scTail: precise polyadenylation site detection and its alternative usage analysis from reads 1 preserved 3' scRNA-seq data

Abstract

Three-prime single-cell RNA-seq (scRNA-seq) has been widely employed to dissect the variability of cellular transcriptomes, while only the cDNAs on reads 2 are routinely used, including to analyze polyadenylation sites (PAS). However, despite of high sequencing noise, we found the cDNAs on reads 1 are highly informative in precisely detecting PAS. Here, we further develop a computational method, scTail, to identify PAS using reads 1 and quantify its expression leveraging reads 2, which enables effective detection of alternative PAS usage (PAU). When compared with other methods, scTail detects PAS more sensitively and precisely. With various experimental data sets, we demonstrated that the combination usage of scTail and BRIE2 can discover differential alternative PAS usage in various biological processes including cell types in human intestinal, disease status of esophageal squamous cell carcinoma, and time point of mouse forelimb histogenesis, revealing critical insights in PAS regulations.