NetBioSIG2012 ugurdogrusoz-cbio
-
Upload
alexander-pico -
Category
Education
-
view
2.356 -
download
0
description
Transcript of NetBioSIG2012 ugurdogrusoz-cbio
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