A Database of human biological pathways Bijay Jassal

www.reactome.orgMicrome meeting June 20111

A Database of human biological pathways

Bijay Jassal


Outline

• What is Reactome?

• Theory

• Basic data-model

• Expansion

• Release cycle

• Curator Tool

• Example – curation

• Example – diagram drawing


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


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…


Theory - Reactions

Pathway steps = the “units” of Reactome

= events in biology

TRANSPORTCLASSIC

BIOCHEMICAL

BINDING

DISSOCIATION

DEGRADATION

PHOSPHORYLATION

DEPHOSPHORYLATION


Reaction Types

Binding

Dimerization

Phosphorylation

Transport

Biochemical


Reactions – physical location of entitiesplasma membrane


Reactions Connect into Pathways

OUTPUTINPUT

CATALYST

OUTPUTINPUT

CATALYST

INPUT OUTPUT

CATALYS

T


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


Compartment (GO)

BiologicalProcess (GO)

Compartment (GO)

Basic Reactome data model

PhysicalEntity(ReferenceEntity)

Event (Reaction)

Event (Pathway)

MolecularFunction (GO)



CatalystActivity

PubMed (lit reference)

Compartment (GO) Compartment (GO)

PubMed (lit reference)

Input(s) Output(s)

Catalyst


Frequently used classes

Event

• Pathway

• Reaction

PhysicalEntity

• Protein (EWAS)

• Complex

• Sets

CatalystActivity

LiteratureReference

Compartment

Species

Summation


Link-outs from Reactome

UniProt

KEGG

Ensembl

Entrez Gene

BioGPS

CTD

dbSNP

UCSC

ChEBI

Compound

PubChem

Compartment, MolecularFunction


Human pathway

PMID:5555 PMID:4444

mouse

cow

Direct evidence

Indirect evidencePMID:8976

PMID:1234

Evidence Tracking – Inferred Reactions


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


REVIEWDATA

FIXDATA

Data Expansion -electronic inferencelinks addedStable Ids added

data

Release overview

Expert

Curator

Curator Tool

Central DB

Release DB


Diagram example


Reactome’s Curator Tool (CT)


Download instructions


Curator Tool – schema view


CT - hierarchical view


CT – ELV view


Curation example

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


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


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


Reaction 2: C5 Epimerization with UDP-D-GlcNAc

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


NEW CHEBI:60101

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


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-)



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


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


Draw the pathway diagram (ELV)


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: [email protected]

A Database of human biological pathways Bijay Jassal

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