title: Accurate detection for a wide range of mutation and editing sites of microRNAs from small RNA high-throughput sequencing profiles.
abstract: 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. We propose 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. We demonstrated that a few non-canonical editing sites were not resulted from mutations in 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 much superior performance for the identification and visualization of the M/E sites of miRNAs from the ever-increasing sRNA HTS profiles.
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming, Yunnan 650500, China Faculty of Information Engineering and Automation, Kunming University of Science and Technology Kunming, Yunnan 650500, China zhengyun5488@gmail.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming, Yunnan 650500, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Ji
authors.affiliation: Advanced Analytics Institute & Centre for Health Technologies, Faculty of Engineering & IT University of Technology Sydney, Australia.
authors.forename: Renhua
authors.initials: R
authors.lastname: Song
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming, Yunnan 650500, China.
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming, Yunnan 650500, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Faculty of Information Engineering and Automation, Kunming University of Science and Technology Kunming, Yunnan 650500, China.
authors.forename: Xiaotuo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming, Yunnan 650500, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Yunnan Key Lab of Primate Biomedicine Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Li
authors.affiliation: Advanced Analytics Institute & Centre for Health Technologies, Faculty of Engineering & IT University of Technology Sydney, Australia jinyan.li@uts.edu.au.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Li
mesh_terms: D000465:Algorithms; D002460:Cell Line; D017353:Gene Deletion; D015723:Gene Library; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016254:Mutagenesis, Insertional / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*
chemical_list: D035683:MicroRNAs