIR

    PubMed Central

    Florea, Liliana; Di Francesco, Valentina; Miller, Jason; Turner, Russell; Yao, Alison; Harris, Michael; Walenz, Brian; Mobarry, Clark; Merkulov, Gennady V.; Charlab, Rosane; Dew, Ian; Deng, Zuoming; Istrail, Sorin; Li, Peter; Sutton, Granger

    2005-01-01

    Designing effective and accurate tools for identifying the functional and structural elements in a genome remains at the frontier of genome annotation owing to incompleteness and inaccuracy of the data, limitations in the computational models, and shifting paradigms in genomics, such as alternative splicing. We present a methodology for the automated annotation of genes and their alternatively spliced mRNA transcripts based on existing cDNA and protein sequence evidence from the same species or projected from a related species using syntenic mapping information. At the core of the method is the splice graph, a compact representation of a gene, its exons, introns, and alternatively spliced isoforms. The putative transcripts are enumerated from the graph and assigned confidence scores based on the strength of sequence evidence, and a subset of the high-scoring candidates are selected and promoted into the annotation. The method is highly selective, eliminating the unlikely candidates while retaining 98% of the high-quality mRNA evidence in well-formed transcripts, and produces annotation that is measurably more accurate than some evidence-based gene sets. The process is fast, accurate, and fully automated, and combines the traditionally distinct gene annotation and alternative splicing detection processes in a comprehensive and systematic way, thus considerably aiding in the ensuing manual curation efforts. PMID:15632090

  18. Apollo: a sequence annotation editor.

    PubMed

    Lewis, S E; Searle, S M J; Harris, N; Gibson, M; Lyer, V; Richter, J; Wiel, C; Bayraktaroglu, L; Birney, E; Crosby, M A; Kaminker, J S; Matthews, B B; Prochnik, S E; Smithy, C D; Tupy, J L; Rubin, G M; Misra, S; Mungall, C J; Clamp, M E

    2002-01-01

    The well-established inaccuracy of purely computational methods for annotating genome sequences necessitates an interactive tool to allow biological experts to refine these approximations by viewing and independently evaluating the data supporting each annotation. Apollo was developed to meet this need, enabling curators to inspect genome annotations closely and edit them. FlyBase biologists successfully used Apollo to annotate the Drosophila melanogaster genome and it is increasingly being used as a starting point for the development of customized annotation editing tools for other genome projects.

  19. Dynamical Density Functional Theory for Orientable Colloids Including Inertia and Hydrodynamic Interactions

    NASA Astrophysics Data System (ADS)

    Durán-Olivencia, Miguel A.; Goddard, Benjamin D.; Kalliadasis, Serafim

    2016-08-01

    Over the last few decades, classical density-functional theory (DFT) and its dynamic extensions (DDFTs) have become powerful tools in the study of colloidal fluids. Recently, previous DDFTs for spherically-symmetric particles have been generalised to take into account both inertia and hydrodynamic interactions, two effects which strongly influence non-equilibrium properties. The present work further generalises this framework to systems of anisotropic particles. Starting from the Liouville equation and utilising Zwanzig's projection-operator techniques, we derive the kinetic equation for the Brownian particle distribution function, and by averaging over all but one particle, a DDFT equation is obtained. Whilst this equation has some similarities with DDFTs for spherically-symmetric colloids, it involves a translational-rotational coupling which affects the diffusivity of the (asymmetric) particles. We further show that, in the overdamped (high friction) limit, the DDFT is considerably simplified and is in agreement with a previous DDFT for colloids with arbitrary-shape particles.

  20. Semantator: semantic annotator for converting biomedical text to linked data.

    PubMed

    Tao, Cui; Song, Dezhao; Sharma, Deepak; Chute, Christopher G

    2013-10-01

    More than 80% of biomedical data is embedded in plain text. The unstructured nature of these text-based documents makes it challenging to easily browse and query the data of interest in them. One approach to facilitate browsing and querying biomedical text is to convert the plain text to a linked web of data, i.e., converting data originally in free text to structured formats with defined meta-level semantics. In this paper, we introduce Semantator (Semantic Annotator), a semantic-web-based environment for annotating data of interest in biomedical documents, browsing and querying the annotated data, and interactively refining annotation results if needed. Through Semantator, information of interest can be either annotated manually or semi-automatically using plug-in information extraction tools. The annotated results will be stored in RDF and can be queried using the SPARQL query language. In addition, semantic reasoners can be directly applied to the annotated data for consistency checking and knowledge inference. Semantator has been released online and was used by the biomedical ontology community who provided positive feedbacks. Our evaluation results indicated that (1) Semantator can perform the annotation functionalities as designed; (2) Semantator can be adopted in real applications in clinical and transactional research; and (3) the annotated results using Semantator can be easily used in Semantic-web-based reasoning tools for further inference.

  1. DAnCER: disease-annotated chromatin epigenetics resource.

    PubMed

    Turinsky, Andrei L; Turner, Brian; Borja, Rosanne C; Gleeson, James A; Heath, Michael; Pu, Shuye; Switzer, Thomas; Dong, Dong; Gong, Yunchen; On, Tuan; Xiong, Xuejian; Emili, Andrew; Greenblatt, Jack; Parkinson, John; Zhang, Zhaolei; Wodak, Shoshana J

    2011-01-01

    Chromatin modification (CM) is a set of epigenetic processes that govern many aspects of DNA replication, transcription and repair. CM is carried out by groups of physically interacting proteins, and their disruption has been linked to a number of complex human diseases. CM remains largely unexplored, however, especially in higher eukaryotes such as human. Here we present the DAnCER resource, which integrates information on genes with CM function from five model organisms, including human. Currently integrated are gene functional annotations, Pfam domain architecture, protein interaction networks and associated human diseases. Additional supporting evidence includes orthology relationships across organisms, membership in protein complexes, and information on protein 3D structure. These data are available for 962 experimentally confirmed and manually curated CM genes and for over 5000 genes with predicted CM function on the basis of orthology and domain composition. DAnCER allows visual explorations of the integrated data and flexible query capabilities using a variety of data filters. In particular, disease information and functional annotations are mapped onto the protein interaction networks, enabling the user to formulate new hypotheses on the function and disease associations of a given gene based on those of its interaction partners. DAnCER is freely available at http://wodaklab.org/dancer/.

  2. A Factor Graph Approach to Automated GO Annotation

    PubMed Central

    Spetale, Flavio E.; Tapia, Elizabeth; Krsticevic, Flavia; Roda, Fernando; Bulacio, Pilar

    2016-01-01

    As volume of genomic data grows, computational methods become essential for providing a first glimpse onto gene annotations. Automated Gene Ontology (GO) annotation methods based on hierarchical ensemble classification techniques are particularly interesting when interpretability of annotation results is a main concern. In these methods, raw GO-term predictions computed by base binary classifiers are leveraged by checking the consistency of predefined GO relationships. Both formal leveraging strategies, with main focus on annotation precision, and heuristic alternatives, with main focus on scalability issues, have been described in literature. In this contribution, a factor graph approach to the hierarchical ensemble formulation of the automated GO annotation problem is presented. In this formal framework, a core factor graph is first built based on the GO structure and then enriched to take into account the noisy nature of GO-term predictions. Hence, starting from raw GO-term predictions, an iterative message passing algorithm between nodes of the factor graph is used to compute marginal probabilities of target GO-terms. Evaluations on Saccharomyces cerevisiae, Arabidopsis thaliana and Drosophila melanogaster protein sequences from the GO Molecular Function domain showed significant improvements over competing approaches, even when protein sequences were naively characterized by their physicochemical and secondary structure properties or when loose noisy annotation datasets were considered. Based on these promising results and using Arabidopsis thaliana annotation data, we extend our approach to the identification of most promising molecular function annotations for a set of proteins of unknown function in Solanum lycopersicum. PMID:26771463

  3. A Factor Graph Approach to Automated GO Annotation.

    PubMed

    Spetale, Flavio E; Tapia, Elizabeth; Krsticevic, Flavia; Roda, Fernando; Bulacio, Pilar

    2016-01-01

    As volume of genomic data grows, computational methods become essential for providing a first glimpse onto gene annotations. Automated Gene Ontology (GO) annotation methods based on hierarchical ensemble classification techniques are particularly interesting when interpretability of annotation results is a main concern. In these methods, raw GO-term predictions computed by base binary classifiers are leveraged by checking the consistency of predefined GO relationships. Both formal leveraging strategies, with main focus on annotation precision, and heuristic alternatives, with main focus on scalability issues, have been described in literature. In this contribution, a factor graph approach to the hierarchical ensemble formulation of the automated GO annotation problem is presented. In this formal framework, a core factor graph is first built based on the GO structure and then enriched to take into account the noisy nature of GO-term predictions. Hence, starting from raw GO-term predictions, an iterative message passing algorithm between nodes of the factor graph is used to compute marginal probabilities of target GO-terms. Evaluations on Saccharomyces cerevisiae, Arabidopsis thaliana and Drosophila melanogaster protein sequences from the GO Molecular Function domain showed significant improvements over competing approaches, even when protein sequences were naively characterized by their physicochemical and secondary structure properties or when loose noisy annotation datasets were considered. Based on these promising results and using Arabidopsis thaliana annotation data, we extend our approach to the identification of most promising molecular function annotations for a set of proteins of unknown function in Solanum lycopersicum.

  4. Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

    PubMed

    Veit, Guido; Avramescu, Radu G; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E; Hegedus, Tamas; Verkman, Alan S; Lukacs, Gergely L

    2014-07-23

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF.

  5. Dynamical density functional theory for arbitrary-shape colloidal fluids including inertia and hydrodynamic interactions

    NASA Astrophysics Data System (ADS)

    Duran-Olivencia, Miguel A.; Goddard, Ben; Kalliadasis, Serafim

    2015-11-01

    Over the last few decades the classical density-functional theory (DFT) and its dynamic extensions (DDFTs) have become a remarkably powerful tool in the study of colloidal fluids. Recently there has been extensive research to generalise all previous DDFTs finally yielding a general DDFT equation (for spherical particles) which takes into account both inertia and hydrodynamic interactions (HI) which strongly influence non-equilibrium properties. The present work will be devoted to a further generalisation of such a framework to systems of anisotropic particles. To this end, the kinetic equation for the Brownian particle distribution function is derived starting from the Liouville equation and making use of Zwanzig's projection-operator techniques. By averaging over all but one particle, a DDFT equation is finally obtained with some similarities to that for spherical colloids. However, there is now an inevitable translational-rotational coupling which affects the diffusivity of asymmetric particles. Lastly, in the overdamped (high friction) limit the theory is notably simplified leading to a DDFT equation which agrees with previous derivations. We acknowledge financial support from European Research Council via Advanced Grant No. 247031.

  6. An Annotated Bibliography of Children's Books with Cajun Themes.

    ERIC Educational Resources Information Center

    Webre, Elizabeth C.

    This annotated bibliography of 45 children's books with Cajun themes includes books using Cajun dialect and common French phrases, books revealing the importance of the family unit and the "joie de vivre" associated with the Cajun culture, and books recording the regional Cajun folklore. Each annotation consists of author, title,…

  7. Orienteering: An Annotated Bibliography = Orientierungslauf: Eine kommentierte Bibliographie.

    ERIC Educational Resources Information Center

    Seiler, Roland, Ed.; Hartmann, Wolfgang, Ed.

    1994-01-01

    Annotated bibliography of 220 books, monographs, and journal articles on orienteering published 1984-94, from SPOLIT database of the Federal Institute of Sport Science (Cologne, Germany). Annotations in English or German. Ten sections including psychological, physiological, health, sociological, and environmental aspects; training and coaching;…

  8. Mastery Learning and Mastery Testing: An Annotated ERIC Bibliography.

    ERIC Educational Resources Information Center

    Wildemuth, Barbara M., Comp.

