title: Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example.
abstract: The 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.
authors: Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, Virginia, United States of America.
authors: Sandra
authors: S
authors: Page
authors: Aybike
authors: A
authors: Birerdinc
authors: Michael
authors: M
authors: Estep
authors: Maria
authors: M
authors: Stepanova
authors: Arian
authors: A
authors: Afendy
authors: Emanuel
authors: E
authors: Petricoin
authors: Zobair
authors: Z
authors: Younossi
authors: Vikas
authors: V
authors: Chandhoke
authors: Ancha
authors: A
authors: Baranova
mesh_terms: D015415:Biomarkers / Q000097:blood*; D018932:Chemokine CCL2 / Q000097:blood*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000097:blood*; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D051188:Knowledge Bases; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D010766:Phosphorylation; D040901:Proteomics; D015398:Signal Transduction; D049490:Systems Biology
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C505661:FASLG protein, human; D053222:Fas Ligand Protein