1. 1 SRI International Bioinformatics GO Term Integration and Curation in Pathway Tools and EcoCyc Ingrid M. Keseler Bioinformatics Research Group SRI International keseler@ai.sri.com

2. 2 SRI International Bioinformatics History of Classification and GO terms in EcoCyc The MultiFun classification scheme was/is used for gene/gene product classification in EcoCyc. Developed by Monica Riley and collaborators Hierarchical classification scheme with 10 major categories for cellular function In 2005, we began to add support for adding GO terms to genes/gene products.

3. 3 SRI International Bioinformatics Why go with GO? GO has become the standard ontology/classification scheme for gene products GO is being actively developed with input from the user communities GO is allowing standardization of annotation across all domains of life l Data mining across genomes l Genome annotation by similarity (e.g. via InterPro, Pfam, TIGRFAM, COG mappings) Tools that take advantage of GO annotations, e.g. microarray data clustering etc.

4. 4 SRI International Bioinformatics The Evolution of GO Within EcoCyc 1.12/2005 -- Mapping of MultiFun terms to GO terms (multifun2go – Ashburner and Lomax): multiple specific GO terms were sometimes mapped to one general MultiFun term, resulting in misleading GO term annotations in EcoCyc; no evidence codes, citations 2.12/2007 -- Mapping of EC reactions to GO terms (ec2go): imported GO terms for enzymes that catalyzed reactions with full EC number assignments; no evidence codes, citations

5. 5 SRI International Bioinformatics 3.4/2008 -- Importing GO term assignments from UniProt; mostly computational evidence codes 4.Since ~2007 -- Manual curation of GO terms based on publications, with evidence codes (mostly experimental) and literature citations 5.Since ~2008 -- EcoCyc and EcoliWiki are the source of the official E. coli gene-association file (in collaboration with J. Hu and D. Siegele, EcoliWiki, Texas A&M) The Evolution of GO Within EcoCyc

6. 6 SRI International Bioinformatics Of Requirements and Differences Specific requirements for GO gene-association file l Presence of evidence codes and citations l Pathway Tools uses a different evidence code ontology; it is therefore necessary to map the evidence codes carefully l Some types of evidence require use of a With/From qualifier in GO – e.g IPI, ISS l Annotation with other qualifiers is not required by GO (e.g. NOT, contributes_to, colocalizes_with) and is not (yet) supported by Pathway Tools

7. 7 SRI International Bioinformatics Tools for the Curator GO classification editor is accessible via the protein editor GO database can be searched in the editor; term definitions are available Tools available locally (ask developers about general availability): l Import new GO database (for newly created terms etc.) l Export gene-association file

8. 8 SRI International Bioinformatics Manual Curation of GO terms Ongoing when we curate or re-curate gene products within EcoCyc No particular effort to back-fill GO terms; e.g. metabolic enzymes get experimental GO term assignments when we re-curate old metabolic pathways, or when new literature appears Texas A&M team is part of the Reference Genome Annotation Project; GO term assignments from EcoliWiki get imported into EcoCyc on a regular basis

9. 9 SRI International Bioinformatics GO Term Statistics for E. coli (8/2009) 3721 gene products annotated with at least one GO term 42724 total GO term annotations, of which there are 6330 non-IEA annotations

10. 10 SRI International Bioinformatics Acknowledgements Peter Karp Suzanne Paley Markus Krummenacker Tomer Altman Jim Hu Debby Siegele GO experts at the GO consortium