    This 136-item annotated bibliography on mastery learning and mastery testing is the result of a computer search of the ERIC data base in February 1977. All entries are listed alphabetically by author. An abstract or annotation is provided for each entry. A subject index is included reflecting the major emphasis of each citation. (RC)

  9. Materials for Teaching Adult Functional Literacy in North Dakota; Annotated Bibliography. Occupational Knowledge, Community Resources, Government and Law, Consumer Economics, Health.

    ERIC Educational Resources Information Center

    Korpi, Barbara, Comp.

    This biliography is intended to help educators locate materials, ideas, and methods which will enable adults to become more functionally literate. Readability levels are provided for many items. The bibliography is divided into six sections. The first section lists materials for the professional educator, including resources, staff development…

  10. Annotated Expressed Sequence Tags (ESTs) from pre-smolt Atlantic salmon (Salmo salar) in a searchable data resource

    PubMed Central

    Adzhubei, Alexei A; Vlasova, Anna V; Hagen-Larsen, Heidi; Ruden, Torgeir A; Laerdahl, Jon K; Høyheim, Bjørn

    2007-01-01

    including searches on function assignments and Gene Ontology terms. Data delivery options include summaries for the datasets and their annotations, detailed self-explanatory annotations, and access to the original BLAST results and Gene Ontology annotation trees. Potential presence of a relatively high number of immune-related genes in the dataset was shown by annotation searches. PMID:17605782

  11. Green’s function molecular dynamics: including finite heights, shear, and body fields

    NASA Astrophysics Data System (ADS)

    Venugopalan, Syam P.; Nicola, Lucia; Müser, Martin H.

    2017-04-01

    The Green’s function molecular dynamics (GFMD) method for the simulation of incompressible solids under normal loading is extended in several ways: shear is added to the GFMD continuum formulation and Poisson numbers as well as the heights of the deformed body can now be chosen at will. In addition, we give the full stress tensor inside the deformed body. We validate our generalizations by comparing our analytical and GFMD results to calculations based on the finite-element method (FEM) and full molecular dynamics simulations. For the investigated systems we observe a significant speed-up of GFMD compared to FEM. While calculation and proof of concept were conducted in two-dimensions only, the methodology can be extended to the three-dimensional case in a straightforward fashion.

  12. Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium

    PubMed Central

    2011-01-01

    Background Complete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. However, determining protein-coding genes for most new genomes is almost completely performed by inference using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function. Results We experimentally annotated the bacterial pathogen Salmonella Typhimurium 14028, using "shotgun" proteomics to accurately uncover the translational landscape and post-translational features. The data provide protein-level experimental validation for approximately half of the predicted protein-coding genes in Salmonella and suggest revisions to several genes that appear to have incorrectly assigned translational start sites, including a potential novel alternate start codon. Additionally, we uncovered 12 non-annotated genes missed by gene prediction programs, as well as evidence suggesting a role for one of these novel ORFs in Salmonella pathogenesis. We also characterized post-translational features in the Salmonella genome, including chemical modifications and proteolytic cleavages. We find that bacteria have a much larger and more complex repertoire of chemical modifications than previously thought including several novel modifications. Our in vivo proteolysis data identified more than 130 signal peptide and N-terminal methionine cleavage events critical for protein function. Conclusion This work highlights several ways in which application of proteomics data can improve the quality of genome annotations to facilitate novel biological insights and provides a comprehensive proteome map of Salmonella as a resource for systems analysis. PMID:21867535

  13. Evaluating techniques for metagenome annotation using simulated sequence data

    PubMed Central

    Randle-Boggis, Richard J.; Helgason, Thorunn; Sapp, Melanie; Ashton, Peter D.

    2016-01-01

    The advent of next-generation sequencing has allowed huge amounts of DNA sequence data to be produced, advancing the capabilities of microbial ecosystem studies. The current challenge is to identify from which microorganisms and genes the DNA originated. Several tools and databases are available for annotating DNA sequences. The tools, databases and parameters used can have a significant impact on the results: naïve choice of these factors can result in a false representation of community composition and function. We use a simulated metagenome to show how different parameters affect annotation accuracy by evaluating the sequence annotation performances of MEGAN, MG-RAST, One Codex and Megablast. This simulated metagenome allowed the recovery of known organism and function abundances to be quantitatively evaluated, which is not possible for environmental metagenomes. The performance of each program and database varied, e.g. One Codex correctly annotated many sequences at the genus level, whereas MG-RAST RefSeq produced many false positive annotations. This effect decreased as the taxonomic level investigated increased. Selecting more stringent parameters decreases the annotation sensitivity, but increases precision. Ultimately, there is a trade-off between taxonomic resolution and annotation accuracy. These results should be considered when annotating metagenomes and interpreting results from previous studies. PMID:27162180

  14. How close can we get waves to wave functions, including potential?

    NASA Astrophysics Data System (ADS)

    Faletič, Sergej

    2016-05-01

    In the following article we show that mechanical waves on a braced string can have the same shapes as important wave functions in introductory quantum mechanics. A braced string is a string with additional transversal springs that serve as external "potential". The aim is not to suggest teaching quantum mechanics with these analogies. Instead, the aim is to provide students with some additional relevant experience in wave mechanics before they are introduced to quantum mechanics. We show how this experience can be used in a constructivist sense as the basis for building quantum concepts. We consider energy transfer along such string and show that penetration of a wave into a region with high "potential" is not unexpected. We also consider energy transfer between two such strings and show that it can appear point-like even though the wave is an extended object. We also suggest that applying quantization of energy transfer to wave phenomena can explain some of the more difficult to accept features of quantum mechanics.

  15. Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice

    PubMed Central

    Weisberg, S; Leibel, R; Tortoriello, D V

    2016-01-01

    Background: Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Leprdb/db on the Kaliss background). Results: In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity. Conclusions: These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance. PMID:27110686

  16. Functional Investigation of Iron-Responsive Microsomal Proteins, including MirC, in Aspergillus fumigatus

    PubMed Central

    Mulvihill, Eoin D.; Moloney, Nicola M.; Owens, Rebecca A.; Dolan, Stephen K.; Russell, Lauren; Doyle, Sean

    2017-01-01

    The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system. FC levels were unaffected following deletion of all other genes encoding microsome-associated proteins. MirC does not appear to play a role in either siderophore export from, or uptake into, A. fumigatus. Label-free quantitative proteomic analysis unexpectedly revealed increased abundance of siderophore biosynthetic enzymes. In addition, increased expression of hapX (7.2 and 13.8-fold at 48 and 72 h, respectively; p < 0.001) was observed in ΔmirC compared to wild-type under iron-replete conditions by qRT-PCR. This was complemented by significantly elevated extracellular triacetylfusarinine C (TAFC; p < 0.01) and fusarinine C (FSC; p < 0.05) siderophore secretion. We conclude that MirC plays an important role in FC biosynthesis and contributes to the maintenance of iron homeostasis in A. fumigatus. PMID:28367141

  17. Review of literature on herbicides, including phenoxy herbicides and associated dioxins. Volume 13: Analysis of recent literature on health effects and Volume 14: Annotated bibliography of recent literature on health effects

    SciTech Connect

    Not Available

    1989-06-15

    The report consists of a bibliography and critical review of scientific literature that became available during 1988 on the health effects of the herbicides (including impurities) used as defoliants in the Vietnam conflict. An attempt has been made to identify all scientific literature (including unpublished reports) relevant to the potential human health effects of the herbicidal preparation commonly referred to as Agent Orange, the herbicidal active ingredients 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichloroacetic acid and their esters, as well as polychlorinated dibenzo-p-dioxin, henceforth referred to as TCDD, known to be contaminating impurities of some phenoxy herbicide preparations, an the herbicides, picloram and cacodylic acid. The scope of the review does not include literature dealing exclusively with the chemistry, analysis, or environmental fate and effects of these compounds.

  18. GRAIL and GenQuest Sequence Annotation Tools

    SciTech Connect

    Xu, Ying; Shah, Manesh B.; Einstein, J. Ralph; Parang, Morey; Snoddy, Jay; Petrov, Sergey; Olman, Victor; Zhang, Ge; Mural, Richard J.; Uberbacher, Edward C.

    1997-12-31

    Our goal is to develop and implement an integrated intelligent system which can recognize biologically significant features in DNA sequence and provide insight into the organization and function of regions of genomic DNA. GRAIL is a modular expert system which facilitates the recognition of gene features and provides an environment for the construction of sequence annotation. The last several years have seen a rapid evolution of the technology for analyzing genomic DNA sequences. The current GRAIL systems (including the e-mail, XGRAIL, JAVA-GRAIL and genQuest systems) are perhaps the most widely used, comprehensive, and user friendly systems available for computational characterization of genomic DNA sequence.

  19. Broken symmetry approach to density functional calculation of zero field splittings including anisotropic exchange interactions

    SciTech Connect

    Kessler, Eva M. V.; Schmitt, Sebastian; Wüllen, Christoph van

    2013-11-14

    The broken symmetry approach to the calculation of zero field splittings (or magnetic anisotropies) of multinuclear transition metal complexes is further developed. A procedure is suggested how to extract spin Hamiltonian parameters for anisotropic exchange from a set of broken symmetry density functional calculations. For isotropic exchange coupling constants J{sub ij}, the established procedure is retrieved, and anisotropic (or pseudodipolar) exchange coupling tensors D{sub ij} are obtained analogously. This procedure only yields the sum of the individual single-ion zero field splitting tensors D{sub i}. Therefore, a procedure based on localized orbitals has been developed to extract the individual single-ion contributions. With spin Hamiltonian parameters at hand, the zero field splittings of the individual spin multiplets are calculated by an exact diagonalization of the isotropic part, followed by a spin projection done numerically. The method is applied to the binuclear cation [LCr(OH){sub 3}CrL]{sup 3+} (L = 1,4,7-trimethyl-1,4,7-triazanonane) for which experimental zero field splittings for all low-energy spin states are known, and to the single-molecule magnet [Fe{sub 4}(CH{sub 3}C(CH{sub 2}O){sub 3}){sub 2}(dpm){sub 6}] (Hdpm = 2,2,6,6-tetramethylheptane-3,5-dione). In both these 3d compounds, the single-ion tensors mainly come from the spin-orbit interaction. Anisotropic exchange is dominated by the spin-dipolar interaction only for the chromium compound. Despite the rather small isotropic exchange couplings in the iron compound, spin-orbit and spin-dipolar contributions to anisotropic exchange are of similar size here.

  20. The Mentally Retarded Offender: Annotated Bibliography.

    ERIC Educational Resources Information Center

    Schilit, Jeffrey; And Others

    An annotated bibliography of approximately 150 books and articles on the mentally retarded offender as well as 30 nonannotated entries are provided. Topics covered include such areas as characteristics of mentally retarded delinquents, rehabilitation of the retarded offender, community services for retarded persons, rights of the mentally…

  1. College Students in Transition: An Annotated Bibliography

    ERIC Educational Resources Information Center

    Foote, Stephanie M., Ed.; Hinkle, Sara M., Ed.; Kranzow, Jeannine, Ed.; Pistilli, Matthew D., Ed.; Miles, LaTonya Rease, Ed.; Simmons, Jannell G., Ed.

    2013-01-01

    The transition from high school to college is an important milestone, but it is only one of many steps in the journey through higher education. This volume is an annotated bibliography of the emerging literature examining the many other transitions students make beyond the first year, including the sophomore year, the transfer experience, and the…

  2. Sexually Transmitted Diseases: A Selective, Annotated Bibliography.

    ERIC Educational Resources Information Center

    Planned Parenthood Federation of America, Inc., New York, NY. Education Dept.

