Various types of mutation and editing (M/E) events in microRNAs (miRNAs) can change the stabilities of pre-miRNAs and/or complementarities between miRNAs and their targets. Small RNA (sRNA) high-throughput sequencing (HTS) profiles can contain many mutated and edited miRNAs. Systematic detection of miRNA mutation and editing sites from the huge volume of sRNA HTS profiles is computationally difficult, as high sensitivity and low false positive rate (FPR) are both required.
Researchers at the Kunming University of Science and Technology have developed a novel method (named MiRME) for an accurate and fast detection of miRNA M/E sites using a progressive sequence alignment approach which refines sensitivity and improves FPR step-by-step. From 70 sRNA HTS profiles with over 1.3 billion reads, MiRME has detected thousands of statistically significant M/E sites, including 3′-editing sites, 57 A-to-I editing sites (of which 32 are novel), as well as some putative non-canonical editing sites. The researchers demonstrated that a few non-canonical editing sites were not resulting from mutations in the genome by integrating the analysis of genome HTS profiles of two human cell lines, suggesting the existence of new editing types to further diversify the functions of miRNAs. Compared with six existing studies or methods, MiRME has shown superior performance for the identification and visualization of the M/E sites of miRNAs from the ever-increasing sRNA HTS profiles.
The main steps, corresponding programs and outputs of the MiRME pipeline
The central part lists the steps whose corresponding programs are given on the left. Programs in purple and black are publicly available ones and those developed in this study, respectively. The right and bottom parts pointed by blue lines are outputs of MiRME. Optionally, the pipeline also compares the predicted editing and SNPs in miRNAs to the reported ones to facilitate the discovery of novel editing and/or SNPs in miRNAs.
Availability – Comprehensive user manual and scripts of the MiRME pipeline, as well as several other auxiliary tools for large-scale analysis can be found here: http://nar.oxfordjournals.org/content/early/2016/05/26/nar.gkw471/suppl/DC1