Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes.

Cancers exhibit extensive mutational heterogeneity, and the resulting long-tail phenomenon complicates the discovery of genes and pathways that are significantly mutated in cancer. We perform a pan-cancer analysis of mutated networks in 3,281 samples from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a new algorithm to find mutated subnetworks that overcomes the limitations of existing single-gene, pathway and network approaches. We identify 16 significantly mutated subnetworks that comprise well-known cancer signaling pathways as well as subnetworks with less characterized roles in cancer, including cohesin, condensin and others.

Network analysis of GWAS data.

Genome-wide association studies (GWAS) identify genetic variants that distinguish a control population from a population with a specific trait. Two challenges in GWAS are: (1) identification of the causal variant within a longer haplotype that is associated with the trait; (2) identification of causal variants for polygenic traits that are caused by variants in multiple genes within a pathway. We review recent methods that use information in protein-protein and protein-DNA interaction networks to address these two challenges.