    This document contains a reference sheet and an annotated bibliography concerned with sexually transmitted diseases (STD). The reference sheet provides a brief, accurate overview of STDs which includes both statistical and background information. The bibliography contains 83 entries, listed alphabetically, that deal with STDs. Books and articles…

  3. Teaching Creative Writing: A Selective, Annotated Bibliography.

    ERIC Educational Resources Information Center

    Bishop, Wendy; And Others

    Focusing on pedagogical issues in creative writing, this annotated bibliography reviews 149 books, articles, and dissertations in the fields of creative writing and composition, and, selectively, feminist and literary theory. Anthologies of original writing and reference books are not included. (MM)

  4. People: Annotated Multiethnic Bibliography K-12.

    ERIC Educational Resources Information Center

    Gilmore, Dolores D., Comp.; Petrie, Kenneth, Comp.

    This annotated bibliography has been compiled to assist personnel in the selection of multiethnic media for schools. The bibliography includes sections entitled "Asian Americans,""Jewish Americans,""Mexican Americans,""Native Americans,""Puerto Rican Americans,""Other Hyphenated Americans," and "All Americans (Multiethnic)." The entries for the…

  5. Document Delivery: An Annotated Selective Bibliography.

    ERIC Educational Resources Information Center

    Khalil, Mounir A.; Katz, Suzanne R.

    1992-01-01

    Presents a selective annotated bibliography of 61 items that deal with topics related to document delivery, including networks; hypertext; interlibrary loan; computer security; electronic publishing; copyright; online catalogs; resource sharing; electronic mail; electronic libraries; optical character recognition; microcomputers; liability issues;…

  6. Parenting: An Annotated Bibliography, 1965-1987.

    ERIC Educational Resources Information Center

    Feinberg, Sandra; And Others

    This annotated bibliography on parenting resources is designed to assist parents and those who work with them to locate books on the many and complex topics that affect family life. The materials included encompass the various stages of parenting, from pregnancy and childbirth through the parenting of adult children. The many topics covered…

  7. Environment and the Community: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Department of Housing and Urban Development, Washington, DC.

    Three hundred and nine citations of books, reports, and articles dating from 1964 to 1971 are included in this annotated bibliography, intended as a selection tool for concerned citizens, architects, builders, and city planners emphasizing the environment of American cities and communities. It is topically arranged into sixteen broad sections with…

  8. Teleconferencing, an annotated bibliography, volume 3

    NASA Technical Reports Server (NTRS)

    Shervis, K.

    1971-01-01

    In this annotated and indexed listing of works on teleconferencing, emphasis has been placed upon teleconferencing as real-time, two way audio communication with or without visual aids. However, works on the use of television in two-way or multiway nets, data transmission, regional communications networks and on telecommunications in general are also included.

  9. Revenue Producing Athletes: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Ervin, Leroy; And Others

    An annotated bibliography on revenue producing sports is presented, with attention to: Proposition 48, exploitation of athletes, legal proceedings, research related to athletes and academic performance, psychological characteristics of athletes, and counseling programs for athletes. Introductions to each of the six topics are included. The section…

  10. Annotated bibliography of psychomotor testing. Technical report

    SciTech Connect

    Ervin, C.

    1987-03-01

    An annotated bibliography of 67 publications in the field of psychomotor testing has been prepared. The collection includes technical reports, journal articles, presented at scientific meetings, books and conference proceedings. The publications were assembled as preliminary work in the development of a dexterity test battery designed to measure the effects of chemical-defense-treatment drugs.

  11. A Semi-Annotated Bibliography: The Wabanakis.

    ERIC Educational Resources Information Center

    Braber, Lee; Dean, Jacquelyn M.

    A companion to the booklet, "A Teacher Manual on Native Americans: The Wabanakis," the semi-annotated bibliography consisting of 235 citations may be used by people who wish to have access to information and research (1890-1982) done about the tribes on the New England and Maritime shores, including the Wabanaki Confederacy composed of…

  12. Project for Global Education: Annotated Bibliography.

    ERIC Educational Resources Information Center

    Institute for World Order, New York, NY.

    Over 260 books, textbooks, articles, pamphlets, periodicals, films, and multi-media packages appropriate for the analysis of global issues at the college level are briefly annotated. Entries include classic books and articles as well as a number of recent (1976-1981) publications. The purpose is to assist students and educators in developing a…

  13. International, Intercultural Communication: Selected Annotated Bibliography.

    ERIC Educational Resources Information Center

    Casmir, Fred L.

    Designed to assist the student, scholar or practitioner interested in the role of culture in communications and human organization, this annotated bibliography cites sources since 1972 on intercultural and international communication. The 78 references are organized as follows: (1) books (including general handbooks for training sojourners or…

  14. Studies of Scientific Disciplines. An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Weisz, Diane; Kruytbosch, Carlos

    Provided in this bibliography are annotated lists of social studies of science literature, arranged alphabetically by author in 13 disciplinary areas. These areas include astronomy; general biology; biochemistry and molecular biology; biomedicine; chemistry; earth and space sciences; economics; engineering; mathematics; physics; political science;…

  15. Communication and Sexuality: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Buley, Jerry, Comp.; And Others

    The entries in this annotated bibliography represent books, educational journals, dissertations, popular magazines, and research studies that deal with the topic of communication and sexuality. Arranged alphabetically by author and also indexed according to subject matter, the titles span a variety of topics, including the following: sex and…

  16. Organizational Communication: A Selected, Annotated Bibliography.

    ERIC Educational Resources Information Center

    Putnam, Linda; Frye, Mary

    Directing the reader to books and articles making significant contributions to theory and research in the field of organizational communication, this annotated bibliography contains 43 entries, including seminal works, exemplars, and state-of-the-art pieces primarily by authors within the field of communication. The entries are grouped into 9…

  17. Suggested Books for Children: An Annotated Bibliography

    ERIC Educational Resources Information Center

    NHSA Dialog, 2008

    2008-01-01

    This article provides an annotated bibliography of various children's books. It includes listings of books that illustrate the dynamic relationships within the natural environment, economic context, racial and cultural identities, cross-group similarities and differences, gender, different abilities and stories of injustice and resistance.

  18. GoMapMan: integration, consolidation and visualization of plant gene annotations within the MapMan ontology.

    PubMed

    Ramsak, Živa; Baebler, Špela; Rotter, Ana; Korbar, Matej; Mozetic, Igor; Usadel, Björn; Gruden, Kristina

    2014-01-01

    GoMapMan (http://www.gomapman.org) is an open web-accessible resource for gene functional annotations in the plant sciences. It was developed to facilitate improvement, consolidation and visualization of gene annotations across several plant species. GoMapMan is based on the MapMan ontology, organized in the form of a hierarchical tree of biological concepts, which describe gene functions. Currently, genes of the model species Arabidopsis and three crop species (potato, tomato and rice) are included. The main features of GoMapMan are (i) dynamic and interactive gene product annotation through various curation options; (ii) consolidation of gene annotations for different plant species through the integration of orthologue group information; (iii) traceability of gene ontology changes and annotations; (iv) integration of external knowledge about genes from different public resources; and (v) providing gathered information to high-throughput analysis tools via dynamically generated export files. All of the GoMapMan functionalities are openly available, with the restriction on the curation functions, which require prior registration to ensure traceability of the implemented changes.

  19. All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs.

    PubMed

    Schork, Andrew J; Thompson, Wesley K; Pham, Phillip; Torkamani, Ali; Roddey, J Cooper; Sullivan, Patrick F; Kelsoe, John R; O'Donovan, Michael C; Furberg, Helena; Schork, Nicholas J; Andreassen, Ole A; Dale, Anders M

    2013-04-01

    Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1-FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci.

  20. Economic values of production and functional traits, including residual feed intake, in Finnish milk production.

    PubMed

    Hietala, P; Wolfová, M; Wolf, J; Kantanen, J; Juga, J

    2014-02-01

    Improving the feed efficiency of dairy cattle has a substantial effect on the economic efficiency and on the reduction of harmful environmental effects of dairy production through lower feeding costs and emissions from dairy farming. To assess the economic importance of feed efficiency in the breeding goal for dairy cattle, the economic values for the current breeding goal traits and the additional feed efficiency traits for Finnish Ayrshire cattle under production circumstances in 2011 were determined. The derivation of economic values was based on a bioeconomic model in which the profit of the production system was calculated, using the generated steady state herd structure. Considering beef production from dairy farms, 2 marketing strategies for surplus calves were investigated: (A) surplus calves were sold at a young age and (B) surplus calves were fattened on dairy farms. Both marketing strategies were unprofitable when subsidies were not included in the revenues. When subsidies were taken into account, a positive profitability was observed in both marketing strategies. The marginal economic values for residual feed intake (RFI) of breeding heifers and cows were -25.5 and -55.8 €/kg of dry matter per day per cow and year, respectively. The marginal economic value for RFI of animals in fattening was -29.5 €/kg of dry matter per day per cow and year. To compare the economic importance among traits, the standardized economic weight of each trait was calculated as the product of the marginal economic value and the genetic standard deviation; the standardized economic weight expressed as a percentage of the sum of all standardized economic weights was called relative economic weight. When not accounting for subsidies, the highest relative economic weight was found for 305-d milk yield (34% in strategy A and 29% in strategy B), which was followed by protein percentage (13% in strategy A and 11% in strategy B). The third most important traits were calving

  1. GI-POP: a combinational annotation and genomic island prediction pipeline for ongoing microbial genome projects.

    PubMed

    Lee, Chi-Ching; Chen, Yi-Ping Phoebe; Yao, Tzu-Jung; Ma, Cheng-Yu; Lo, Wei-Cheng; Lyu, Ping-Chiang; Tang, Chuan Yi

    2013-04-10

    Sequencing of microbial genomes is important because of microbial-carrying antibiotic and pathogenetic activities. However, even with the help of new assembling software, finishing a whole genome is a time-consuming task. In most bacteria, pathogenetic or antibiotic genes are carried in genomic islands. Therefore, a quick genomic island (GI) prediction method is useful for ongoing sequencing genomes. In this work, we built a Web server called GI-POP (http://gipop.life.nthu.edu.tw) which integrates a sequence assembling tool, a functional annotation pipeline, and a high-performance GI predicting module, in a support vector machine (SVM)-based method called genomic island genomic profile scanning (GI-GPS). The draft genomes of the ongoing genome projects in contigs or scaffolds can be submitted to our Web server, and it provides the functional annotation and highly probable GI-predicting results. GI-POP is a comprehensive annotation Web server designed for ongoing genome project analysis. Researchers can perform annotation and obtain pre-analytic information include possible GIs, coding/non-coding sequences and functional analysis from their draft genomes. This pre-analytic system can provide useful information for finishing a genome sequencing project.

