ABSTRACT
UNLABELLED: Recent studies have revealed that a small non-coding RNA, microRNA (miRNA) down-regulates its mRNA targets. This effect is regarded as an important role in various biological processes. Many studies have been devoted to predicting miRNA-target interactions. These studies indicate that the interactions may only be functional in some specific tissues, which depend on the characteristics of an miRNA. No systematic methods have been established in the literature to investigate the correlation between miRNA-target interactions and tissue specificity through microarray data. In this study, we propose a method to investigate miRNA-target interaction-supported tissues, which is based on experimentally validated miRNA-target interactions. The tissue specificity results by our method are in accordance with the experimental results in the literature. AVAILABILITY AND IMPLEMENTATION: Our analysis results are available at http://tsmti.mbc.nctu.edu.tw/ and http://www.stat.nctu.edu.tw/hwang/tsmti.html.
Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Neoplasms/genetics , RNA Interference , RNA, Messenger/genetics , Algorithms , Cluster Analysis , Computational Biology/methods , Databases, Nucleic Acid , Humans , Internet , Tissue BanksABSTRACT
Predicting miRNA target genes is one of the important issues in bioinformatics. The correlation analysis is a widely used method for exploring miRNA targets through microarray data. However, the experimental results show that correlation analysis leads to large false positive or negative results. In addition, the correlation analysis is not appropriate when multiple miRNAs simultaneously regulate a gene. Recently, the relative R squared method (RRSM) has been proposed for miRNA target prediction, which is shown to be superior to some existing methods. To adopt the RRSM, we need first to set thresholds to select a proportion of potential targets. In the previous studies, the threshold is set to be fixed, which does not depend on the characteristic of a gene. Due to the diversity of the functions of genes, a data-dependent threshold may be more feasible in real data applications than a data-independent threshold. In this study, we propose a threshold selection method which is based on the distribution of the relative R squared statistic. The proposed method is shown to significantly improve the previous prediction results by selecting more experimentally validated targets.
Subject(s)
Computational Biology/methods , MicroRNAs/metabolism , Statistics as Topic , Animals , Computer Simulation , Databases, Genetic , Gene Expression Profiling , Humans , Mice , MicroRNAs/geneticsABSTRACT
MicroRNAs (miRNAs) are small endogenously expressed non-coding RNAs that regulate target messenger RNAs in various biological processes. In recent years, there have been many studies concentrated on the discovery of new miRNAs and identification of their mRNA targets. Although researchers have identified many miRNAs, few miRNA targets have been identified by actual experimental methods. To expedite the identification of miRNA targets for experimental verification, in the literature approaches based on the sequence or microarray expression analysis have been established to discover the potential miRNA targets. In this study, we focus on the human miRNA target prediction and propose a generalized relative R² method (RRSM) to find many high-confidence targets. Many targets have been confirmed from previous studies. The targets for several miRNAs discovered by the HITS-CLIP method in a recent study have also been selected by our study.
