A database of biological pathways David Croft Reactome

Reactome: a database of biological pathways History Started off as Genome Knowledgebase (GKB) spring 2001 Initially tried to capture and standardize the language used to describe molecular processes 2001/2002 realized that what we are trying to capture are reactions and pathways Re-branded as Reactome June 2004

Reactome: a database of biological pathways Reaction Example 1: Enzymatic

Reactome: a database of biological pathways Reaction Example 2: Transport

Reactome: a database of biological pathways Reaction Example 3: Signaling Dimerization Phosphorylation

Reactome: a database of biological pathways A Reactome Pathway inputoutput catalyst inputoutput catalyst inputoutput catalyst Compartment

Reactome: a database of biological pathways Reactome Data Model Events: Reactions Pathways Entities: Proteins Complexes Small compounds Modulation: Inhibition Activation

Reactome: a database of biological pathways Reactome Data Model – The Awful Truth

Reactome: a database of biological pathways Where Reactome’s Data Comes From Expert and curator create outline of new pathway Expert fills in details Curator enters information into database Reviewer (another expert) checks biological correctness Curator (staff) Expert (recruited) Reviewer (recruited)

Reactome: a database of biological pathways Release cycle Repository Release DB Extract finished & reviewed topics Computationally project pathways to other organisms Add useful cross-references (ENSEMBL, UniProt, etc.) Not publicly accessible

Reactome: a database of biological pathways Links to External Databases BROAD KEGG COMPOUND ChEBI Dictybase EC EMBL ENSEMBL Entrez EntrezGene Flybase GO (function, process, compartment) HapMap IntAct KEGG Gene MIM PubChem Compound PubChem Substance RefSeq SGD UCSC UniProt Wormbase

Reactome: a database of biological pathways Links out from Reactome GO molecular function Compartment biological process KEGG compound Chebi UniProt PubMed

Reactome: a database of biological pathways Projecting Reactions to Other Species I A + ATP A + ADP -P B Human A + ATP A + ADP -P B Mouse BA Drosophila Reaction not inferred Protein not inferred + ATP

Reactome: a database of biological pathways Projecting Reactions to Other Species II Notch signaling Human - manually curated Drosophila - electronically inferred

Reactome: a database of biological pathways Protein-Protein Interactions Types of derived interaction: Direct complex Indirect complex Reaction Neighboring reaction

Reactome: a database of biological pathways Coverage - Current Apoptosis Cell cycle DNA repair Transcription, mRNA processing, translation, post- translational modification Signaling pathways (insulin, NOTCH, opioid, NGF, EGFR, FGFR, Rho GTPases II, Opioid) Hemostasis Metabolism (energy, amino acid, lipid, nucleotide, xenobiotic) Synaptic transmission Lipoproteins – HDL and VLDL

Reactome: a database of biological pathways Coverage - Planned Regulation of Insulin Norepinephrine &Serotonin Neurotransmitter Release Cycles GPCR signaling Axonal guidance Due by Summer 2009

Reactome: a database of biological pathways Reactome by Numbers Pathways 960 Reactions 3203 Proteins 3702(~14% SwissProt human) Complexes 2583 Literature refs 4769 June 2009

Reactome: a database of biological pathways Reactome APIs Yes Web services Yes BioMart NoYesJava NoYesPerl Firewall tunnelingRemote accessAPI Full details of BioMart at:

Reactome: a database of biological pathways BioMart Dataset PK FK Pathway Protein Full details of BioMart at: Gene Small molecule

Reactome: a database of biological pathways BioMart Advantages Query without needing to know data model Scales for big datasets Easy linking to other Marts (federation)

Reactome: a database of biological pathways BioMart and Reactome: Datasets Main tables: Complex Pathway Reaction Interaction Dimension tables: Gene Protein Small Molecule Literature reference

Reactome: a database of biological pathways BioMart and Reactome: GUI

Reactome: a database of biological pathways BioMart and Reactome: Web Services ** Perl API also available **

Reactome: a database of biological pathways BioModels A repository of curated biological models Models obtained from submissions, literature & collaborations Two-way linking with Reactome

Reactome: a database of biological pathways The Team CSHL/OICR Lincoln Stein (PI) Gopal Gopinath, Marc Gillespie, Bruce May, Mike Caudy, Jill Hemish (curators) Guanming Wu, Alexander Kanapin (developers) EBI Ewan Birney, Henning Hermjakob (co-PIs) Esther Schmidt, Imre Vastrik, David Croft, Gavin O’Kelly (developers) Bernard de Bono, Bijay Jassal, Phani Vijay Garapati, Steven Jupe (curators) NYU Peter D’Eustachio (co-PI; editor-in-chief) Lisa Matthews (curator) Shahana Mahajan (curator) NHGRI P41 HG EU STRP, EMI-CD EBI Industry program Grants

Tutorial David Croft Reactome

Reactome: a database of biological pathways Front Page Navigator Search Species Starry-sky Top-level pathways

Reactome: a database of biological pathways Exercise 1

Reactome: a database of biological pathways How to Search Rectome

Reactome: a database of biological pathways Customizing Search Results Put all results on one web page (i.e. no pagination) Select the type of result you would like to see

Reactome: a database of biological pathways Exercise 2

Reactome: a database of biological pathways Pathway Event hierarchy Description Participants Export

Reactome: a database of biological pathways Exercise 3

Reactome: a database of biological pathways Reaction diagram Reactants, products, catalyst.

Reactome: a database of biological pathways Exercise 4

Reactome: a database of biological pathways Protein Links to other databases Cellular compartment Posttranslational modifications

Reactome: a database of biological pathways Exercise 5

Reactome: a database of biological pathways SkyPainter – Numeric Values (e.g. Expression) #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 … Download: srv/mp/file-exchange/E-MEXP- 345_Reactome.txt Usable identifiers: UniProt RefSeq Ensembl MIM Entrez Gene Affymetrix GO KEGG COMPOUND ChEBI

Reactome: a database of biological pathways SkyPainter – expression data display Step through, stop/start dataset display Toggle pathway names

Reactome: a database of biological pathways SkyPainter – Overrepresented Events Decreasing significance

Reactome: a database of biological pathways Exercise 6

Reactome: a database of biological pathways BioMart – selecting your dataset

Reactome: a database of biological pathways BioMart – filters

Reactome: a database of biological pathways BioMart – attributes Check to get attribute

Reactome: a database of biological pathways BioMart – results

Reactome: a database of biological pathways Exercise 7

Reactome: a database of biological pathways Reactome Links to BioModels Links to BioModels

Reactome: a database of biological pathways BioModels Web Page Online simulation

Reactome: a database of biological pathways JWS Simulation Parameters & initial concentrations Run the model

Reactome: a database of biological pathways Exercise 8

Reactome: a database of biological pathways Other Reactome features Editorial Calendar (navigation bar  Content) Extended search (navigation bar  Tools) PathFinder (navigation bar  Tools)

Reactome: a database of biological pathways The End.