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ISMB, June.26.2005

ISMB, June.26.2005. From protein sequences…to protein networks. Query Sequence GACTGCATTAC. Cellular response of interest. Database DNA and protein sequences. Database / Scaffold of Molecular Interactions. Family of homologous genes. Interaction pathways associated with

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ISMB, June.26.2005

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  1. ISMB, June.26.2005

  2. From protein sequences…to protein networks Query Sequence GACTGCATTAC Cellular response of interest Database DNA and protein sequences Database / Scaffold of Molecular Interactions Family of homologous genes Interaction pathways associated with cellular response

  3. Core Features • Customize network data display using visual styles • Powerful graph layout tools • Easily organize multiple networks • Easily navigate large networks • Filter the network • Plugin API Cytoscape.org • Additional features are available as plugins.  • jActiveModules: identify significant “active” subnetworks • Expression Correlation Network: cluster expression data • Agilent Literature Search: build networks by extracting interactions from scientific literature. • MCODE: finds clusters of highly interconnected regions in networks • cPath: query, retrieve and visualize interactions from the MSKCC Cancer Pathway database • BiNGO:determine which Gene Ontology (GO) categories are statistically over-represented in a set of genes • Motif Finder: runs a Gibbs sampling motif detector on sequences for nodes in a Cytoscape network. • CytoTalk: Interact with Cytoscape from Perl, Python, R, shell scripts or C or C++ programs. Cytoscape is a freely-available (open-source, java-based) bioinformatics software platform forvisualizing biological networks (e.g. molecular interaction networks) andanalyzing networks with gene expression profiles and other state data. • Input/Output • Protein protein interactions from BIND, TRANSFAC databases • Gene functional annotations from Gene Ontology (GO) and KEGG databases • Biological models from Systems Biology Markup Language (SBML) • cPath: Cancer Pathway database • Proteomics Standards Initiative Molecular Interaction (PSI-MI) or Biopathway Exchange Language (BioPAX) formats • Oracle Spatial Network data model

  4. Outline • Introduction (5 min) • Cytoscape as a network integration and query tool • Basic features demo (15 min) • Load network • Navigate/Zoom/Select/Filter Nodes • Create subnetworks • Visual styles • Layout • Plugin demo (20 min) • MCODE and BiNGO • Agilent Literature Search Plug-in • cPATH and BioPAX plugin • Plugin development intro (10 min) • Upcoming features – Version 2.2 (5 min) • Future work (5 min) www.cytoscape.org

  5. cPath PlugIn • cPath: Overview • cPath: XML Web Service • cPath Cytoscape PlugIn • Demo: Download sample protein-protein interaction network. • Demo: Drill down to protein details. www.cytoscape.org

  6. www.cytoscape.org

  7. cPath: XML Web Services API • Provides a URL-HTTP XML Web Services API to all cPath Data. • Formats: • PSI-MI: Proteomics Standards Initiative Molecular Interaction Format • BioPAX: Biological Pathway Exchange Format • Commands: • Query by keyword; query by interactor name; query by Pub Med ID, etc. • Example Query: • http://www.cbio.mskcc.org/cpath/webservice.do?version=1.0&cmd=get_by_interactor_name_xref&q=P04273&format=psi_mi&startIndex=0&organism=&maxHits=10 www.cytoscape.org

  8. cPath Cytoscape PlugIn • Enables Cytoscape users to easily query, download and visually render interactions stored in cPath. • Utilizes the cPath XML Web Service • Automatically bundled with Cytoscape 2.1 • Works out of the box • Additional details available on the Cytoscape PlugIn home page: • http://cytoscape.org/plugins2.php www.cytoscape.org

  9. cPath PlugIn Demo

  10. cPath PlugIn Demo

  11. BioPAX Plugin Demo www.cytoscape.org

  12. Plugin Development • Cytoscape is a development platform for computational network biology • “Just write the algorithm” • 100% open source Java 1.4 • Java 1.5 when stable on Mac • Rich core + plugin API • Plugins are independently licensed • Template code samples www.cytoscape.org

  13. Hello World Plugin! http://cytoscape.org/cgi-bin/moin.cgi/Hello_World_Plugin www.cytoscape.org

  14. Getting Started • Read “Concepts Document” on wiki • Follow “Cytoscape Plugin Tutorial” on wiki • Visit API Javadoc www.cytoscape.org

  15. New Features for 2.2 • Due October 2005 • Improved node/edge attribute browsing/editing • Network editing v1.0 • Gene Ontology annotation support • Window panels • Easier network comparison (side-by-side) www.cytoscape.org

  16. www.cytoscape.org

  17. FUTURE DIRECTIONS:Cross-comparison of networks • Alignment of networks across species (network conservation) • Correspondence between physical and genetic networks • Conserved regions in the presence vs. absence of stimulus Baker’s yeast (Saccharomyes cerevisiae) Fruit fly(Drosophila melanogaster) Nematode worm(Caenorhabditis elegans) www.cytoscape.org http://www.pathblast.org

  18. Network alignment with PathBLAST P is a path in the global alignment graph. The v and e represent vertices and edges in P. The value p(v) is the prob. of true homology for the proteins aligned at v. The value q(e) is the prob. that the protein interaction at e is real, i.e., not a false-positive.

