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- Title
Network signatures link hepatic effects of anti-diabetic interventions with systemic disease parameters.
- Authors
Kelder, Thomas; Verschuren, Lars; van Ommen, Ben; van Gool, Alain J.; Radonjic, Marijana
- Abstract
Background Multifactorial diseases such as type 2 diabetes mellitus (T2DM), are driven by a complex network of interconnected mechanisms that translate to a diverse range of complications at the physiological level. To optimally treat T2DM, pharmacological interventions should, ideally, target key nodes in this network that act as determinants of disease progression. Results We set out to discover key nodes in molecular networks based on the hepatic transcriptome dataset from a preclinical study in obese LDLR-/- mice recently published by Radonjic et al. Here, we focus on comparing efficacy of anti-diabetic dietary (DLI) and two drug treatments, namely PPARA agonist fenofibrate and LXR agonist T0901317. By combining knowledgebased and data-driven networks with a random walks based algorithm, we extracted network signatures that link the DLI and two drug interventions to dyslipidemia-related disease parameters. Conclusions This study identified specific and prioritized sets of key nodes in hepatic molecular networks underlying T2DM, uncovering pathways that are to be modulated by targeted T2DM drug interventions in order to modulate the complex disease phenotype.
- Subjects
DISEASE progression; PHENOTYPES; DYSLIPIDEMIA; DIABETES; GENOTYPE-environment interaction
- Publication
BMC Systems Biology, 2014, Vol 8, Issue 1, p1
- ISSN
1752-0509
- Publication type
Article
- DOI
10.1186/s12918-014-0108-0