A database of biological pathways David Croft Reactome

A database of biological pathways

David Croft

Reactome

Reactome: a database of biological pathways

www.reactome.org

27.02.082

History

• Started off as Genome Knowledgebase (GKB) spring 2001

• Initially tried to capture and standardize the language used to describe molecular processes

• 2001/2002 realized that what we are trying to capture are reactions and pathways

• Re-branded as Reactome June 2004


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Reaction Example 1: Enzymatic


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Reaction Example 2: Transport


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Reaction Example 3: Signaling

Dimerization

Phosphorylation


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A Reactome Pathway

input output

catalyst

input output

catalyst

input output

catalyst

Compartment


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Reactome Data Model

Events:• Reactions• Pathways

Entities:• Proteins• Complexes• Small compounds

Modulation:• Inhibition• Activation


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Reactome Data Model – The Awful Truth


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Where Reactome’s Data Comes From

• Expert and curator create outline of new pathway

• Expert fills in details

• Curator enters information into database

• Reviewer (another expert) checks biological correctness

Curator

(staff)

Expert

(recruited)

Reviewer

(recruited)


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Release cycle

Repository

ReleaseDB

Extract finished & reviewed topics

Computationally project pathways to other organisms

Add useful cross-references (ENSEMBL, UniProt, etc.)

www.reactome.org

Not publicly accessible


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Links to External Databases

• BROAD

• KEGG COMPOUND

• ChEBI

• Dictybase

• EC

• EMBL

• ENSEMBL

• Entrez

• EntrezGene

• Flybase

• GO (function, process, compartment)

• HapMap

• IntAct

• KEGG Gene

• MIM

• PubChem Compound

• PubChem Substance

• RefSeq

• SGD

• UCSC

• UniProt

• Wormbase


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Links out from Reactome

• GO • molecular function• Compartment• biological process

• KEGG compound• Chebi

• UniProt

• PubMed


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Projecting Reactions to Other Species I

A + ATP A + ADP-PB

Human

A + ATP A + ADP-P

BMouse

BA

DrosophilaReaction notinferred

Protein notinferred

+ ATP


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Projecting Reactions to Other Species II

Notch signaling

Human - manually curated

Drosophila - electronically inferred


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Protein-Protein Interactions

Types of derived interaction:

• Direct complex

• Indirect complex

• Reaction

• Neighboring reaction


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Coverage - Current

• Apoptosis

• Cell cycle

• DNA repair

• Transcription, mRNA processing, translation, post-translational modification

• Signaling pathways (insulin, NOTCH, opioid, NGF, EGFR, FGFR, Rho GTPases II, Opioid)

• Hemostasis

• Metabolism (energy, amino acid, lipid, nucleotide, xenobiotic)

• Synaptic transmission

• Lipoproteins – HDL and VLDL


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Coverage - Planned

• Regulation of Insulin• Norepinephrine &Serotonin Neurotransmitter Release

Cycles• GPCR signaling• Axonal guidance

Due by Summer 2009


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Reactome by Numbers

• Pathways 960

• Reactions 3203

• Proteins 3702(~14% SwissProt human)

• Complexes 2583

• Literature refs 4769

June 2009


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Reactome APIs

YesYesWeb services

YesYesBioMart

NoYesJava

NoYesPerl

Firewall tunnelingRemote accessAPI

Full details of BioMart at: www.biomart.org


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BioMart Dataset

PK

PK

FK FK

FKPathway

Protein

Full details of BioMart at: www.biomart.org

Gene

Small molecule


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BioMart Advantages

• Query without needing to know data model

• Scales for big datasets

• Easy linking to other Marts (federation)


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BioMart and Reactome: Datasets

Main tables:

• Complex

• Pathway

• Reaction

• Interaction

Dimension tables:

• Gene

• Protein

• Small Molecule

• Literature reference


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BioMart and Reactome: GUI


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BioMart and Reactome: Web Services

http://www.reactome.org:5555/biomart/martservice?query=...

<Query virtualSchemaName = "default" >

<Dataset name = “reaction" interface = "default" >

<Attribute name = "stableidentifier_identifier" />

<Attribute name = "_displayname" />

<Attribute name = "referencedatabase_uniprot" />

<Filter name = "referencepeptidesequence_uniprot_id_list" value = “O00311"/>

</Dataset>

</Query>

** Perl API also available **


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BioModels

• A repository of curated biological models

• Models obtained from submissions, literature & collaborations

• Two-way linking with Reactome

www.ebi.ac.uk/biomodels


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The Team• CSHL/OICR

• Lincoln Stein (PI)• Gopal Gopinath, Marc Gillespie, Bruce May, Mike Caudy, Jill

Hemish (curators)• Guanming Wu, Alexander Kanapin (developers)

• EBI• Ewan Birney, Henning Hermjakob (co-PIs)• Esther Schmidt, Imre Vastrik, David Croft, Gavin O’Kelly

(developers) • Bernard de Bono, Bijay Jassal, Phani Vijay Garapati, Steven Jupe

(curators)• NYU

• Peter D’Eustachio (co-PI; editor-in-chief)• Lisa Matthews (curator)• Shahana Mahajan (curator)

Tutorial

David Croft

Reactome


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Front Pagewww.reactome.org

NavigatorSearch

Species

Starry-sky

Top-levelpathways


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Exercise 1


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How to Search Rectome


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Customizing Search Results

Put all results on one web page (i.e. nopagination)

Select the type of resultyou would like to see


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Exercise 2


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Pathway

Eventhierarchy Description

Participants

Export

www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=109581


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Exercise 3


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Reaction

Reactiondiagram

Reactants,products,catalyst.

www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=74711


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Exercise 4


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Proteinwww.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70597

Links to otherdatabases

Cellularcompartment

Posttranslationalmodifications


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Exercise 5


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SkyPainter – Numeric Values (e.g. Expression)

#ID value1P20248 2.381255P14635 2.078063Q01094 1.358003P08319 1.274531O95067 1.251352P12004 1.031162P30305 1.654142P16104 1.274092P33992 1.560363P35249 1.185243O94913 2.410139Q13415 1.085086Q15054 1.148979P30307 2.270973O75496 0.796653P49736 0.998988Q13243 2.634955P50613 1.466119O75419 1.853295P30304 0.863513O96017 0.889464P38398 1.068929P06730 1.789461P15927 0.89531P30038 0.655572P51530 1.060222P17174 1.611088P35250 0.58771…

Download: www.ebi.ac.uk/systems-srv/mp/file-exchange/E-MEXP-345_Reactome.txt

Usable identifiers:

•UniProt

•RefSeq

•Ensembl

•MIM

•Entrez Gene

•Affymetrix

•GO

•KEGG COMPOUND

•ChEBI


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SkyPainter – expression data display

Step through,stop/startdataset display

Toggle pathwaynames


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SkyPainter – Overrepresented Events

Decreasingsignificance


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Exercise 6


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BioMart – selecting your dataset


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BioMart – filters


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BioMart – attributes

Check to get

attribute


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BioMart – results


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Exercise 7


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Reactome Links to BioModels

Links toBioModels


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BioModels Web Page

Onlinesimulation


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JWS Simulation

Parameters & initialconcentrations

Run the model


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Exercise 8


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Other Reactome features

• Editorial Calendar (navigation bar Content)• Extended search (navigation bar Tools)• PathFinder (navigation bar Tools)


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The End.

Documents

A database of biological pathways David Croft Reactome