Joined up ontologies: incorporating the Gene Ontology into the UMLS

The Gene Ontology (GO) Controlled vocabulary for describing molecular biology  hierarchical  multiple parentage allowed  defined terms

Structure of GO (Created using the tool GenNav, developed at NLM)

The ontologies Where does it act? What processes is it involved in? What does it do? gene product

The ontologies Where does it act? What processes is it involved in? What does it do?molecular function gene product

The ontologies Where does it act? What processes is it involved in? What does it do?molecular function biological process gene product

The ontologies Where does it act? What processes is it involved in? What does it do?molecular function cellular component biological process gene product

Gene annotation: assigning GO terms to gene products Genes or gene products GO terms “linked” to gene products Gene products annotated to all 3 ontologies May be linked to more than one term in each ontology DNA binding regulation of transcription nucleus ATP dependent helicase

Queries across databases mouse rat yeast fly Find me all gene products with ‘DNA binding activity’… DNA binding osmosensory signaling pathway regulation of transcription nucleus signal transducer nuclease DNA binding toxin catabolism helicase nucleus cytoplasm membrane mitotic cell cycle

Associating with different levels of ontology (Created using the tool GenNav, developed at NLM)

GO and other systems Useful to equate GO with other systems  Mappings files e.g. ec2go  References in GO as dbxrefs e.g. BioCyc  References in other systems e.g. BRENDA (in process) UMLS Metathesaurus

GO into UMLS Unified Medical Language System  Long-term project at NLM  Three parts: specialist lexicon; sematic network; Metathesaurus  Metathesaurus interrelates biomedical vocabularies  Includes ~60 vocabularies including SNOMED and MeSH.

Inserting GO into UMLS inversion  converting GO to correct format for UMLS insertion  inserting GO using matching algorithms editing  all concepts containing GO term reviewed by hand

Statistics % of GO in sources with other concepts, by source CSP2002 (Computer Retrieval of Information on Scientific Projects Thesaurus) 7.34 % MSH2003_2002_08_14 (Medical Subject Headings) % SNMI98 (Systemized Nomenclature of Human and Veterinary Medicine) % GO CRISP MeSH SNOMED

Potential applications Mining abstracts using GO terms: DNA helicase ; GO: UMLS MeSH term GO MeSH

Status of GO into UMLS Molecular function ontology already inserted Hope to insert other two ontologies by April Release GO with UMLS by end of year

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) National Library of Medicine Alexa McCray Stuart Nelson Bill Hole Oak Ridge Institute for Science and Education National Library of Medicine U. S. Department of Energy 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].