Thu, 21 Aug 2008 14:10:24 BST CiteULike: tmmurali's Lai http://www.citeulike.org/user/tmmurali/author/Lai CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/tmmurali/article/1477440 <i>PLoS Genetics, Vol. 3, No. 6. (1 June 2007), e96.</i><br /><br />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. Network-Based Analysis of Affected Biological Processes in Type 2 Diabetes Models Manway Liu Arthur Liberzon Sek Kong Weil Lai Peter Park Isaac Kohane Simon Kasif doi:10.1371/journal.pgen.0030096 PLoS Genetics, Vol. 3, No. 6. (1 June 2007), e96. 2007-07-24T19:33:50-00:00 2007 PLoS Genetics 3 6 e96 active-networks http://www.citeulike.org/user/tmmurali/article/1402831 <i>PLoS Genetics, Vol. 3, No. 6. (1 June 2007), e96.</i><br /><br />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. Network-Based Analysis of Affected Biological Processes in Type 2 Diabetes Models Manway Liu Arthur Liberzon Sek Kong Weil Lai Peter Park Isaac Kohane Simon Kasif doi:10.1371/journal.pgen.0030096 PLoS Genetics, Vol. 3, No. 6. (1 June 2007), e96. 2007-06-21T18:07:09-00:00 2007 PLoS Genetics 3 6 e96 active-networks http://www.citeulike.org/user/tmmurali/article/1880339 <i>Nature, Vol. 450, No. 7167., pp. 219-232.</i> Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures Alexander Stark Michael Lin Pouya Kheradpour Jakob Pedersen Leopold Parts Joseph Carlson Madeline Crosby Matthew Rasmussen Sushmita Roy Ameya Deoras Graham Ruby Julius Brennecke Harvard Curators Berkeley Emily Hodges Angie Hinrichs Anat Caspi Benedict Paten Seung-Won Park Mira Han Morgan Maeder Benjamin Polansky Bryanne Robson Stein Aerts Jacques van Helden Bassem Hassan Donald Gilbert Deborah Eastman Michael Rice Michael Weir Matthew Hahn Yongkyu Park Colin Dewey Lior Pachter James Kent David Haussler Eric Lai David Bartel Gregory Hannon Thomas Kaufman Michael Eisen Andrew Clark Douglas Smith Susan Celniker William Gelbart Manolis Kellis doi:10.1038/nature06340 Nature, Vol. 450, No. 7167., pp. 219-232. 2007-11-07T18:45:14-00:00 Nature 0028-0836 450 7167 219 232 Nature Publishing Group comparative_genomics