Reactome - a curated knowledgebase of human biological pathways and
processes
Overview
• What is Reactome?
• The Reactome Website Browsing and Seaching the Reactome Website
Viewing Pathways
Viewing Reactions
Viewing Proteins
• Reactome Use Cases Skypainter
3rd Party Tools
• Future Directions and Questions
Nature. 2000 Oct 12;407(6805):770-6.The biochemistry of apoptosis.
A picture paints a thousand words…
...BUT
• is not computationally accessible• doesn’t convey enough detail
Reactome Rationale
http://www.reactome.org
Background
• Open source project
• Started off as Genome Knowledgebase (GKB) in 2001
• Re-branded as Reactome in 2004
• Reactome is a free, expert-authored, peer-reviewed knowledgebase of pathways and reactions in human biology
• Data Analysis and Visualization Tools
• Data downloads – interaction, BioPAX, SBML, etc.
• Curated human data are used to infer orthologous events in 22 non-human species
• Model organism Reactomes: Arabidopsis, Gallus, Drosophila, (Oryzae)
Reactome aims to help guide biological research by organising
published pathway data and making it freely available
Theory - Reactions
• Basic “unit” of Reactome
• Represents many events and states found in biology.
BINDING DEGRADATION
TRANSPORT
PHOSPHORYLATION
DEPHOSPHORYLATION
“CLASSICAL”
BIOCHEMICAL
DISSOCIATION
Compartment
Reactome Reaction & Pathway
Pathway
Pathway Reaction Reaction
CatalystActivity
OutputReaction
Input 1
Input 2
Regulation
1) Recruit bench scientists to write modules.2) Authors use a software tool to describe their
pathway.• All molecules must be identified explicitly.• 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.5) Public Release of Curated data every 3 months.6) Rolling review every 2 years by expert.7) Pathways updates.
Where the Data Comes From
Reactome Pathway Coverage
Human 4076 protein 3032 complexes3669 reactions 1081 pathways
Other species in Reactome
• Primary focus: manual curation of human reactions
• Some human reactions are manually inferred from other species (lack of experimental evidence in human)
• For each release, a set of electronically inferred pathways and reactions for non-human species is produced based on orthology data (OrthoMCL system)
human(Homo sapiens)
rat(Rattus norvegicus)
mouse(Mus musculus)
rice(Oryza savita)
chicken(Gallus gallus)
baker’s yeast(Saccharomyces
cerevisiae)
Model Organism Reactomes
Increasing Coverage
• Reactome will hit 5000 proteins by end of 2010.– There are ~20,000 genes in genome
• To get more coverage, we added 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.
Corona Data Sources & Combined Network
• Pathway databases – INOH, PANTHER, KEGG, CellMap, PID
• Bimolecular interactions– Human interactions from BioGrid, BIND, IntACT, HRPD
– Interlogs from yeast, worm, fly
• Shared GO terms• Gene co-expression data
– Multiple sources
• Transcription factors/targets– TRED
• Literature mining– GeneWays
10,956 proteins209,988 interactions
46% coverage of UniProt
Figure: 15% of the combined network
The Reactome Website
The Reactome Website
Exploring the Pathway
http://www.reactome.org/cgi-bin/eventbrowser?ID=69278
Understanding the Reaction
http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_6891
Reactiondiagram
Reactants,products,catalyst.
Your Favourite Protein
http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70597
Links to otherdatabases
Cellularcompartment
Searching Reactome
Reactome Use Cases
Using Reactome to Explore your Experimental data
Curated
F.I.
SkyPainter
Usable identifiers:
•UniProt
•RefSeq
•Ensembl
•OMIM
•Entrez Gene
•Affymetrix
•GO
•KEGG COMPOUND
•ChEBI
• Visualize High Throughput Datasets Using the Reactome “Starry Sky”• Determine which events (reactions and/or pathways) are overrepresented in a list of
genes/proteins/small molecules• Many identifiers can be submitted
http://www.reactome.org/cgi-bin/skypainter2
NP_000005 NP_001080NP_005836 NP_005461 NP_009297
Overrepresented Events (GBM Sequenced Genes)
Decreasingsignificance
Overrepresentation Analysis (with Numerical Values)Step through,
stop/startdataset display
Using Reactome to Explore Cancer Datasets
Applying Reactome to Cancer
Challenges in treating cancer:
Every tumor is different
Every cancer patient is different
Illumina/Solexa
ABI/SOLiD
• Drastic decrease in costs per genome
• Capacity greater than one Gigabase per run
• Applications: DNA, RNA, chromatin (i.e. epigenome)
New Sequencing Technologies
Genes and Pathways associated with Cancer
Download Reactome Data
SBML
Local installation
Data entry tool
API
BioPAX
“Interactions”
“MySQL Dump”
Textbook
http://www.reactome.org/download/index.html
Exploring Experimental Cancer data sets using Cytoscape and Reactome data
Reactome - In progress
• Website re-design
• New Entity-level view for pathway layout based upon SBGN
• New “Pathway Analysis” portal incl. overrepresentation analysis
• Colouring of Entity-level view with user-supplied data
In Progress: Entity Level Viewer
Future
• Creating Reactomes for model organisms
• Active recruitment of authors to create pathway modules
• Reactome’s focus is normal human biology – how about pathological pathways?
• Integrating Chemoinformatics resources into Reactome
Summary
Web
Data
Tools
Reactome: an encyclopedia of pathways and provides data mining
tools for life scientists
Thank you
Please email comments and suggestions to [email protected]
Follow Reactome at
http://www.facebook.com/group.php?gid=244908260192
http://twitter.com/reactome
http://www.linkedin.com/groups?gid=2118372
http://mail.reactome.org/mailman/listinfo/reactome-announce