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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) release

Cell cycle, G2/M and checkpoints T Lorca (LM) 2005-12

Chromosome maintenance - telomeres E Blackburn, J Seidel (MG) 2005-12

DNA replication - REVISION J Borowiec, B Tye, et al. (GG) 2006-03

Transcription, PolI - REVISION (MG) 2006-03

Cell cycle, mitotic + checkpoints T Lorca (LM) late 2006

Chromosome maintenance - trinucleotide repeats (LM) future

Electron transport chain (oxidative phosphorylation) S Ferguson (BJ) 2005-12

Xenobiotic metabolism phase 2 (BJ) 2006-06

Intermediary metabolism - REVISION (tbn+PD) future

HIV life cycle F Bushman, A Rice, J Skowronski, et al. (GG) 2005-12

Influenza virus life cycle R Scheuermann (MG) 2006-03

Immune System - Complement Cascade J Trowsdale (BdB) 2006-03

Hematopoiesis - B-lymphopoiesis Singh (GG) future

Insulin receptor cascade, Drosophila L Partridge et al. (BJ) 2005-12

Signaling pathways - opioid signaling LeNovere (BJ) 2006-03

Signaling pathways - NGF signaling S Nasi (BJ) 2006-06

Insulin receptor cascade, human J Scott (BdB) late 2006

P53-related signaling S Lowe (GG) late 2006

Formation of gap junctions (LM) future

Cell motility: actin T Parsons, A Westbrook et al. (LM) future

ABC transporters (PD) future

Signaling pathways - small GTPases (PD) future

Synaptic transmission (GG,MG) late 2006

Hematopoiesis - Erythropoiesis (GG) future

Melanization (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 signaling

Human - 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

B

A

B+ ADP-P

C

Human

A+ ATP

B

A

B+ ADP-P

C

Mouse

A

B

C

Drosophila

Not inferred

Front pageFront page

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other species

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UniProtEnsembl

MIMKEGG

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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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