A protein-centric approach for exome variant aggregation enables sensitive association analysis with clinical outcomes.

ABSTRACT: Somatic mutations are early drivers of tumorigenesis and tumor progression. However, the mutations typically occur at variable positions across different individuals, resulting in the data being too sparse to test meaningful associations between variants and phenotypes. To overcome this challenge, we devised a novel approach called Gene-to-Protein-to-Disease (GPD) which accumulates variants into new sequence units as the degree of genetic assault on structural or functional units of each protein. The variant frequencies in the sequence units were highly reproducible between two large cancer cohorts. Survival analysis identified 232 sequence units in which somatic mutations had deleterious effects on overall survival, including consensus driver mutations obtained from multiple calling algor

SUBMITTER: Li GXH 

PROVIDER: S-EPMC7160030 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature