A novel network regularized matrix decomposition method to detect mutated cancer genes in tumour samples with inter-patient heterogeneity

摘要

Inter-patient heterogeneity is a major challenge for mutated cancer genes detection which is crucial to advance cancer diagnostics and therapeutics. To detect mutated cancer genes in heterogeneous tumour samples, a prominent strategy is to determine whether the genes are recurrently mutated in their interaction network context. However, recent studies show that some cancer genes in different perturbed pathways are mutated in different subsets of samples. Subsequently, these genes may not display significant mutational recurrence and thus remain undiscovered even in consideration of network information. We develop a novel method called mCGfinder to efficiently detect mutated cancer genes in tumour samples with inter-patient heterogeneity. Based on matrix decomposition framework incorporated with gene interaction network information, mCGfinder can successfully measure the significance of mutational recurrence of genes in a subset of samples. When applying mCGfinder on TCGA somatic mutation datasets of five types of cancers, we find that the genes detected by mCGfinder are significantly enriched for known cancer genes, and yield substantially smaller p-values than other existing methods. All the results demonstrate that mCGfinder is an efficient method in detecting mutated cancer genes.