Accurate detection for a wide range of mutation and editing sites of microRNAs from small RNA high-throughput sequencing profiles

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...

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Bibliographic Details
Published in:Nucleic acids research 2016-08, Vol.44 (14), p.e123-e123
Main Authors: Zheng, Yun, Ji, Bo, Song, Renhua, Wang, Shengpeng, Li, Ting, Zhang, Xiaotuo, Chen, Kun, Li, Tianqing, Li, Jinyan
Format: Article
Language:English
Subjects:
Algorithms
Cell Line
Gene Deletion
Gene Library
Genome, Human
High-Throughput Nucleotide Sequencing - methods
Humans
Methods Online
MicroRNAs - genetics
MicroRNAs - metabolism
Mutagenesis, Insertional - genetics
Mutation - genetics
Polymorphism, Single Nucleotide - genetics
RNA Editing - genetics
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkw471