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Structure and function in the Structure and function in the Reactome datamodel Reactome datamodel

Bernard de Bono

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http://brie8.cshl.org/http://brie8.cshl.org/

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1) Data Model1) Data Model

2) 2) Orthology projectionsOrthology projections

3) Interfacing3) Interfacing

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module expert (curator) releaseCell cycle, G2/M and checkpoints T Lorca (LM) 2005-12Chromosome maintenance - telomeres E Blackburn, J Seidel (MG) 2005-12DNA replication - REVISION J Borowiec, B Tye, et al. (GG) 2006-03Transcription, PolI - REVISION (MG) 2006-03Cell cycle, mitotic + checkpoints T Lorca (LM) late 2006Chromosome maintenance - trinucleotide repeats (LM) futureElectron transport chain (oxidative phosphorylation) S Ferguson (BJ) 2005-12Xenobiotic metabolism phase 2 (BJ) 2006-06Intermediary metabolism - REVISION (tbn+PD) futureHIV life cycle F Bushman, A Rice, J Skowronski, et al. (GG) 2005-12Influenza virus life cycle R Scheuermann (MG) 2006-03Immune System - Complement Cascade J Trowsdale (BdB) 2006-03Hematopoiesis - B-lymphopoiesis Singh (GG) futureInsulin receptor cascade, Drosophila L Partridge et al. (BJ) 2005-12Signaling pathways - opioid signaling LeNovere (BJ) 2006-03

Signaling pathways - NGF signaling S Nasi (BJ) 2006-06Insulin receptor cascade, human J Scott (BdB) late 2006P53-related signaling S Lowe (GG) late 2006Formation of gap junctions (LM) futureCell motility: actin T Parsons, A Westbrook et al. (LM) futureABC transporters (PD) futureSignaling pathways - small GTPases (PD) futureSynaptic transmission (GG,MG) late 2006Hematopoiesis - Erythropoiesis (GG) futureMelanization (BdB) future

HIV life cycle

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http://brie8.cshl.org/http://brie8.cshl.org/

http://brie8.cshl.org/cgi-bin/tutorialhttp://brie8.cshl.org/cgi-bin/tutorial

EntityWithAccessionedSequence-referenceEntity (ReferenceSequence)-hasModifiedResidue-startCoordinate (default 1, 0 if unknown)-endCoordinate (default -1, 0 if unknown)

SimpleEntity-referenceEntity (ReferenceMolecule)

DefinedSet-hasInstance-species

UndefinedSet-hasExample-referenceEntity (ReferenceMoleculeClass)-species

CandidateSet-hasConfirmedMember-hasCandidate-species

GenomeEncodedEntity-species

PhysicalEntity-name-compartment

Complex-hasComponent-species

EntityWithRepeatedUnits-repeatedUnit-species-minUnitCount-maxUnitCount

Class hierarchy with attributes

Arrows point from super-class to sub-classNote that sub-classes inherit the attributes of the super-class

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• Provides Reactome curated referenced GO annotations where they do not currently exist in GOA• Provides stronger experimental evidence for GOA annotation supported only by computational inferences. • Improves the accuracy and consistency of the annotations in both databases.

Collaboration between GO and Reactome

• Reactome pathway --> GO Biological Processes• Reactome catalyst activity --> GO Molecular Function• Cellular location of Reactome reactions --> GO Cellular Compartment• Location of Reactome reaction input/output etc.-->GO Cellular Compartment

The GO consortium will soon cross-reference GO terms back to theircorresponding concepts in Reactome.

Cross-references between Reactome and GO

Comparison and sharing of annotations between Reactome and GOA

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http://brie8.cshl.org/http://brie8.cshl.org/

http://brie8.cshl.org/cgi-bin/viewhttp://brie8.cshl.org/cgi-bin/view

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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 reactions is produced based on orthology data (from human to other species)

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http://brie8.cshl.org/http://brie8.cshl.org/

http://brie8.cshl.org/cgi-bin/tutorialhttp://brie8.cshl.org/cgi-bin/tutorial

http://www.reactome.org/http://www.reactome.org/

Notch signalingHuman - manually curated

Drosophila - electronically inferred

Reaction inference

• Orthologue mapping based on the OrthoMCL system for a set of diverse, well-annotated species

• Includes (recent) paralogues• Complex threshold (not all components

of a complex need to have orthologues)

