Combinatorial Detection of Conserved Alteration Patterns for Identifying Cancer Subnetworks

Abstract

AbstractBackgroundAdvances in large scale tumor sequencing have lead to an understanding that there are combinations of genomic and transcriptomic alterations speciflc to tumor types, shared across many patients. Unfortunately, computational identiflcation of functionally meaningful shared alteration patterns, impacting gene/protein interaction subnetworks, has proven to be challenging.FindingsWe introduce a novel combinatorial method, cd-CAP, for simultaneous detection of connected subnetworks of an interaction network where genes exhibit conserved alteration patterns across tumor samples. Our method differentiates distinct alteration types associated with each gene (rather than relying on binary information of a gene being altered or not), and simultaneously detects multiple alteration proflle conserved subnetworks.ConclusionsIn a number of The Cancer Genome Atlas (TCGA) data sets, cd-CAP identifled large biologically signiflcant subnetworks with conserved alteration patterns, shared across many tumor samples.