Ashley J Vargas1, John Quackenbush2, Kimberly Glass3. 1. Harvard School of Public Health, Harvard University, Boston, MA, USA; Cancer Prevention Fellowship Program, National Cancer Institute, Rockville, MD, USA. 2. Harvard School of Public Health, Harvard University, Boston, MA, USA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. 3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: rekrg@channing.harvard.edu.
Abstract
BACKGROUND: Weight loss may decrease risk of colorectal cancer in obese individuals, yet its effect in the colorectum is not well understood. We used integrative network modeling, Passing Attributes between Networks for Data Assimilation, to estimate transcriptional regulatory network models from mRNA expression levels from rectal mucosa biopsies measured pre- and post-weight loss in 10 obese, pre-menopausal women. RESULTS: We identified significantly greater regulatory targeting of glucose transport pathways in the post-weight loss regulatory network, including "regulation of glucose transport" (FDR=0.02), "hexose transport" (FDR=0.06), "glucose transport" (FDR=0.06) and "monosaccharide transport" (FDR=0.08). These findings were not evident by gene expression analysis alone. Network analysis also suggested a regulatory switch from NFΚB1 to MAX control of MYC post-weight loss. CONCLUSIONS: These network-based results expand upon standard gene expression analysis by providing evidence for a potential mechanistic alteration caused by weight loss.
BACKGROUND:Weight loss may decrease risk of colorectal cancer in obese individuals, yet its effect in the colorectum is not well understood. We used integrative network modeling, Passing Attributes between Networks for Data Assimilation, to estimate transcriptional regulatory network models from mRNA expression levels from rectal mucosa biopsies measured pre- and post-weight loss in 10 obese, pre-menopausal women. RESULTS: We identified significantly greater regulatory targeting of glucose transport pathways in the post-weight loss regulatory network, including "regulation of glucose transport" (FDR=0.02), "hexose transport" (FDR=0.06), "glucose transport" (FDR=0.06) and "monosaccharide transport" (FDR=0.08). These findings were not evident by gene expression analysis alone. Network analysis also suggested a regulatory switch from NFΚB1 to MAX control of MYC post-weight loss. CONCLUSIONS: These network-based results expand upon standard gene expression analysis by providing evidence for a potential mechanistic alteration caused by weight loss.
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