A signature-agnostic test for differences between tumor mutation spectra reveals carcinogen and ancestry effects.

ABSTRACT: Mutational signatures contain valuable information about the mutational processes shaping cancer genomes. However, despite dozens of tools to identify signatures in cancer samples, there is not an established metric for statistically comparing mutational signature results and quantifying the overall significance of differences among complex mixtures of signatures. To close this methodological gap, we demonstrate that a signature-agnostic metric for measuring differences in mutation spectra - the aggregate mutation spectrum distance permutation method (AMSD) - can discover differences overlooked by signature analysis. First, we reanalyzed a study of carcinogen exposure in mice, identifying statistically significant shifts in mutation spectra caused by eleven of twenty tested carcinogens. On

SUBMITTER: Hart SFM 

PROVIDER: S-EPMC12139916 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature