CytoscapeAn Open Source Platform for Biological Network Analysis and Visualization

Keiichiro OnoCytoscape Core Developer TeamUniversity of California, San Diego

Trey Ideker Lab

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Thanks for Attending!

- Who am I?- Keiichiro Ono

- Cytoscape Core Developer since 2005- Area of Interest: Data Integration & Visualization- University of California, San Diego Trey Ideker Lab

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Outline

- What is Cytoscape?

- How to Use Basic Features of Cytoscape

- Cytoscape 3 and Beyond3

What is Cytoscape?

Cytoscape

- Open source platform for biological network data integration, analysis, and visualization

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- Free! (LGPL)- Developed and maintained by

universities, companies, and research institutions

- De-facto standard software in biological network research community

- Expandable by Apps

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Introduction to Biological Network Analysis Using

Cytoscape11

Network?

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Human Interactome data from BioGRID visualized by Cytoscape

Twitter Visualization

M20

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M19

M12

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M6

M17M2

M15

M5M11

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M8M1

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Network of Networks

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Human-Curated Pathways

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Network = Nodes + Edges

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Nodes and Edges in Biology

- Protein - Protein- Protein - DNA- Genetic (Epistasis)

- Synthetic lethality

- Biochemical Reactions

- Compound - Enzyme - Compound

Cartoon representation of a complex between DNA and the protein p53

Node

NodeEdge

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Undirected Network- Protein - Protein Interaction

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Directed Network

KEGG Pathway (TCA Cycle) visualized by Cytoscape KGMLReader20

KEGG Global Map Visualized by Cytoscape21

1.Load Networks (Get network data)‏2.Load Attributes (Get data about networks)‏3.Analyze and Visualize Networks 4.Prepare for Publication

- A specific example of this workflow:− Cline, et al. “Integration of biological networks and gene

expression data using Cytoscape”, Nature Protocols, 2, 2366-2382 (2007).

Cytoscape Workflow

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Network Data

Annotated Networks

Attributes

Analyzed Data

Apps

<?xml version="1.0" encoding="UTF-8"?><graphml xmlns="http://graphml.graphdrawing.org/xmlns" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://graphml.graphdrawing.org/xmlns http://graphml.graphdrawing.org/xmlns/1.0/graphml.xsd"><!-- Created by igraph --> <key id="degree" for="node" attr.name="degree" attr.type="double"/> <key id="betweenness" for="node" attr.name="betweenness"

attr.type="double"/> <graph id="G" edgedefault="directed"> <node id="n0"> <data key="degree">79</data> <data key="betweenness">0</data> </node> <node id="n1"> <data key="degree">9</data> <data key="betweenness">167</data> </node> <node id="n2"> <data key="degree">18</data> <data key="betweenness">75</data> </node> <node id="n3"> <data key="degree">8</data> <data key="betweenness">12</data> </node> <node id="n4"> <data key="degree">26</data> <data key="betweenness">210</data> </node> <node id="n5"> <data key="degree">29</data> <data key="betweenness">320</data> </node> Import Networks

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Network Data Formats- SIF

- GML

- XGMML

- GraphML

- BioPAX

- PSI-MI

- SBML

- KGML (KEGG)

- Excel

- Delimited Text Table

- CSV

- Tab

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I Don’t Have a Network!

- Don’t worry - There are tons of public interaction data sets

- Cytoscape can import those public data sets directly via Internet.

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Which Database?- Protein - Protein

- STRING, IntAct - Genetic

- BioGRID- Protein - Compound

- ChEMBL- Human-Curated

Pathways- KEGG, Reactome,

PathwayCommons27

PSICQUIC- Standardized

mechanism to access public interaction data sets

- In short, you can search multiple databases at once

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Import Attributes29

What are Attributes?

- Any data that describes or provides details about nodes, edges, and networks.

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BRCA1

NCBI Gene ID 672

On Chromosome 17

GO Terms:DNA RepairCell Cycle

DNA Binding

Ensemble ID ENSG00000012048

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Why we need attributes?- Analysis

- It is hard to get biologically meaningful analysis result only from network topology (= structure)

- Meaningful Visualization- Expression values - Node Color

- Gene Function - Node Shape- etc.

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Node Attributes

- Gene Expression Data

- Human-readable gene names

- Gene Ontology Terms

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Edge Attributes

- Interaction Detection Methods

- Y2H, NMR, affinity chromatography, etc.

- Interaction Type

- Physical, genetic, predicted

- Publication ID

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Network Attributes

- Experiment details

- Pathway Metadata

- Description

- Publication ID

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Public Data Source

- Access directly from Cytoscape, or

- Import as Table (Text/Excel)

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Mapping Key in the Network

Mapping Key in the Table

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Analysis38

Network Analysis

- Filtering- Calculate network statistics by

Network Analyzer- Degree distribution,centrality, etc.

- Advanced analysis by Apps

- Analysis is a huge topic in Cytoscape, so I’ll show you only the very basic features only.

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Filtering

- Find nodes and edges with specific conditions- Pick nodes with degree > 5- Select edges extracted from

publication X- Find nodes annotated by GO term ID Y

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Visualization

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Layouts

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Biological Data Visualization

- Help others to understand your data

- Emphasize what you want to tell by the image

- Use color, shape, size of objects effectively!

- Tamara Munzner Web Site: http://www.cs.ubc.ca/~tmm/

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テキスト

Visual Style

- Collection of mappings from Attributes to Visual Properties

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Default View Editor

Discrete Mapping Editor

Continuous Mapping Editor

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Prepare for Publication

- Network images can be exported as PDF/PS/PNG/JPG.

- Use PDF for your publications

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Real World Examples

http://cytoscape-publications.tumblr.com

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Expanding Cytoscape with Apps57

Cytoscape Apps

- Were called Plugins- Add new features to Cytoscape- Large app developer/user community

- This is the reason why Cytoscape is so popular!

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http://apps.cytoscape.org

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AllegroMCODE APCluster APID2NET BioQualiPlugin BLAST2SimilarityGraph BNMatch CABIN CalculateNodeDegree CentiScaPe ChemViz clusterExplorerPlugin clusterMaker ClusterONE ClusterViz COMA CommFinder CyClus3D CyOog cytoHubba Cytomcl DualLayout dynamicXpr EnhancedSearch EnrichmentMap ExprEssence GraMoFoNe GraphletCounter HiderSlider jActiveModules mcl-new MCODE MINE NeMo NetAtlas NetCirChro netMatch NetworkAnalyzer NetworkEvolut ion OmicsAnalyzer OmicsViz OrthoNets PanGIA Per turbat ionAna lyzer P innac leZ RandomNetworks RDFScsape Reactome F Is RemainingDegreeDistribution ReOrientPlugin ShortestPath Plugin SimTrek structureViz TransClust VennDiagramGenerator VistaClaraPlugin WordCloud BiNoM bioCycPlugin Biogr idPlugin BiomartCl ient BioNetBui lder BisoGenet ConsensusPathDBplugin CoryneRegNetLoader CyThesaurus-ID-Mapping CytoSQL DroID Genoscape GPML-Plugin GraphMLReader IntActWSClient iRefScape KGMLReader MetScape MiMIplugin NCBIClient NCBIEntrezGeneUserInterface Pathintegrator PhosphositePlus Web Service Client Module PICRClient PSICQUICUniversalClient ReConn SessionForWeb SFLDLoader StringWSClient Superpathways-Plugin 3DScape Agi lentLiteratureSearch Cytoprophet DisGeNET DomainGraph ExpressionCorrelation GeneMANIA MetaNetter MONET BiNGO BubbleRouter ClueGO CommonAttributes DisplayNetworkFromFlatFile FluxViz FunNetViz HyperEdgeEditor PiNGO CyGoose CytoscapeRPC GroovyScriptingEngine JavaScriptEngine MiSink PythonScriptingEngine RubyScriptingEngine ScriptEngineManager addParentNeighbors AdvancedNetworkMerge batchTool BiLayout commandTool coreCommands CyAnimator edgeLengthPlugin edgeLister EpiTrace FERN FM3 GoogleChartFunctions GroupTool MetaNodePlugin2 Multi levelLayoutPlugin NamedSelection NatureProtocolsWorkflow NeighborHighlight NetLink nodeCharts PhyloTree VennDiagrams

140+ Apps

A Must Read

A travel guide to Cytoscape pluginsRintaro Saito, Michael E Smoot, Keiichiro Ono, Johannes Ruscheinski, Peng-Liang Wang, Samad Lotia, Alexander R Pico, Gary D Bader, Trey Ideker (2012)Nature Methods 9 (11) p. 1069-1076

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Advanced Topics

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Custom Graphics63

Nested Networks64

Upcoming Projects

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- Cytoscape 3

- Integration to Web

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HUGE Update

C

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What’s New in 3?- New Visualization features

- Edge Bend, Background Images- Server-side applications- Headless Mode (Command-line)- More advanced visualization by new

rendering engines- For developers: Cleaner API

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Release Schedule- User Beta - available now- 3.0 Final Release

- At Cytoscape Retreat 2012 @UCSF- December 13, 14

- For more information, please visit:

http://www.cytoscape.org/cy3.html

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cytoscape.js

- JavaScript version of Cytoscape for network visualization on the web browsers

- Subset of Cytoscape functions- Will be integrated more to Cytoscape 3!

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Getting Help

- Two Google Groups

- cytoscape-discuss@googlegroups.com

- cytoscape-helpdesk@googlegroups.com

- ANY question is OK!

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NIH GM070743-01

P01 HG005062

P41 RR031228 (NRNB)

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www.cytoscape.org