1. BiNoM Tutorial Andrei Zinovyev, Laurence Calzone UMR U900 INSERM/Institut Curie/Ecole des Mines de Paris Wednesday, April 30th

2. BiNoM is a plugin for Cytoscape http://cytoscape.org/

3. Install and Start Cytoscape+BiNoM 1) Download Cytoscape installer version 2.4.0 from http://cytoscape.orghttp://cytoscape.org 2) Download BiNoM from http://bioinfo-out.curie.fr/projects/binom/BiNoM_all.jar 3) Copy BiNoM_all.jar into the ‘plugins’ folder of Cytoscape 4) Remove (better, backup) xercesImpl.jar from the ‘lib’ folder of Cytoscape Attention : BiNoM is not yet compatible with the latest version of Cytoscape 2.6.0. These technical issues will be resolved very soon.

4. Starting course about Cytoscape

5. Short introduction into Cytoscape

6. Main concept : directed graph with attributes source target Attribute1Name : Value Attribute2Name : Value AttributeYName : Value AttributeXName : Value

7. Short introduction into Cytoscape Selected nodes

8. Short introduction into Cytoscape

9. BiNoM – Biological Network Manager

10. Naming convension

11. Section 1. Basic Network Analysis tools in BiNoM

12. Importing CellDesigner (SBML) files Open NFKB_final.xml example

13. Importing CellDesigner (SBML) files Reaction network

14. Choose in the menu Plugins / BiNoM Analysis / Prune graph Initial network Result of operation

15. Choose in the menu Plugins / BiNoM Analysis / Monomolecular reactions to edges Initial network Result of operation

16. Choose in the menu Plugins / BiNoM Analysis / Exclude intermediate nodes Initial networkResult of operation

17. Choose in the menu Plugins / BiNoM Analysis / Material components NFkB IkB Initial network

18. BiNoM Analysis / Get cycle decomposition Apply from the initial network

19. 1. Select NFkB@nucleus and IkB_alpha:NFkB nodes (holding Shift key) 2. Choose in the menu: Plugins / BiNoM Analysis / Path analysis

21. BiNoM I/O: Export current network to CellDesigner 1.Select some nodes 2.File->New->Network->From selected nodes, all edges 3.BiNoM I/O->Export current network to CellDesigner 4.Associate the network with NFKB_final.xml 5.Save to a new xml file 6.Open the newly created file in CellDesigner

22. Section 2. BiNoM and BioPAX

23. Biological PAthway eXchange format BioPAX Molecular Interactions Pro:Pro All:All PSI Biochemical Reactions SBML, CellML Regulatory Pathways Low Detail High Detail Genetic Interactions Interaction Networks Molecular Non-molecular Pro:Pro TF:Gene Genetic Metabolic Pathways Low Detail High Detail Database Exchange Formats Simulation Model Exchange Formats Small Molecules (CML) Rate Formulas

24. BioPAX is formulated on Web Ontology Language (OWL) BioPAX level 2.0

25. Importing BioPAX files Open example file at Desktop/ Pathway Charting/ MAPK_Reactome.owl

26. Reaction network (RN) Apply Layout -> yFiles -> Organic layout

27. Pathway hierachy (PS) Apply Layout -> yFiles -> Hierarchic layout

28. Protein-protein interactions (PP) Apply Layout -> yFiles -> Organic layout

29. Example of combined view Apply Plugins->Merge networks

30. Alternative Pathway view Reimport the MAPK_Reactome example with new pathway hierarchy options

31. Get BioPAX annotation Plugins / BiNoM BioPAX Utils/BioPAX Property Editor Select some Nodes first

32. Get BioPAX annotation BiNoM BioPAX Utils/BioPAX Property Editor Browse by clicking at the color labels

33. Get Complete BioPAX annotation Plugins / BiNoM BioPAX Utils / BioPAX Class tree…

34. Exporting subnetwork: 1.Select subtree 2.File->New->Network->From selected nodes, all edges

35. Exporting subnetwork: 3. Plugins->BiNoM->Export current network to BioPAX 4. Associate with MAPK_Reactome 5. Save to ERK2.owl

36. Exporting subnetwork: 6. Reopen ERK2.owl using Plugin->BiNoM I/O-> Import BioPAX

37. Section 3. Using BiNoM with pathway databases

38. Pathway Database -> BioPAX -> BiNoM query Cancer Cell Map Reactome BioBase INOH HumanCyc Nature/NCI Pathway Interaction KEGG BiNoM Big BioPAX file

39. To work with big BioPAX file, BiNoM user should generate BioPAX index Reactome.owl file Reactome Index.xgmml file BiNoM Query Network

40. Preparing database: Plugins / BiNoM BioPAX Query / Generate Index

41. Loading index: Plugins / BiNoM BioPAX Query / Load Index The accession number file (list of synonyms) is optional. It facilitates identifying proteins by name or other Ids

42. Plugins / BiNoM BioPAX Query -> Select entities IGF_1 IGFBP_3 pRB

43. Plugins / BiNoM BioPAX Query / Standard query

44. Get all reactions in which IGF_1 is involved Plugins / BiNoM BioPAX Query / Standard query

45. Extract all selected reaction annotations Plugins / BiNoM BioPAX Query / Standard query

46. Plugins / BiNoM Analysis / Extract Reaction Network Plugins / BiNoM Analysis / Mono-molecular Reactions To Edges Simplifying the query result view

47. Finding the shortest path from one protein to another Plugins / BiNoM BioPAX Query / Index Path Analysis

48. Finding the shortest path and suboptimal path from one protein to another Plugins / BiNoM BioPAX Query / Index Path Analysis 1) Select nodes 2) Open dialog, change parameters 3) Apply hierarchic layout

49. Q: Why are there some hanging nodes in the tree? A: Because there are connections “through complexes”