1. Distinct metabolic network states manifest in the gene expression profiles of pediatric inflammatory bowel disease patients and controls
- Author
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Marc-Thorsten Hütt, Michael Krawczak, Christoph Fretter, Carolin Knecht, and Philip Rosenstiel
- Subjects
Male ,0301 basic medicine ,Adolescent ,Metabolic network ,Biology ,Bioinformatics ,Inflammatory bowel disease ,Article ,03 medical and health sciences ,Text mining ,Gene expression ,medicine ,Multidimensional scaling analysis ,Data Mining ,Humans ,Intestinal Mucosa ,Child ,Multidisciplinary ,business.industry ,Gene Expression Profiling ,Inflammatory Bowel Diseases ,medicine.disease ,Phenotype ,Intestines ,Crosstalk (biology) ,030104 developmental biology ,Gene Expression Regulation ,Case-Control Studies ,Child, Preschool ,Female ,business ,Metabolic Networks and Pathways ,Biological network - Abstract
Information on biological networks can greatly facilitate the function-orientated interpretation of high-throughput molecular data. Genome-wide metabolic network models of human cells, in particular, can be employed to contextualize gene expression profiles of patients with the goal of both, a better understanding of individual etiologies and an educated reclassification of (clinically defined) phenotypes. We analyzed publicly available expression profiles of intestinal tissues from treatment-naive pediatric inflammatory bowel disease (IBD) patients and age-matched control individuals, using a reaction-centric metabolic network derived from the Recon2 model. By way of defining a measure of ‘coherence’, we quantified how well individual patterns of expression changes matched the metabolic network. We observed a bimodal distribution of metabolic network coherence in both patients and controls, albeit at notably different mixture probabilities. Multidimensional scaling analysis revealed a bisectional pattern as well that overlapped widely with the metabolic network-based results. Expression differences driving the observed bimodality were related to cellular transport of thiamine and bile acid metabolism, thereby highlighting the crosstalk between metabolism and other vital pathways. We demonstrated how classical data mining and network analysis can jointly identify biologically meaningful patterns in gene expression data.
- Published
- 2016
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