Pathway (Network) Informatics @ MSKCC

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Pathway (Network) Informatics _at_ MSKCC

• Gary Bader (Sander Lab)
• Alex Lash (Bioinformatics Core)
• Ethan Cerami, Rob Sheridan
• http//cbio.mskcc.org

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cBio _at_ MSKCC

• Computational Biology Center
• Sander group
• 4 fellows, 3 developers, 1 research associate
• Bioinformatics Core Alex Lash
• 3 research staff, 1 developer, 1 computing, 3
  admin
• Visiting Faculty Jose Vilar
• 6 Additional faculty positions
• http//cbio.mskcc.org/people

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MSKCC cBio Pathway Initiatives

• BioPAX Biological pathway exchange format
  (collaboration)
• cPath MSKCC cancer pathway database
• Cytoscape Biomolecular network analysis tool
  (collaboration)

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BioPAXA Data Exchange Format for Biological
Pathways

• BioPAX Workgroup
• www.biopax.org

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BioPAX Supporting Groups

• Groups
• Memorial Sloan-Kettering Cancer Center C.
  Sander, J. Luciano, M. Cary, G. Bader
• SRI Bioinformatics Research Group P. Karp, S.
  Paley, J. Pick
• University of Colorado Health Sciences Center I.
  Shah
• Harvard Medical School Aviv Regev
• BioPathways Consortium J. Luciano, E. Neumann,
  V. Schachter
• Argonne National Laboratory N. Maltsev
• Samuel Lunenfeld Research Insitute C. Hogue
• Collaborating Organizations
• Proteomics Standards Initiative (PSI)
  (psidev.sf.net)
• Systems Biology Markup Language (SBML)
• CellML
• Chemical Markup Language (CML)

• Databases
• BioCyc (www.biocyc.org)
• BIND (www.bind.ca)
• WIT (wit.mcs.anl.gov/WIT2)
• Grants
• Department of Energy

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BioPAX

• BioPAX Biological Pathway Exchange
• Data exchange format for pathway data
• Include support for these pathway types
• Metabolic pathways
• Signaling pathways
• Protein-protein interactions
• Genetic regulatory pathways
• Accommodate representations used in gt100 existing
  databases such as BioCyc, BIND, WIT, aMAZE, KEGG,
  GK, CMAP-PW

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BioPAX Motivation
Common good
Before DEF
After DEF
Promotes collaboration (big science),
accessibility
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Exchange Formats in the Pathway Data Space
Database Exchange Formats
Simulation Model Exchange Formats
SBML, CellML
PSI
Biochemical Reactions
Protein Interaction Networks
Rate Formulas
Metabolic Pathways Low Detail High
Detail
Regulatory Pathways Low Detail High
Detail
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Exchange Formats in the Pathway Data Space
Database Exchange Formats
Simulation Model Exchange Formats
BioPAX
Small Molecules (CML)
SBML, CellML
PSI
Molecular Interactions ProPro
AllAll
Biochemical Reactions
Genetic Interactions
Rate Formulas
Metabolic Pathways Low Detail High
Detail
Interaction Networks Molecular
Non-molecular ProPro TFGene
Genetic
Regulatory Pathways Low Detail High
Detail
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cPath - Cancer Pathway Database

• Cell death/apoptosis
• Growth regulation
• Angiogenesis
• DNA damage response
• Cell Cycle limitless replicative potential
• Cytoskeleton - metastasis, tissue invasion

Weinberg, R.A. Cell 2000
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cPath

• Content Follow MSKCC strengths
• Curate specific pathways
• E.g. Joan Massague TGF-beta pathway
• Study specific tumors
• E.g. William Gerald Pediatric neuroblastoma
• Use case Pathway data integration tool
• Local research tool - IP restrictions
• Web-based MySQL/Java/Tomcat URL based web
  service API returns XML

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CytoscapeBiomolecular Network Analysis

• Benno Schwikowski (ISB)
• Trey Ideker (UCSD)
• Chris Sander (MSKCC)
• http//www.cytoscape.org

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Cytoscape

• Collaboration ISB, UCSD, MSKCC
• Java-based network and expression analysis tool,
  plugins
• Front end and analysis tool for pathway, gene
  expression databases
• Open source - LGPL
• www.cytoscape.org

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Visual Mapping

• Graph has node and edge attributes
• E.g. expression data, interaction type
• Mapped to visual attributes
• E.g. node/edge size, shape, color, font

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Network Analysis

• Plugins for
• Networks and Transcriptional Profiling
• Active Modules (UCSD)
• Activity Centers (MSKCC)
• Expression tools (ISB)
• General networks
• MCODE network clustering (MSKCC)
• Open architecture to develop new plugins

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caBIG Contributions

• Convert public pathway resources into BioPAX and
  load into cPath/CMAP
• PSI-MI PPI, BioPAX pathway data model
• Curate cancer specific pathways from literature
  (high-quality, unique)
• Make cPath, Cytoscape available to caBIG
• Documentation, support, integration

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Current Status

• BioPAX
• Level 1 is nearing release
• Metabolism GKB/Protégé lt-gt OWL (XML)
• XML Schema later
• cPath
• V1.0 PSI-MI, Java/Tomcat, LGPL
• Expand to BioPAX later
• Cytoscape (Java)
• V1.1 Fully functional V2.0 Beta V1.0 cPath DB
  layer
• Development IDEA, CVS, Ant, Mantis