DiffInvex identifies evolutionary shifts in driver gene repertoires during tumorigenesis and chemotherapy.

ABSTRACT: Somatic cells can transform into tumors due to mutations, and the tumors further evolve towards increased aggressiveness and therapy resistance. We develop DiffInvex, a framework for identifying changes in selection acting on individual genes in somatic genomes, drawing on an empirical mutation rate baseline derived from non-coding DNA that accounts for shifts in neutral mutagenesis during cancer evolution. We apply DiffInvex to >11,000 somatic whole-genome sequences from ~30 cancer types or healthy tissues, identifying genes where point mutations are under conditional positive or negative selection during exposure to specific chemotherapeutics, suggesting drug resistance mechanisms occurring via point mutation. DiffInvex identifies 11 genes exhibiting treatment-associated selection for di

SUBMITTER: Khalil A 

PROVIDER: S-EPMC12075687 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature