Swan, H. K.; Baran, A. M.; Aparicio-Puerta, E.; Halushka, M. K.; Jun, S.-H.; McCall, M. N.

MicroRNAs (miRNAs) are non-coding RNAs, approximately 18 - 24 nucleotides in length, with important gene regulatory functions. In small RNA sequencing (sRNA-seq), observed iso- forms of miRNA, called isomiRs, arise from my biological and technical processes. Alterations in isomiR expression has been linked to a wide variety of human diseases, from cancers to neurological diseases. However, it is difficult to distinguish be- tween technical and biological isomiRs. We present PARiS, an algorithm for the Probabilistic Assignment and Repartitioning of isomiR Sequences, that identifies technical error isomiRs in sRNA-seq data and reassigns them to their most likely biologi- cal source. We assess the ability of PARiS to identify and remove error isomiR sequences in a realistic simulation study. Addition- ally, we compare PARiS to alternative approaches, focusing on downstream miRNA-level differential expression analysis in a variety of settings, including a set of simulated datasets, an ex- perimental benchmark dataset, and three colorectal adenocar- cinoma cell lines.