Liu, ManwayLiberzon, ArthurKong, Sek WonLai, Weil RPark, PeterKohane, IsaacKasif, Simon2011-03-192007Liu, Manway, Arthur Liberzon, Sek Won Kong, Weil R. Lai, Peter J. Park, Isaac S. Kohane, and Simon Kasif. 2007. Network-based analysis of affected biological processes in type 2 diabetes models. PLoS Genetics 3(6): e96.1553-7390http://nrs.harvard.edu/urn-3:HUL.InstRepos:4745737Type 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.en-USJournal Article2011-03-1910.1371/journal.pgen.0030096