1 Structure and function in the Reactome datamodel Bernard de Bono

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3 1) Data Model 2) Orthology projections 3) Interfacing 1) Data Model 2) Orthology projections 3) Interfacing

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moduleexpert (curator)release Cell cycle, G2/M and checkpointsT Lorca (LM) Chromosome maintenance - telomeresE Blackburn, J Seidel (MG) DNA replication - REVISIONJ Borowiec, B Tye, et al. (GG) Transcription, PolI - REVISION(MG) Cell cycle, mitotic + checkpointsT Lorca (LM)late 2006 Chromosome maintenance - trinucleotide repeats(LM)future Electron transport chain (oxidative phosphorylation)S Ferguson (BJ) Xenobiotic metabolism phase 2(BJ) Intermediary metabolism - REVISION(tbn+PD)future HIV life cycleF Bushman, A Rice, J Skowronski, et al. (GG) Influenza virus life cycleR Scheuermann (MG) Immune System - Complement CascadeJ Trowsdale (BdB) Hematopoiesis - B-lymphopoiesisSingh (GG)future Insulin receptor cascade, DrosophilaL Partridge et al. (BJ) Signaling pathways - opioid signalingLeNovere (BJ) Signaling pathways - NGF signalingS Nasi (BJ) Insulin receptor cascade, humanJ Scott (BdB)late 2006 P53-related signalingS Lowe (GG)late 2006 Formation of gap junctions(LM)future Cell motility: actinT 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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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-class Note 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 their corresponding concepts in Reactome. Cross-references between Reactome and GO Comparison and sharing of annotations between Reactome and GOA

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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)

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 page

Pathway event hierarchy

authors summary species GO term other species Pathway description

UniProt Ensembl MIM KEGG UCSC ChEBI Compound Pathway participants

Pathway data export

… BioPAX pathway converted from "Apoptosis" in the Reactome database. Apoptosis … P63167 P98170 Q15628 P55211 P55957 P10415 P19438 P48454 Q9BXH1 O43521 P55210 Q07817 Q96FJ2 P31946 P45983 P30419 Q13794 P25445 Q12933 Q92934 P42574 P99999 O14727 Q14790 P48023 P31749 P63098 Q13158 P01375 Q13546 Q16611 P50591 Q07812 Q9NR28 O14763 Q96LC9 Q92851 P10144 Pathway data export

#IDvalue1 P P Q P O P P P P P O Q Q P O P Q P O P O P P P P P P P … Usable identifiers: UniProt RefSeq Ensembl MIM Entrez Gene KEGG COMPOUND ChEBI Affymetrix GO Skypainter

Skypainter coloring according to the numeric values provided

143E_HUMAN 1C06_HUMAN 2AAB_HUMAN 2ABB_HUMAN 2B11_HUMAN 2B14_HUMAN 2B17_HUMAN 2B18_HUMAN 2B19_HUMAN 2B1A_HUMAN 2B1B_HUMAN 3BH2_HUMAN 3BP2_HUMAN 41_HUMAN A1A2_HUMAN A1AT_HUMAN A2AC_HUMAN A2AP_HUMAN A2MG_HUMAN A3B1_HUMAN A4GT_HUMAN A4_HUMAN A8B1_HUMAN AAAS_HUMAN AAC3_HUMAN AAC4_HUMAN AACT_HUMAN … Skypainter

Skypainter coloring according to the number of “hits”

Download Database SBML “Interactions” Local installation Data entry tool

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