netbiosig2012 ugurdogrusoz-cbio
DESCRIPTION
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.TRANSCRIPT
Network Visualization and Analysis in 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
cBio Cancer Genomics Portal
Goal: Make complex genomic data available through an intuitive interface Allow explorative data analysis / hypothesis testing / visualization
Cerami et al. 2012, Cancer Discovery
cBio Cancer Genomics Portal
Cerami et al. 2012, Cancer Discovery
Workflow of network analysis
Cerami et al 2010, Nucl Acids Res
Pathway Commons
Workflow of network analysis
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.
Pre-filtered network based on alteration frequencies
The network below contains 54 nodes, including your 4 query genes and the 50 most frequently altered neighbor genes(out of 463).
4 query genes 50 most frequentlyaltered neighbor genes out of 463
Query genes: CDKN2A MDM2 MDM4 TP53
Workflow of network analysis
Genomic data overlaid on interaction network
Genomic data overlaid on interaction network
Alteration frequency: the % of samples that were altered on the gene
Genomic data overlaid on interaction network
Genomic data•mutation•copy number•mRNA expression
Color gradient•white to red•based on alteration frequency
Further filtering by genomic alterations
Slide to threshold value
Filter genes by alteration frequency
Or type threshold value
Further filtering by genomic alterationsGene with total alteration frequency 12% or less filtered out
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
Filtering by interaction type & source
Interactionsmerged by default
Shown individually
Type (color-coded) & source shown in interaction details
Interactions
Filtering by interaction type & source
Filtering by interaction type & source
Automatic network layout
Recalculate layout after filtering
Recalculate layout
Change layout options
Re-submit selected genes to the portal
Iterative network analysis
• Data source is DrugBank database (http://www.drugbank.ca)
• Only drugs targeting specified genes shown
New cBioPortal featuresDrug – gene targeting
Drugs of specified genes
Level of detail:-None-FDA approved only-All
Inspect details including:-Targeted genes-Corresponding DrugBank page
Other new cBioPortal featuresNetwork visualization service for IGV
• Glioblastoma, RB pathway
Other new cBioPortal featuresCross-cancer query
Other new cBioPortal featuresOncoprint improvements
Mutation detailsProtein/phosphoprotein event call
Other new cBioPortal featuresMutation diagram
Other new cBioPortal featuresMany new cancer studies
• 21 (5 of them published, rest provisional) cancer studies
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)
Acknowledgements
• MSKCC– S. Onur Sumer– Jianjiong Gao– B. Arman Aksoy– Benjamin E. Gross– Nikolaus Schultz– Ethan Cerami– Chris Sander
• Bilkent University– S. Onur Sumer– Sinan Sonlu– Naim Kucukdemirci– Istemi Bahceci