Transcriptome-wide splicing quantification in single cells

Abstract Single cell RNA-seq (scRNA-seq) has revolutionised our understanding of transcriptome variability, with profound implications both fundamental and translational. While scRNA-seq provides a comprehensive measurement of stochasticity in transcription, the limitations of the technology have prevented its application to dissect variability in RNA processing events such as splicing. Here we present BRIE (Bayesian Regression for Isoform Estimation), a Bayesian hierarchical model which resolves these problems by learning an informative prior distribution from sequence features. We show that BRIE yields reproducible estimates of exon inclusion ratios in single cells and provides an effective tool for differential isoform quantification between scRNA-seq data sets. BRIE therefore expands the scope of scRNA-seq experiments to probe the stochasticity of RNA-processing.