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Reactome: A Curated Database of Human Biological Pathways Lincoln Stein Infectious Disease Ontologies CSHL 2007 My Screen Found Lots of Genes: Now What? Fuzzy Hairball? Long List of GO Terms? Boehringer-Mannheim, ca 1970 Fauré et al Bioinformatics 22 (14): e124 (2002) Reactome A computable representation of human pathways and reactions. Uses a “chemical” reaction model to represent causality. Molecules identified explicitly – including small molecules, proteins, complexes, post-translational modifications, compartments. Exportable as SBML, BioPax, PDF and MySQL dumps. Open Source Authored & curated by experts in the field. Home Page A Pathway Page A Reaction Page Reaction Details Where the Data Comes From 1) Recruit bench scientists to write modules. 2) Authors use a software tool to describe their pathway. 1) All molecules must be identified explicitly. 2) All assertions backed up by literature references. 3) Curators work with authors to ensure consistency and completeness. 4) Module checked by peer review & software before publication. Author Tool SkyPainter – Overrepresentation Analysis Increasing Coverage Add non-Reactome data sets to create a “corona” of less reliable data around each pathway. Corona connected to pathway components by probable functional interaction links. Enhanced Skypainter Reactome & Infectious Disease Via collaboration with Richard Scheuermann, have created an influenza lifecycle module. 64 reactions, 338 molecules Modeling issues: Is the virion a molecular complex? A compartment? A cell? When is it OK for the proteins of two species to interact? We’d encourage other groups to do this for more pathogens. Physiology vs Pathophysiology Reactome databases Normal physiological pathways Pathophysiological pathways Non-Reactome databases specialized for infecious disease Ontology dbs WIKIs Pathogen metagenome databases etc Pathophysiology<->Physiology Pathogen-specific database Reactome Database Credits Cold Spring Harbor Laboratory European Bioinformatics Institute Gene Ontology Consortium Lincoln Stein Peter D'Eustachio Gopal Gopinathrao Lisa Matthews Marc Gillespie Guanming Wu Ewan Birney Imre Vastrik Bernardo de Bono Esther Schmidt Bijay Jassal David Croft Suzanna Lewis Richard Scheuermann & Co. NHGRI Grant # R01 HG002639 and a subcontract from the NIGMS-funded Cell Migration Consortium