Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example

dc.contributor.authorPage, Sandra
dc.contributor.authorBirerdinc, Aybike
dc.contributor.authorEstep, Michael
dc.contributor.authorStepanova, Maria
dc.contributor.authorAfendy, Arian
dc.contributor.authorPetricoin, Emanuel
dc.contributor.authorYounossi, Zobair
dc.contributor.authorChandhoke, Vikas
dc.contributor.authorBaranova, Ancha
dc.description.abstractThe discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model. Two soluble biomarkers, CCL-2 and FasL, were inferred in silico as relevant to NAFLD pathogenesis. Predictive performance of these biomarkers was studied using serum samples collected from patients with histologically proven NAFLD. Serum levels of both molecules, in combination with clinical and demographic data, were predictive of hepatic fibrosis in a cohort of NAFLD patients. Our study suggests that (1) NASH-specific disruption of the kinase-driven signaling cascades in visceral adipose tissue lead to detectable changes in the levels of soluble molecules released into the bloodstream, and (2) biomarkers discovered in silico could contribute to predictive models for non-malignant chronic diseases.
dc.description.sponsorshipThe study was essentially self-funded. ELISA kits were purchased by one of the co-authors (EP). Access to Metacore and Pathway studio software were purchased by GMUand Inova Hospital, respectively. No external funding was used.
dc.identifier.citationPage S, Birerdinc A, Estep M, Stepanova M, Afendy A, et al. (2013) Knowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example. PLoS ONE 8(2): e56009. doi:10.1371/journal.pone.0056009
dc.publisherPublic Library of Science
dc.rights© 2013 Page et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.titleKnowledge-Based Identification of Soluble Biomarkers: Hepatic Fibrosis in NAFLD as an Example


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