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1 Network Analysis with Cytoscape Chia-Lang Hsu Ueng-Cheng gyang

2 2 What is Cytoscape? Cytoscape is a network visualization and analysis tool. An extensible platform for bioinformatics software development. 100 % open-source java Current version is

3 3 Main window Network management panel Main network view window Network overview panel Attribute browser panel

4 4 Building & Storing Interaction Network Cytoscape reads an interaction network in three ways: A simple interaction file (.sif,.txt,.csv et al.) A standard dformat tknown as Graph Markup Language (.gml format) A XML standard called XGMML (extensible graph markup and modeling language) etc. SIF specifies nodes and interactions only, while GML and XGMML store additional information about network layout and allows network data exchange with a variety of other network display programs. A simple network: B A C D A B A D BC C D D B

5 5 Import & Export Network Network (multiple file types) SIF, GML, XGMML et al. Network from Table (Text/MS Excel) TXT, XLS Network from web services

6 6 Add more information into network Node and edge attributes

7 7 Hands-on exercises I Build your network Practice basic Cytoscape operation (import & export network, navigation)

8 8 Visual Styles Click here for managing visual styles

9 9 Export & Import your visual styles profiles *.props format file

10 Manage visual styles according to node and edge attributes 10

11 11 Edit network To add a node to a network, drag and drop a node shape from the palette onto the canvas. To connect two nodes with an edge,, drag and drop an arrow shape onto a node on the canvas. Alternative approach Click on the canvas to add a node. Ctrl + click on the first node and then click on the second nodes to connect two nodes with an edge. Click right-button and select Deleted Selected Nodes and Edges to remove nodes and edges.

12 12 Hands-on exercises II Set your visual properties and edit your network

13 13 Layout Hierarchic Original Circular Organic

14 Layout 14

15 15 Filter String filter Numerical filter Node topology filter Edge interaction filter Node interaction filter

16 16 Plugins Install plugins via Plugins Manage Plugins Or install manually Download from website and copy the *.jar files to plugins subdirectory of the Cytoscape root directory

17 17 Hands-on exercises III U l d fil f i Use layout and filter functions (galfiltered.sif and galexpdata_attr.csv)

18 18 Demo U k fi ddi Use network to find disease gene SCA1 as an example

19 19 Rationale for a quantitative approach Phenotypes (e.g. disease or functions) obtained from OMIM,GO, MGI or literature. Phenotype-specific gene list (or Diseasespecific gene list) Measure the distance of the path from candidate gene to disease genes closeness Candidate region Prioritize candidate gene(s) Candidate gene list

20 20 Visualization may quickly reveal the candidate genes Disease genes IPIR Disease related interactome All genes in the candidate region Label candidate gene IPIR (Integrated Protein Interaction Resource) is maintained by ABC t /i i / 20

21 21 Hands-on exercises IV To find the potential disease gene of SCA2 sca_network.sif: SCA related interactome sca_disease_genes.txt: t SCA related ltddisease genes candidate_genes.txt: candidate genes of SCA2

22 22 References Cytoscape online tutorial Cytoscape User Manual Cline MS et al. (2007) Integration of biological networks and gene expression data using Cytoscape. Nat. Protoc. 2: