The Gene Ontology: a real-life ontology, progress and future. Jane Lomax EMBL-EBI

What is the Gene Ontology? Controlled vocabulary - GO –Terms and relationships –Bottom-up approach Annotation of proteins to terms –Gene association files Software/database development Freely available

The vocabulary GO is divided into three sub-vocabularies: –biological process broad series of events, can either be at the level of the cell or organism e.g. circulation, glycolysis –molecular function direct activities e.g. catalysis, binding –cellular component site of action e.g. nucleus, ribosome

The vocabulary Hierarchical Directed Acyclic Graph –terms have one or more parents is-a and part-of relations

How is GO maintained? Several full-time editors Requests from community –database curators, researchers, software developers –SourceForge tracker GO Consortium meetings for large changes Mailing lists

OBO - Open Biological Ontologies GO is a member vocabulary of OBO A repository for biological structured vocabularies –Freely available without license –Common syntax –Orthogonal to existing ontologies

Future developments File format –Current GO flat file format partly redundant difficult to parse –New format Extensible e.g. new relationship types can be specified minimal redundancy, but human readable easier to parse Moving to a database being the primary form of GO

Formalizing GO Informality is a common criticism of GO –developed by biologists, for biologists Now beginning work ‘decomposing’ GO using ProLog –Terms broken down into constituent parts e.g. regulation of heart development –New terms could be created from orthogonal ontologies e.g. anotomical Work translating GO in DL, reasoning across the ontologies

GO into UMLS GO now released as part of the NLM’s Unified Medical Language System Metathesaurus Links biomedical vocabularies including MeSH and SNOMED. The process of including GO in UMLS highlighted problems in both systems

GO synonyms Text strings associated with GO terms Often do not have identical meaning to term Reduces utility in e.g. semantic matching Developed relationships between terms and synonyms –soon to be fully implemented in GO

FlyBase & Berkeley Drosophila Genome Project Saccharomyces Genome Database PomBase (Sanger Institute) Rat Genome Database Genome Knowledge Base (CSHL) The Institute for Genomic Research Compugen, Inc The Arabidopsis Information Resource WormBase DictyBase Mouse Genome Informatics Swiss-Prot/TrEMBL/InterPro Pathogen Sequencing Unit (Sanger Institute) The Gene Ontology Consortium is supported by an R01 grant from the National Human Genome Research Institute (NHGRI) [grant HG02273]. SGD is supported by a P41, National Resources, grant from the NHGRI [grant HG01315]; MGD by a P41 from the NHGRI [grant HG00330]; GXD by the National Institute of Child Health and Human Development [grant HD33745]; FlyBase by a P41 from the NHGRI [grant HG00739] and by the Medical Research Council, London. TAIR is supported by the National Science Foundation [grant DBI ]. WormBase is supported by a P41, National Resources, grant from the NHGRI [grant HG02223]; RGD is supported by an R01 grant from the NHLBI [grant HL64541]; DictyBase is supported by an R01 grant from the NIGMS [grant GM064426].