  2. A semantic analysis of the annotations of the human genome

    PubMed Central

    Khatri, Purvesh; Done, Bogdan; Rao, Archana; Done, Arina

    2008-01-01

    The correct interpretation of any biological experiment depends in an essential way on the accuracy and consistency of the existing annotation databases. Such databases are ubiquitous and used by all life scientists in most experiments. However, it is well known that such databases are incomplete and many annotations may also be incorrect. In this paper we describe a technique that can be used to analyze the semantic content of such annotation databases. Our approach is able to extract implicit semantic relationships between genes and functions. This ability allows us to discover novel functions for known genes. This approach is able to identify missing and inaccurate annotations in existing annotation databases, and thus help improve their accuracy. We used our technique to analyze the current annotations of the human genome. From this body of annotations, we were able to predict 212 additional gene–function assignments. A subsequent literature search found that 138 of these gene–functions assignments are supported by existing peer-reviewed papers. An additional 23 assignments have been confirmed in the meantime by the addition of the respective annotations in later releases of the Gene Ontology database. Overall, the 161 confirmed assignments represent 75.95% of the proposed gene–function assignments. Only one of our predictions (0.4%) was contradicted by the existing literature. We could not find any relevant articles for 50 of our predictions (23.58%). The method is independent of the organism and can be used to analyze and improve the quality of the data of any public or private annotation database. Availability http://vortex.cs.wayne.edu/papers/semantic_analysis_bioinfo.pdf Contact sod@cs.wayne.edu PMID:15955782

  3. Applying negative rule mining to improve genome annotation

    PubMed Central

    Artamonova, Irena I; Frishman, Goar; Frishman, Dmitrij

    2007-01-01

    Background Unsupervised annotation of proteins by software pipelines suffers from very high error rates. Spurious functional assignments are usually caused by unwarranted homology-based transfer of information from existing database entries to the new target sequences. We have previously demonstrated that data mining in large sequence annotation databanks can help identify annotation items that are strongly associated with each other, and that exceptions from strong positive association rules often point to potential annotation errors. Here we investigate the applicability of negative association rule mining to revealing erroneously assigned annotation items. Results Almost all exceptions from strong negative association rules are connected to at least one wrong attribute in the feature combination making up the rule. The fraction of annotation features flagged by this approach as suspicious is strongly enriched in errors and constitutes about 0.6% of the whole body of the similarity-transferred annotation in the PEDANT genome database. Positive rule mining does not identify two thirds of these errors. The approach based on exceptions from negative rules is much more specific than positive rule mining, but its coverage is significantly lower. Conclusion Mining of both negative and positive association rules is a potent tool for finding significant trends in protein annotation and flagging doubtful features for further inspection. PMID:17659089

  4. The GATO gene annotation tool for research laboratories.

    PubMed

    Fujita, A; Massirer, K B; Durham, A M; Ferreira, C E; Sogayar, M C

    2005-11-01

    Large-scale genome projects have generated a rapidly increasing number of DNA sequences. Therefore, development of computational methods to rapidly analyze these sequences is essential for progress in genomic research. Here we present an automatic annotation system for preliminary analysis of DNA sequences. The gene annotation tool (GATO) is a Bioinformatics pipeline designed to facilitate routine functional annotation and easy access to annotated genes. It was designed in view of the frequent need of genomic researchers to access data pertaining to a common set of genes. In the GATO system, annotation is generated by querying some of the Web-accessible resources and the information is stored in a local database, which keeps a record of all previous annotation results. GATO may be accessed from everywhere through the internet or may be run locally if a large number of sequences are going to be annotated. It is implemented in PHP and Perl and may be run on any suitable Web server. Usually, installation and application of annotation systems require experience and are time consuming, but GATO is simple and practical, allowing anyone with basic skills in informatics to access it without any special training. GATO can be downloaded at [http://mariwork.iq.usp.br/gato/]. Minimum computer free space required is 2 MB.

  5. Gene calling and bacterial genome annotation with BG7.

    PubMed

    Tobes, Raquel; Pareja-Tobes, Pablo; Manrique, Marina; Pareja-Tobes, Eduardo; Kovach, Evdokim; Alekhin, Alexey; Pareja, Eduardo

    2015-01-01

    New massive sequencing technologies are providing many bacterial genome sequences from diverse taxa but a refined annotation of these genomes is crucial for obtaining scientific findings and new knowledge. Thus, bacterial genome annotation has emerged as a key point to investigate in bacteria. Any efficient tool designed specifically to annotate bacterial genomes sequenced with massively parallel technologies has to consider the specific features of bacterial genomes (absence of introns and scarcity of nonprotein-coding sequence) and of next-generation sequencing (NGS) technologies (presence of errors and not perfectly assembled genomes). These features make it convenient to focus on coding regions and, hence, on protein sequences that are the elements directly related with biological functions. In this chapter we describe how to annotate bacterial genomes with BG7, an open-source tool based on a protein-centered gene calling/annotation paradigm. BG7 is specifically designed for the annotation of bacterial genomes sequenced with NGS. This tool is sequence error tolerant maintaining their capabilities for the annotation of highly fragmented genomes or for annotating mixed sequences coming from several genomes (as those obtained through metagenomics samples). BG7 has been designed with scalability as a requirement, with a computing infrastructure completely based on cloud computing (Amazon Web Services).

  6. Joint likelihood function of cluster counts and n -point correlation functions: Improving their power through including halo sample variance

    NASA Astrophysics Data System (ADS)

    Schaan, Emmanuel; Takada, Masahiro; Spergel, David N.

    2014-12-01

    Naive estimates of the statistics of large-scale structure and weak lensing power spectrum measurements that include only Gaussian errors exaggerate their scientific impact. Nonlinear evolution and finite-volume effects are both significant sources of non-Gaussian covariance that reduce the ability of power spectrum measurements to constrain cosmological parameters. Using a halo model formalism, we derive an intuitive understanding of the various contributions to the covariance and show that our analytical treatment agrees with simulations. This approach enables an approximate derivation of a joint likelihood for the cluster number counts, the weak lensing power spectrum and the bispectrum. We show that this likelihood is a good description of the ray-tracing simulation. Since all of these observables are sensitive to the same finite-volume effects and contain information about the nonlinear evolution, a combined analysis recovers much of the "lost" information. For upcoming weak lensing surveys, we estimate that a joint analysis of power spectrum, number counts and bispectrum will produce an improvement of about 30-40% in determinations of the matter density and the scalar amplitude. This improvement is equivalent to doubling the survey area.

  7. Solar Tutorial and Annotation Resource (STAR)

    NASA Astrophysics Data System (ADS)

    Showalter, C.; Rex, R.; Hurlburt, N. E.; Zita, E. J.

    2009-12-01

    We have written a software suite designed to facilitate solar data analysis by scientists, students, and the public, anticipating enormous datasets from future instruments. Our “STAR" suite includes an interactive learning section explaining 15 classes of solar events. Users learn software tools that exploit humans’ superior ability (over computers) to identify many events. Annotation tools include time slice generation to quantify loop oscillations, the interpolation of event shapes using natural cubic splines (for loops, sigmoids, and filaments) and closed cubic splines (for coronal holes). Learning these tools in an environment where examples are provided prepares new users to comfortably utilize annotation software with new data. Upon completion of our tutorial, users are presented with media of various solar events and asked to identify and annotate the images, to test their mastery of the system. Goals of the project include public input into the data analysis of very large datasets from future solar satellites, and increased public interest and knowledge about the Sun. In 2010, the Solar Dynamics Observatory (SDO) will be launched into orbit. SDO’s advancements in solar telescope technology will generate a terabyte per day of high-quality data, requiring innovation in data management. While major projects develop automated feature recognition software, so that computers can complete much of the initial event tagging and analysis, still, that software cannot annotate features such as sigmoids, coronal magnetic loops, coronal dimming, etc., due to large amounts of data concentrated in relatively small areas. Previously, solar physicists manually annotated these features, but with the imminent influx of data it is unrealistic to expect specialized researchers to examine every image that computers cannot fully process. A new approach is needed to efficiently process these data. Providing analysis tools and data access to students and the public have proven

  8. MitoFish and MitoAnnotator: a mitochondrial genome database of fish with an accurate and automatic annotation pipeline.

    PubMed

    Iwasaki, Wataru; Fukunaga, Tsukasa; Isagozawa, Ryota; Yamada, Koichiro; Maeda, Yasunobu; Satoh, Takashi P; Sado, Tetsuya; Mabuchi, Kohji; Takeshima, Hirohiko; Miya, Masaki; Nishida, Mutsumi

    2013-11-01

    Mitofish is a database of fish mitochondrial genomes (mitogenomes) that includes powerful and precise de novo annotations for mitogenome sequences. Fish occupy an important position in the evolution of vertebrates and the ecology of the hydrosphere, and mitogenomic sequence data have served as a rich source of information for resolving fish phylogenies and identifying new fish species. The importance of a mitogenomic database continues to grow at a rapid pace as massive amounts of mitogenomic data are generated with the advent of new sequencing technologies. A severe bottleneck seems likely to occur with regard to mitogenome annotation because of the overwhelming pace of data accumulation and the intrinsic difficulties in annotating sequences with degenerating transfer RNA structures, divergent start/stop codons of the coding elements, and the overlapping of adjacent elements. To ease this data backlog, we developed an annotation pipeline named MitoAnnotator. MitoAnnotator automatically annotates a fish mitogenome with a high degree of accuracy in approximately 5 min; thus, it is readily applicable to data sets of dozens of sequences. MitoFish also contains re-annotations of previously sequenced fish mitogenomes, enabling researchers to refer to them when they find annotations that are likely to be erroneous or while conducting comparative mitogenomic analyses. For users who need more information on the taxonomy, habitats, phenotypes, or life cycles of fish, MitoFish provides links to related databases. MitoFish and MitoAnnotator are freely available at http://mitofish.aori.u-tokyo.ac.jp/ (last accessed August 28, 2013); all of the data can be batch downloaded, and the annotation pipeline can be used via a web interface.

  9. MitoFish and MitoAnnotator: A Mitochondrial Genome Database of Fish with an Accurate and Automatic Annotation Pipeline

    PubMed Central

    Iwasaki, Wataru; Fukunaga, Tsukasa; Isagozawa, Ryota; Yamada, Koichiro; Maeda, Yasunobu; Satoh, Takashi P.; Sado, Tetsuya; Mabuchi, Kohji; Takeshima, Hirohiko; Miya, Masaki; Nishida, Mutsumi

    2013-01-01

    Mitofish is a database of fish mitochondrial genomes (mitogenomes) that includes powerful and precise de novo annotations for mitogenome sequences. Fish occupy an important position in the evolution of vertebrates and the ecology of the hydrosphere, and mitogenomic sequence data have served as a rich source of information for resolving fish phylogenies and identifying new fish species. The importance of a mitogenomic database continues to grow at a rapid pace as massive amounts of mitogenomic data are generated with the advent of new sequencing technologies. A severe bottleneck seems likely to occur with regard to mitogenome annotation because of the overwhelming pace of data accumulation and the intrinsic difficulties in annotating sequences with degenerating transfer RNA structures, divergent start/stop codons of the coding elements, and the overlapping of adjacent elements. To ease this data backlog, we developed an annotation pipeline named MitoAnnotator. MitoAnnotator automatically annotates a fish mitogenome with a high degree of accuracy in approximately 5 min; thus, it is readily applicable to data sets of dozens of sequences. MitoFish also contains re-annotations of previously sequenced fish mitogenomes, enabling researchers to refer to them when they find annotations that are likely to be erroneous or while conducting comparative mitogenomic analyses. For users who need more information on the taxonomy, habitats, phenotypes, or life cycles of fish, MitoFish provides links to related databases. MitoFish and MitoAnnotator are freely available at http://mitofish.aori.u-tokyo.ac.jp/ (last accessed August 28, 2013); all of the data can be batch downloaded, and the annotation pipeline can be used via a web interface. PMID:23955518

  10. All SNPs Are Not Created Equal: Genome-Wide Association Studies Reveal a Consistent Pattern of Enrichment among Functionally Annotated SNPs

    PubMed Central

    Schork, Andrew J.; Thompson, Wesley K.; Pham, Phillip; Torkamani, Ali; Roddey, J. Cooper; Sullivan, Patrick F.; Kelsoe, John R.; O'Donovan, Michael C.; Furberg, Helena; Schork, Nicholas J.; Andreassen, Ole A.; Dale, Anders M.

    2013-01-01

    Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1−FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci. PMID:23637621

  11. Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies.

    PubMed

    Haas, Brian J; Delcher, Arthur L; Mount, Stephen M; Wortman, Jennifer R; Smith, Roger K; Hannick, Linda I; Maiti, Rama; Ronning, Catherine M; Rusch, Douglas B; Town, Christopher D; Salzberg, Steven L; White, Owen

    2003-10-01

    The spliced alignment of expressed sequence data to genomic sequence has proven a key tool in the comprehensive annotation of genes in eukaryotic genomes. A novel algorithm was developed to assemble clusters of overlapping transcript alignments (ESTs and full-length cDNAs) into maximal alignment assemblies, thereby comprehensively incorporating all available transcript data and capturing subtle splicing variations. Complete and partial gene structures identified by this method were used to improve The Institute for Genomic Research Arabidopsis genome annotation (TIGR release v.4.0). The alignment assemblies permitted the automated modeling of several novel genes and >1000 alternative splicing variations as well as updates (including UTR annotations) to nearly half of the approximately 27 000 annotated protein coding genes. The algorithm of the Program to Assemble Spliced Alignments (PASA) tool is described, as well as the results of automated updates to Arabidopsis gene annotations.

  12. Evaluation of medication list completeness, safety, and annotations.

    PubMed

    Owen, Michael C; Chang, Nancy M; Chong, David H; Vawdrey, David K

    2011-01-01

    Clinical documents frequently contain a list of a patient's medications. Missing information about the dosage, route, or frequency of a medication impairs clinical communication and may harm patients. We examined 253 medication lists. There were 181 lists (72%) with at least one medication missing a dose, route, or frequency. Missing information was judged to be potentially harmful in 47 of the lists (19% of 253) by three physician reviewers (kappa=0.69). We also observed that many lists contained additional information included as annotations, prompting a secondary thematic analysis of the annotations. Fifty-five of the 253 lists (22%) contained one or more annotations. The most frequent types of annotations were comments about the patient's medical history, the clinician's treatment plan changes, and the patient's adherence to a medication. Future development of electronic medication reconciliation tools to improve medication list completeness should also support annotating the medication list in a flexible manner.

  13. RASTtk: A modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes

    DOE PAGES

    Brettin, Thomas; Davis, James J.; Disz, Terry; ...

    2015-02-10

    The RAST (Rapid Annotation using Subsystem Technology) annotation engine was built in 2008 to annotate bacterial and archaeal genomes. It works by offering a standard software pipeline for identifying genomic features (i.e., protein-encoding genes and RNA) and annotating their functions. Recently, in order to make RAST a more useful research tool and to keep pace with advancements in bioinformatics, it has become desirable to build a version of RAST that is both customizable and extensible. In this paper, we describe the RAST tool kit (RASTtk), a modular version of RAST that enables researchers to build custom annotation pipelines. RASTtk offersmore » a choice of software for identifying and annotating genomic features as well as the ability to add custom features to an annotation job. RASTtk also accommodates the batch submission of genomes and the ability to customize annotation protocols for batch submissions. This is the first major software restructuring of RAST since its inception.« less

  14. Mulligan Concept manual therapy: standardizing annotation.

    PubMed

    McDowell, Jillian Marie; Johnson, Gillian Margaret; Hetherington, Barbara Helen

    2014-10-01

    Quality technique documentation is integral to the practice of manual therapy, ensuring uniform application and reproducibility of treatment. Manual therapy techniques are described by annotations utilizing a range of acronyms, abbreviations and universal terminology based on biomechanical and anatomical concepts. The various combinations of therapist and patient generated forces utilized in a variety of weight-bearing positions, which are synonymous with Mulligan Concept, challenge practitioners existing annotational skills. An annotation framework with recording rules adapted to the Mulligan Concept is proposed in which the abbreviations incorporate established manual therapy tenets and are detailed in the following sequence of; starting position, side, joint/s, method of application, glide/s, Mulligan technique, movement (or function), whether an assistant is used, overpressure (and by whom) and numbers of repetitions or time and sets. Therapist or patient application of overpressure and utilization of treatment belts or manual techniques must be recorded to capture the complete description. The adoption of the Mulligan Concept annotation framework in this way for documentation purposes will provide uniformity and clarity of information transfer for the future purposes of teaching, clinical practice and audit for its practitioners.

  15. An Annotated Bibliography on Children.

    ERIC Educational Resources Information Center

    Bureau of Libraries and Educational Technology (DHEW/OE), Washington, DC.

    This annotated bibliography is a highly selective list of materials published in the last five years on the major problems, trends, methodologies and achievements in the field of child development. It contains annotated references to approximately 500 books, periodicals, technical reports, government documents, legislative materials, professional…

  16. A predator-prey model with a holling type I functional response including a predator mutual interference

    USGS Publications Warehouse

    Seo, G.; DeAngelis, D.L.

    2011-01-01

    The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses. ?? 2011 Springer Science+Business Media, LLC.

  17. The value of statistical or bioinformatics annotation for rare variant association with quantitative trait.

    PubMed

    Byrnes, Andrea E; Wu, Michael C; Wright, Fred A; Li, Mingyao; Li, Yun

    2013-11-01

    In the past few years, a plethora of methods for rare variant association with phenotype have been proposed. These methods aggregate information from multiple rare variants across genomic region(s), but there is little consensus as to which method is most effective. The weighting scheme adopted when aggregating information across variants is one of the primary determinants of effectiveness. Here we present a systematic evaluation of multiple weighting schemes through a series of simulations intended to mimic large sequencing studies of a quantitative trait. We evaluate existing phenotype-independent and phenotype-dependent methods, as well as weights estimated by penalized regression approaches including Lasso, Elastic Net, and SCAD. We find that the difference in power between phenotype-dependent schemes is negligible when high-quality functional annotations are available. When functional annotations are unavailable or incomplete, all methods suffer from power loss; however, the variable selection methods outperform the others at the cost of increased computational time. Therefore, in the absence of good annotation, we recommend variable selection methods (which can be viewed as "statistical annotation") on top of regions implicated by a phenotype-independent weighting scheme. Further, once a region is implicated, variable selection can help to identify potential causal single nucleotide polymorphisms for biological validation. These findings are supported by an analysis of a high coverage targeted sequencing study of 1,898 individuals.

  18. Mutant laboratory mice with abnormalities in pigmentation: annotated tables.

    PubMed

    Nakamura, Motonobu; Tobin, Desmond J; Richards-Smith, Beverly; Sundberg, John P; Paus, Ralf

    2002-01-01

    Mammalian pigment cell research has recently entered a phase of significantly increased activity due largely to the exploitation of the many mutant mouse stocks that are coming on stream. Numerous transgenic, targeted mutagenesis (so-called 'knockouts'), conditional (so-called 'gene switch') and spontaneous mutant mice develop abnormal coat color phenotypes. The number of mice that exhibit such abnormalities is increasing exponentially as genetic engineering methods become routine. Since defined abnormalities in such mutant mice provide important clues to the as yet often poorly understood functional roles of many gene products, this overview includes a corresponding, annotated table of mutant mice with pigmentation alterations. These range from early developmental defects via a large array of coat color abnormalities to a melanoma metastasis model. This overview should provide helpful pointers to investigators who are looking for mouse models to explore or to compare functional activities of genes of interest and for comparing coat color phenotypes of spontaneous or genetically engineered mouse mutants with novel ones. Secondly, this review includes a table of mouse models of specific human diseases with genetically defined pigmentation abnormalities. In summary, this annotated table should serve as a useful reference for anyone interested in the molecular controls of pigmentation.

  19. SATPdb: a database of structurally annotated therapeutic peptides.

    PubMed

    Singh, Sandeep; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Bhalla, Sherry; Usmani, Salman Sadullah; Gautam, Ankur; Tuknait, Abhishek; Agrawal, Piyush; Mathur, Deepika; Raghava, Gajendra P S

    2016-01-04

    SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics.

  20. Open semantic annotation of scientific publications using DOMEO

    PubMed Central

    2012-01-01

    Background Our group has developed a useful shared software framework for performing, versioning, sharing and viewing Web annotations of a number of kinds, using an open representation model. Methods The Domeo Annotation Tool was developed in tandem with this open model, the Annotation Ontology (AO). Development of both the Annotation Framework and the open model was driven by requirements of several different types of alpha users, including bench scientists and biomedical curators from university research labs, online scientific communities, publishing and pharmaceutical companies. Several use cases were incrementally implemented by the toolkit. These use cases in biomedical communications include personal note-taking, group document annotation, semantic tagging, claim-evidence-context extraction, reagent tagging, and curation of textmining results from entity extraction algorithms. Results We report on the Domeo user interface here. Domeo has been deployed in beta release as part of the NIH Neuroscience Information Framework (NIF, http://www.neuinfo.org) and is scheduled for production deployment in the NIF’s next full release. Future papers will describe other aspects of this work in detail, including Annotation Framework Services and components for integrating with external textmining services, such as the NCBO Annotator web service, and with other textmining applications using the Apache UIMA framework. PMID:22541592

  1. Bovine Genome Database: supporting community annotation and analysis of the Bos taurus genome

    PubMed Central

    2010-01-01

    Background A goal of the Bovine Genome Database (BGD; http://BovineGenome.org) has been to support the Bovine Genome Sequencing and Analysis Consortium (BGSAC) in the annotation and analysis of the bovine genome. We were faced with several challenges, including the need to maintain consistent quality despite diversity in annotation expertise in the research community, the need to maintain consistent data formats, and the need to minimize the potential duplication of annotation effort. With new sequencing technologies allowing many more eukaryotic genomes to be sequenced, the demand for collaborative annotation is likely to increase. Here we present our approach, challenges and solutions facilitating a large distributed annotation project. Results and Discussion BGD has provided annotation tools that supported 147 members of the BGSAC in contributing 3,871 gene models over a fifteen-week period, and these annotations have been integrated into the bovine Official Gene Set. Our approach has been to provide an annotation system, which includes a BLAST site, multiple genome browsers, an annotation portal, and the Apollo Annotation Editor configured to connect directly to our Chado database. In addition to implementing and integrating components of the annotation system, we have performed computational analyses to create gene evidence tracks and a consensus gene set, which can be viewed on individual gene pages at BGD. Conclusions We have provided annotation tools that alleviate challenges associated with distributed annotation. Our system provides a consistent set of data to all annotators and eliminates the need for annotators to format data. Involving the bovine research community in genome annotation has allowed us to leverage expertise in various areas of bovine biology to provide biological insight into the genome sequence. PMID:21092105

  2. 25 CFR 1000.361 - Will the annual review include a review of the Secretary's residual trust functions?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Trust Evaluation Review Annual Trust... 25 Indians 2 2010-04-01 2010-04-01 false Will the annual review include a review of the Secretary's residual trust functions? 1000.361 Section 1000.361 Indians OFFICE OF THE ASSISTANT...

  3. Ontological Annotation with WordNet

    SciTech Connect

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob; Hohimer, Ryan E.; White, Amanda M.

    2006-06-06

    Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

  4. Automating Ontological Annotation with WordNet

    SciTech Connect

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob L.; Hohimer, Ryan E.; White, Amanda M.

