Title
Network signatures link hepatic effects of anti-diabetic interventions with systemic disease parameters
Author
Kelder, T.
Verschuren, L.
van Ommen, B.
van Gool, A.J.
Radonjic, M.
Publication year
2014
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 knowledge-based 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.
Subject
ELSS - Earth, Life and Social Sciences
Life
Healthy Living
Biomedical Innovation
Metabolic health
Network biology
Systems biology
Transcriptomics
Type II diabetes mellitus
MSB - Microbiology and Systems Biology
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http://resolver.tudelft.nl/uuid:ae3fd39d-e00e-41ce-81d3-ce00e1725d9f
DOI
https://doi.org/10.1186/s12918-014-0108-0
TNO identifier
516528
ISSN
1752-0509
Source
BMC Systems Biology, 8 (8)
Document type
article