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Metabolites 2017, 7(4), 51; https://doi.org/10.3390/metabo7040051

Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

1
Interfaculty Bioinformatics Unit and SIB Swiss Institute of Bioinformatics, University of Bern, Baltzerstrasse 6, 3012 Bern, Switzerland
2
Department of BioMedical Research, University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland
3
Department of Visceral Surgery and Medicine, Department of Hepatology, Inselspital, University Hospital of Bern, 3010 Bern, Switzerland
4
Division of Systems Pharmacology and Pharmacogenomics, Samuel J. and Joan B. Williamson Institute, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, 11201 New York, NY, USA
*
Author to whom correspondence should be addressed.
Received: 11 September 2017 / Revised: 30 September 2017 / Accepted: 5 October 2017 / Published: 8 October 2017
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Abstract

About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states. View Full-Text
Keywords: metabolomics; robust regression analysis; metabolic perturbation networks; hepatitis B virus; hepatitis C virus; glycolysis; gluconeogenesis; pentose phosphate pathway; glucose transporters; TCA cycle metabolomics; robust regression analysis; metabolic perturbation networks; hepatitis B virus; hepatitis C virus; glycolysis; gluconeogenesis; pentose phosphate pathway; glucose transporters; TCA cycle
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Simillion, C.; Semmo, N.; Idle, J.R.; Beyoğlu, D. Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients. Metabolites 2017, 7, 51.

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