Transcript Reactome - a curated knowledgebase of human biological

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
Reactome Rationale
A picture paints a thousand words…
...BUT
• is not computationally accessible
• doesn’t convey enough detail
Nature. 2000 Oct 12;407(6805):770-6.
The biochemistry of apoptosis.
http://www.reactome.org
Background
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Open source project
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Started off as Genome Knowledgebase (GKB) in 2001
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Re-branded as Reactome in 2004
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Reactome is a free, expert-authored, peer-reviewed knowledgebase of pathways and
reactions in human biology
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Data Analysis and Visualization Tools
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Data downloads – interaction, BioPAX, SBML, etc.
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Curated human data are used to infer orthologous events in 22 non-human species
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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.
DEGRADATION
BINDING
DISSOCIATION
DEPHOSPHORYLATION
PHOSPHORYLATION
“CLASSICAL”
TRANSPORT
BIOCHEMICAL
Reactome Reaction & Pathway
Regulation
Input 1
Output
Reaction
Input 2
Compartment
CatalystActivity
Pathway
Pathway
Reaction
Reaction
Where the Data Comes From
1)
2)
Recruit bench scientists to write modules.
Authors use a software tool to describe their
pathway.
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3)
4)
5)
6)
7)
All molecules must be identified explicitly.
All assertions backed up by literature references.
Curators work with authors to ensure consistency
and completeness.
Module checked by peer review & software before
publication.
Public Release of Curated data every 3 months.
Rolling review every 2 years by expert.
Pathways updates.
Reactome Pathway Coverage
Human
4076 protein
3669 reactions
3032 complexes
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)
rice
(Oryza savita)
mouse
(Mus musculus)
chicken
(Gallus gallus)
rat
(Rattus norvegicus)
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
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INOH, PANTHER, KEGG, CellMap, PID
• Bimolecular interactions
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Human interactions from BioGrid, BIND, IntACT, HRPD
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Interlogs from yeast, worm, fly
• Shared GO terms
• Gene co-expression data
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Multiple sources
• Transcription factors/targets
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TRED
• Literature mining
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GeneWays
10,956 proteins
209,988 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
Reaction
diagram
Reactants,
products,
catalyst.
http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_6891
Your Favourite Protein
Links to other
databases
Cellular
compartment
http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70597
Searching Reactome
Reactome Use Cases
Using Reactome to Explore your Experimental data
Curated
F.I.
SkyPainter
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Visualize High Throughput Datasets Using the Reactome “Starry Sky”
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Determine which events (reactions and/or pathways) are overrepresented in a list of
genes/proteins/small molecules
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Many identifiers can be submitted
Usable identifiers:
NP_000005
NP_001080
NP_005836
NP_005461
NP_009297
•UniProt
•RefSeq
•Ensembl
•OMIM
•Entrez Gene
•Affymetrix
•GO
•KEGG COMPOUND
•ChEBI
http://www.reactome.org/cgi-bin/skypainter2
Overrepresented Events (GBM Sequenced Genes)
Decreasing
significance
Overrepresentation Analysis (with Numerical Values)
Step through,
stop/start
dataset display
Using Reactome to Explore Cancer Datasets
Applying Reactome to Cancer
Challenges in treating cancer:
 Every tumor is different
 Every cancer patient is different
New Sequencing Technologies
• Drastic decrease in costs per
genome
• Capacity greater than one
Gigabase per run
Illumina/Solexa
• Applications: DNA, RNA,
chromatin (i.e. epigenome)
ABI/SOLiD
Genes and Pathways associated with Cancer
Download Reactome Data
“MySQL Dump”
“Interactions”
SBML
BioPAX
Textbook
Local installation
Data entry tool
API
http://www.reactome.org/download/index.html
Exploring Experimental Cancer data sets using
Cytoscape and Reactome data
Reactome - In progress
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Website re-design
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New Entity-level view for pathway layout based upon SBGN
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New “Pathway Analysis” portal incl. overrepresentation analysis
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Colouring of Entity-level view with user-supplied data
In Progress: Entity Level Viewer
Future
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Creating Reactomes for model organisms
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Active recruitment of authors to create pathway modules
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Reactome’s focus is normal human biology – how about pathological pathways?
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Integrating Chemoinformatics resources into Reactome
Summary
Tools
Web
Data
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