title: Entropy-based model for miRNA isoform analysis.
abstract: MiRNAs have been widely studied due to their important post-transcriptional regulatory roles in gene expression. Many reports have demonstrated the evidence of miRNA isoform products (isomiRs) in high-throughput small RNA sequencing data. However, the biological function involved in these molecules is still not well investigated. Here, we developed a Shannon entropy-based model to estimate isomiR expression profiles of high-throughput small RNA sequencing data extracted from miRBase webserver. By using the Kolmogorov-Smirnov statistical test (KS test), we demonstrated that the 5p and 3p miRNAs present more variants than the single arm miRNAs. We also found that the isomiR variant, except the 3' isomiR variant, is strongly correlated with Minimum Free Energy (MFE) of pre-miRNA, suggesting the intrinsic feature of pre-miRNA should be one of the important factors for the miRNA regulation. The functional enrichment analysis showed that the miRNAs with high variation, particularly the 5' end variation, are enriched in a set of critical functions, supporting these molecules should not be randomly produced. Our results provide a probabilistic framework for miRNA isoforms analysis, and give functional insights into pre-miRNA processing.
authors.affiliation: State Key Lab of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China; Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, College of Life and Environmental Science, Wenzhou University, Wenzhou, 325035, China.
authors.forename: Shengqin
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Lab of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tu
authors.affiliation: State Key Lab of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Lab of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China; Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100781, China.
authors.forename: Zuhong
authors.initials: Z
authors.lastname: Lu
mesh_terms: D001483:Base Sequence; D019277:Entropy; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D059368:RNA Isoforms / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D059368:RNA Isoforms