Transcript Reactome is - the Reactome Wiki

A curated database of biological pathways
www.reactome.org
Why are pathways important?
• Deep response
• Pathways are how cells work - going beyond the “parts list”
into mechanisms at the cellular level is a fundamental
advance in knowledge.
• Shallow response
• Lots of ‘Omics’ datasets require data integration.
Reactome is …
• Manually curated and peer-reviewed database of pathways and
processes in human biology
• Open source and open access
• Basic Unit of Reactome = “Reaction”
• Extensively cross-referenced
• Infer orthologous events in non-human species (Data Expansion)
• M/O Reactomes: Arabidopsis, Gallus, Drosophila, (Oryzae)
• Provides tools for browsing, searching, analyzing and visualizing
pathway data – Pathway Analysis, Expression Overlay, Species
Comparison, Biomart…
• Data Portability – BioPAX, SBML, PSI-MITAB, etc.
Reactome Home Page
4
Visualization
www.reactome.org
Data Visualization and Analysis
ID Mapping, Over-representation and expression analysis
Human EGFR Pathway
Increasing Coverage:
Reactome Functional Interaction Network
• Networks provide better coverage and when combined with pathway information can offer
clues to mechanism.
• Add non-Reactome data sets to create a “corona” of interaction data around each pathway.
Data Sources
Pathway databases
Protein-protein interactions
Shared GO terms
Gene co-expression data
Transcription factors/targets
Literature mining
10,956 proteins (58% in pathways)
209,988 interactions (47% in pathways)
46% coverage of UniProt
Figure: 15% of the combined network
Molecular Interaction Overlay – PSIQUIC WS
PSICQUIC Registry
APID
BIND
BioGrid
ChEMBL
DIP
InnateDB
IntAct
iRefIndex
MatrixDB
MINT
MPIDB
Reactome
Reactome-FIs
STRING
Human EGFR Pathway
Data Exchange Formats
• Promote data integration, analysis and visualization.
• PSI MITAB – representing interaction data* (*infer interactions from the complexes
and reactions).
• SBML – representing models of biochemical pathways, reactions and networks.
• BioPAX – used for representing pathway and network data.
Integrative Data Analysis using Reactome Functional
Interaction Network Cytoscape Plug-in
Reactome F.I. Network
Expt/Clinical Data
Create a Biological Hypothesis!
Predict Disease Gene Function
Classify Patients & Samples
Extract mutated, over-expressed,
down-regulated, amplified,
deleted genes
Datasets
T2D
GBM
Ovarian Cancer
Breast Cancer
Prostate Cancer
TCGA
ICGC
Apply
clustering
algorithms
Disease/Canc
er
Subnetwork
Disease/Ca
ncer
“Modules”
Pathway
Annotation
Guanming Wu, Irina Kalatskaya, Christina Yung
Programmatic Access
• Application programming interfaces (API) are important to connect and
automate data exchange between local programs and databases.
• BioMart API
• MySQL/Perl API
• MySQL/Java API
• SOAP/WSDL
• Flat files
• Database dumps
• Local site install
Uber-portal Integration (Data Warehouses) and other exports
Other Data Exports
• Gene Ontology, Protein Ontology
• HapMap and UCSC Genome Browsers
• GSEA
• WikiPathways, Wormbase, PDB
Summary
• Pathway databases are an integral part of the scientific enterprise.
• Reactome has deployed a user-friendly web site that promotes
integrated research on pathways and networks.
• Data visualization
• Data analysis
• Data expansion
• Data integration
• Data standards/exports
• Develop and distribute open software and standard operating
procedures for the management of pathway information.
Credits
OICR/CSHL
NYU
EBI
Lincoln Stein
Peter D'Eustachio
Ewan Birney
Michael Caudy
Shahana Mahajan
Henning Hermjakob
Marc Gillespie
Lisa Matthews
David Croft
Robin Haw
Veronica Shamovsky
Phani Garapati
Irina Kalatskaya
Bijay Jassal
Bruce May
Steven Jupe
Leontius Pradhana
Nelson Ndegwa
Guanming Wu
Gavin O’Kelly
Christina Yung
Esther Schmidt
Supported by grants from the US National Institutes of Health (P41
HG003751) and EU grant LSHG-CT-2005-518254 "ENFIN”