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Robin Haw 15-19th August 2012 COMBINE – Toronto Meeting www.reactome.org. Reforming Reactome. Ministry of Economic Development and Innovation. What is Reactome?. Open source and open access pathway database
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Robin Haw 15-19th August 2012 COMBINE – Toronto Meeting www.reactome.org Reforming Reactome Ministry of Economic Development and Innovation
What is Reactome? • Open source and open access pathway database • 1300+ human pathways encompassing metabolism, signaling, gene regulation, and other biological processes • Extensively cross-referenced to external bioinformatics databases • Tools and datasets for browsing and visualizing pathway data, and interpreting your experimental data. www.reactome.org
Data model in a nutshell • Reactome is a Reaction Network Database • Explicitly describe biological processes as a series of biochemical reactions and events • Represents many events and states found in biology. Regulation (GO biol process) Input 1 Output 1 Reaction Input 2 Output 2 CatalystActivity (GO mol function) location (GO cell component) protein (UniProt) or molecule (ChEBI) or complex (GO/PRO) or ncRNA (miRBase) or disease variants (UniProt) therapeutics (ChEBI)
Curation Pipeline Pathways in Other Databases BioPAX Importer SBML Importer KGML Importer Automated Curation Manual Curation Author Web Pages Reviewer Author Tool CGI Scripts Curator Live DB Curator Tool Dev DB RC DB Data Expansion by electronic inference using mutual best hits from human to model organisms
Focus on Disease Topics • Not new to Reactome! • Reorganized the Pathway Hierarchy. • Modified the Data Model. • Updating the Pathway Browser. • Annotate: • An infection introduces new proteins into the cell. • The amount of a normal protein is changed and this changes the function of the protein. • A mutation (somatic or germline) changes the function of a protein. • Mode of action of anti-cancer therapeutics and antibodies.
Disease Curation We need a more systematic disease ontology! Details of EGFRvIII mutant in Signaling by EGFR in Cancer
Pathway BrowserDivide reaction space into ~170 canonical pathways Amyloid Pathway • Google-map style pathway diagrams with overlays
Open access and open source data MySQL db ID Mapping Interactions GOA SBML BioPAX GSEA Protege Textbook Local install Author tool Curator tool Reactome FI
Reactome supports Data Standards Available for single pathways. PSICQUIC is an effort to standardize the access to molecular interaction databases. PSI-MITAB is the data exchange format. BioPAX level 2 & 3. Available for single pathways or for the whole database. SBML level 2.3. Available for single pathways or for the whole database.
Interaction Overlay using PSICQUICVisualizing Protein-protein Interactions • Download molecular interaction data as PSI-MITAB file
Continuing Priorities • Increase the number of curated proteins and other functional entities. • Supplement normal pathways with variant reactions representing disease states. • Improve annotation consistency and enrich the data model. • Continued support for SBGN, SBML, BioPAX and PSI. • Enhance the web site and other resources to meet the needs of a growing and diverse user community.
Acknowledgements • MarijaOrlic-Milacic • Karen Rothfels • Lisa Matthews • Marc Gillespie • Guanming Wu • Irina Kalatskaya • Christina Yung • Michael Caudy • David Croft • Adrian Duong • PhaniGarapati • BijayJassal • Steve Jupe • Bruce May • Antonio FabregatMundo • Veronica Shamovsky • Heeyeon Song • Joel Weiser • Mark Williams • Henning Hermjakob • Peter D’Eustachio • Lincoln Stein Ministry of Economic Development and Innovation