Identification of cancer mini-drivers by deciphering selective landscape in the cancer genome.

ABSTRACT: Cancer development is driven by somatic evolution and clonal selection. However, traditional selective pressure analysis methods have treated all sites within a gene equally, such a gene-level model oversimplifies the complexity of cancer evolution. In this study, we introduced CN/CS-calculator, a novel site-specific method that can capture selective pressures acting across different gene sites. By deciphering the interplay between the selection pattern and the function of a gene in oncogenesis, CN/CS-calculator uncovers a unique class of mini-driver genes, which exhibit weak positive selection, with certain critical sites providing context-dependent promoter effects on the fitness of cancer subclones while others are constrained by evolutionary conservation. Our method emphasizes the impo

SUBMITTER: Zhu X 

PROVIDER: S-EPMC12784965 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature