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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Genomics+Inform
2015 ; 13
(3
): 76-80
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The Construction of Regulatory Network for Insulin-Mediated Genes by Integrating
Methods Based on Transcription Factor Binding Motifs and Gene Expression
Variations
#MMPMID26523131
Jung H
; Han S
; Kim S
Genomics Inform
2015[Sep]; 13
(3
): 76-80
PMID26523131
show ga
Type 2 diabetes mellitus is a complex metabolic disorder associated with multiple
genetic, developmental and environmental factors. The recent advances in gene
expression microarray technologies as well as network-based analysis
methodologies provide groundbreaking opportunities to study type 2 diabetes
mellitus. In the present study, we used previously published gene expression
microarray datasets of human skeletal muscle samples collected from 20 insulin
sensitive individuals before and after insulin treatment in order to construct
insulin-mediated regulatory network. Based on a motif discovery method
implemented by iRegulon, a Cytoscape app, we identified 25 candidate regulons,
motifs of which were enriched among the promoters of 478 up-regulated genes and
82 down-regulated genes. We then looked for a hierarchical network of the
candidate regulators, in such a way that the conditional combination of their
expression changes may explain those of their target genes. Using Genomica, a
software tool for regulatory network construction, we obtained a hierarchical
network of eight regulons that were used to map insulin downstream signaling
network. Taken together, the results illustrate the benefits of combining
completely different methods such as motif-based regulatory factor discovery and
expression level-based construction of regulatory network of their target genes
in understanding insulin induced biological processes and signaling pathways.