Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome

Nat Commun. 2020 Feb 10;11(1):811. doi: 10.1038/s41467-020-14600-w.

Abstract

The molecular and clinical features of a complex disease can be influenced by other diseases affecting the same individual. Understanding disease-disease interactions is therefore crucial for revealing shared molecular mechanisms among diseases and designing effective treatments. Here we introduce Flow Centrality (FC), a network-based approach to identify the genes mediating the interaction between two diseases in a protein-protein interaction network. We focus on asthma and COPD, two chronic respiratory diseases that have been long hypothesized to share common genetic determinants and mechanisms. We show that FC highlights potential mediator genes between the two diseases, and observe similar outcomes when applying FC to 66 additional pairs of related diseases. Further, we perform in vitro perturbation experiments on a widely replicated asthma gene, GSDMB, showing that FC identifies candidate mediators of the interactions between GSDMB and COPD-associated genes. Our results indicate that FC predicts promising gene candidates for further study of disease-disease interactions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Asthma / complications
  • Asthma / genetics*
  • Asthma / metabolism
  • Cell Line
  • Computational Biology / methods
  • Gene Expression Profiling
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Neoplasm Proteins / genetics
  • Protein Interaction Maps / genetics*
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Reproducibility of Results

Substances

  • GSDMB protein, human
  • Neoplasm Proteins