Department of Gastroenterology, The First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, China.
Department of Nursing, Shandong Medical College, Jinan, Shandong, China.
Cancer Biomark. 2017 Dec 6;20(4):617-625. doi: 10.3233/CBM-170595.
It is crucially important to discover the relationships between genes and microRNAs (miRNAs) in cancer. Thus, we proposed a combined bioinformatics method integrating Pearson's correlation coefficient (PCC), Lasso, and causal inference method (IDA) to identify the potential miRNA targets for stomach adenocarcinoma (STAD) using Borda count election.
Firstly, the ensemble method integrating PCC, IDA, and Lasso was used to predict miRNA targets. Subsequently, to validate the performance ability of this ensemble method, comparisons between verified database and predicted miRNA targets were implemented. Pathway analysis for target genes in the top 1000 miRNA-mRNA interactions was implemented to discover significant pathways. Finally, the top 10 target genes were identified based on predicted times > 3.
The ensemble approach was confirmed to be a feasible method to predict miRNA targets The 527 target genes of the top 1000 miRNA-mRNA interactions were enriched in 21 pathways. Of note, cell adhesion molecules (CAMs) was the most significant one. The top 10 target genes were identified based on predicted times > 3, such as GABRA3, CSAG1 and PTPN7. These targets were all predicted by 4 times. Moreover, GABRA3 and CSAG1 were simultaneously targeted by miRNA-105-1, miRNA-105-2, and miRNA-767. Significantly, among these top 10 targets, PTPN7 and GABRA3-miRNA interactions owned the highest correlation with 691.
The combined bioinformatics method integrating PCC, IDA, and Lasso might be a valuable method for miRNA target prediction, and dys-regulated expression of miRNAs and their potential targets might be prominently involved in the pathogenesis of STAD.
发现癌症中基因与 microRNA(miRNA)之间的关系至关重要。因此,我们提出了一种结合 Pearson 相关系数(PCC)、Lasso 和因果推断方法(IDA)的综合生物信息学方法,使用 Borda 计数选举来识别胃腺癌(STAD)的潜在 miRNA 靶标。
首先,使用集成 PCC、IDA 和 Lasso 的集成方法预测 miRNA 靶标。随后,为了验证该集成方法的性能能力,对验证数据库与预测 miRNA 靶标进行了比较。对 top1000 miRNA-mRNA 相互作用中的靶基因进行了通路分析,以发现显著的通路。最后,根据预测次数>3,确定了 top10 个靶基因。
该综合方法被证实是一种可行的预测 miRNA 靶标的方法。top1000 miRNA-mRNA 相互作用中的 527 个靶基因富集在 21 条通路上。值得注意的是,细胞黏附分子(CAMs)是最显著的一个。根据预测次数>3,确定了 top10 个靶基因,如 GABRA3、CSAG1 和 PTPN7。这些靶基因均被预测 4 次。此外,GABRA3 和 CSAG1 同时被 miRNA-105-1、miRNA-105-2 和 miRNA-767 靶向。重要的是,在这 10 个靶基因中,PTPN7 和 GABRA3-miRNA 相互作用与 691 具有最高的相关性。
该综合生物信息学方法结合了 PCC、IDA 和 Lasso,可能是一种有价值的 miRNA 靶标预测方法,miRNA 及其潜在靶标的失调表达可能显著参与了 STAD 的发病机制。