NetBioSIG2012 ugurdogrusoz-cbio


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The cBio Cancer Genomics Portal ( 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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  • B) The RB Oncoprint, alterations of genes in this pathway tend to be mutually exclusiveC) Many RB1 mutations may have strong functional consequences as predicted by MutationAccessor.orgD) CDK4 mRNA expression is elevated in amplified casesE) Cases with an RB pathway alteration have worse overall survival than cases without an RB pathway alterationF) Network tab provides interactive analysis and visualization of networks altered in the chosen cancer study
  • The network of interest built from genes of interest consists of pathways and interactions derived from the open-source Pathway Commons project.
  • PC provides a central, convenient point of access to multiple publicly available pathway and interaction databases. It does so by integrating data sources formatted in the BioPAX or PSI–MI standards, and making all data sets available via a unified web site, a single web service interface and a batch download site.
  • Glioblastoma: TP53 Pathway (4 genes)
  • Links to IGV for visualization of DNA copy-number changes (through Web Start)
  • Links to IGV for visualization of DNA copy-number changes (through Web Start)
  • Cross-cancer functionality enables users to query across all cancer studies in our database
  • OncoPrints are compact means of visualizing distinct genomic alterations, including somatic mutations, copy number alterations, and mRNA expression changes across a set of cases. They are extremely useful for visualizing gene set and pathway alterations across a set of cases, and for visually identifying trends, such as trends in mutual exclusivity or co-occurence between gene pairs within a gene set. Individual genes are represented as rows, and individual cases or patients are represented as columns.
  • Mutation Diagrams show mutations in the context of protein domains.
  • 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 ( -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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