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NetBioSIG2012 ugurdogrusoz-cbio

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The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource
for interactively exploring multidimensional cancer genomics data sets. It provides simple and intuitive integrated access to cancer genomics data, including copy number, mutation, mRNA and microRNA expression, methylation and protein and phosphoprotein data, on more than 5,000 tumor samples from 20 cancer studies (including 16 TCGA cancer types).
During the past year, we have added network visualization and analysis features to
the cBio Portal. These new features enable researchers to analyze genomic alterations in the context of known biological pathways and interaction networks, and to more easily mine data generated by the TCGA. A network of interest is derived from the Pathway Commons project, based on the query genes specified by the user. Multidimensional genomic data are overlaid onto each node of the network, highlighting the frequency of somatic mutation and copy number alteration (and optionally mRNA up/down-regulation). Users can manage the complexity of the network by filtering by total alteration frequency of genes or by type and source of the interactions. This provides an effective means of managing network complexity, while automatically highlighting those genes most directly relevant to the cancer type in question. In addition, drugs and drug target data can optionally be shown in relation to the network of interest. In this talk, we would like to illustrate the main network analysis features using data from the TCGA project. We will also discuss our future plans for the network view.

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NetBioSIG2012 ugurdogrusoz-cbio

  1. 1. Network Visualization and Analysisin the cBio Cancer Genomics Portal U. Dogrusoz, S.O. Sumer, S. Sonlu, J. Gao, B.A. Aksoy, B.E. Gross, N. Schultz, E. Cerami, C. Sander
  2. 2. cBio Cancer Genomics PortalGoal:Make complex genomic data available through an intuitive interfaceAllow explorative data analysis / hypothesis testing / visualization Cerami et al. 2012, Cancer Discovery
  3. 3. cBio Cancer Genomics Portal Cerami et al. 2012, Cancer Discovery
  4. 4. Workflow of network analysis
  5. 5. Pathway Commons Cerami et al 2010, Nucl Acids Res
  6. 6. Workflow of network analysis
  7. 7. Hairball Problem Complete network for TP53, MDM2, MDM4 & CDKN2A (463 interacting neighbors)This complete network can be downloaded in SIF or GraphML in cBio Portal.
  8. 8. Pre-filtered network based on alteration frequencies The network below contains 54 nodes, including your 4 query genes and the 50 most frequently genes out 463 altered neighbor genes(out of 463). Query genes: CDKN2A MDM2 MDM4 TP53
  9. 9. Workflow of network analysis
  10. 10. Genomic data overlaid on interaction network
  11. 11. Genomic data overlaid on interaction networkAlteration frequency: the % of samples that were altered on the gene
  12. 12. Genomic data overlaid on interaction network Color gradient •white to red •based on alteration frequencyGenomic data•mutation•copy number•mRNA expression
  13. 13. Further filtering by genomic alterations Filter genes by alteration frequency Slide to threshold Or type value threshold value
  14. 14. Further filtering by genomic alterations Gene with total alteration frequency 12% or less filtered out
  15. 15. Filtering by genes of interest Hide selected genes from the network Search genes by name Select genes from canvas or gene list under Genes tab
  16. 16. Filtering by interaction type & source Interactions Interactions merged by default Type (color-coded) & source shown in interaction details Shown individually
  17. 17. Filtering by interaction type & source
  18. 18. Filtering by interaction type & source
  19. 19. Automatic network layout Change layoutRecalculate optionslayoutRecalculatelayout afterfiltering
  20. 20. Iterative network analysis Re-submit selected genes to the portal
  21. 21. Drugs of New cBioPortal featuresspecified genes Drug – gene targeting • Data source is DrugBank database of detail: Level (http://www.drugbank.ca) -NoneInspect details targeting specified-FDA approved only • Only drugs genes shownincluding: -All-Targeted genes-CorrespondingDrugBank page
  22. 22. Other new cBioPortal features Network visualization service for IGV• Glioblastoma, RB pathway
  23. 23. Other new cBioPortal features Cross-cancer query
  24. 24. Other new cBioPortal features Oncoprint improvementsProtein/phosphoprotein Mutation details event call
  25. 25. Other new cBioPortal features Mutation diagram
  26. 26. Other new cBioPortal features Many new cancer studies• 21 (5 of them published, rest provisional) cancer studies
  27. 27. Work in progress and future plans• SBGN-compliant viewer (GSoC) – Networks presented in SBGN Process Description language• Construct Network-of-Interest from Genes-of- Interest using linker paths (Dogrusoz et al, 2009, BMC Bioinf)• Roundtrip analysis (query, modify, re-query, …)• Better/incremental layout• Use Cytoscape Web 2 (html5 version)
  28. 28. Acknowledgements• Bilkent University • MSKCC – S. Onur Sumer – S. Onur Sumer – Sinan Sonlu – Jianjiong Gao – Naim Kucukdemirci – B. Arman Aksoy – Istemi Bahceci – Benjamin E. Gross – Nikolaus Schultz – Ethan Cerami – Chris Sander

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