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

Simillion, Cedric; Semmo, Nasser; Idle, Jeffrey; Beyoglu, Diren (2017). Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients. Metabolites, 7(4) MDPI 10.3390/metabo7040051

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Semmo, Nasser; Idle, Jeffrey and Beyoglu, Diren

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2218-1989

Publisher:

MDPI

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

31 Jan 2018 16:55

Last Modified:

05 Mar 2018 12:52

Publisher DOI:

10.3390/metabo7040051

PubMed ID:

28991180

Uncontrolled Keywords:

TCA cycle gluconeogenesis glucose transporters glycolysis hepatitis B virus hepatitis C virus metabolic perturbation networks metabolomics pentose phosphate pathway robust regression analysis

BORIS DOI:

10.7892/boris.109564

URI:

https://boris.unibe.ch/id/eprint/109564

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