Allele-specific transcriptional effects of subclonal copy number alterations enable genotype-phenotype mapping in cancer cells.

ABSTRACT: Subclonal copy number alterations are a prevalent feature in tumors with high chromosomal instability and result in heterogeneous cancer cell populations with distinct phenotypes. However, the extent to which subclonal copy number alterations contribute to clone-specific phenotypes remains poorly understood. We develop TreeAlign, which computationally integrates independently sampled single-cell DNA and RNA sequencing data from the same cell population. TreeAlign accurately encodes dosage effects from subclonal copy number alterations, the impact of allelic imbalance on allele-specific transcription, and obviates the need to define genotypic clones from a phylogeny a priori, leading to highly granular definitions of clones with distinct expression programs. These improvements enable clone-

SUBMITTER: Shi H 

PROVIDER: S-EPMC10954741 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature