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Reactome A database of biological pathways and processes Steve Jupe

Reactome A database of biological pathways and processes Steve Jupe. Rationale – Journal information. Nature 407(6805):770-6.The Biochemistry of Apoptosis.

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Reactome A database of biological pathways and processes Steve Jupe

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  1. ReactomeA database of biological pathways and processesSteve Jupe

  2. Rationale – Journal information Nature 407(6805):770-6.The Biochemistry of Apoptosis. “Caspase-8 is the key initiator caspase in the death-receptor pathway. Upon ligand binding, death receptors such as CD95 (Apo-1/Fas) aggregate and form membrane-bound signalling complexes (Box 3). These complexes then recruit, through adapter proteins, several molecules of procaspase-8, resulting in a high local concentration of zymogen. The induced proximity model posits that under these crowded conditions, the low intrinsic protease activity of procaspase-8 (ref. 20) is sufficient to allow the various proenzyme molecules to mutually cleave and activate each other (Box 2). A similar mechanism of action has been proposed to mediate the activation of several other caspases, including caspase-2 and the nematode caspase CED-3 (ref. 21).” How can this be represented as computationally-accessible reactions and pathways?

  3. Rationale - Figures A picture paints a thousand words… • but…. • Not computer readable • Omits key details • Assumes or infers Nature. 2000 Oct 12;407(6805):770-6. The biochemistry of apoptosis.

  4. Reactome is… • A free, online, open-sourcecurated database of pathways and reactions in human biology • Authored by expert biologists, maintained by Reactome editorial staff (curators) • Mapped to cellular compartment (but not tissue or developmental stage)

  5. Reactome is… • Extensively cross-referenced • Used to infer orthologous events in 20 non-human species • Tools for data analysis – Pathway Analysis, Expression Overlay, Species Comparison, Biomart…

  6. BINDING DEGRADATION DISSOCIATION DEPHOSPHORYLATION PHOSPHORYLATION CLASSIC BIOCHEMICAL TRANSPORT Theory - Reactions • Pathway steps - the “units” of Reactome • Encapsulate events and states found in biology

  7. Reaction Example 1: Enzymatic

  8. Reaction Example 2: Transport REACT_1338.3

  9. Other Reaction Types Dimerization Phosphorylation

  10. Reactions Connect into Pathways CATALYST CATALYST CATALYST INPUT OUTPUT INPUT OUTPUT OUTPUT INPUT

  11. Evidence Tracking – Inferred Reactions PMID:5555 PMID:4444 Direct evidence Direct evidence human Indirect evidence PMID:8976 mouse Indirect evidence PMID:1234 cow

  12. Data Expansion - Link-outs From Reactome GO Molecular Function Compartment Biological process KEGG, ChEBI – small molecules UniProt – proteins Sequence dbs – Ensembl, OMIM, Entrez Gene, RefSeq, HapMap, UCSC, KEGG Gene PubMed references – literature evidence for events

  13. Species Selection

  14. Data Expansion – Projecting to Other Species Human B A A + ATP -P + ADP Mouse B A A + ATP + ADP -P Drosophila B Reaction not inferred + ATP A No orthologue - Protein not inferred

  15. Exportable Protein-Protein Interactions • Are electronically inferred from complex and reaction data • Interaction between proteins in the same complex or reaction • Lists of interaction data from “downloads” tab • Visit the Readme document for more details

  16. Coverage – Current TOC

  17. Planned Coverage – Editorial Calendar

  18. Reactome Tools • Interactive Pathway Browser • Pathway Mapping and Over-representation • Expression overlay onto pathways • Molecular Interaction overlay • Biomart

  19. Tutorial

  20. Front Page http://reactome.oicr.on.ca Navigation bar Sidebar Main text

  21. Exercise 1

  22. The Pathway Browser

  23. Pathways tab – pathway hierarchy Pathway Reaction Black-box

  24. Exercise 2

  25. The Pathway Browser - Pathway Diagrams Boxes are proteins, sets or complexes. Ovals are small molecules. Green boxes are proteins or sets, blue are complexes. Regulation +ve -ve Input Reaction node Catalyst Outputs Compartment Transition Binding Dissociation Omitted Uncertain

  26. Exercise 3

  27. Navigating in the Pathway Browser I Home and Analyze buttons Search Click here Highlights Details here Click here to open pathway diagram...

  28. Navigating in the Pathway Browser II Highlights Details here Click here Zoom

  29. Exercise 4

  30. The Details Panel

  31. Exercise 5

  32. Pathway Analysis

  33. Pathway Analysis – Overrepresentation ‘Top-level’ Reveal next level P-val, In set/In pathway

  34. Exercise 6 Check this!

  35. Species Comparison I

  36. Species Comparison II Yellow = human/rat Blue = human only Grey = not relevant Black = Complex

  37. Exercise 7

  38. Expression Analysis I

  39. ‘Hot’ = high ‘Cold’ = low Expression Analysis II Step through Data columns

  40. Exercise 8

  41. Molecular Interaction Overlay

  42. Exercise 9

  43. BioMart – selecting your dataset

  44. BioMart – filters

  45. BioMart – attributes Check to get attribute

  46. BioMart – results

  47. Exercise 10

  48. The End

  49. Author Biology expert Curator Reviewer 2nd expert Where Reactome’s Data Comes From

  50. Data Provision EXPERT CURATOR REVIEWER • Expert in the field • Recruited in various ways • jamborees, workshops etc. • Provide information on biological system • Curators can be experts

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