Protein-structure-guided discovery of functional mutations across 19 cancer types

Somatic Mutations in Protein Domains Protein Domain Hotspots Reveal Functional Mutations across Genes in Can- cer

In cancer genomics, frequent recurrence of mutations in independent tumor samples is a strong indication of functional impact. However, rare functional mutations can escape detection by recurrence analysis for lack of statistical power. We address this problem by extending the notion of recurrence of mutations from single genes to gene families that share homologous protein domains. In addition...

An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types

MOTIVATION Identification of altered pathways that are clinically relevant across human cancers is a key challenge in cancer genomics. Precise identification and understanding of these altered pathways may provide novel insights into patient stratification, therapeutic strategies and the development of new drugs. However, a challenge remains in accurately identifying pathways altered by somatic...

Discovery and saturation analysis of cancer genes across 21 tumour types

A comparative analysis of network mutation burdens across 21 tumor types augments discovery from cancer genomes

Heterogeneity across cancer makes it difficult to find driver genes with intermediate (2-20%) and low frequency (<2%) mutations1, and we are potentially missing entire classes of networks (or pathways) of biological and therapeutic value. Here, we quantify the extent to which cancer genes across 21 tumor types have an increased burden of mutations in their immediate gene network derived from fu...

The effects of mutational processes and selection on driver mutations across cancer types

Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data to infer the independent effects of mutation and selection on driver mutation complement. First, we detect associations ...