Knecht, C., Fretter, C., Rosenstiel, Philip, Krawczak, Michael and Hutt, M. T. (2016) Distinct metabolic network states manifest in the gene expression profiles of pediatric inflammatory bowel disease patients and controls. Scientific Reports, 6 . DOI 10.1038/srep32584.

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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 treatmentnaive 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.

Document Type:	Article
Additional Information:	Times Cited: 0 Knecht, Carolin Fretter, Christoph Rosenstiel, Philip Krawczak, Michael Huett, Marc-Thorsten
Keywords:	Dynamic networks, Inflammatory bowel disease
Research affiliation:	Kiel University Kiel University > Kiel Marine Science OceanRep > The Future Ocean - Cluster of Excellence
Refereed:	Yes
Open Access Journal?:	Yes
Publisher:	Nature Research
Projects:	Future Ocean
Date Deposited:	27 Feb 2017 08:29
Last Modified:	23 Sep 2019 23:53
URI:	https://oceanrep.geomar.de/id/eprint/36168

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