title: Diet-induced weight loss leads to a switch in gene regulatory network control in the rectal mucosa.
abstract: 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.
  
  
  
  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.
  
  
  
  These network-based results expand upon standard gene expression analysis by providing evidence for a potential mechanistic alteration caused by weight loss.
authors.affiliation: Harvard School of Public Health, Harvard University, Boston, MA, USA; Cancer Prevention Fellowship Program, National Cancer Institute, Rockville, MD, USA.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Vargas
authors.affiliation: Harvard School of Public Health, Harvard University, Boston, MA, USA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.affiliation: 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.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Glass
mesh_terms: D000328:Adult; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction; D005260:Female; D053263:Gene Regulatory Networks; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012007:Rectum / Q000378:metabolism*; D015431:Weight Loss / Q000235:genetics*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C067850:Myc associated factor X; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D005947:Glucose
keywords: Colorectal cancer; Colorectum; Diet; Gene network; Gene regulation; Weight loss