Network-based analysis of affected biological processes in type 2 diabetes models.
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.
Liu
Manway
M
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America. manwayl@bu.edu
Liberzon
Arthur
A
Kong
Sek Won
SW
Lai
Weil R
WR
Park
Peter J
PJ
Kohane
Isaac S
IS
Kasif
Simon
S
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology; D049490:Systems Biology
D007328:Insulin