Coexpression network based on natural variation in human gene expression reveals gene interactions and functions

Genome Res. 2009 Nov;19(11):1953-62. doi: 10.1101/gr.097600.109. Epub 2009 Oct 1.

Abstract

Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes.

Publication types

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

MeSH terms

  • Asians / genetics
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Blacks / genetics
  • Cell Line, Transformed
  • China
  • DEAD-box RNA Helicases
  • Diabetes Mellitus, Type 1 / genetics
  • Epistasis, Genetic*
  • Gene Expression Profiling / methods*
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease / genetics
  • Genomics / methods*
  • Haplotypes
  • Humans
  • Interferon-Induced Helicase, IFIH1
  • Japan
  • Models, Genetic
  • Proto-Oncogene Proteins c-yes
  • Whites / genetics

Substances

  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1

Associated data

  • GEO/GSE12526