a database of human biological pathways bijay jassal
DESCRIPTION
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 curated - PowerPoint PPT PresentationTRANSCRIPT
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
www.reactome.orgMicrome meeting June 20113
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
www.reactome.orgMicrome meeting June 20114
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…
www.reactome.orgMicrome meeting June 20115
Theory - Reactions
Pathway steps = the “units” of Reactome
= events in biology
TRANSPORTCLASSIC
BIOCHEMICAL
BINDING
DISSOCIATION
DEGRADATION
PHOSPHORYLATION
DEPHOSPHORYLATION
www.reactome.orgMicrome meeting June 20116
Reaction Types
Binding
Dimerization
Phosphorylation
Transport
Biochemical
www.reactome.orgMicrome meeting June 20117
Reactions – physical location of entitiesplasma membrane
www.reactome.orgMicrome meeting June 20118
Reactions Connect into Pathways
OUTPUTINPUT
CATALYST
OUTPUTINPUT
CATALYST
INPUT OUTPUT
CATALYS
T
www.reactome.orgMicrome meeting June 20119
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
www.reactome.orgMicrome meeting June 201110
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
www.reactome.orgMicrome meeting June 201111
Frequently used classes
Event
• Pathway
• Reaction
PhysicalEntity
• Protein (EWAS)
• Complex
• Sets
CatalystActivity
LiteratureReference
Compartment
Species
Summation
www.reactome.orgMicrome meeting June 201112
Link-outs from Reactome
UniProt
KEGG
Ensembl
Entrez Gene
BioGPS
CTD
dbSNP
UCSC
ChEBI
Compound
PubChem
Compartment, MolecularFunction
www.reactome.orgMicrome meeting June 201113
Human pathway
PMID:5555 PMID:4444
mouse
cow
Direct evidence
Indirect evidencePMID:8976
PMID:1234
Evidence Tracking – Inferred Reactions
www.reactome.orgMicrome meeting June 201114
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
www.reactome.orgMicrome meeting June 201115
REVIEWDATA
FIXDATA
Data Expansion -electronic inferencelinks addedStable Ids added
data
Release overview
Expert
Curator
Curator Tool
Central DB
Release DB
www.reactome.orgMicrome meeting June 201116
Diagram example
www.reactome.orgMicrome meeting June 201117
Reactome’s Curator Tool (CT)
www.reactome.orgMicrome meeting June 201118
Download instructions
www.reactome.orgMicrome meeting June 201119
Curator Tool – schema view
www.reactome.orgMicrome meeting June 201120
CT - hierarchical view
www.reactome.orgMicrome meeting June 201121
CT – ELV view
www.reactome.orgMicrome meeting June 201122
Curation example
Biosynthesis of UDP-N-acetyl-L-fucosamine, a Precursor to the Biosynthesis of Lipopolysaccharide in Pseudomonas aeruginosa Serotype O11* (PubMed:15778500)
www.reactome.orgMicrome meeting June 201123
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
www.reactome.orgMicrome meeting June 201124
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
www.reactome.orgMicrome meeting June 201125
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-)
www.reactome.orgMicrome meeting June 201126
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
www.reactome.orgMicrome meeting June 201127
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
www.reactome.orgMicrome meeting June 201128
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
www.reactome.orgMicrome meeting June 201129
Draw the pathway diagram (ELV)
www.reactome.orgMicrome meeting June 201130
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]