a database of human biological pathways bijay jassal

www.reactome.orgMicrome meeting June 20111

A Database of human biological pathways

Bijay Jassal

www.reactome.orgMicrome meeting June 20112

Outline

• What is Reactome?

• Theory

• Basic data-model

• Expansion

• Release cycle

• Curator Tool

• Example – curation

• Example – diagram drawing

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Reactome is…

Free, online, open-source curateddatabase of pathways and reactions in human biology

Authored by expert biologists, maintained byReactome editorial staff (curators)

Mapped to cellular compartment

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Extensively cross-referenced

Tools for data analysis – Pathway Analysis, Expression Overlay, Species Comparison, Biomart…

Used to infer orthologous events in 20 non-human species

Reactome is…

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Theory - Reactions

Pathway steps = the “units” of Reactome

= events in biology

TRANSPORTCLASSIC

BIOCHEMICAL

BINDING

DISSOCIATION

DEGRADATION

PHOSPHORYLATION

DEPHOSPHORYLATION

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Reaction Types

Binding

Dimerization

Phosphorylation

Transport

Biochemical

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Reactions – physical location of entitiesplasma membrane

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Reactions Connect into Pathways

OUTPUTINPUT

CATALYST

OUTPUTINPUT

CATALYST

INPUT OUTPUT

CATALYS

T

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Basic Reactome data model

Glucose(cytosol)

Glucose(extracellular)

CHEBI:17925

AKT1(nucleoplasm)

AKT1(cytosol)

PDK1:AKT1(cytosol)

Phosphorylated AKT1(cytosol)

UniProt:P31749

PhysicalEntity (SimpleEntity))

PhysicalEntity (EWAS)

ReferenceEntity

compartment

Altered state

complexed

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Compartment (GO)

BiologicalProcess (GO)

Compartment (GO)

Basic Reactome data model

PhysicalEntity(ReferenceEntity)

Event (Reaction)

Event (Pathway)

MolecularFunction (GO)

PhysicalEntity(ReferenceEntity)

PhysicalEntity(ReferenceEntity)

CatalystActivity

PubMed (lit reference)

Compartment (GO) Compartment (GO)

PubMed (lit reference)

Input(s) Output(s)

Catalyst

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Frequently used classes

Event

• Pathway

• Reaction

PhysicalEntity

• Protein (EWAS)

• Complex

• Sets

CatalystActivity

LiteratureReference

Compartment

Species

Summation

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Link-outs from Reactome

UniProt

KEGG

Ensembl

Entrez Gene

BioGPS

CTD

dbSNP

UCSC

ChEBI

Compound

PubChem

Compartment, MolecularFunction

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Human pathway

PMID:5555 PMID:4444

mouse

cow

Direct evidence

Indirect evidencePMID:8976

PMID:1234

Evidence Tracking – Inferred Reactions

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Data Expansion – Projecting to Other Species

A + ATP A + ADP-PB

Human

A + ATP A + ADP-P

BMouse

BA

Drosophila

Reaction notinferred

No orthologue - Protein not inferred

+ ATP

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REVIEWDATA

FIXDATA

Data Expansion -electronic inferencelinks addedStable Ids added

data

Release overview

Expert

Curator

Curator Tool

Central DB

Release DB

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Diagram example

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Reactome’s Curator Tool (CT)

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Download instructions

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Curator Tool – schema view

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CT - hierarchical view

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CT – ELV view

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Curation example

Biosynthesis of UDP-N-acetyl-L-fucosamine, a Precursor to the Biosynthesis of Lipopolysaccharide in Pseudomonas aeruginosa Serotype O11* (PubMed:15778500)

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Pathway: UDP-L-FucNAc biosynthesis

Create instance of Pathway class with name, summary and literature

reference(s)

Reactions

1. C4, C6 dehydratation of UDP-D-GlcNAc

2. C5 Epimerization with UDP-D-GlcNAc

3. C3 epimerization of UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-)

4. C4 reduction of UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-)

5. Epimerization of UDP-L-PneNAc

http://wiki.reactome.org/index.php/New_Reactome_Curator_Guide

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Reaction 1: C4, C6 dehydratation of UDP-D-GlcNAc

NEW CHEBI:62375UDP-2-acetamido-2,6-dideoxy-alpha;-D-xylo-4-hexulose (2-)

CHEBI:57705

Pseudomonas aeruginosaUniProt:Q9XC61 GO MF:0016836

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Reaction 2: C5 Epimerization with UDP-D-GlcNAc

NEW CHEBI:62375UDP-2-acetamido-2,6-dideoxy-alpha;-D-xylo-4-hexulose (2-)

Pseudomonas aeruginosaUniProt:Q9XC61 GO MF:0016857

NEW CHEBI:60101

UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-)

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Reaction 3: C3 epimerization of UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-)

NEW CHEBI:62377

NEW CHEBI:60101

UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-)

UDP-2-acetamido-2,6-dideoxy-beta-L-arabino-hex-4-ulose(2-)

Pseudomonas aeruginosaUniProt:Q9XC60 GO MF:0016857

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Reaction 4: C4 reduction of UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-)

Pseudomonas aeruginosaUniProt:Q9XC60 GO MF??

NEW CHEBI:62377

UDP-2-acetamido-2,6-dideoxy-beta-L-xylo-4-hexulose(2-)

NEW CHEBI:62372

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Reaction 5: Epimerization of UDP-L-PneNAc

UDP-L-FucNAc

(CHEBI:62241)

NEW CHEBI:62372

Possible modification stereoisomery of C1 of

CHEBI:62241 (racemic) to alpha stereoisomer

Pseudomonas aeruginosaUniProt: Q9XC59 GO MF:0016857

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Draw the pathway diagram (ELV)

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The Team• OICR

• Lincoln Stein (PI)• Bruce May, Guanming Wu, Robin Haw, Marija Orlic-Milacic, Karen

Rothfels, Joel Weiser, Christina Yung, Cheryl Song

• EBI• Ewan Birney (co-PI), Henning Hermjakob (co-PI)• David Croft, Bijay Jassal, Phani Vijay Garapati, Steven Jupe, Mark William,

Antonio Fabregat Mundo

• NYU• Peter D’Eustachio (co-PI; editor-in-chief)• Lisa Matthews, Marc Gillespie, Mike Caudy, Veronica Shamovsky

• NHGRI P41 HG003751• EU Sixth Framework

Programme (LSHG-CT-2003-503269)

• EBI Industry program

Gra

nts

e-mail: help@reactome.org