RT Journal Article
SR Electronic
T1 MAAPER: model-based analysis of alternative polyadenylation using 3’ end-linked reads
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.21.436343
DO 10.1101/2021.03.21.436343
A1 Wei Vivian Li
A1 Dinghai Zheng
A1 Ruijia Wang
A1 Bin Tian
YR 2021
UL http://biorxiv.org/content/early/2021/03/22/2021.03.21.436343.abstract
AB Most eukaryotic genes harbor multiple cleavage and polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms. APA regulation has been implicated in a diverse array of physiological and pathological conditions. While RNA sequencing tools that generate reads containing the PAS, named onSite reads, have been instrumental in identifying PASs, they have not been widely used. By contrast, a growing number of methods generate reads that are close to the PAS, named nearSite reads, including the 3’ end counting strategy commonly used in single cell analysis. How these nearSite reads can be used for APA analysis, however, is poorly studied. Here, we present a computational method, named model-based analysis of alternative polyadenylation using 3’ end-linked reads (MAAPER), to examine APA using nearSite reads. MAAPER uses a probabilistic model to predict PASs for nearSite reads with high accuracy and sensitivity, and examines different types of APA events, including those in 3’UTRs and introns, with robust statistics. We show MAAPER’s accuracy with data from both bulk and single cell RNA samples and its applicability in unpaired or paired experimental designs. Our result also highlights the importance of using well annotated PASs for nearSite read analysis.Competing Interest StatementThe authors have declared no competing interest.