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1
Structure and function in the Structure and function in the Reactome datamodel Reactome datamodel
Bernard de Bono
3
1) Data Model1) Data Model
2) 2) Orthology projectionsOrthology projections
3) Interfacing3) Interfacing
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
8
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
• 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
14
http://brie8.cshl.org/http://brie8.cshl.org/
http://brie8.cshl.org/cgi-bin/viewhttp://brie8.cshl.org/cgi-bin/view
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)
18
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/
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)
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
<?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
Pat
hway
Pat
hway
data
exp
ort
data
exp
ort
#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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