Integrated transcriptomic correlation network analysis identifies COPD molecular determinants

Sci Rep. 2020 Feb 25;10(1):3361. doi: 10.1038/s41598-020-60228-7.

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome. Network-based analysis implemented by SWIM software can be exploited to identify key molecular switches - called "switch genes" - for the disease. Genes contributing to common biological processes or defining given cell types are usually co-regulated and co-expressed, forming expression network modules. Consistently, we found that the COPD correlation network built by SWIM consists of three well-characterized modules: one populated by switch genes, all up-regulated in COPD cases and related to the regulation of immune response, inflammatory response, and hypoxia (like TIMP1, HIF1A, SYK, LY96, BLNK and PRDX4); one populated by well-recognized immune signature genes, all up-regulated in COPD cases; one where the GWAS genes AGER and CAVIN1 are the most representative module genes, both down-regulated in COPD cases. Interestingly, 70% of AGER negative interactors are switch genes including PRDX4, whose activation strongly correlates with the activation of known COPD GWAS interactors SERPINE2, CD79A, and POUF2AF1. These results suggest that SWIM analysis can identify key network modules related to complex diseases like COPD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD79 Antigens / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Gene Regulatory Networks / genetics*
  • Genes, Switch / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / classification
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • RNA-Binding Proteins / genetics
  • Receptor for Advanced Glycation End Products / genetics
  • Serpin E2 / genetics
  • Software*
  • Transcriptome / genetics*

Substances

  • AGER protein, human
  • CAVIN1 protein, human
  • CD79 Antigens
  • RNA-Binding Proteins
  • Receptor for Advanced Glycation End Products
  • Serpin E2