OrthoMCL Flow chart

Reaction inference - basic principle

A+ ATP

BAB

+ ADP-P

C

Human

A+ ATP

BAB

+ ADP-P

C

Mouse

A

B

C

Drosophila

Not inferred

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other species

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UniProtEnsembl

MIMKEGG

UCSC

ChEBICompound

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<?xml version="1.0" encoding="UTF-8" ?><sbml xmlns="http://www.sbml.org/sbml/level2" level="2" version="1" xmlns:html="http://www.w3.org/1999/xhtml"><model name="R_109581"><listOfCompartments><compartment name="R_cytosol" id="R_cytosol"/><compartment name="R_extracellular_region" id="R_extracellular_region"/><compartment name="R_mitochondrial_intermembrane_space" id="R_mitochondrial_intermembrane_space"/><compartment name="R_mitochondrial_outer_membrane" id="R_mitochondrial_outer_membrane"/><compartment name="R_plasma_membrane" id="R_plasma_membrane"/></listOfCompartments><listOfSpecies><species name="R_114236_Apoptosis_regulator_Bcl_X" compartment="R_mitochondrial_outer_membrane" id="R_114236_Apoptosis_regulator_Bcl_X" /><species name="R_114240_NOXA_BCL2" compartment="R_mitochondrial_outer_membrane" id="R_114240_NOXA_BCL2" /><species name="R_114242_BAD_protein" compartment="R_mitochondrial_outer_membrane" id="R_114242_BAD_protein" /><species name="R_114243_BAD_BCL_xl" compartment="R_mitochondrial_outer_membrane" id="R_114243_BAD_BCL_xl" /><species name="R_114244_Cytochrome_c" compartment="R_mitochondrial_intermembrane_space" id="R_114244_Cytochrome_c" />…

<?xml version="1.0" encoding="UTF-8"?><rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns="http://www.biopax.org/release/biopax-level2.owl#" xmlns:rdfs="http://www.w3.org/2000/01/rdf-schema#" xmlns:owl="http://www.w3.org/2002/07/owl#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" xml:base="http://www.biopax.org/release/biopax-level2.owl#"> <owl:Ontology rdf:about=""> <owl:imports rdf:resource="http://www.biopax.org/Downloads/Level2v0.92/biopax-level2.owl" /> <rdfs:comment rdf:datatype="http://www.w3.org/2001/XMLSchema#string">BioPAX pathway converted from "Apoptosis" in the Reactome database.</rdfs:comment> </owl:Ontology> <pathway rdf:ID="Apoptosis"> <PATHWAY-COMPONENTS rdf:resource="#Activation__myristolyation_of_BID_and_translocation_to_mitochondriaStep" /> <PATHWAY-COMPONENTS rdf:resource="#Apoptotic_execution__phaseStep" /> <PATHWAY-COMPONENTS rdf:resource="#Extrinsic_Pathway_for_ApoptosisStep" /> <PATHWAY-COMPONENTS rdf:resource="#Intrinsic_Pathway_for_ApoptosisStep" /> <PATHWAY-COMPONENTS rdf:resource="#Activation_of__Effector_CaspasesStep" /> <ORGANISM rdf:resource="#Homo_sapiens" /> <NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Apoptosis</NAME> <SHORT-NAME rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Apoptosis</SHORT-NAME> <XREF rdf:resource="#Reactome109581" />…

P63167P98170Q15628P55211P55957P10415P19438P48454Q9BXH1O43521P55210Q07817Q96FJ2P31946P45983P30419Q13794P25445Q12933Q92934P42574P99999O14727Q14790P48023P31749P63098Q13158P01375Q13546Q16611P50591Q07812Q9NR28O14763Q96LC9Q92851P10144

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#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…

Usable identifiers:

•UniProt

•RefSeq

•Ensembl

•MIM

•Entrez Gene

•KEGG COMPOUND

•ChEBI

•Affymetrix

•GO

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143E_HUMAN1C06_HUMAN2AAB_HUMAN2ABB_HUMAN2B11_HUMAN2B14_HUMAN2B17_HUMAN2B18_HUMAN2B19_HUMAN2B1A_HUMAN2B1B_HUMAN3BH2_HUMAN3BP2_HUMAN41_HUMANA1A2_HUMANA1AT_HUMANA2AC_HUMANA2AP_HUMANA2MG_HUMANA3B1_HUMANA4GT_HUMANA4_HUMANA8B1_HUMANAAAS_HUMANAAC3_HUMANAAC4_HUMANAACT_HUMAN…

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