Identification of new regulatory genes through expression pattern analysis of a global RNA-seq dataset from a Helicobacter pylori co-culture system

Sci Rep. 2020 Jul 13;10(1):11506. doi: 10.1038/s41598-020-68439-8.


Helicobacter pylori is a gram-negative bacterium that persistently colonizes the human stomach by inducing immunoregulatory responses. We have used a novel platform that integrates a bone marrow-derived macrophage and live H. pylori co-culture with global time-course transcriptomics analysis to identify new regulatory genes based on expression patterns resembling those of genes with known regulatory function. We have used filtering criteria based on cellular location and novelty parameters to select 5 top lead candidate targets. Of these, Plexin domain containing 2 (Plxdc2) was selected as the top lead immunoregulatory target. Loss of function studies with in vivo models of H. pylori infection as well as a chemically-induced model of colitis, confirmed its predicted regulatory function and significant impact on modulation of the host immune response. Our integrated bioinformatics analyses and experimental validation platform has enabled the discovery of new immunoregulatory genes. This pipeline can be used for the identification of genes with therapeutic applications for treating infectious, inflammatory, and autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Coculture Techniques
  • Computer Simulation
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Genes, Regulator / genetics*
  • Helicobacter Infections / genetics*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / pathogenicity
  • Humans
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Mice
  • RNA-Seq
  • Receptors, Cell Surface / genetics


  • PLXDC2 protein, human
  • Receptors, Cell Surface