Weighted Gene Coexpression Network Analysis Reveals the Critical lncRNAs and mRNAs in Development of Hirschsprung's Disease

J Comput Biol. 2020 Jul;27(7):1115-1129. doi: 10.1089/cmb.2019.0261. Epub 2019 Oct 24.

Abstract

Hirschsprung's disease (HSCR) is a common newborn defect. This study aimed to identify critical genes involved in the development of HSCR. Differently expressed genes (DEGs) of public data set GSE98502 were analyzed using paired t-test. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.8. Besides, Coexpression network of long noncoding RNAs (lncRNAs)-mRNAs (message RNA) were constructed using weighted gene coexpression network analysis. The key modules were filtered out by calculating the module-trait correlations. Then, hub genes were screened and the expression of these genes was further validated in an independent data set GSE96854. We identified 864 DEGs enriched in 19 GO biological functions such as negative regulation of growth and regulation of heart contraction; 11 KEGG pathways such as mineral absorption and protein digestion and absorption. lncRNAs-mRNAs coexpressed network was constructed, including 8 modules and 177 genes. Hub lncRNAs, including LINC00619, LINC00924, LINC00261, and DRAIC, were identified. Hub mRNAs, including CYCS, CCND1, BDKRB, ITGA6, and TNNC1, were mainly enriched in cancer pathways, p53 signaling pathway, and calcium signaling pathway. The expressions of the hub mRNAs were successfully validated by another independent GSE96854 data set. Our findings indicated the hub lncRNAs, including LINC00619, LINC00924, LINC00261, and DRAIC, as well as hub mRNAs, including CYCS, CCND1, BDKRB, ITGA6, and TNNC1, might involve in the progression of HSCR, and these genes might provide new clinical biomarkers for risk evaluation of HSCR.

Keywords: Hirschsprung's disease; clinical biomarker; weight gene coexpression network analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cluster Analysis
  • Gene Expression Profiling
  • Gene Ontology
  • Gene Regulatory Networks*
  • Hirschsprung Disease / etiology
  • Hirschsprung Disease / genetics*
  • Humans
  • Infant, Newborn
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • Reproducibility of Results

Substances

  • RNA, Long Noncoding
  • RNA, Messenger