Cross-validation of metabolic phenotypes in SARS-CoV-2 infected subpopulations using targeted liquid chromatography-mass spectrometry (LC-MS)
Author(s)
Type
Journal Article
Abstract
To ensure biological validity in metabolic phenotyping, findings must be replicated in independent sample sets. Targeted workflows have long been heralded as ideal platforms for such validation due to their robust quantitative capability. We evaluated the capability of liquid chromatography-mass spectrometry (LC-MS) assays targeting organic acids and bile acids to validate metabolic phenotypes of SARS-CoV-2 infection. Two independent sample sets were collected: (1) Australia: plasma, SARS-CoV-2 positive (n = 20), noninfected healthy controls (n = 22) and COVID-19 disease-like symptoms but negative for SARS-CoV-2 infection (n = 22). (2) Spain: serum, SARS-CoV-2 positive (n = 33) and noninfected healthy controls (n = 39). Multivariate modeling using orthogonal projections to latent structures discriminant analyses (OPLS-DA) classified healthy controls from SARS-CoV-2 positive (Australia; R2 = 0.17, ROC-AUC = 1; Spain R2 = 0.20, ROC-AUC = 1). Univariate analyses revealed 23 significantly different (p < 0.05) metabolites between healthy controls and SARS-CoV-2 positive individuals across both cohorts. Significant metabolites revealed consistent perturbations in cellular energy metabolism (pyruvic acid, and 2-oxoglutaric acid), oxidative stress (lactic acid, 2-hydroxybutyric acid), hypoxia (2-hydroxyglutaric acid, 5-aminolevulinic acid), liver activity (primary bile acids), and host-gut microbial cometabolism (hippuric acid, phenylpropionic acid, indole-3-propionic acid). These data support targeted LC-MS metabolic phenotyping workflows for biological validation in independent sample sets.
Date Issued
2024-04-05
Date Acceptance
2024-02-23
Citation
Journal of Proteome Research, 2024, 23 (4), pp.1313-1327
ISSN
1535-3893
Publisher
American Chemical Society
Start Page
1313
End Page
1327
Journal / Book Title
Journal of Proteome Research
Volume
23
Issue
4
Copyright Statement
Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0 .
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38484742
Subjects
ACIDS
bile acids
Biochemical Research Methods
Biochemistry & Molecular Biology
COVID-19
DISCOVERY
HIPPURATE
hypoxia
INFLUENZA
LC-MS
Life Sciences & Biomedicine
MARKER
metabolic phenotyping
metabolic phenotyping array
organic acids
oxidative stress
PLASMA
SARS-CoV-2
Science & Technology
TCA cycle
validation
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-03-14