Department of Electronics and Communication Engineering, Heritage Institute of Technology, Kolkata 700107, India; Department of Computer Science and Engineering, Jadavpur University, Kolkata 700032, India.
Department of Computer Science and Engineering, Jadavpur University, Kolkata 700032, India.
Comput Biol Chem. 2020 Feb;84:107152. doi: 10.1016/j.compbiolchem.2019.107152. Epub 2019 Nov 18.
microRNAs (miRNAs) are short, non-coding, endogenous RNA molecule that regulates messenger RNAs (mRNAs) at the post-transcriptional level. The discovery of this regulatory relationship between miRNAs and mRNAs is an important research direction. In this regard, our method proposed an integrated approach to identify the mRNA targets of dysregulated miRNAs using next-generation sequencing data from six cancer types. For this analysis, a sensible combination of data mining tools is chosen. In particular, Random Forest, log-transformed Fold change, and Pearson correlation coefficient are considered to find the potential miRNA-mRNA pairs. During this study, we have identified six cancer-specific overlapping sets of miRNAs whose classification accuracy is always higher than 91%. Furthermore, a promising correlation signature of significantly dysregulated miRNAs and mRNAs are recognized. A comprehensive analysis found that the cumulative percentage of negative correlation coefficients is higher than its positive counterpart. Moreover, experimentally validated miRNA-target interactions databases called miRTarBase is used to validate significantly correlated mRNAs. According to our study, the smallest set of significantly dysregulated miRNAs is 43 in PRAD data, while for mRNAs the smallest set is 238 in the LUAD cancer type. The obtained miRNA-mRNA pairs are subjected to do pathway enrichment analysis and gene ontology analysis. Regulatory roles of these dysregulated miRNAs with associated diseases are identified by constructing a regulatory network between miRNAs and associated diseases. Moreover, the relation between miRNAs expression level and patient survival is also analyzed. To conclude, the miRNA-mRNA pairs identified in this study may serve as promising candidates for subsequent in-vitro validation.
微小 RNA(miRNAs)是短的、非编码的、内源性的 RNA 分子,在转录后水平调节信使 RNA(mRNAs)。miRNAs 和 mRNAs 之间这种调节关系的发现是一个重要的研究方向。在这方面,我们的方法提出了一种综合方法,使用来自六种癌症类型的下一代测序数据来鉴定失调 miRNAs 的 mRNA 靶标。对于这种分析,选择了合理的组合数据挖掘工具。特别是,随机森林、对数变换的倍数变化和皮尔逊相关系数被认为是发现潜在的 miRNA-mRNA 对的方法。在这项研究中,我们已经确定了六个癌症特异性重叠的 miRNA 集,其分类准确性始终高于 91%。此外,还识别了具有显著失调的 miRNAs 和 mRNAs 的有前途的相关特征签名。综合分析发现,负相关系数的累积百分比高于其正对应物。此外,还使用称为 miRTarBase 的经过实验验证的 miRNA 靶标相互作用数据库来验证显著相关的 mRNAs。根据我们的研究,PRAD 数据中显著失调 miRNAs 的最小集合是 43 个,而 LUAD 癌症类型中 mRNAs 的最小集合是 238 个。获得的 miRNA-mRNA 对进行途径富集分析和基因本体分析。通过构建 miRNA 和相关疾病之间的调控网络,确定这些失调 miRNAs 的调控作用及其相关疾病。此外,还分析了 miRNAs 表达水平与患者生存之间的关系。总之,本研究中鉴定的 miRNA-mRNA 对可能作为后续体外验证的有前途的候选物。