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Workshop: Introduction to Cytoscape at UT-KBRIN Bioinformatics Summit 2014 (4/11/2014)

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Presentation slides for Bioinformatics Summit 2014 (4/11/2014)

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Workshop: Introduction to Cytoscape at UT-KBRIN Bioinformatics Summit 2014 (4/11/2014)

  1. 1. Keiichiro Ono UC, San Diego Trey Ideker Lab Bioinformatics Summit 2014 4/11/2014 Cytoscape An Open Source Platform for 
 Biological Network Analysis and Visualization
  2. 2. - Thanks for Attending! - Keiichiro Ono - Cytoscape Core Developer since 2005 - Core module design & implementation - Area of Interest: Data Integration & Visualization - University of California, San Diego Trey Ideker Lab
  3. 3. Made with Cytoscape
  4. 4. Agenda - What is Cytoscape? - Data Integration, Analysis, and Visualization with Cytoscape - Cytoscape Ecosystem - Cytoscape Future Plan
  5. 5. What is Cytoscape?
  6. 6. An Open Source Platform for Biological Network Data Integration, Analysis and Visualization Cytoscape
  7. 7. Cytoscape - Open Source (LGPL) - Free for both commercial and academic use - Developed and maintained by universities, companies, and research institutions - De-facto standard software in biological network research community - Expandable by Apps - This is why Cytoscape is a Platform, not a simple desktop application
  8. 8. Network Data Analysis Analysis Visualization
  9. 9. Network Data Analysis Analysis s Visualization Desktop Gephi Cytoscape matplotlib Cytoscape.js
  10. 10. Network Dat Analysis Graph Analysis NetworkX igraph Cytoscape Python Pandas NumPy SciPy Excel IPython 3rd Party Apps NetworkAnalyzer
  11. 11. Network Data Analysis Analysis Graph Analysis NetworkX igraph Cytoscape Python Pandas NumPy SciPy Excel Visualization Desktop Gephi Cytoscape matplotlib Web Cytoscape.js sigma.js d3 NDV3 d3.chart Google Charts Data Storage Graph Neo4j GraphX Document MongoDB Relational MySQL IPython 3rd Party Apps NetworkAnalyzer
  12. 12. Network?
  13. 13. Network = Nodes + Edges
  14. 14. 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
  15. 15. Undirected Network
  16. 16. EP300 PPARG SMARCD3 STMN1 SMARCA4 OPTN ATP6V1C1 PSMD1 HTT PRNP HNRNPUL1 CCDC88A CLU HSP90AB1 SMARCD3 MAP4K4 MIF4GD USP11 MARCH6TUBB EDF1 CHD8 Protein-Protein Interactions
  17. 17. Directed Network KEGG Pathway (TCA Cycle) visualized by Cytoscape KGMLReader
  18. 18. Human-Curated Pathways KEGG Pathway Visualized by Cytoscape
  19. 19. KEGG Global Map Visualized by Cytoscape
  20. 20. The Challenge in Network Biology
  21. 21. C. Elegans Interactome from BioGRID Database ?
