PLoS Genetics (Jun 2007)

Network-based analysis of affected biological processes in type 2 diabetes models.

  • Manway Liu,
  • Arthur Liberzon,
  • Sek Won Kong,
  • Weil R Lai,
  • Peter J Park,
  • Isaac S Kohane,
  • Simon Kasif

DOI
https://doi.org/10.1371/journal.pgen.0030096
Journal volume & issue
Vol. 3, no. 6
p. e96

Abstract

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Type 2 diabetes mellitus is a complex disorder associated with multiple genetic, epigenetic, developmental, and environmental factors. Animal models of type 2 diabetes differ based on diet, drug treatment, and gene knockouts, and yet all display the clinical hallmarks of hyperglycemia and insulin resistance in peripheral tissue. The recent advances in gene-expression microarray technologies present an unprecedented opportunity to study type 2 diabetes mellitus at a genome-wide scale and across different models. To date, a key challenge has been to identify the biological processes or signaling pathways that play significant roles in the disorder. Here, using a network-based analysis methodology, we identified two sets of genes, associated with insulin signaling and a network of nuclear receptors, which are recurrent in a statistically significant number of diabetes and insulin resistance models and transcriptionally altered across diverse tissue types. We additionally identified a network of protein-protein interactions between members from the two gene sets that may facilitate signaling between them. Taken together, the results illustrate the benefits of integrating high-throughput microarray studies, together with protein-protein interaction networks, in elucidating the underlying biological processes associated with a complex disorder.