ReadZS detects cell type-specific and developmentally regulated RNA processing programs in single-cell RNA-seq

RNA processing (RNAP), including splicing and alternative polyadenylation, is crucial to gene function and regulation, but methods to detect RNAP from single-cell RNA sequencing data are limited by reliance on pre-existing annotations, peak-calling heuristics, and collapsing measurements by cell type. We introduce ReadZS, the first annotation-free statistical approach to identify regulated RNAP in single cells. ReadZS discovers cell type-specific RNAP in the human lung and conserved, developmentally regulated RNAP in mammalian spermatogenesis - including global 3 UTR shortening in human spermatogenesis. ReadZS also discovers global 3 UTR lengthening in Arabidopsis root development, highlighting the usefulness of this method in under-annotated transcriptomes.