Inverse Game Theory Characterizes Frequency-Dependent Selection Driven by Karyotypic Diversity in Triple Negative Breast Cancer.

ABSTRACT: Chromosomal instability (CIN), characterized by pervasive copy number alterations (CNAs), significantly contributes to cancer progression and therapeutic resistance. CNAs drive intratumoral genetic heterogeneity, creating distinct subpopulations whose interactions shape tumor evolution through frequency-dependent selection. Here, we introduce, ECO-K (Ecological-Karyotypes), an inverse game theory framework that infers subpopulation interactions from longitudinal single-cell whole genome sequencing data. Applying this approach to serially-passaged, triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs), we systematically identified frequency-dependent selection dynamics governed by karyotypic diversity. Notably, in one PDX lineage, we found consistent evidence

SUBMITTER: Veith T 

PROVIDER: S-EPMC11974723 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature