Research interests

Functional and Comparative Genome Informatics
My research focuses on functional and comparative genome informatics. I work on the development of systems to integrate and interrogate genetic, genomic and phenotypic information. I am one of the leaders of the Gene Ontology (GO) project and I have been deeply involved with the work of the GO Consortium since its inception. The Gene Ontology project is an international effort to provide controlled structured vocabularies for molecular biology that serve as terminologies, classifications and ontologies to further data integration, analysis and reasoning. My interest in bio-ontologies stems as well from the work I do as a principal investigator with the Mouse Genome Informatics (MGI) project at The Jackson Laboratory. The MGI system is a model organism community database resource that provides integrated information about the genetics, genomics and phenotypes of the laboratory mouse. My current research projects combine bio-ontologies and database knowledge systems to represent disease processes with the objective of discovering molecular elements that contribute to particular pathologies such as lung cancer.

The Gene Ontology Consortium
Widespread use of the GO system for functional annotation of genomes enables comparative analysis of genome-size data sets. Understanding and supporting the GO annotation process and bringing new groups into the GO community is essential to the continued development of a broad, integrated network of biological information that can be transparently shared to enable and advance knowledge discovery. The GO Consortium group now consists of 19 model organism databases and genome-annotation groups who work cooperatively to construct the GO bio-ontologies, to provide functional annotations for a wide variety of organisms, and to support a GO information resource. GO participants located at The Jackson Laboratory lead ontology development projects, develop new software applications for the GO project, and provide GO annotations for mouse gene products. Other core groups of the GO project include an ontology development group based at the European Bioinformatics Institute in the United Kingdom, a software and resource development group based at Lawrence Berkeley National Laboratory, and a production database group based at Stanford University. Notable accomplishments of the GO Consortium this year included:

Initiation of the 'reference genome' project to provide comprehensive functional annotations across the gene ortholog sets of the major model organisms for genes implicated in human diseases;

Revision of subtrees of the GO to update and extend the representation of early central nervous system development processes;

Development of new community functional annotation systems for genes involved in immunological processes;
ontological improvements including " is a complete" updates for all domains; and

Publishing of an electronic GO newsletter to inform our community on GO developments.

Our work with the Gene Ontology Consortium complements our local continuing efforts to enhance the representation of genes and gene products in the MGI system. We contribute an updated mouse GO annotation file to the GO database each week.

The Mouse Genome Informatics Project
MGI supports scientific research that uses the laboratory mouse as a model for the study of human biology and disease. MGI data are curated both from the biomedical literature and from co-curated data loads from other major bioinformatics resources. My research group is responsible for the functional and comparative annotation of mouse genes in the MGI resource. This work includes defining the mouse gene set (in co-curation with other informatics resource providers), indexing the biomedical literature for functional annotation, providing official gene nomenclature along with a robust set of synonyms, and extending the representation of relationships between mouse, human and rat genes and genomes. We work closely with the MGI Sequences and Sequence Maps group (see report by Carol J. Bult) to resolve sequence-based inconsistencies in the representations of the mouse genome and the sequence and mapping data integrated in MGI and between MGI and other informatics resource centers such as the NCBI, Ensembl and the UniProt groups. We also work closely with the MGI Phenotypes group (see report by Janan Eppig) to support the development of standards for the representation of phenotype/genotype data in MGI.

Major projects this year included:

Incorporation of orthology sets for chimpanzee and dog genes and gene models to complement our existing focus on human and rat orthologs;

Collaborations with scientific community experts in the nomenclature revisions of 16 gene families, including tubulin, kallikrein, keratin, late cornified envelope, and vomeronasal 2 receptor; and

Revision of the literature review and curation process to reflect emergence of electronic publication resources.

MGI-GO Scientific Curators are using a combination of algorithmic and manual approaches to update annotations of mouse gene products to the GO vocabularies. Currently, more than 17,500 mouse genes have at least preliminary GO annotations and over 9,700 have annotations based on experimental assays in mouse. We use data-mining and other strategies to semi-automate gene annotation to the GO. The highest quality annotations, however, depend on skilled scientific curators who review published literature for information that provides experimental verification for the GO attributions.

