ASPEN: Robust detection of allelic dynamics in single cell RNA-seq.

ABSTRACT: Single-cell RNA-seq data from F1 hybrids provides a unique framework for dissecting complex regulatory phenomena, but allelic measurements are limited by technical noise. Here, we present ASPEN, a statistical method for modeling allelic mean and variance in single-cell transcriptomic data from F1 hybrids. ASPEN uses a sensitive mapping pipeline and adaptive shrinkage to distinguish allelic imbalance and variance in single cells. Through extensive simulation based on sparse droplet-based single-cell data, ASPEN demonstrates improved sensitivity and control of false discoveries compared to existing approaches. Applied to mouse brain organoids and T cells, ASPEN identifies genes with incomplete X inactivation, stochastic monoallelic expression, and significant deviations in allelic variance.

SUBMITTER: Petrova V 

PROVIDER: S-EPMC12424800 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature