Faculty Bibliography
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191
Gramene 2013: comparative plant genomics resources
Gramene (http://www.gramene.org) is a curated online resource for comparative functional genomics in crops and model plant species, currently hosting 27 fully and 10 partially sequenced reference genomes in its build number 38. Its strength derives from the application of a phylogenetic framework for genome comparison and the use of ontologies to integrate structural and functional annotation data. Whole-genome alignments complemented by phylogenetic gene family trees help infer syntenic and orthologous relationships. Genetic variation data, sequences and genome mappings available for 10 species, including Arabidopsis, rice and maize, help infer putative variant effects on genes and transcripts. The pathways section also hosts 10 species-specific metabolic pathways databases developed in-house or by our collaborators using Pathway Tools software, which facilitates searches for pathway, reaction and metabolite annotations, and allows analyses of user-defined expression datasets. Recently, we released a Plant Reactome portal featuring 133 curated rice pathways. This portal will be expanded for Arabidopsis, maize and other plant species. We continue to provide genetic and QTL maps and marker datasets developed by crop researchers. The project provides a unique community platform to support scientific research in plant genomics including studies in evolution, genetics, plant breeding, molecular biology, biochemistry and systems biology.
PMCID:3964986
PMID: 24217918
ISSN: 0305-1048
CID: 782552
Protein Ontology: a controlled structured network of protein entities
The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to UniProtKB in that PRO's organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO's representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments.
PMCID:3964965
PMID: 24270789
ISSN: 0305-1048
CID: 652102
Pathway databases: making chemical and biological sense of the genomic data flood
Pathway databases are a means to systematically associate proteins with their functions and link them into networks that describe the reaction space of an organism. Here, the Reactome Knowledgebase provides a convenient example to illustrate strategies used to assemble such a reaction space based on manually curated experimental data, approaches to semiautomated extension of these manual annotations to infer annotations for a large fraction of a species' proteins, and the use of networks of functional annotations to infer pathway relationships among variant proteins that have been associated with disease risk through genome-wide surveys and resequencing studies of tumors.
PMCID:3678733
PMID: 23706629
ISSN: 1074-5521
CID: 361782
Gene Ontology annotations and resources
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.
PMCID:3531070
PMID: 23161678
ISSN: 1362-4962
CID: 2953432
Annotating cancer variants and anti-cancer therapeutics in reactome
Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of "cancer" pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics.
PMCID:3712731
PMID: 24213504
ISSN: 2072-6694
CID: 3663682
The Gene Ontology: enhancements for 2011
The Gene Ontology (GO) (http://www.geneontology.org) is a community bioinformatics resource that represents gene product function through the use of structured, controlled vocabularies. The number of GO annotations of gene products has increased due to curation efforts among GO Consortium (GOC) groups, including focused literature-based annotation and ortholog-based functional inference. The GO ontologies continue to expand and improve as a result of targeted ontology development, including the introduction of computable logical definitions and development of new tools for the streamlined addition of terms to the ontology. The GOC continues to support its user community through the use of e-mail lists, social media and web-based resources.
ISI:000298601300084
ISSN: 0305-1048
CID: 2337532
Recent advances in biocuration: meeting report from the Fifth International Biocuration Conference [Meeting Abstract]
The 5th International Biocuration Conference brought together over 300 scientists to exchange on their work, as well as discuss issues relevant to the International Society for Biocuration's (ISB) mission. Recurring themes this year included the creation and promotion of gold standards, the need for more ontologies, and more formal interactions with journals. The conference is an essential part of the ISB's goal to support exchanges among members of the biocuration community. Next year's conference will be held in Cambridge, UK, from 7 to 10 April 2013. In the meanwhile, the ISB website provides information about the society's activities (http://biocurator.org), as well as related events of interest.
PMCID:3483532
PMID: 23110974
ISSN: 1758-0463
CID: 2953412
The representation of protein complexes in the Protein Ontology (PRO)
ABSTRACT: BACKGROUND: Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. DESCRIPTION: We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. CONCLUSION: PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species
PMCID:3189193
PMID: 21929785
ISSN: 1471-2105
CID: 139625
Reactome pathway analysis to enrich biological discovery in proteomics data sets
Reactome (http://www.reactome.org) is an open-source, expert-authored, peer-reviewed, manually curated database of reactions, pathways and biological processes. We provide an intuitive web-based user interface to pathway knowledge and a suite of data analysis tools. The Pathway Browser is a Systems Biology Graphical Notation-like visualization system that supports manual navigation of pathways by zooming, scrolling and event highlighting, and that exploits PSI Common Query Interface web services to overlay pathways with molecular interaction data from the Reactome Functional Interaction Network and interaction databases such as IntAct, ChEMBL and BioGRID. Pathway and expression analysis tools employ web services to provide ID mapping, pathway assignment and over-representation analysis of user-supplied data sets. By applying Ensembl Compara to curated human proteins and reactions, Reactome generates pathway inferences for 20 other species. The Species Comparison tool provides a summary of results for each of these species as a table showing numbers of orthologous proteins found by pathway from which users can navigate to inferred details for specific proteins and reactions. Reactome's diverse pathway knowledge and suite of data analysis tools provide a platform for data mining, modeling and analysis of large-scale proteomics data sets. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP 8)
PMCID:4617659
PMID: 21751369
ISSN: 1615-9861
CID: 150116
Human and chicken TLR pathways: manual curation and computer-based orthology analysis
The innate immune responses mediated by Toll-like receptors (TLR) provide an evolutionarily well-conserved first line of defense against microbial pathogens. In the Reactome Knowledgebase we previously integrated annotations of human TLR molecular functions with those of over 4000 other human proteins involved in processes such as adaptive immunity, DNA replication, signaling, and intermediary metabolism, and have linked these annotations to external resources, including PubMed, UniProt, EntrezGene, Ensembl, and the Gene Ontology to generate a resource suitable for data mining, pathway analysis, and other systems biology approaches. We have now used a combination of manual expert curation and computer-based orthology analysis to generate a set of annotations for TLR molecular function in the chicken (Gallus gallus). Mammalian and avian lineages diverged approximately 300 million years ago, and the avian TLR repertoire consists of both orthologs and distinct new genes. The work described here centers on the molecular biology of TLR3, the host receptor that mediates responses to viral and other doubled-stranded polynucleotides, as a paradigm for our approach to integrated manual and computationally based annotation and data analysis. It tests the quality of computationally generated annotations projected from human onto other species and supports a systems biology approach to analysis of virus-activated signaling pathways and identification of clinically useful antiviral measures
PMCID:3035812
PMID: 21052677
ISSN: 1432-1777
CID: 134159