Publications

• Blake JA, Bult CJ, Eppig JT, Kadin JA, Richardson JE; Mouse Genome Database Group. 2009. The Mouse Genome Database genotypes::phenotypes. Nucleic Acids Res. 37(Database):D712-9.
• Altman RB, Bergman CM, Blake J, Blaschke C, Cohen A, Gannon F, Grivell L, Hahn U, Hersh W, Hirschman L, Jensen LJ, Krallinger M, Mons B, O'Donoghue SI, Peitsch MC, Rebholz-Schuhmann D, Shatkay H, Valencia A. 2008. Text mining for biology--the way forward: opinions from leading scientists. Genome Biol. 9(suppl 2):S7. PMC2559991
• Bult CJ, Eppig JT, Kadin JA, Richardson JE, Blake JA; Mouse Genome Database Group. 2008. The Mouse Genome Database (MGD): mouse biology and model systems. Nucleic Acids Res. 36(Database):D724-8.
• Hill DP, Smith B, McAndrews-Hill MS, Blake JA. 2008. Gene Ontology annotations: what they mean and where they come from. BMC Bioinformatics 9:Suppl 5:S2. PMC2367625
• Lovering RC, Camon EB, Blake JA, Diehl AD. 2008. Access to immunology through the Gene Ontology. Immunology 125(2):154-60.
• Pena-Castillo L, Tasan M, Blake JA, [40 authors]Ö Roth FP. 2008. A critical assessment of M. musculus gene function prediction using integrated genomic evidence. Genome Biology 9(Suppl 1):S2. PMC2447536
• Tasan M, Tian W, Hill DP, Gibbons FD, Blake JA, Roth FP. 2008. An en masse phenotype and function prediction system for M. musculus. Genome Biology. 9:S8. PMC2447542
• The Gene Ontology Consortium*. 2008. The Gene Ontology (GO) Project in 2008. Nucleic Acids Res. 36(Database):D440-4.
• Blake JA and Harris MA. 2008. The Gene Ontology(GO) Project: Structured Vocabularies for Molecular Biology and Their Application to Genome and Expression Analysis. In: Current Protocols in Bioinformatics (23)7.2.1-7.2.9.
• Bult CJ, Eppig JT, Kadin JA, Richardson JE, Blake JA. 2007. The Mouse Genome Database (MGD): mouse biology and model systems. Nucleic Acids Res.
• Diehl AD, Lee JA, Scheuermann RH, Blake JA. 2007. Ontology development for biological systems: Immunology. Bioinformatics 31(epub):.
• Eppig JT, Blake JA, Bult CJ, Kadin JA, Richardson JE and Mouse Genome Database Group. 2007. The mouse genome database(MGD): new features facilitating a model system. Nucleic Acids Res 35:D630-7.
• Eppig JT, Blake JA, Bult CJ, Richardson JE, Kadin JA, Ringwald M and the MGI Staff. 2007. Mouse Genome Informatics (MGI) resources for pathology and toxicology. Toxicol Pathol 35:456-7.
• Natale DA, Arighi CN, Barker WC, Blake JA, Chang T-C, Hu Z, Liu H, Smith B, Wu CH. 2007. Framework for a Protein Ontology. BMC Bioinformatics 8(Suppl 9):S1.
• Blake JA, Bult CJ. 2006. Beyond the data deluge: data integration and bio-ontologiees. J Biomen Inform 39:314-320.
• Blake JA, Eppig JT, Bult CJ, Kadin JA, Richardson JE, and Mouse Genome Database Group. 2006. The Mouse Genome Database (MGD): updates and enhancements. Nucl Acids Res 34:D562-D567.
• Eppig JT, Blake JA, Bult CJ, Kadin JA, Richardson JE. 2006. The Mouse Genome Database(MGD): new features facilitation a model system. Nucleic Acids Research epub(Nov 29):.
• Dolan M,Camon E, Blake JA. 2005. A Procedure for Assessing GO Annotation Consistency. Bioinformatics 21(suppl 1):i136-i143.
• Drabkin HJ, Hollenbeck C, Hill DP and Blake JA. 2005. Ontological visualization of protein-protein interactions. BMC Bioinfornatics 6:29.
• Eppig JT, Bult CJ,Kadin JA, Richardson JE, Blake JA, Anagnostopoulos A, Baldarelli RM, Baya M, Beal JS et al. 2005. The Mouse Genome Database (MGD) : from genes to mice ---a community resource for mouse biology. Nucleic Acids Res 33 :D471-5.
• Santos C, Blake J, States DJ. 2005. Supplementary data need to be kept in public repositories. Nature 438:738.
• Bada M, Stevens R, Goble C, Gil Y,Ashburner M, Blake JA, Harris M, and Lewis S. 2004. A Short Study on the Success of the Gene Ontology. Journal of Web Semantics 1(2):.
• Blake J. 2004. Bio-ontologies-fast and furious. Nat Biotechnol 22(6):773-4.
• Bult CJ,Blake JA,Richardson JE,Kadin JA,Eppig JT,and the Mouse Genome Database Group*. 2004. The Mouse Genome Database (MGD): integrating biology with the genome. Nucleic Acids Research 32:D476-D481.
