Reactome - a curated knowledgebase of human biological pathways and processes

1. Reactome- a curated knowledgebase of human biological pathways and processes

2. Overview • What is Reactome? • The Reactome Website • Browsing and Seaching the Reactome Website • Viewing Pathways • Viewing Reactions • Viewing Proteins • Reactome Use Cases • Skypainter • 3rd Party Tools • Future Directions and Questions

3. Reactome Rationale A picture paints a thousand words… • ...BUT • is not computationally accessible • doesn’t convey enough detail Nature. 2000 Oct 12;407(6805):770-6. The biochemistry of apoptosis. http://www.reactome.org

4. Background • Open source project • Started off as Genome Knowledgebase (GKB) in 2001 • Re-branded as Reactome in 2004 • Reactome is a free, expert-authored, peer-reviewed knowledgebase of pathways and reactions in human biology • Data Analysis and Visualization Tools • Data downloads – interaction, BioPAX, SBML, etc. • Curated human data are used to infer orthologous events in 22 non-human species • Model organism Reactomes: Arabidopsis, Gallus, Drosophila, (Oryzae) Reactome aims to help guide biological research by organising published pathway data and making it freely available

5. Theory - Reactions • Basic “unit” of Reactome • Represents many events and states found in biology. DEGRADATION BINDING DISSOCIATION DEPHOSPHORYLATION PHOSPHORYLATION “CLASSICAL” BIOCHEMICAL TRANSPORT

6. Reactome Reaction & Pathway Compartment Regulation Input 1 Reaction Output Input 2 CatalystActivity Pathway Pathway Reaction Reaction

7. Where the Data Comes From • Recruit bench scientists to write modules. • Authors use a software tool to describe their pathway. • All molecules must be identified explicitly. • All assertions backed up by literature references. • Curators work with authors to ensure consistency and completeness. • Module checked by peer review & software before publication. • Public Release of Curated data every 3 months. • Rolling review every 2 years by expert. • Pathways updates.

8. Reactome Pathway Coverage Human 4076 protein 3032 complexes 3669 reactions 1081 pathways

9. human (Homo sapiens) rat (Rattus norvegicus) 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 pathways and reactions for non-human species is produced based on orthology data (OrthoMCL system) rice (Oryza savita) chicken (Gallus gallus) mouse (Mus musculus) baker’s yeast (Saccharomyces cerevisiae)

10. Model Organism Reactomes

11. Increasing Coverage • Reactome will hit 5000 proteins by end of 2010. • There are ~20,000 genes in genome • To get more coverage, we added non-Reactome data sets to create a “corona” of less reliable data around each pathway. • Corona connected to pathway components by probable functional interaction links.

12. Corona Data Sources & Combined Network • Pathway databases • INOH, PANTHER, KEGG, CellMap, PID • Bimolecular interactions • Human interactions from BioGrid, BIND, IntACT, HRPD • Interlogs from yeast, worm, fly • Shared GO terms • Gene co-expression data • Multiple sources • Transcription factors/targets • TRED • Literature mining • GeneWays 10,956 proteins 209,988 interactions 46% coverage of UniProt Figure: 15% of the combined network

13. The Reactome Website

14. The Reactome Website

15. Exploring the Pathway http://www.reactome.org/cgi-bin/eventbrowser?ID=69278

16. Reaction diagram Understanding the Reaction Reactants, products, catalyst. http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_6891

17. Your Favourite Protein http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70597 Links to other databases Cellular compartment

18. Searching Reactome

19. Reactome Use Cases

20. Using Reactome to Explore your Experimental data Curated F.I.

21. SkyPainter • Visualize High Throughput Datasets Using the Reactome “Starry Sky” • Determine which events (reactions and/or pathways) are overrepresented in a list of genes/proteins/small molecules • Many identifiers can be submitted Usable identifiers: • UniProt • RefSeq • Ensembl • OMIM • Entrez Gene • Affymetrix • GO • KEGG COMPOUND • ChEBI NP_000005 NP_001080 NP_005836 NP_005461 NP_009297 http://www.reactome.org/cgi-bin/skypainter2

22. Overrepresented Events (GBM Sequenced Genes) Decreasing significance

23. Overrepresentation Analysis (with Numerical Values) Step through, stop/start dataset display

24. Using Reactome to Explore Cancer Datasets

25. Applying Reactome to Cancer • Challenges in treating cancer: • Every tumor is different • Every cancer patient is different

26. New Sequencing Technologies • Drastic decrease in costs per genome • Capacity greater than one Gigabase per run • Applications: DNA, RNA, chromatin (i.e. epigenome) Illumina/Solexa ABI/SOLiD

27. Genes and Pathways associated with Cancer

28. Download Reactome Data “MySQL Dump” “Interactions” SBML BioPAX Textbook Local installation Data entry tool API http://www.reactome.org/download/index.html

29. Exploring Experimental Cancer data sets using Cytoscape and Reactome data

30. Reactome - In progress • Website re-design • New Entity-level view for pathway layout based upon SBGN • New “Pathway Analysis” portal incl. overrepresentation analysis • Colouring of Entity-level view with user-supplied data

31. In Progress: Entity Level Viewer

32. Future • Creating Reactomes for model organisms • Active recruitment of authors to create pathway modules • Reactome’s focus is normal human biology – how about pathological pathways? • Integrating Chemoinformatics resources into Reactome

33. Summary Tools Web Data Reactome: an encyclopedia of pathways and provides data mining tools for life scientists

34. Thank you Please email comments and suggestions to help@reactome.org Follow Reactome at http://www.facebook.com/group.php?gid=244908260192 http://twitter.com/reactome http://www.linkedin.com/groups?gid=2118372 http://mail.reactome.org/mailman/listinfo/reactome-announce