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

OutputReactionInput 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

(Saccharomycescerevisiae)

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 help@reactome.org

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