    2006-01-22

    Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

  5. The MC-DFT approach including the SCS-MP2 energies to the new Minnesota-type functionals.

    PubMed

    Liu, Po-Chun; Hu, Wei-Ping

    2014-08-05

    We have applied the multicoefficient density functional theory (MC-DFT) to four recent Minnesota functionals, including M06-2X, M08-HX, M11, and MN12-SX on the performance of thermochemical kinetics. The results indicated that the accuracy can be improved significantly using more than one basis set. We further included the SCS-MP2 energies into MC-DFT, and the resulting mean unsigned errors (MUEs) decreased by approximately 0.3 kcal/mol for the most accurate basis set combinations. The M06-2X functional with the simple [6-311+G(d,p)/6-311+G(2d,2p)] combination gave the best performance/cost ratios for the MC-DFT and MC-SCS-MP2|MC-DFT methods with MUE of 1.58 and 1.22 kcal/mol, respectively.

  6. Morphosyntactic annotation of CHILDES transcripts*

    PubMed Central

    SAGAE, KENJI; DAVIS, ERIC; LAVIE, ALON; MACWHINNEY, BRIAN; WINTNER, SHULY

    2014-01-01

    Corpora of child language are essential for research in child language acquisition and psycholinguistics. Linguistic annotation of the corpora provides researchers with better means for exploring the development of grammatical constructions and their usage. We describe a project whose goal is to annotate the English section of the CHILDES database with grammatical relations in the form of labeled dependency structures. We have produced a corpus of over 18,800 utterances (approximately 65,000 words) with manually curated gold-standard grammatical relation annotations. Using this corpus, we have developed a highly accurate data-driven parser for the English CHILDES data, which we used to automatically annotate the remainder of the English section of CHILDES. We have also extended the parser to Spanish, and are currently working on supporting more languages. The parser and the manually and automatically annotated data are freely available for research purposes. PMID:20334720

  7. NECTAR: a database of codon-centric missense variant annotations.

    PubMed

    Gong, Sungsam; Ware, James S; Walsh, Roddy; Cook, Stuart A

    2014-01-01

    NECTAR (Non-synonymous Enriched Coding muTation ARchive; http://nectarmutation.org) is a database and web application to annotate disease-related and functionally important amino acids in human proteins. A number of tools are available to facilitate the interpretation of DNA variants identified in diagnostic or research sequencing. These typically identify previous reports of DNA variation at a given genomic location, predict its effects on transcript and protein sequence and may predict downstream functional consequences. Previous reports and functional annotations are typically linked by the genomic location of the variant observed. NECTAR collates disease-causing variants and functionally important amino acid residues from a number of sources. Importantly, rather than simply linking annotations by a shared genomic location, NECTAR annotates variants of interest with details of previously reported variation affecting the same codon. This provides a much richer data set for the interpretation of a novel DNA variant. NECTAR also identifies functionally equivalent amino acid residues in evolutionarily related proteins (paralogues) and, where appropriate, transfers annotations between them. As well as accessing these data through a web interface, users can upload batches of variants in variant call format (VCF) for annotation on-the-fly. The database is freely available to download from the ftp site: ftp://ftp.nectarmutation.org.

  8. Annotated Bibliography of Recent Research Related to Academic Advising

    ERIC Educational Resources Information Center

    Mottarella, Karen, Comp.

    2011-01-01

    This article presents an annotated bibliography of recent research related to academic advising. It includes research papers that focus on advising and a special section of the "Journal of Career Development" that is devoted to multicultural graduate advising relationships.

  9. Media Themes and Threads: Annotated Bibliography on Gifted Females.

    ERIC Educational Resources Information Center

    Landrum, Mary S.; Ramsay, Shula G.

    1989-01-01

    This annotated bibliography describes 15 journal articles on gifted females. Topics include: educational strategies; personality outcomes; special guidance concerns; internal barriers to the realization of potential; life satisfaction; teacher attitudes; psychological development; nontraditional vocational enrollment; sex differences; career…

  10. Large-scale functional annotation and expanded implementations of the P{wHy} hybrid transposon in the Drosophila melanogaster genome.

    PubMed

    Myrick, Kyl V; Huet, François; Mohr, Stephanie E; Alvarez-García, Inés; Lu, Jeffrey T; Smith, Mark A; Crosby, Madeline A; Gelbart, William M

    2009-07-01

    Whole genome sequencing of the model organisms has created increased demand for efficient tools to facilitate the genome annotation efforts. Accordingly, we report the further implementations and analyses stemming from our publicly available P{wHy} library for Drosophila melanogaster. A two-step regime-large scale transposon mutagenesis followed by hobo-induced nested deletions-allows mutation saturation and provides significant enhancements to existing genomic coverage. We previously showed that, for a given starting insert, deletion saturation is readily obtained over a 60-kb interval; here, we perform a breakdown analysis of efficiency to identify rate-limiting steps in the process. Transrecombination, the hobo-induced recombination between two P{wHy} half molecules, was shown to further expand the P{wHy} mutational range, pointing to a potent, iterative process of transrecombination-reconstitution-transrecombination for alternating between very large and very fine-grained deletions in a self-contained manner. A number of strains also showed partial or complete repression of P{wHy} markers, depending on chromosome location, whereby asymmetric marker silencing allowed continuous phenotypic detection, indicating that P{wHy}-based saturational mutagenesis should be useful for the study of heterochromatin/positional effects.

  11. dcGOR: an R package for analysing ontologies and protein domain annotations.

    PubMed

    Fang, Hai

    2014-10-01

    I introduce an open-source R package 'dcGOR' to provide the bioinformatics community with the ease to analyse ontologies and protein domain annotations, particularly those in the dcGO database. The dcGO is a comprehensive resource for protein domain annotations using a panel of ontologies including Gene Ontology. Although increasing in popularity, this database needs statistical and graphical support to meet its full potential. Moreover, there are no bioinformatics tools specifically designed for domain ontology analysis. As an add-on package built in the R software environment, dcGOR offers a basic infrastructure with great flexibility and functionality. It implements new data structure to represent domains, ontologies, annotations, and all analytical outputs as well. For each ontology, it provides various mining facilities, including: (i) domain-based enrichment analysis and visualisation; (ii) construction of a domain (semantic similarity) network according to ontology annotations; and (iii) significance analysis for estimating a contact (statistical significance) network. To reduce runtime, most analyses support high-performance parallel computing. Taking as inputs a list of protein domains of interest, the package is able to easily carry out in-depth analyses in terms of functional, phenotypic and diseased relevance, and network-level understanding. More importantly, dcGOR is designed to allow users to import and analyse their own ontologies and annotations on domains (taken from SCOP, Pfam and InterPro) and RNAs (from Rfam) as well. The package is freely available at CRAN for easy installation, and also at GitHub for version control. The dedicated website with reproducible demos can be found at http://supfam.org/dcGOR.

  12. ArrayPlex: distributed, interactive and programmatic access to genome sequence, annotation, ontology, and analytical toolsets

    PubMed Central

    Killion, Patrick J; Iyer, Vishwanath R

    2008-01-01

    ArrayPlex is a software package that centrally provides a large number of flexible toolsets useful for functional genomics, including microarray data storage, quality assessments, data visualization, gene annotation retrieval, statistical tests, genomic sequence retrieval and motif analysis. It uses a client-server architecture based on open source components, provides graphical, command-line, and programmatic access to all needed resources, and is extensible by virtue of a documented application programming interface. ArrayPlex is available at . PMID:19014503

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

    PubMed Central

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

    2012-01-01

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

  14. Benchmark Calculations of Energetic Properties of Groups 4 and 6 Transition Metal Oxide Nanoclusters Including Comparison to Density Functional Theory.

    PubMed

    Fang, Zongtang; Both, Johan; Li, Shenggang; Yue, Shuwen; Aprà, Edoardo; Keçeli, Murat; Wagner, Albert F; Dixon, David A

    2016-08-09

    The heats of formation and the normalized clustering energies (NCEs) for the group 4 and group 6 transition metal oxide (TMO) trimers and tetramers have been calculated by the Feller-Peterson-Dixon (FPD) method. The heats of formation predicted by the FPD method do not differ much from those previously derived from the NCEs at the CCSD(T)/aT level except for the CrO3 nanoclusters. New and improved heats of formation for Cr3O9 and Cr4O12 were obtained using PW91 orbitals instead of Hartree-Fock (HF) orbitals. Diffuse functions are necessary to predict accurate heats of formation. The fluoride affinities (FAs) are calculated with the CCSD(T) method. The relative energies (REs) of different isomers, NCEs, electron affinities (EAs), and FAs of (MO2)n (M = Ti, Zr, Hf, n = 1-4) and (MO3)n (M = Cr, Mo, W, n = 1-3) clusters have been benchmarked with 55 exchange-correlation density functional theory (DFT) functionals including both pure and hybrid types. The absolute errors of the DFT results are mostly less than ±10 kcal/mol for the NCEs and the EAs and less than ±15 kcal/mol for the FAs. Hybrid functionals usually perform better than the pure functionals for the REs and NCEs. The performance of the two types of functionals in predicting EAs and FAs is comparable. The B1B95 and PBE1PBE functionals provide reliable energetic properties for most isomers. Long range corrected pure functionals usually give poor FAs. The standard deviation of the absolute error is always close to the mean errors, and the probability distributions of the DFT errors are often not Gaussian (normal). The breadth of the distribution of errors and the maximum probability are dependent on the energy property and the isomer.

  15. Literacy and Basic Education: A Selected, Annotated Bibliography. Annotated Bibliography #3.

    ERIC Educational Resources Information Center

    Michigan State Univ., East Lansing. Non-Formal Education Information Center.

    A selected annotated bibliography on literacy and basic education, including contributions from practitioners in the worldwide non-formal education network and compiled for them, has three interrelated themes: integration of literacy programs with broader development efforts; the learner-centered or "psycho-social" approach to literacy,…

  16. Graph-based sequence annotation using a data integration approach.

    PubMed

    Pesch, Robert; Lysenko, Artem; Hindle, Matthew; Hassani-Pak, Keywan; Thiele, Ralf; Rawlings, Christopher; Köhler, Jacob; Taubert, Jan

    2008-08-25

    The automated annotation of data from high throughput sequencing and genomics experiments is a significant challenge for bioinformatics. Most current approaches rely on sequential pipelines of gene finding and gene function prediction methods that annotate a gene with information from different reference data sources. Each function prediction method contributes evidence supporting a functional assignment. Such approaches generally ignore the links between the information in the reference datasets. These links, however, are valuable for assessing the plausibility of a function assignment and can be used to evaluate the confidence in a prediction. We are working towards a novel annotation system that uses the network of information supporting the function assignment to enrich the annotation process for use by expert curators and predicting the function of previously unannotated genes. In this paper we describe our success in the first stages of this development. We present the data integration steps that are needed to create the core database of integrated reference databases (UniProt, PFAM, PDB, GO and the pathway database Ara-Cyc) which has been established in the ONDEX data integration system. We also present a comparison between different methods for integration of GO terms as part of the function assignment pipeline and discuss the consequences of this analysis for improving the accuracy of gene function annotation. The methods and algorithms presented in this publication are an integral part of the ONDEX system which is freely available from http://ondex.sf.net/.

  17. Deburring: an annotated bibliography. Volume VI

    SciTech Connect

    Gillespie, L.K.

    1980-07-01

    An annotated summary of 138 articles and publications on burrs, burr prevention and deburring is presented. Thirty-seven deburring processes are listed. Entries cited include English, Russian, French, Japanese, and German language articles. Entries are indexed by deburring processes, author, and language. Indexes also indicate which references discuss equipment and tooling, how to use a proces economics, burr properties, and how to design to minimize burr problems. Research studies are identified as are the materials deburred.

  18. eXamine: Exploring annotated modules in networks

    PubMed Central

    2014-01-01

    Background Biological networks have a growing importance for the interpretation of high-throughput “omics” data. Integrative network analysis makes use of statistical and combinatorial methods to extract smaller subnetwork modules, and performs enrichment analysis to annotate the modules with ontology terms or other available knowledge. This process results in an annotated module, which retains the original network structure and includes enrichment information as a set system. A major bottleneck is a lack of tools that allow exploring both network structure of extracted modules and its annotations. Results This paper presents a visual analysis approach that targets small modules with many set-based annotations, and which displays the annotations as contours on top of a node-link diagram. We introduce an extension of self-organizing maps to lay out nodes, links, and contours in a unified way. An implementation of this approach is freely available as the Cytoscape app eXamine Conclusions eXamine accurately conveys small and annotated modules consisting of several dozens of proteins and annotations. We demonstrate that eXamine facilitates the interpretation of integrative network analysis results in a guided case study. This study has resulted in a novel biological insight regarding the virally-encoded G-protein coupled receptor US28. PMID:25002203

  19. Benchmark Calculations of Energetic Properties of Groups 4 and 6 Transition Metal Oxide Nanoclusters Including Comparison to Density Functional Theory

    SciTech Connect

    Fang, Zongtang; Both, Johan; Li, Shenggang; Yue, Shuwen; Aprà, Edoardo; Keçeli, Murat; Wagner, Albert F.; Dixon, David A.

    2016-08-09

    The heats of formation and the normalized clustering energies (NCEs) for the group 4 and group 6 transition metal oxide (TMO) trimers and tetramers have been calculated by the Feller-Peterson-Dixon (FPD) method. The heats of formation predicted by the FPD method do not differ much from those previously derived from the NCEs at the CCSD(T)/aT level except for the CrO3 nanoclusters. New and improved heats of formation for Cr3O9 and Cr4O12 were obtained using PW91 orbitals instead of Hartree-Fock (HF) orbitals. Diffuse functions are necessary to predict accurate heats of formation. The fluoride affinities (FAs) are calculated with the CCSD(T) method. The relative energies (REs) of different isomers, NCEs, electron affinities (EAs), and FAs of (MO2)n ( M = Ti, Zr, Hf, n = 1 – 4 ) and (MO3)n ( M = Cr, Mo, W, n = 1 – 3) clusters have been benchmarked with 55 exchange-correlation DFT functionals including both pure and hybrid types. The absolute errors of the DFT results are mostly less than ±10 kcal/mol for the NCEs and the EAs, and less than ±15 kcal/mol for the FAs. Hybrid functionals usually perform better than the pure functionals for the REs and NCEs. The performance of the two types of functionals in predicting EAs and FAs is comparable. The B1B95 and PBE1PBE functionals provide reliable energetic properties for most isomers. Long range corrected pure functionals usually give poor FAs. The standard deviation of the absolute error is always close to the mean errors and the probability distributions of the DFT errors are often not Gaussian (normal). The breadth of the distribution of errors and the maximum probability are dependent on the energy property and the isomer.

  20. dictyBase 2015: Expanding data and annotations in a new software environment

    PubMed Central

    Jimenez-Morales, David; Dodson, Robert J.; Chisholm, Rex L.

    2015-01-01

    dictyBase is the model organism database for the social amoeba Dictyostelium discoideum and related species. The primary mission of dictyBase is to provide the biomedical research community with well-integrated high quality data, and tools that enable original research. Data presented at dictyBase is obtained from sequencing centers, groups performing high throughput experiments such as large-scale mutagenesis studies, and RNAseq data, as well as a growing number of manually added functional gene annotations from the published literature, including Gene Ontology, strain, and phenotype annotations. Through the Dicty Stock Center we provide the community with an impressive amount of annotated strains and plasmids. Recently dictyBase accomplished a major overhaul to adapt an outdated infrastructure to the current technological advances, thus facilitating the implementation of innovative tools and comparative genomics. It also provides new strategies for high quality annotations that enable bench researchers to benefit from the rapidly increasing volume of available data. dictyBase is highly responsive to its users needs, building a successful relationship that capitalizes on the vast efforts of the Dictyostelium research community. dictyBase has become the trusted data resource for Dictyostelium investigators, other investigators or organizations seeking information about Dictyostelium, as well as educators who use this model system. PMID:26088819

  1. dictyBase 2015: Expanding data and annotations in a new software environment.

    PubMed

    Basu, Siddhartha; Fey, Petra; Jimenez-Morales, David; Dodson, Robert J; Chisholm, Rex L

    2015-08-01

    dictyBase is the model organism database for the social amoeba Dictyostelium discoideum and related species. The primary mission of dictyBase is to provide the biomedical research community with well-integrated high quality data, and tools that enable original research. Data presented at dictyBase is obtained from sequencing centers, groups performing high throughput experiments such as large-scale mutagenesis studies, and RNAseq data, as well as a growing number of manually added functional gene annotations from the published literature, including Gene Ontology, strain, and phenotype annotations. Through the Dicty Stock Center we provide the community with an impressive amount of annotated strains and plasmids. Recently, dictyBase accomplished a major overhaul to adapt an outdated infrastructure to the current technological advances, thus facilitating the implementation of innovative tools and comparative genomics. It also provides new strategies for high quality annotations that enable bench researchers to benefit from the rapidly increasing volume of available data. dictyBase is highly responsive to its users needs, building a successful relationship that capitalizes on the vast efforts of the Dictyostelium research community. dictyBase has become the trusted data resource for Dictyostelium investigators, other investigators or organizations seeking information about Dictyostelium, as well as educators who use this model system.

  2. Semia: semi-automatic interactive graphic editing tool to annotate ambulatory ECG records.

    PubMed

    Dorn, Roman; Jager, Franc

    2004-09-01

    We designed and developed a special purpose interactive graphic editing tool semi-automatic (Semia) to annotate transient ischaemic ST segment episodes and other non-ischaemic ST segment events in 24h ambulatory electrocardiogram (ECG) records. The tool allows representation and viewing of the data, interaction with the data globally and locally at different resolutions, examining data at any point, manual adjustment of heart-beat fiducial points, and manual and automatic editing of annotations. Efficient and fast display of ambulatory ECG signal waveforms, display of diagnostic and morphology feature-vector time-series, dynamic interface controls, and automated procedures to help annotate, made the tool efficient, user friendly and usable. Human expert annotators used the Semia tool to successfully annotate the Long-Term ST database (LTST DB), a result of a multinational effort. The tool supported paperless editing of annotations at dislocated geographical sites. We present design, characteristic "look and feel", functionality, and development of Semia annotating tool.

  3. Publication Production: An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Firman, Anthony H.

    1994-01-01

    Offers brief annotations of 52 articles and papers on document production (from the Society for Technical Communication's journal and proceedings) on 9 topics: information processing, document design, using color, typography, tables, illustrations, photography, printing and binding, and production management. (SR)

  4. Blast2GO: A Comprehensive Suite for Functional Analysis in Plant Genomics

    PubMed Central

    Conesa, Ana; Götz, Stefan

    2008-01-01

    Functional annotation of novel sequence data is a primary requirement for the utilization of functional genomics approaches in plant research. In this paper, we describe the Blast2GO suite as a comprehensive bioinformatics tool for functional annotation of sequences and data mining on the resulting annotations, primarily based on the gene ontology (GO) vocabulary. Blast2GO optimizes function transfer from homologous sequences through an elaborate algorithm that considers similarity, the extension of the homology, the database of choice, the GO hierarchy, and the quality of the original annotations. The tool includes numerous functions for the visualization, management, and statistical analysis of annotation results, including gene set enrichment analysis. The application supports InterPro, enzyme codes, KEGG pathways, GO direct acyclic graphs (DAGs), and GOSlim. Blast2GO is a suitable tool for plant genomics research because of its versatility, easy installation, and friendly use. PMID:18483572

  5. The 2008 update of the Aspergillus nidulans genome annotation: a community effort

    PubMed Central

    Wortman, Jennifer Russo; Gilsenan, Jane Mabey; Joardar, Vinita; Deegan, Jennifer; Clutterbuck, John; Andersen, Mikael R.; Archer, David; Bencina, Mojca; Braus, Gerhard; Coutinho, Pedro; von Döhren, Hans; Doonan, John; Driessen, Arnold J.M.; Durek, Pawel; Espeso, Eduardo; Fekete, Erzsébet; Flipphi, Michel; Estrada, Carlos Garcia; Geysens, Steven; Goldman, Gustavo; de Groot, Piet W.J.; Hansen, Kim; Harris, Steven D.; Heinekamp, Thorsten; Helmstaedt, Kerstin; Henrissat, Bernard; Hofmann, Gerald; Homan, Tim; Horio, Tetsuya; Horiuchi, Hiroyuki; James, Steve; Jones, Meriel; Karaffa, Levente; Karányi, Zsolt; Kato, Masashi; Keller, Nancy; Kelly, Diane E.; Kiel, Jan A.K.W.; Kim, Jung-Mi; van der Klei, Ida J.; Klis, Frans M.; Kovalchuk, Andriy; Kraševec, Nada; Kubicek, Christian P.; Liu, Bo; MacCabe, Andrew; Meyer, Vera; Mirabito, Pete; Miskei, Márton; Mos, Magdalena; Mullins, Jonathan; Nelson, David R.; Nielsen, Jens; Oakley, Berl R.; Osmani, Stephen A.; Pakula, Tiina; Paszewski, Andrzej; Paulsen, Ian; Pilsyk, Sebastian; Pócsi, István; Punt, Peter J.; Ram, Arthur F.J.; Ren, Qinghu; Robellet, Xavier; Robson, Geoff; Seiboth, Bernhard; Solingen, Piet van; Specht, Thomas; Sun, Jibin; Taheri-Talesh, Naimeh; Takeshita, Norio; Ussery, Dave; vanKuyk, Patricia A.; Visser, Hans; van de Vondervoort, Peter J.I.; de Vries, Ronald P.; Walton, Jonathan; Xiang, Xin; Xiong, Yi; Zeng, An Ping; Brandt, Bernd W.; Cornell, Michael J.; van den Hondel, Cees A.M.J.J.; Visser, Jacob; Oliver, Stephen G.; Turner, Geoffrey

    2010-01-01

    The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. PMID:19146970

  6. The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts.

    PubMed

    Yamasaki, Chisato; Murakami, Katsuhiko; Fujii, Yasuyuki; Sato, Yoshiharu; Harada, Erimi; Takeda, Jun-ichi; Taniya, Takayuki; Sakate, Ryuichi; Kikugawa, Shingo; Shimada, Makoto; Tanino, Motohiko; Koyanagi, Kanako O; Barrero, Roberto A; Gough, Craig; Chun, Hong-Woo; Habara, Takuya; Hanaoka, Hideki; Hayakawa, Yosuke; Hilton, Phillip B; Kaneko, Yayoi; Kanno, Masako; Kawahara, Yoshihiro; Kawamura, Toshiyuki; Matsuya, Akihiro; Nagata, Naoki; Nishikata, Kensaku; Noda, Akiko Ogura; Nurimoto, Shin; Saichi, Naomi; Sakai, Hiroaki; Sanbonmatsu, Ryoko; Shiba, Rie; Suzuki, Mami; Takabayashi, Kazuhiko; Takahashi, Aiko; Tamura, Takuro; Tanaka, Masayuki; Tanaka, Susumu; Todokoro, Fusano; Yamaguchi, Kaori; Yamamoto, Naoyuki; Okido, Toshihisa; Mashima, Jun; Hashizume, Aki; Jin, Lihua; Lee, Kyung-Bum; Lin, Yi-Chueh; Nozaki, Asami; Sakai, Katsunaga; Tada, Masahito; Miyazaki, Satoru; Makino, Takashi; Ohyanagi, Hajime; Osato, Naoki; Tanaka, Nobuhiko; Suzuki, Yoshiyuki; Ikeo, Kazuho; Saitou, Naruya; Sugawara, Hideaki; O'Donovan, Claire; Kulikova, Tamara; Whitfield, Eleanor; Halligan, Brian; Shimoyama, Mary; Twigger, Simon; Yura, Kei; Kimura, Kouichi; Yasuda, Tomohiro; Nishikawa, Tetsuo; Akiyama, Yutaka; Motono, Chie; Mukai, Yuri; Nagasaki, Hideki; Suwa, Makiko; Horton, Paul; Kikuno, Reiko; Ohara, Osamu; Lancet, Doron; Eveno, Eric; Graudens, Esther; Imbeaud, Sandrine; Debily, Marie Anne; Hayashizaki, Yoshihide; Amid, Clara; Han, Michael; Osanger, Andreas; Endo, Toshinori; Thomas, Michael A; Hirakawa, Mika; Makalowski, Wojciech; Nakao, Mitsuteru; Kim, Nam-Soon; Yoo, Hyang-Sook; De Souza, Sandro J; Bonaldo, Maria de Fatima; Niimura, Yoshihito; Kuryshev, Vladimir; Schupp, Ingo; Wiemann, Stefan; Bellgard, Matthew; Shionyu, Masafumi; Jia, Libin; Thierry-Mieg, Danielle; Thierry-Mieg, Jean; Wagner, Lukas; Zhang, Qinghua; Go, Mitiko; Minoshima, Shinsei; Ohtsubo, Masafumi; Hanada, Kousuke; Tonellato, Peter; Isogai, Takao; Zhang, Ji; Lenhard, Boris; Kim, Sangsoo; Chen, Zhu; Hinz, Ursula; Estreicher, Anne; Nakai, Kenta; Makalowska, Izabela; Hide, Winston; Tiffin, Nicola; Wilming, Laurens; Chakraborty, Ranajit; Soares, Marcelo Bento; Chiusano, Maria Luisa; Suzuki, Yutaka; Auffray, Charles; Yamaguchi-Kabata, Yumi; Itoh, Takeshi; Hishiki, Teruyoshi; Fukuchi, Satoshi; Nishikawa, Ken; Sugano, Sumio; Nomura, Nobuo; Tateno, Yoshio; Imanishi, Tadashi; Gojobori, Takashi

    2008-01-01

    Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein-protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group.

  7. The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts*

    PubMed Central

    2008-01-01

    Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein–protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group. PMID:18089548

  8. Evolview v2: an online visualization and management tool for customized and annotated phylogenetic trees.

    PubMed

    He, Zilong; Zhang, Huangkai; Gao, Shenghan; Lercher, Martin J; Chen, Wei-Hua; Hu, Songnian

    2016-07-08

    Evolview is an online visualization and management tool for customized and annotated phylogenetic trees. It allows users to visualize phylogenetic trees in various formats, customize the trees through built-in functions and user-supplied datasets and export the customization results to publication-ready figures. Its 'dataset system' contains not only the data to be visualized on the tree, but also 'modifiers' that control various aspects of the graphical annotation. Evolview is a single-page application (like Gmail); its carefully designed interface allows users to upload, visualize, manipulate and manage trees and datasets all in a single webpage. Developments since the last public release include a modern dataset editor with keyword highlighting functionality, seven newly added types of annotation datasets, collaboration support that allows users to share their trees and datasets and various improvements of the web interface and performance. In addition, we included eleven new 'Demo' trees to demonstrate the basic functionalities of Evolview, and five new 'Showcase' trees inspired by publications to showcase the power of Evolview in producing publication-ready figures. Evolview is freely available at: http://www.evolgenius.info/evolview/.

  9. Evolview v2: an online visualization and management tool for customized and annotated phylogenetic trees

    PubMed Central

    He, Zilong; Zhang, Huangkai; Gao, Shenghan; Lercher, Martin J.; Chen, Wei-Hua; Hu, Songnian

    2016-01-01

    Evolview is an online visualization and management tool for customized and annotated phylogenetic trees. It allows users to visualize phylogenetic trees in various formats, customize the trees through built-in functions and user-supplied datasets and export the customization results to publication-ready figures. Its ‘dataset system’ contains not only the data to be visualized on the tree, but also ‘modifiers’ that control various aspects of the graphical annotation. Evolview is a single-page application (like Gmail); its carefully designed interface allows users to upload, visualize, manipulate and manage trees and datasets all in a single webpage. Developments since the last public release include a modern dataset editor with keyword highlighting functionality, seven newly added types of annotation datasets, collaboration support that allows users to share their trees and datasets and various improvements of the web interface and performance. In addition, we included eleven new ‘Demo’ trees to demonstrate the basic functionalities of Evolview, and five new ‘Showcase’ trees inspired by publications to showcase the power of Evolview in producing publication-ready figures. Evolview is freely available at: http://www.evolgenius.info/evolview/. PMID:27131786

  10. Unification of dynamic density functional theory for colloidal fluids to include inertia and hydrodynamic interactions: derivation and numerical experiments.

    PubMed

    Goddard, B D; Nold, A; Savva, N; Yatsyshin, P; Kalliadasis, S

    2013-01-23

    Starting from the Kramers equation for the phase-space dynamics of the N-body probability distribution, we derive a dynamical density functional theory (DDFT) for colloidal fluids including the effects of inertia and hydrodynamic interactions (HI). We compare the resulting theory to extensive Langevin dynamics simulations for both hard rod systems and three-dimensional hard sphere systems with radially symmetric external potentials. As well as demonstrating the accuracy of the new DDFT, by comparing with previous DDFTs which neglect inertia, HI, or both, we also scrutinize the significance of including these effects. Close to local equilibrium we derive a continuum equation from the microscopic dynamics which is a generalized Navier-Stokes-like equation with additional non-local terms governing the effects of HI. For the overdamped limit we recover analogues of existing configuration-space DDFTs but with a novel diffusion tensor.

  11. Nonlinear Deep Kernel Learning for Image Annotation.

    PubMed

    Jiu, Mingyuan; Sahbi, Hichem

    2017-02-08

    Multiple kernel learning (MKL) is a widely used technique for kernel design. Its principle consists in learning, for a given support vector classifier, the most suitable convex (or sparse) linear combination of standard elementary kernels. However, these combinations are shallow and often powerless to capture the actual similarity between highly semantic data, especially for challenging classification tasks such as image annotation. In this paper, we redefine multiple kernels using deep multi-layer networks. In this new contribution, a deep multiple kernel is recursively defined as a multi-layered combination of nonlinear activation functions, each one involves a combination of several elementary or intermediate kernels, and results into a positive semi-definite deep kernel. We propose four different frameworks in order to learn the weights of these networks: supervised, unsupervised, kernel-based semisupervised and Laplacian-based semi-supervised. When plugged into support vector machines (SVMs), the resulting deep kernel networks show clear gain, compared to several shallow kernels for the task of image annotation. Extensive experiments and analysis on the challenging ImageCLEF photo annotation benchmark, the COREL5k database and the Banana dataset validate the effectiveness of the proposed method.

  12. Hymenoptera Genome Database: integrating genome annotations in HymenopteraMine

    PubMed Central

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

    2016-01-01

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

  13. Hymenoptera Genome Database: integrating genome annotations in HymenopteraMine.

    PubMed

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

    2016-01-04

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

  14. Visualizing Genomic Annotations with the UCSC Genome Browser.

    PubMed

    Hung, Jui-Hung; Weng, Zhiping

    2016-11-01

    Genomic data and annotations are rapidly accumulating in databases such as the UCSC Genome Browser, NCBI, and Ensembl. Given the massive scale of these genomic databases, it is important to be able to easily retrieve known data and annotations of a specified genomic locus. For example, for a newly identified cis-regulatory element bound by a transcription factor, questions that immediately come to mind include whether the element is near a transcriptional start site and, if so, the name of the corresponding gene, and whether the histones or DNA at the locus are modified. The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. This protocol describes how to use the UCSC Genome Browser to visualize selected tracks at specified genomic regions, download the data and annotations for further analysis, and retrieve multiple sequence alignments and their conservation scores.

  15. Sma3s: A Three-Step Modular Annotator for Large Sequence Datasets

    PubMed Central

    Muñoz-Mérida, Antonio; Viguera, Enrique; Claros, M. Gonzalo; Trelles, Oswaldo; Pérez-Pulido, Antonio J.

    2014-01-01

    Automatic sequence annotation is an essential component of modern ‘omics’ studies, which aim to extract information from large collections of sequence data. Most existing tools use sequence homology to establish evolutionary relationships and assign putative functions to sequences. However, it can be difficult to define a similarity threshold that achieves sufficient coverage without sacrificing annotation quality. Defining the correct configuration is critical and can be challenging for non-specialist users. Thus, the development of robust automatic annotation techniques that generate high-quality annotations without needing expert knowledge would be very valuable for the research community. We present Sma3s, a tool for automatically annotating very large collections of biological sequences from any kind of gene library or genome. Sma3s is composed of three modules that progressively annotate query sequences using either: (i) very similar homologues, (ii) orthologous sequences or (iii) terms enriched in groups of homologous sequences. We trained the system using several random sets of known sequences, demonstrating average sensitivity and specificity values of ∼85%. In conclusion, Sma3s is a versatile tool for high-throughput annotation of a wide variety of sequence datasets that outperforms the accuracy of other well-established annotation algorithms, and it can enrich existing database annotations and uncover previously hidden features. Importantly, Sma3s has already been used in the functional annotation of two published transcriptomes. PMID:24501397

  16. Sma3s: a three-step modular annotator for large sequence datasets.

    PubMed

    Muñoz-Mérida, Antonio; Viguera, Enrique; Claros, M Gonzalo; Trelles, Oswaldo; Pérez-Pulido, Antonio J

    2014-08-01

    Automatic sequence annotation is an essential component of modern 'omics' studies, which aim to extract information from large collections of sequence data. Most existing tools use sequence homology to establish evolutionary relationships and assign putative functions to sequences. However, it can be difficult to define a similarity threshold that achieves sufficient coverage without sacrificing annotation quality. Defining the correct configuration is critical and can be challenging for non-specialist users. Thus, the development of robust automatic annotation techniques that generate high-quality annotations without needing expert knowledge would be very valuable for the research community. We present Sma3s, a tool for automatically annotating very large collections of biological sequences from any kind of gene library or genome. Sma3s is composed of three modules that progressively annotate query sequences using either: (i) very similar homologues, (ii) orthologous sequences or (iii) terms enriched in groups of homologous sequences. We trained the system using several random sets of known sequences, demonstrating average sensitivity and specificity values of ~85%. In conclusion, Sma3s is a versatile tool for high-throughput annotation of a wide variety of sequence datasets that outperforms the accuracy of other well-established annotation algorithms, and it can enrich existing database annotations and uncover previously hidden features. Importantly, Sma3s has already been used in the functional annotation of two published transcriptomes.

  17. MSTor: A program for calculating partition functions, free energies, enthalpies, entropies, and heat capacities of complex molecules including torsional anharmonicity

    NASA Astrophysics Data System (ADS)

    Zheng, Jingjing; Mielke, Steven L.; Clarkson, Kenneth L.; Truhlar, Donald G.

    2012-08-01

    We present a Fortran program package, MSTor, which calculates partition functions and thermodynamic functions of complex molecules involving multiple torsional motions by the recently proposed MS-T method. This method interpolates between the local harmonic approximation in the low-temperature limit, and the limit of free internal rotation of all torsions at high temperature. The program can also carry out calculations in the multiple-structure local harmonic approximation. The program package also includes six utility codes that can be used as stand-alone programs to calculate reduced moment of inertia matrices by the method of K