• Evsikov A, deVries WN, Peaston AE, Radford EE, Fancher KS,Chen FH,Blake JA,Bult CJ,Latham KE,Soltor D,Knowles BB. 2004. Systems biology of the 2-cell mouse embryo. Cytogenet Genome Res 105:240-250.
• Hill DP, Begley DA, Finger JH, Hayamizu TF, McCright IJ, Smith CM, Beal JS, Corbani LE, Blake JA, Eppig JT, Kadin JA, Richardson JE, Ringwald M. 2004. The Mouse Gene Expression Database (GXD): Updates and Enhancements. Nucleic Acids Research 32:D568-D571.
• Richardson JE, Kadin JA, Blake JA, Bult CJ, Eppig JT, Ringwald M and the Mouse Genome Informatics Group.. 2004. From sipping on a straw to drinking from a fire hose; data integration in a public genome database. Data Engineering, Proceedings. 20th International Conference pp. 795-798.
• The Gene Ontology Consortium*. 2004. The Gene Ontology (GO) Database and Informatics Resource. Nucleic Acids Research 32:D258-D261.
• Tuason O, Chen L, Liu H, Blake JA, Friedman C. 2004. Biological nomenclatures: source of lexical knowledge and ambiguity. Pac Symp Biocomput 238-49.
• Baldarelli RM, Hill DP, Blake JA, Adachi J, Furuno M, Bradt D, Corbani LE, Cousins S, Frazer KS, Qi D, Yang L, Ramachandran S, Reed D, Zhu Y, Kasukawa T, Ringwald M, King BL, Maltais LJ, McKenzie LM, Schriml L, Maglott D, Church D, Pruitt K, Okazaki Y, Hayashizaki Y, Eppig JT, Richardson JE, Kadin JA, Bult CJ. 2003. Connecting Sequence and Biology in the Laboratory Mouse. Genome Res 13(6b):1505-1529.
• Blake JA, Richardson JE, Bult CJ, Kadin JA, Eppig JT and the Mouse Genome Database Group. 2003. The Mouse Genome Database. Nucleic Acids Res 31:193-5.
• Schriml LM, Hill DP, Blake JA, Bono H, Wynshaw-Boris A, Paven W, Ring BZ, Beisel K, Setou M, Okazaki Y, Hayashizaki Y. 2003. Human Disease Genes and their cloned Mouse Orthologs: Exploration of the FANTOM2 dataset. Genome Res 13(6b):1496-1501.
• Blake JA, Eppig JT, Bult CJ. 2003. Mouse and Rat Genome Informatics. In: Bioinformatics for Geneticists.. M.R. Barnes and I.C. Gray (eds.), Wiley Press, London.
• Blake JA, Richardson JE, Bult CJ, Kadin JA, Eppig JT and the Mouse Genome Database Group. 2002. The Mouse Genome Database (MGD): The model organism database for the laboratory mouse. Nucleic Acids Res 30(1):113-5.
• Eppig JT, Blake JA, Burkart DL, Goldsmith CW, Lutz CM, Smith CL. 2002. Corralling conditional mutations: A unified resource for mouse phenotypes. Genesis 32(2):63-5.
• Hill DP, Blake JA, Richardson JE and Ringwald M. 2002. Extension and Integration of the Gene Ontology (GO): Combining GO vocabularies with external vocabularies. Genome Res 12:1982-91.
• Maltais LJ, Blake JA, Chu T, Lutz CM, Eppig JT, Jackson I. 2002. Rules and guidelines for mouse gene, allele, and mutation nomenclature: a condensed version. Genomics 79(4):471-4.
• The FANTOM Consortium and the RIKEN Genome Exploration Research Group Phase I and II team*. 2002. Analysis of the mouse transcriptome based on the functional annotation of 60,770 full-length cDNAs. Nature 420:563-73.
• Blake JA, Eppig JT, Richardson JE, Bult CJ, Kadin JA, and the Mouse Genome Database Group. 2001. The Mouse Genome Database (MGD): Integration Nexus for the laboratory mouse. Nucleic Acids Res 29(1):91-94.
• Hill DP, Davis AP, Richardson JA, Corradi J, Ringwald M, Eppig JT, Blake JA. 2001. Strategies for biological annotation of mammalian systems: Implementing gene ontologies in mouse genome informatics. Genomics 74(1):121-8.
• The Gene Ontology Consortium. 2001. Creating the Gene Ontology Resource: Design and Implementation. Genome Res 11(8):1425-33.
• Kawai J, Shinagawa A, Shibata K, Yoshino M, Itoh M, Ishii Y, Arakawa T, Hara A, Fukunishi Y, Konno H, Adachi J, Fukuda S, Aizawa K, Izawa M, Nishi K, Kiyosawa H, Kondo S, Yamanaka I, Saito T, Okazaki Y, Gojobori T, Bono H, Kasukawa T, Saito R, Kadota K, Matsuda H, Ashburner M, Batalov S, Casavant T, Fleischmann W, Gaasterland T, Gissi C, King B, Kochiwa H, Kuehl P, Lewis S, Matsuo Y, Nikaido I, Pesole G, Quackenbush J, Schriml LM, Staubli F, Suzuki R, Tomita M, Wagner L, Washio T, Sakai K, Okido. 2001. Functional annotation of a full-length mouse cDNA collection. Nature 409(6821):685-90.

