Cytoscape Workshop at Salk: Introduction to Cytoscape

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Cytoscape An Open Source Platform for Biological Network Analysis and Visualization Keiichiro Ono Cytoscape Core Developer Team University of California, San Diego Trey Ideker Lab 1

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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 2

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Outline - What is Cytoscape? - How to Use Basic Features of Cytoscape - Cytoscape 3 and Beyond 3

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What is Cytoscape?

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Cytoscape - Open source platform for biological network data integration, analysis, and visualization 5

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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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A KPNA3 HRAS BUB1 EN FAM175A CDK8 ARIH1 CHGA ELAC2 FBXW4 FGF11 EP400 UBA1 GTF2F1 HERC2 MLH1 GTF2E1 TRIM28 HSD17B1 TAF2G PLK1 AURKA BIRC5 NEK2 YRDC PLK3 RNF2 JUN DNAJA3 CDK1 CREBBP CCNA2 ORC2L ID4 CDC25C TRRAP NEK10 XRCC3 ACACA ORC3L C11orf30 GMNN C17orf70 CASP3 PGR CHGB 9606.ENSP00000358154 RNASEL RCHY1 UIMC1 CDK13 RARB FAM175B ERBB2 PMS2 STK11 SMAD3 TP53 FANCE FANCC CHD8 RAD17 WHSC2 MED13 HIST1H4A RNF53 CREB1 PSAP MAP2K1 RPA1 WWP1 ANTXR1 PALB2 BRCC3 PEG3 FBXL7 JUND AP2B1 FLI1 TOPBP1 ECHDC1 MSH2 FANCB TSPAN9 DCUN1D1 FBXO25 MED17 CDC25A PARP2 RNF31 ELK4 TOX3 ECT2 CDK4 PPP1CA SMARCB1 SMARCC2 FBXO11 HYRC GSTP1 SMC1A MED24 PIAS4 BATF MAD2L1 PIAS1 SUMO2 CNR1 MDM2 PMS1 RNF8 SUGT1 UBA52 ELK1 MELK UBB RBM LMO7 WT1 NBR1 PPP1R3A ERCC4 RBL1 ERCC1 XRCC5 MRE11A RNF144B ETS1 WRN NMI SHFM1 EZH2 ERCC2 TUBB2A MAP3K4 HIC1 PML DCAF11 CDKN1A APLP2 CDC45 TSPAN17 NUP153 EGFR FBXL3 CTCFL SMARCE1 GATA3 CHEK2 TOP3A EIF4G1 DDB1 PAX6 KRT14 PPT1 CDK16 SMARCD2 SMARCC DHFR TUBA4A IGF1R RNF168 BRCA1 PPM1D JUNB MED21 FANCA HMMR CDKN1B NUSAP1 RAD9A

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Introduction to Biological Network Analysis Using Cytoscape 11

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Network? 12

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Human Interactome data from BioGRID visualized by Cytoscape

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Twitter Visualization

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M20 M10 M18 M9 M19 M12 M7 M6 M17 M2 M15 M5 M11 M4 M8 M1 M3 M16 M13 M14 Network of Networks 15

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Human-Curated Pathways 16

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Network = Nodes + Edges 17

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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 Node Edge 18

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Undirected Network - Protein - Protein Interaction 19

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Directed Network KEGG Pathway (TCA Cycle) visualized by Cytoscape KGMLReader 20

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KEGG Global Map Visualized by Cytoscape 21

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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 22

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Network Data Annotated Networks Attributes Analyzed Data Apps

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79 0 9 167 18 75 8 12 26 210 29 320 Import Networks 24

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Network Data Formats - SIF - GML - XGMML - GraphML - BioPAX - PSI-MI - SBML - KGML (KEGG) - Excel - Delimited Text Table - CSV - Tab 25

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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. 26

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Which Database? - Protein - Protein - STRING, IntAct - Genetic - BioGRID - Protein - Compound - ChEMBL - Human-Curated Pathways - KEGG, Reactome, PathwayCommons 27

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PSICQUIC - Standardized mechanism to access public interaction data sets - In short, you can search multiple databases at once 28

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Import Attributes 29

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What are Attributes? - Any data that describes or provides details about nodes, edges, and networks. 30

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BRCA1 NCBI Gene ID 672 On Chromosome 17 GO Terms: DNA Repair Cell Cycle DNA Binding Ensemble ID ENSG00000012048 31

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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. 32

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Node Attributes - Gene Expression Data - Human-readable gene names - Gene Ontology Terms 33

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Edge Attributes - Interaction Detection Methods - Y2H, NMR, afﬁnity chromatography, etc. - Interaction Type - Physical, genetic, predicted - Publication ID 34

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Network Attributes - Experiment details - Pathway Metadata - Description - Publication ID 35

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Public Data Source - Access directly from Cytoscape, or - Import as Table (Text/Excel) 36

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Mapping Key in the Network Mapping Key in the Table 37

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Analysis 38

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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. 39

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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 40

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Visualization 44

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? 45

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Layouts 46

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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/ 47

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Visual Style - Collection of mappings from Attributes to Visual Properties 48

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Default View Editor Discrete Mapping Editor Continuous Mapping Editor 49

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Prepare for Publication - Network images can be exported as PDF/ PS/PNG/JPG. - Use PDF for your publications 55

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Real World Examples http://cytoscape-publications.tumblr.com 56

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Expanding Cytoscape with Apps 57

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Cytoscape Apps - Were called Plugins - Add new features to Cytoscape - Large app developer/user community - This is the reason why Cytoscape is so popular! 58

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http://apps.cytoscape.org 59

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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 NetworkEvolution OmicsAnalyzer OmicsViz OrthoNets PanGIA PerturbationAnalyzer PinnacleZ RandomNetworks RDFScsape Reactome FIs RemainingDegreeDistribution ReOrientPlugin ShortestPath Plugin SimTrek structureViz TransClust VennDiagramGenerator VistaClaraPlugin WordCloud BiNoM bioCycPlugin BiogridPlugin BiomartClient BioNetBuilder 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 AgilentLiteratureSearch 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 MultilevelLayoutPlugin NamedSelection NatureProtocolsWorkflow NeighborHighlight NetLink nodeCharts PhyloTree VennDiagrams 140+ Apps

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A Must Read A travel guide to Cytoscape plugins Rintaro 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 61

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Advanced Topics 62

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Custom Graphics 63

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Nested Networks 64

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Upcoming Projects 65

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- Cytoscape 3 - Integration to Web 3 66

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HUGE Update C 2 3 67

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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 69

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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 70

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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! 71

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Getting Help - Two Google Groups - [email protected] - [email protected] - ANY question is OK! 74

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NIH GM070743-01 P01 HG005062 P41 RR031228 (NRNB) 75