Exploiting allele-specific transcriptional effects of subclonal copy number alterations for genotype-phenotype mapping in cancer cell populations.

ABSTRACT: Somatic copy number alterations drive aberrant gene expression in cancer cells. In tumors with high levels of chromosomal instability, subclonal copy number alterations (CNAs) are a prevalent feature which often result in heterogeneous cancer cell populations with distinct phenotypes¹. However, the extent to which subclonal CNAs contribute to clone-specific phenotypes remains poorly understood, in part due to the lack of methods to quantify how CNAs influence gene expression at a subclone level. We developed TreeAlign, which computationally integrates independently sampled single-cell DNA and RNA sequencing data from the same cell population and explicitly models gene dosage effects from subclonal alterations. We show through quantitative benchmarking data and application to hum

SUBMITTER: Shi H 

PROVIDER: S-EPMC9882029 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature