Lisa Matthews, 1 Esther Schmidt, 2 Suzanna Lewis, 3 David Croft, 2 Bernard de Bono, 2 Peter D'Eustachio, 1 Marc Gillespie, 1 Gopal Gopinath, 1 Bijay Jassal, 2 Imre Vastrik, 2 Guanming Wu, 1 Ewan Birney, 2 and Lincoln Stein 1 1 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; 2 European Bioinformatics Institute, Hinxton, UK; 3 Lawrence Berkeley National Lab, Berkeley CA Reactome is a curated, refereed resource of human biological processes that can be browsed and queried at a public web site, Processes are annotated by tracking participating physical entities and the locations of these entities in the cell. Data objects in Reactome are linked to GO in three ways: functions of molecules in reactions (binding, catalysis, etc.) are specified with Molecular_Function terms; locations of molecules and events are specified with Cellular_Component terms; and events (both multistep pathways and single step reactions) are described with Biological_Process terms. These links are supported by manually curated citations to the published research literature. Reactome is working to increase the numbers and types of annotations shared with GO and improve the mapping between Reactome Pathways and Reactions and GO Process and Function terms. Goals: 1. To provide Reactome curated referenced GO annotations where they do not currently exist in GOA. 2. To provide stronger experimental evidence for GOA annotation, to supersede annotations only supported by computational inferences. 3. To improve the accuracy and consistency of the annotations in both databases by carrying out automated comparisons and manually checking discrepancies. Progress: We are submitting Molecular Function and Biological Process annotations, bi- annually, now ~50 annotations/submission, with the TAS evidence code. Accuracy and consistency checks comparing GO terms applied to the same human proteins in both databases have revealed < 10 potential discrepancies in each analysis. Potential discrepancies are defined as cases in which the terms applied do not match and are in different branches of the hierarchy. None of the discrepancies analyzed have revealed improper term usage. To boost the volume of Reactome annotations submitted to GOA, we will: 1. start submitting Cellular Component annotations in the near future. This will occur following the implementation of stable identifiers (Summer of 2006). 2. improve the mapping between Reactome Reactions and Pathways and GO Molecular Function and Biological Process respectively. Overview Development of Reactome is supported by grants R01 HG from NHGRI / NIH and LSHG-CT from the EU (6th Framework Programme), and by a sub- contract from the NIH-funded Cell Migration Consortium. Home page Pathway page Reaction page Download page The Reactome:GOA collaboration Current GO term usage in Reactome Retrofitting GO terms to Reactome GO OntologyReactome ReactionReactome Pathway function983 (56%)not applicable process131 (8%)183 (26%) compartment1510 (92%)524 (74%) Creating a closer mapping between Reactome reactions /pathways and GO molecular functions / biological processes Issue: 34% of Reactome reactions and 74% of pathways have not been mapped to GO. Approach to align GO and Reactome concepts: 1. Retro-fix of existing annotations: Progress: -Created an applet that displays GO and Reactome term/concept trees highlighting terms that do not map (below) -Pilot projects testing different approaches to identify the quickest way to improve mappings 1. Side by side mapping (GO and Reactome curators look at both GO and Reactome trees to identify fixes either by GO term addition or applying an existing term missed by Reactome curator. 2. Look to see how many unmapped terms could be fixed by adding missing “part of” relationships in GO. Results: - Mapping pilot I (65 Reactome terms under apoptosis) shows that the time taken to review terms is about 4.2 minutes/term. Finding references and generate definition for GO (13 min = average of 5), entering term request (1.5 min), applying the missing term to Reactome (3 min). This averages to about 19 min/term x 1000 unmapped terms = min = 39 (8 hr) days. -Mapping project II (in progress). GO and Reactome term lists can both be browsed with the option of highlighting terms that have been mapped between the two hierarchies. Terms hyperlink to their corresponding entries in QuickGO and Reactome. Hierarchies can be viewed either alphabetically or in tree format. Synchronizing selection aligns Reactome and GO hierarchies to show selected term from one hierarchy and term to which it has been mapped in the other hierarchy. Both Reactome and GO vocabularies can be searched for terms of interest from within the tool.