Community/University Service

• 1995 to 1997 — Community Service — NSF – Research Collections in Systematics and Ecology Advisory Panel
• 2001 to 2003 — Community Service — NIH - BISTI pre-National Programs of Excellence in Biomedical Computing (NPEBC) Advisory Panel.
• 2003 to 2009 — Community Service — External Scientific Advisory Board, Saccharomyces Genome Database (SGD) (NHGRI).
• 2003 to 2009 — Community Service — External Scientific Advisory Panel for the MDI-BL Toxicogenomics
• 2003 to 2005 — Community Service — External Scientific Panel for the Pharmacogenetics Research Network
• 2003 to 2006 — Community Service — External Scientific Advisory Board, TIGR Rice Genome Annotation Project (NSF)
• 2004 to 2009 — Community Service — TREC Genomics Track - Steering Committee (NIST)
• 2004 to 2004 — Community Service — NIH: INBRE Review Panel
• 2004 to 2005 — Community Service — NIH Ad Hoc Study Section Member: Genomics, Computational Biology and Technology (GCAT).
• 2005 to 2005 — Community Service — Special Editor, PLOS Genetics: Fantom 3 issue.
• 2005 to 2008 — Community Service — Program Committee – Intelligent Systems for Molecular Biology (ISMB).
• 2005 to 2005 — Community Service — Program Committee – Pacific Symposium on Biocomputing Meeting
• 2005 to 2005 — Community Service — Program Committee – European Conference on Computational Biology.
• 2005 to 2005 — Community Service — Program Committee - Data Integration in the Life Sciences Meeting.
• 2006 to 2009 — Community Service — NIH Study Section: Genomics, Computational Biology, and Technology (GCAT).
• 2006 to 2006 — Community Service — NHLBI Cardiovascular Strategic Planning Working Group #11
• 2006 to 2009 — Community Service — External Scientific Advisory Board, UniProt (Universal Protein Resource)
• 2006 to 2009 — Community Service — External Scientific Advisory Panel, PharmacoGenetics KnowledgeBase (PharmaGKB)
• 2006 to 2008 — Community Service — 2006-2008 Program Committee – Bio-Ontologies SIG; ISMB meeting.
• 2008 to 2009 — Community Service — CIHR (Canada Institutes of Health Research) External Scientific Advisory Board. “Model Organism Interactions and Human Diseases” project.
• 2008 to 2008 — Community Service — Reviewer. Center for Scientific Review at NIH, study section concerning computational biology