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 (scRNA-seq) allows the comparison of expression distribution between the two alleles of a diploid organism and thus the characterization of allele-specific bursting. Researchers at the University of Pennsylvania have developed 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. The reserchers apply SCALE to mouse blastocyst and human fibroblast cells and find that, globally, cis control in gene expression overwhelmingly manifests as differences in burst frequency.

Overview of analysis pipeline of SCALE


SCALE takes as input allele specific read counts at heterozygous loci and carries out three major steps: (i) an empirical Bayes method for gene classification, (ii) a Poisson-Beta hierarchical model to estimate allele-specific transcriptional kinetics with adjustment of technical variability and cell size, (iii) a hypothesis testing framework to test the two alleles of a gene have differential bursting kinetics and/or non-independent firing.

Availability – SCALE is an open-source R package available at

Jiang Y, Zhang NR, Li M. (2017) Modeling allele-specific gene expression by single-cell RNA sequencing. bioRXiv [Epub ahead of print]. [abstract]

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