Data Mining and Text Mining Laboratory, Department of Bioinformatics, Bharathiar University, Coimbatore, Tamilnadu, India.
Data Mining and Text Mining Laboratory, Department of Bioinformatics, Bharathiar University, Coimbatore, Tamilnadu, India.
Comput Biol Chem. 2021 Jun;92:107500. doi: 10.1016/j.compbiolchem.2021.107500. Epub 2021 Apr 25.
Dilated Cardiomyopathy (DCM) is a multifactorial condition often leading to heart failure in many clinical cases. Due to the high number of DCMincidence reported as familial, a gene level network based study was conducted utilizing high throughput next generation sequencing data. We exploited the exome and transcriptome sequencing data in NCBI-SRA database to construct a high confidence scale-free regulatory network consisting of lncRNA, miRNA, mRNA and Transcription Factors (TFs). Analysis of RNA-Seq data revealed 477 differentially expressed coding transcripts and 77 lncRNAs. 268 miRNAs regulated either lncRNAs or mRNAs. Out of the 477 coding transcripts that are deregulated, 82 were TFs. We identified three major hub nodeslncRNA (XIST), miRNA (hsa-miR-195-5p) and mRNA (NOVA1) from the network. We also found putative disease associations of DCM with diabetes and DCM with hypoventillation syndrome. Five highly connected modules were also identified from the network. The hubs showed significant connectivity with the modules.Through this study we were able to gain insights into the underlying lncRNA-miRNA-mRNA-TF network. From a high throughput dataset we have isolated a handful of probable targets that may be utilized for studying the mechanisms of DCM development and progression to heart failure.
扩张型心肌病（DCM）是一种多因素疾病，在许多临床病例中常导致心力衰竭。由于报道的 DCM 家族发病率较高，因此进行了基于基因水平网络的研究，利用高通量下一代测序数据。我们利用 NCBI-SRA 数据库中的外显子组和转录组测序数据，构建了一个由 lncRNA、miRNA、mRNA 和转录因子（TF）组成的高可信度无标度调控网络。对 RNA-Seq 数据的分析显示，有 477 个差异表达的编码转录本和 77 个 lncRNA。268 个 miRNA 调节 lncRNA 或 mRNA。在失调的 477 个编码转录本中，有 82 个是 TF。我们从网络中鉴定出三个主要的枢纽节点 lncRNA（XIST）、miRNA（hsa-miR-195-5p）和 mRNA（NOVA1）。我们还发现了 DCM 与糖尿病和 DCM 与低通气综合征的潜在疾病关联。还从网络中鉴定出五个高度连接的模块。枢纽与模块显示出显著的连通性。通过这项研究，我们能够深入了解潜在的 lncRNA-miRNA-mRNA-TF 网络。从高通量数据集，我们分离出了一些可能用于研究 DCM 发展和进展为心力衰竭的机制的可能靶标。
