Construction of an integrated gene regulatory network link to stress-related immune system in cattle

Genetica. 2017 Oct;145(4-5):441-454. doi: 10.1007/s10709-017-9980-z. Epub 2017 Aug 20.


The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

Keywords: Integrated network; Module network; Promoter analysis; RNA-Seq.

MeSH terms

  • Animals
  • Cattle
  • Cattle Diseases / genetics*
  • Cattle Diseases / immunology*
  • Gene Regulatory Networks*
  • Immune System / physiology*
  • Male
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Stress, Physiological / genetics*
  • Stress, Physiological / immunology*
  • Transcription Factors / metabolism


  • RNA, Messenger
  • Transcription Factors