Integrated regulatory network based on lncRNA-miRNA-mRNA-TF reveals key genes and sub-networks associated with dilated cardiomyopathy.

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.