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  3 rd Party Tools Future Directions and Questions

3. Nature. 2000 Oct 12;407(6805):770-6. The biochemistry of apoptosis. A picture paints a thousand words…...BUT is not computationally accessible doesn’t convey enough detail Reactome Rationale 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. BINDING DEGRADATION TRANSPORT PHOSPHORYLATION DEPHOSPHORYLATION “CLASSICAL” BIOCHEMICAL DISSOCIATION

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

7. 1)Recruit bench scientists to write modules. 2)Authors use a software tool to describe their pathway. All molecules must be identified explicitly. All assertions backed up by literature references. 3)Curators work with authors to ensure consistency and completeness. 4)Module checked by peer review & software before publication. 5)Public Release of Curated data every 3 months. 6)Rolling review every 2 years by expert. 7)Pathways updates. Where the Data Comes From

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

9. 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) human (Homo sapiens) rat (Rattus norvegicus) mouse (Mus musculus) rice (Oryza savita) chicken (Gallus gallus) 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

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

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

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 Usable identifiers: UniProt RefSeq Ensembl OMIM Entrez Gene Affymetrix GO KEGG COMPOUND ChEBI 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 http://www.reactome.org/cgi-bin/skypainter2 NP_000005 NP_001080 NP_005836 NP_005461 NP_009297

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

27. Genes and Pathways associated with Cancer

28. Download Reactome Data SBML Local installation Data entry tool API BioPAX “Interactions” “MySQL Dump” Textbook 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 Web Data Tools Reactome: an encyclopedia of pathways and provides data mining tools for life scientists

34. Thank you Please email comments and suggestions to help@reactome.orghelp@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