  19. Example yeast/worm/fly alignments Roded Sharan et al. PNAS 2005

  20. Integration of genetic and physical interactions 160 between-pathway models 101 within-pathway models Num interactions:1,102 genetic933 physical Ryan Kelley et al. Nature Biotechnology 2005

  21. A between-pathway model

  22. Upcoming Events • Cytoscape ConferenceNov 30th and Dec 1st, 2005 • RECOMB Satellite Conference on Network Biology and Gene RegulationDec 2nd-4th, 2005 Mailing lists • cytoscape-announce@googlegroups.com • cytoscape-discuss@googlegroups.com www.cytoscape.org

  23. Cytoscape Team Benno Schwikowski Lee Hood Richard Bonneau Rowan Christmas Past contributors: Iliana Avila-Campillo Larissa Kamenkovich Andrew Markiel Paul Shannon Trey Ideker Nerius Landys Ryan Kelley Chris Workman Past contributors: Nada Amin Owen Ozier Jonathan Wang Mark Anderson Chris Sander Gary Bader Ethan Cerami Rob Sheridan Ben Gross Agilent Annette Adler Allan Kuchinsky Aditya Vailaya Mike Creech

  24. Funding Sources • NIH (NIGMS) R01 GM070743-01 Program Manager: John Whitmarsh • NCI caBIG Ken Buetow, Peter Covitz • Unilever, PLC Guy Werner • PathBLAST network comparison NSF Quantitative Systems BiologyProgram Manager: Mitra Basu www.cytoscape.org

  25. Layout • 16 algorithms available through plugins • Zooming, hide/show, alignment www.cytoscape.org

  26. yFiles Organic

  27. yFiles Circular

  28. Visual Styles • Map graph attributes to visual attributes • Define visual styles for later use • Graph has node and edge attributes • E.g. expression data, interaction type, GO function • Mapped to visual attributes • E.g. node/edge size, shape, color, font… • Take continuous gene expression data and visualize it as continuous node colors www.cytoscape.org

  29. Visual Styles Load “Your Favorite Network”

  30. Visual Styles Load “Your Favorite Expression” Dataset

  31. Visual Styles Map expression values to node colors using a continuous mapper

  32. Visual Styles Expression data mapped to node colors

  33. Visual Styles • Node attributes: node color, border color, border type, node shape, size, label, font • Edge attributes: edge color, line types, arrows, label, font • Multidimensional visual attribute mapping soon www.cytoscape.org

  34. MCODE and Biomodules Plugins (MSKCC and ISB) • Clusters in a protein-protein interaction network have been shown to represent protein complexes and parts of pathways • Clusters in a protein similarity network represent protein families • Network clustering is available through the MCODE Cytoscape plugin www.cytoscape.org

  35. Proteasome 26S Ribosome Proteasome 20S RNA Splicing RNA Pol core

  36. Biomodules (ISB) Prinz S, Avila-Campillo I, Aldridge C, Srinivasan A, Dimitrov K, Siegel AF, and Galitski T Genome Res. 2004 14: 380-390

  37. Output ALFA Network Terms Context Bind Cleave Inhibit Promote Catalyze Convert to ALFA Query Output Cytoscape Network Meta-Search Classify Sentence Into Interaction Type Normalize Nouns (User Context/BNS) Retrieved Documents Yes Extract Nouns/Verbs (User Context/ BNS) Is Interesting Sentence? Sentence Tokenization Get Document Query Interface No Information Extraction Routine Agilent Literature Search Plugin for Cytoscape www.cytoscape.org

  38. www.cytoscape.org

  39. Cytoscape Network produced by Literature Search. Abstract from the scientific literature Sentences for an edge www.cytoscape.org

  40. Active Modules (UCSD) Ideker T, Ozier O, Schwikowski B, Siegel AF Bioinformatics. 2002;18 Suppl 1:S233-40 www.cytoscape.org

  41. Active Modules www.cytoscape.org

  42. Biomodules (ISB) Prinz S, Avila-Campillo I, Aldridge C, Srinivasan A, Dimitrov K, Siegel AF, and Galitski T Genome Res. 2004 14: 380-390 www.cytoscape.org

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