Cytoscape and networks

1. Cytoscape and networks David Amar http://tau.ac.il/~davidama/bioinfo_tutorials

2. Network biology • Overview: systems biology • Represent molecular entities • Represent interactions • Two main data types • Pathways • Interaction networks

3. Biological interaction networks • Nodes: genes or other molecules • Edges: evidence for some interaction – can contain weights, directions Magtanong et al. 2011 Nature

4. Biological interaction networks • Nodes: genes/proteins or other molecules • Edges based on evidence for interaction Gene co-expression Protein-protein interaction Genetic interaction Breker and Schuldiner 2009 Voineagu et al. 2011 Nature

5. Cytoscape • Cytoscape is an open source software for integrating, visualizing, and analyzing networks. • This tutorial describes the Cytoscape 3 user interface. • Outline • Basics • Load and visualize data • Customize • Applications • Clustering • Enrichment analysis • GeneMANIA • Modmap • Gene expression analysis

6. Cytoscape Basics

7. Initial window Main Network View, initially blank.  The toolbar, contains command buttons, the name is shown when the mouse pointer hovers over it. Control Panel: lists the available networks by name Network Overview Pane Table Panel: can be used to display node, edge, and network table data

8. Load data: import from databases

9. Load data: import from databases  The initial window enables searching in the big public databases

10. Load data: import from databases  Search example: by gene name  Choose databases

11. Import result The imported networks by name Basic statistics

12. Look at a network Main Network View  The toolbar, contains command buttons, the name is shown when the mouse pointer hovers over it. Control Panel: lists the available networks by name Network Overview Pane: move around! Table Panel: displays node, edge, and network table data

13. Search for a gene Information about the marked nodes

14. Load data: import all interactions

15. Load data: import all interactions

16. Import result The new network

17. Load data: from files • We sometimes have our own data • From papers • A special search in a database • Our experiment (e.g., correlation between genes) • Famous formats • SIF • A table • OWL – for pathways, “complex” text • But easy to get and very informative once uploaded

18. Load from files

19. Load from files Contains an interaction network of 331 genes from Ideker et al. 2001 Science

20. Load data: from SIF files Text: name1<space or tab>interaction_type<space or tab>name2

21. Load data: from a table • From excel files or tab-delimited text tables

22. Load data: from a table

23. Load data: from a table Set where to look for the nodes and the type

24. Load data: from a table OPTIONAL: Click on the columns that you want to be kept as “attributes”

25. Result

26. Load data: OWL • Good for looking at pathways • This example: data from the Reactome database

27. Load data: result Directed edges: signaling

28. Zoom

29. Zoom Focus on a selected region (nodes in yellow)

30. Zoom: result Move around

31. Get a sub-network

32. Get a sub-network The sub-network was created below the original network

33. Save the session • We imported six networks • Before we start modifying them lets save the session • File -> Save Sanity check: close Cytoscape and load the session!

34. Remarks • At this point we know to load data from databases and files • We can perform simple navigation, zoom and save • We saved different networks each its own visualization ‘rules’ • A good habit that saves troubles: save a session for each visualization type • Multiple networks, but keep a consistent visualization

35. Modifying and saving a visualization • Cytoscape supports countless options • Layouts • Node size, color, label… • Edge width, line type… • We will show main examples that are enough to start • To save the graph as an image:

36. Change the layout

37. Organic layout

38. Circular layout • Places all of the nodes in a circular arrangement. • Very quick • Partitions the network into disconnected parts and independently lays out those parts.

39. Force-directed Uses physical simulation that models the nodes as physical objects and the edges as springs connecting those objects together.

40. Change layout scale

41. Change the scale Before: scale is 1 Scale is 8

42. Style  Open and modify

43. The IntActnetowrk: node color

44. The IntActnetowrk: node color  Node color  Each column represents some information that we have Discrete: set a value for each type of information

45. Applications

46. Apps • Cytoscape also has many tools called ‘apps’ • Install by going to Apps -> App Manager • Applications support • Advanced analysis • Biological analysis • Integrating data • Import special data

47. I) Find and annotate dense areas • Use an app that “clusters” the network • Biological assumption • We look for protein communities • Many interactions within • Probably share function • Gene function prediction

48. Step 1: remove duplicated edges • Sometimes nodes are linked by more than one edge • Multiple evidence for interaction • Remove them for clustering and simpler visualization

49. Step 2: use ClusterViz

50. Step 3: look at the results All clusters Sorted by size Select a cluster