A Case Study on Predicting Transcription Factors and Gene Networks

• Activity Number: 372
• Type: Contributed
• Date/Time: Tuesday, August 6, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Korean International Statistical Society
• Author(s): Dongseok Choi*+ and Lauren Hayashi and Kathryn Carr and Mary J. Kelley and Ted S. Acott
• Companies: Oregon Health & Science Univ and Oregon Health & Science University and Oregon Health & Science University and Oregon Health & Science University and Oregon Health & Science University
• Keywords: Transcription factors ; Gene networks ; Microarrays ; Consensus matrix ; Consensus sequence ; Cluster analysis

Abstract

TNFa is a key mediator of the therapeutic effects of laser trabeculoplasty on glaucoma. TNFa treatment increases matrix metalloproteinases (MMPs), enzymes that initiate turnover in the extracellular matrix (ECM), of trabecular meshwork (TM) cells. To further study ECM remodeling and its effects on aqueous humor outflow resistance, we conducted secondary data analyses to identify gene networks and their putative transcription factor binding sites by gene expression in response to TNFa treatment in TM cells. Significance Analysis of Microarrays was performed to identify differentially expressed genes with a q-value < 5%. TightClust cluster analysis produced small groups of significant genes by temporal patterns. Tight clusters up-regulated at 24 and 48 hours were analyzed for gene networks by Metacore. DNA promoter sequences for 5K bp upstream with 2K bp were analyzed by CisModule to identify putative cis-regulatory motifs. The consensus sequences were identified by TRANSFAC Professional database against known motifs. The Metacore analysis produced several interesting gene networks. Further validation studies will confirm the functionality of the networks and transcription factors.