Stochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.

ABSTRACT: Cancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present a formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein-Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data. Applying our model to sublines derived from single cells of a mouse melanoma revealed that sublines with distinct phenotypes are underlined by different patterns of gene expression adaptation, indicating non-genetic mechanisms of cancer evolution. Sublines previously observed to be resistant to anti-CTLA4 treatment showed adaptive expression of genes related to invasion and non-canonical Wnt signaling, whereas sub

SUBMITTER: Hirsch MG 

PROVIDER: S-EPMC11867576 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature