A simultaneous exploratory and quantitative amino acid and biogenic amine metabolic profiling platform for rapid disease phenotyping via UPLC-QToF-MS

Gray, Nicola; Lawler, Nathan G.; Yang, Rongchang; Morillon, Aude-Claire; Gay, Melvin; Bong, Sze-How; Holmes, Elaine; Nicholson, Jeremy K.; Whiley, Luke

doi:10.1016/j.talanta.2020.121872

Cited by 25 publications

(31 citation statements)

References 37 publications

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“…Measurement of 42 metabolite concentrations was performed using ultrahigh-performance liquid chromatography–mass spectrometry (UHPLC-MS) based on validated assays to provide full quantification for amino acids and the products of tryptophan catabolism. − Full details of both assays can be found in the Supporting Information and are described briefly below.…”

Section: Methodsmentioning

confidence: 99%

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Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses

et al. 2021

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We performed quantitative metabolic phenotyping of blood plasma in parallel with cytokine/chemokine analysis from participants who were either SARS-CoV-2 (+) (n = 10) or SARS-CoV-2 (-) (n = 49). SARS-CoV-2 positivity was associated with a unique metabolic phenotype and demonstrated a complex systemic response to infection, including severe perturbations in amino acid and kynurenine metabolic pathways. Nine metabolites were elevated in plasma and strongly associated with infection (quinolinic acid, glutamic acid, nicotinic acid, aspartic acid, neopterin, kynurenine, phenylalanine, 3-hydroxykynurenine, and taurine; p < 0.05), while four metabolites were lower in infection (tryptophan, histidine, indole-3-acetic acid, and citrulline; p < 0.05). This signature supports a systemic metabolic phenoconversion following infection, indicating possible neurotoxicity and neurological disruption (elevations of 3-hydroxykynurenine and quinolinic acid) and liver dysfunction (reduction in Fischer's ratio and elevation of taurine). Finally, we report correlations between the key metabolite changes observed in the disease with concentrations of proinflammatory cytokines and chemokines showing strong immunometabolic disorder in response to SARS-CoV-2 infection.

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Section: Methodsmentioning

confidence: 99%

“…The quantification of biogenic amines and amino acids was performed according to methods previously reported. , In brief, 27 amino acids were quantified from 10 μL of plasma. Sample extraction was completed using a Biomek i5 sample automation system (Beckman Coulter, Mount Waverley, VIC 3149, Australia).…”

Section: Methodsmentioning

confidence: 99%

Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses

et al. 2021

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“…Following a standard suite of NMR and targeted MS assays, 34 biogenic amines 59 and 15 tryptophan pathway parameters 60 were measured by mass spectrometry and 112 lipoprotein parameters, and glucose, 23 plus glycoproteins, and novel supramolecular phospholipid composite biomarkers previously identified and measured by NMR spectroscopy. 54 In addition, we calculated multiple ratios.…”

Section: Methodsmentioning

confidence: 99%

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

et al. 2021

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We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of “Post-Acute COVID-19 Syndrome”, colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients ( n = 27) were compared with controls ( n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients ( n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine ( p = 3.6 × 10 –3 versus controls) and reduced glutamine/glutamate ratio ( p = 6.95 × 10 –8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower ( p = 4.2 × 10 –3 ) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ 2 p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a ...

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“…Novel NMR spectroscopic and mass spectrometric technologies are the most readily applied methods to generate multivariate profiles of metabolites for exploratory and targeted analysis. These advanced metabolic phenotyping methods and comprehensive data analyses have provided deep insight into biomarker signatures and metabolic pathways of the disease, such as lipoproteins (Kimhofer et al 2020 ; Lodge et al 2021a , 2021c ; Loo et al 2020 ), glycoproteins (Lodge et al 2021b ), lipids (Lawler et al 2021 ) and other key metabolites (Gray et al 2021 ), as well as the correlations between these metabolic parameters and inflammatory cytokines/chemokines (Bergamaschi et al 2021 ; Lawler et al 2021 ).…”

Section: Ii: Covid-19 and Molecular Phenomicsmentioning

confidence: 99%

Report on the 3rd Board Meeting of the International Human Phenome Consortium

Tian

Liu

Chen³

et al. 2022

Phenomics

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A simultaneous exploratory and quantitative amino acid and biogenic amine metabolic profiling platform for rapid disease phenotyping via UPLC-QToF-MS

Cited by 25 publications

References 37 publications

Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses

Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome

Report on the 3rd Board Meeting of the International Human Phenome Consortium

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