Transcript Training - Duke University

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
Ewan Birney
Imre Vastrik
Bernardo de Bono
Esther Schmidt
Bijay Jassal
David Croft
Suzanna Lewis
Marc Gillespie
Guanming Wu
Richard Scheuermann & Co.
NHGRI Grant # R01 HG002639
and a subcontract from the NIGMS-funded Cell Migration Consortium