SCALE: modeling allele-specific gene expression by single-cell RNA sequencing

Allele-specific expression is traditionally studied by bulk RNA sequencing, which measures average expression across cells. Single-cell RNA sequencing allows the comparison of expression distribution between the two alleles of a diploid organism and the characterization of allele-specific bursting. Here, we propose SCALE to analyze genome-wide allele-specific bursting, with adjustment of technical variability. SCALE detects genes exhibiting allelic differences in bursting parameters and genes whose alleles burst non-independently. We apply SCALE to mouse blastocyst and human fibroblast cells and find that cis control in gene expression overwhelmingly manifests as differences in burst frequency. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-017-1200-8) contains supplementary material, which is available to authorized users.