  22. 22. Biological Networks - Tell us anything by themselves - Just a big hairball…
  23. 23. Module 1 Module 2
  24. 24. In other words…
  25. 25. Module 1 Need a tool to extract meaningful biological modules
  26. 26. Basic Use Case
  27. 27. Networks Public Interaction Databases
  28. 28. List of Genes
  29. 29. Other Data
  30. 30. is NOT a... - Cytoscape is a powerful tool, but cannot do everything - Simulator - Fully-featured Pathway diagram editor - Statistical network analysis tool suite - Still, you can implement these as Apps though
  31. 31. Our Focus
  32. 32. Large-Scale Network Analysis and Visualization Human Interactome data from BioGRID visualized by Cytoscape
  33. 33. Agenda - What is Cytoscape? - Data Integration, Analysis, and Visualization with Cytoscape - Cytoscape Ecosystem - Cytoscape Future Plan
  34. 34. Introduction to Biological Network Analysis with Cytoscape
  35. 35. 1. Data Integration
 (Load Networks and Tables) 2. Data Analysis 3. Visualization Basic Workflow 4. Prepare for Publication
  36. 36. Network Data Annotated Networks Attributes Analyzed Data
  37. 37. Cline, et al. “Integration of biological networks and gene expression data using Cytoscape”, Nature Protocols, 2, 2366-2382 (2007). Protocol Paper
  38. 38. <?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
  39. 39. Network Data Formats - SIF - GML - XGMML - GraphML - BioPAX - PSI-MI - SBML - KGML (KEGG) - Excel - Text Table - CSV - Tab
  40. 40. Network Data Source - From your own experiment - Public database - Search known interactions by list of genes
  41. 41. Public Interaction Databases
  42. 42. Which Database? - Protein - Protein - STRING - IntAct - Genetic - BioGRID - Protein - Compound - ChEMBL
  43. 43. Which Database? - Human-Curated Pathways - KEGG - Reactome - WikiPathways - PathwayCommons
  44. 44. Import Tables
  45. 45. NCBI Gene ID 672 On Chromosome 17 GO Terms DNA Repair Cell Cycle DNA Binding Ensemble ID ENSG00000012048 BRCA1
  46. 46. Data Tables for Cytoscape - Example: - Numeric - Gene expression profiles - Network statistics calculated in other applications, such as R - Confidence scores for edges - Text (or categorical) - GO annotation for genes - List of genes related to disease X - Targets for FDA approved drugs - Genes on KEGG Pathway Y - Clusters / group / community calculated in external programs - …
  47. 47. Your Data Sets - Anything saved as a table can be loaded into Cytoscape - Excel - Tab Delimited Document - CSV - As long as proper mapping key is available, Cytoscape can map them to your networks.
  48. 48. Mapping Key in the Network Mapping Key in the Table
  49. 49. Network Data Annotated Networks Attributes Analyzed Data
  50. 50. Analysis
  51. 51. Network Analysis - Filtering - Calculate network statistics by Network Analyzer - Degree distribution,centrality, etc. - Advanced analysis by Apps
  52. 52. Filtering (Selection) - Simple, but powerful feature to extract sub networks from large data sets - Select nodes and edges with specific conditions - Pick nodes with degree > 5 - Select edges extracted from publication X - Find nodes on KEGG Pathway X
  53. 53. Other Selection Command: First Neighbor of Nodes CTR+6
  54. 54. Create New Sub-Network From Selection CTR+N
  55. 55. Summary: Selection - Create filter from your biological question: - Select all nodes annotated with GO term “DNA repair” and have two or more know interaction - Select all genes directly interact with brca1, brca2, etc. - Extract subnetwork by CTR+N
  56. 56. Network Data Annotated Networks Attributes Analyzed Data
  57. 57. Visualization
  58. 58. - Goal: Help others to understand your data - Emphasize what you want to tell - Use color, shape, size of objects effectively! - Excellent resource for data visualization - Tamara Munzner’s Web Site: 
 http://www.cs.ubc.ca/~tmm/ Data Visualization
  59. 59. Map Attributes to Visual Properties
  60. 60. Visual Style - Collection of mappings from Attributes to Visual Properties
  61. 61. Visual Style - Example Mappings: - Expression profiles to node color - Object type (protein, compounds, complex, etc.) to node shape - Interaction type (Protein-Protein, Protein-DNA, etc.) to edge line style
  62. 62. Layouts
  63. 63. Previous Example
  64. 64. GCN4 HIS7 ILV2 RPL16A CBF1 YOR264W YGR058W YGR136W YBR190W YCR086W YNL050C ACS2 FPR1 SNP1HMO1 PRP21 TAH18 SIP4 HOM3 PGK1 RPS17A RPL18B HSP42 ARG1 FCY1 SRP1 MCK1 YDR412W PHO13 PHO4 PHO84 RPS24B PDC1 RPL18A RPS24A PFK27 YPT1RAP1 ENO1 SEC17 GCR1 PHO5 GDS1 TPI1 CLB2 ADH1 CDC19 ENO2 ICL1 MSN5 SNC2 SEC9 DDI1 CBF5 SNC1 SSO2 YGR203W GCR2 HXT11 RFA2PDR3 SYF3 CAR1 PDR1 AST1 YNL047C CLB1 TIF5 HSL1 CKS1 NIP1 YML114C PMA1 TIF35 PRT1 RPS8B GPD2PRE10 GNA1 TIF34 YDR070C RLM1 HSP150 CDC6 YDL023C YIL113W SSN6 BFR2 KNS1 TUP1 YKL161C SSL2 VPS21 RPL25 HIS3 TFA1 HIS4 PEP7 TFB1 NCE103 SIN4 GPA1 MSL5 ATC1 SST2 CNS1 PRP40 TOR1 BUD6 YGR046W HSC82 MSL1 BAS1 YGL161C SKO1 PEP12 YDR100W YNL164C YNL091W SUC2 RPL42B HSP82 MUD2 AHP1 CIN4 RPL34B RPL11B SXM1 RPL16B RPL11A RPL31A RPL10 CUP1B SSA4 GFD1 GCN3 HRP1 RNA15 NAB2 CHK1 APG7 YLR345W SFH1 ADE4 RAD52 MET16 TRP4 HXT9 RFA1 HSP26 GIP1 PCL10 PHO85 PCL5 GSY2 PIG2 HSF1 GAC1 CUP1A YOR315W GLC7 APG12 REG2 AUT1 GIP2 APG5 GLC8 PIS1 CTT1 CYC7CLN3 SLT2 CDC42 MFA2 MCM1 MFA1 STE12 SWI4 FBP1 LYS9 DMC1 MLS1 DCP1 PCK1 GAL3 SWI5 GAL1 MIG1 GAL80 FAR1 GAL11 GAL10 HAP4 GAL4 GAL7 STE4 GAL2 GCY1 RPA135 MAM33 CYB2 YDR032C SPC24 ASN1 HEX3 LSM8 YEL015W PRP9 TEM1 YMR044W ECI1 YNR053C TAF25 MTH1 YHR198C MPT1 GLN1 GDH2 YER116C UGA1 SNF3YLR432W GLN3 PDC5 YIL105C RPS28B RPS28A LSM4 LSM2 HAP1 STE11 SPA2 STE50 STE5 CYC1 HAP3 YER124C HAP2 GIC2CDC28 STE2 BAR1 ALPHA2
  65. 65. YBR190W YCR086W YNL050C ACS2 SNP1 PRP21 TAH18 SIP4 PGK1 RPS17A RPL18B HSP42 ARG1 FCY1 SRP1 MCK1 YDR412W PHO13 PHO4 PHO84 RPS24B PDC1 RPL18A RPS24A PFK27 YPT1RAP1 ENO1 SEC17 GCR1 PHO5 GDS1 TPI1 CLB2 ADH1 CDC19 ENO2 ICL1 MSN5 SNC2 SEC9 CBF5 SNC1 SSO2 YGR203W GCR2 YNL047C CLB1 HSL1 ML114C PMA1 HSP150 CDC6 YIL113W SSL2 VPS21 RPL25 HIS3 HIS4 PEP7 TFB1 NCE103 SIN4 GPA1 MSL5 ATC1 SST CNS1 PRP40 TOR BUD6 HSC82 MSL1 BAS1 YGL161C SKO1 PEP12 YDR100W YNL164C YNL091W SUC2 RPL42B HSP82 MUD2 AHP1 CIN4 PIS1 CTT CYC7CLN3 SLT2 CDC42 MFA2 MCM1 MFA1 STE12 SWI4 FBP1 LYS9 DMC1 MLS1 DCP1 PCK1 GAL3 SWI5 GAL1 MIG1 GAL80 FAR1 GAL11 GAL10 HAP4 GAL4 GAL7 STE4 GAL2 GCY1 HEX3 LSM8 YEL015W PRP9 TEM1 YMR044W YNR053C TAF25 MTH1 MPT1 GDH2 YER116C SNF3YLR432W GLN3 PDC5 YIL105C RPS28B RPS28A LSM4 LSM2 HAP1 STE11 SPA2 STE50 STE5 CYC1 HAP3 YER124C HAP2 GIC2CDC28 STE2 BAR1 ALPHA2
  66. 66. Real World Examples http://cytoscape-publications.tumblr.com
  67. 67. Apps
  68. 68. Cytoscape Apps - Extension programs to add new features to Cytoscape (were called Plugins) - Large App developer/ user community - This is why Cytoscape is so successful in life science community!
  69. 69. (As of 4/5/2014) APPS.CYTOSCAPE.ORG
  70. 70. Quick Overview of Apps 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
  71. 71. 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
  72. 72. 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
  73. 73. Agenda - What is Cytoscape? - Data Integration, Analysis, and Visualization with Cytoscape - Cytoscape Ecosystem - Cytoscape Future Plan
  74. 74. Cytoscape Ecosystem JS
  75. 75. Cytoscape Family - Version 2.x - Legacy version - Last release for 2.x is 2.8.3. - Version 3.x - Current production version - Latest version: 3.1.0 - Important Note: Apps for 2.x is not compatible with 3.x
 (We have similar problem like Python…)
  76. 76. Cytoscape Family - cytoscape.js: Library for web applications JS
  77. 77. Cytoscape 3.1.0
  78. 78. JS
  79. 79. JS
  80. 80. Cytoscape.js Network Visualization Library Running on Web Browsers
  81. 81. What is cytoscape.js? A Javascript Library for network visualization, not a web application! Need to write some code to use it on the web browsers…
  82. 82. Complete desktop application for network analysis and visualization ! Written in Java ! Expandable by Apps ! For Users A Javascript Library for network visualization, not a web application! ! Written in JavaScript ! Expandable by Extensions ! For Developers JS
  83. 83. Analysis Data Integration Cytoscape Desktop Cytoscape.js Visualization Minimal Analysis Cytoscape Web Desktop Layout Visual Style Visual Style Layout Visualization
  84. 84. Integration to Cytoscape New in Cytoscape 3.1.0: Export Networks and Visual Styles to Cytoscape.js Format JS
  85. 85. Export to HTML5 Session Feature for users: you can view networks on web browsers with Cytoscape.js Under development… We need early adapters for testing! JS
  86. 86. Future Plan
  87. 87. Future Plan - Integration to external tools - Access from Python, R, Perl, etc. - More integration to Cytoscape.js - Cytoscape Cyberinfrastructure (Cytoscape CI)
  88. 88. Cytoscape CI: Background - The size of data biologists have to analyze is still growing - Desktop machines are powerful, but not enough for large scale data analysis - Clusters / Clouds - Using multiple computing resources as external service is normal for biological data analysis… - Scalability Service 1 Service 2
  89. 89. Cytoscape Cyberinfrastructure Internet Service 1 Service 2 NDEx (DB) Web Browser Cytoscape Desktop
  90. 90. App Development
  91. 91. github.com/cytoscape
  92. 92. Developer Documents - http://opentutorials.cgl.ucsf.edu/index.php/ Portal:Cytoscape3
  93. 93. Collaboration
  94. 94. Collaboration - Once you are ready to use Cytoscape for real-world problems, National Resources for Network Biology (NRNB) is always open for collaboration! - NRNB Provides support for both of - Scientific Research - Application / Tool Development - nrnb.org
  95. 95. - - Two Google Groups - cytoscape- discuss@googlegroups.com - cytoscape- helpdesk@googlegroups.com - ANY question is OK! Getting Help
  96. 96. General Introduction ! ! ! ! ! Advanced Topics - Effective Visualization Techniques - External Tools ! ! Part 2Part 1
  97. 97. Q1. How many of you have never used Cytoscape?
  98. 98. Q2. How many of you regularly use R/Python/MATLAB?
  99. 99. www.cytoscape.org
  100. 100. 2014 Keiichiro Ono kono@ucsd.edu

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