Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy

Ruifang Li-Gao*, David A. Hughes, Saskia le Cessie, Renée de Mutsert, Martin den Heijer, Frits R. Rosendaal, Ko Willems van Dijk, Nicholas J. Timpson, Dennis O. Mook-Kanamori

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Introduction

It is crucial to understand the factors that introduce variability before applying metabolomics to clinical and biomarker research.

Objectives

We quantified technical and biological variability of both fasting and postprandial metabolite concentrations measured using H-1 NMR spectroscopy in plasma samples.

Methods

In the Netherlands Epidemiology of Obesity study (n = 6,671), 148 metabolite concentrations (101 metabolites belonging to lipoprotein subclasses) were measured under fasting and postprandial states (150 minutes after a mixed liquid meal). Technical variability was evaluated among 265 fasting and 851 postprandial samples, with the identical blood plasma sample being measured twice by the same laboratory protocol. Biological reproducibility was assessed by measuring 165 individuals twice across time for evaluation of short- (3 years) biological variability. Intra-class coefficients (ICCs) were used to assess variability. The ICCs of the fasting metabolites were compared with the postprandial metabolites using two-sided paired Wilcoxon test separately for short- and long-term measurements.

Results

Both fasting and postprandial metabolite concentrations showed high technical reproducibility using H-1 NMR spectroscopy (median ICC = 0.99). Postprandial metabolite concentrations revealed slightly higher ICC scores than fasting ones in short-term repeat measures (median ICC in postprandial and fasting metabolite concentrations 0.72 versus 0.67, Wilcoxon p-value = 8.0x10(-14)). Variability did not increase further in a long-term repeat measure, with median ICC in postprandial of 0.64 and in fasting metabolite concentrations 0.66.

Conclusion

Technical reproducibility is excellent. Biological reproducibility of postprandial metabolite concentrations showed a less or equal variability than fasting metabolite concentrations over time.

Original languageEnglish
Article numbere0218549
Number of pages14
JournalPLoS ONE
Volume14
Issue number6
DOIs
Publication statusPublished - 2019

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Metabolites
Nuclear magnetic resonance spectroscopy
Fasting
Plasmas
Epidemiology
Netherlands
Biomarkers
Lipoproteins
Blood

Keywords

  • EPIDEMIOLOGY
  • METABOLOMICS

Cite this

Li-Gao, R., Hughes, D. A., Cessie, S. L., Mutsert, R. D., Heijer, M. D., Rosendaal, F. R., ... Mook-Kanamori, D. O. (2019). Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy. PLoS ONE, 14(6), [e0218549]. https://doi.org/10.1371/journal.pone.0218549
Li-Gao, Ruifang ; Hughes, David A. ; Cessie, Saskia le ; Mutsert, Renée de ; Heijer, Martin den ; Rosendaal, Frits R. ; Dijk, Ko Willems van ; Timpson, Nicholas J. ; Mook-Kanamori, Dennis O. / Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy. In: PLoS ONE. 2019 ; Vol. 14, No. 6.
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title = "Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy",
abstract = "IntroductionIt is crucial to understand the factors that introduce variability before applying metabolomics to clinical and biomarker research.ObjectivesWe quantified technical and biological variability of both fasting and postprandial metabolite concentrations measured using H-1 NMR spectroscopy in plasma samples.MethodsIn the Netherlands Epidemiology of Obesity study (n = 6,671), 148 metabolite concentrations (101 metabolites belonging to lipoprotein subclasses) were measured under fasting and postprandial states (150 minutes after a mixed liquid meal). Technical variability was evaluated among 265 fasting and 851 postprandial samples, with the identical blood plasma sample being measured twice by the same laboratory protocol. Biological reproducibility was assessed by measuring 165 individuals twice across time for evaluation of short- (3 years) biological variability. Intra-class coefficients (ICCs) were used to assess variability. The ICCs of the fasting metabolites were compared with the postprandial metabolites using two-sided paired Wilcoxon test separately for short- and long-term measurements.ResultsBoth fasting and postprandial metabolite concentrations showed high technical reproducibility using H-1 NMR spectroscopy (median ICC = 0.99). Postprandial metabolite concentrations revealed slightly higher ICC scores than fasting ones in short-term repeat measures (median ICC in postprandial and fasting metabolite concentrations 0.72 versus 0.67, Wilcoxon p-value = 8.0x10(-14)). Variability did not increase further in a long-term repeat measure, with median ICC in postprandial of 0.64 and in fasting metabolite concentrations 0.66.ConclusionTechnical reproducibility is excellent. Biological reproducibility of postprandial metabolite concentrations showed a less or equal variability than fasting metabolite concentrations over time.",
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author = "Ruifang Li-Gao and Hughes, {David A.} and Cessie, {Saskia le} and Mutsert, {Ren{\'e}e de} and Heijer, {Martin den} and Rosendaal, {Frits R.} and Dijk, {Ko Willems van} and Timpson, {Nicholas J.} and Mook-Kanamori, {Dennis O.}",
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Li-Gao, R, Hughes, DA, Cessie, SL, Mutsert, RD, Heijer, MD, Rosendaal, FR, Dijk, KWV, Timpson, NJ & Mook-Kanamori, DO 2019, 'Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy', PLoS ONE, vol. 14, no. 6, e0218549. https://doi.org/10.1371/journal.pone.0218549

Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy. / Li-Gao, Ruifang; Hughes, David A.; Cessie, Saskia le; Mutsert, Renée de; Heijer, Martin den; Rosendaal, Frits R.; Dijk, Ko Willems van; Timpson, Nicholas J.; Mook-Kanamori, Dennis O.

In: PLoS ONE, Vol. 14, No. 6, e0218549, 2019.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Assessment of reproducibility and biological variability of fasting and postprandial plasma metabolite concentrations using 1H NMR spectroscopy

AU - Li-Gao, Ruifang

AU - Hughes, David A.

AU - Cessie, Saskia le

AU - Mutsert, Renée de

AU - Heijer, Martin den

AU - Rosendaal, Frits R.

AU - Dijk, Ko Willems van

AU - Timpson, Nicholas J.

AU - Mook-Kanamori, Dennis O.

PY - 2019

Y1 - 2019

N2 - IntroductionIt is crucial to understand the factors that introduce variability before applying metabolomics to clinical and biomarker research.ObjectivesWe quantified technical and biological variability of both fasting and postprandial metabolite concentrations measured using H-1 NMR spectroscopy in plasma samples.MethodsIn the Netherlands Epidemiology of Obesity study (n = 6,671), 148 metabolite concentrations (101 metabolites belonging to lipoprotein subclasses) were measured under fasting and postprandial states (150 minutes after a mixed liquid meal). Technical variability was evaluated among 265 fasting and 851 postprandial samples, with the identical blood plasma sample being measured twice by the same laboratory protocol. Biological reproducibility was assessed by measuring 165 individuals twice across time for evaluation of short- (3 years) biological variability. Intra-class coefficients (ICCs) were used to assess variability. The ICCs of the fasting metabolites were compared with the postprandial metabolites using two-sided paired Wilcoxon test separately for short- and long-term measurements.ResultsBoth fasting and postprandial metabolite concentrations showed high technical reproducibility using H-1 NMR spectroscopy (median ICC = 0.99). Postprandial metabolite concentrations revealed slightly higher ICC scores than fasting ones in short-term repeat measures (median ICC in postprandial and fasting metabolite concentrations 0.72 versus 0.67, Wilcoxon p-value = 8.0x10(-14)). Variability did not increase further in a long-term repeat measure, with median ICC in postprandial of 0.64 and in fasting metabolite concentrations 0.66.ConclusionTechnical reproducibility is excellent. Biological reproducibility of postprandial metabolite concentrations showed a less or equal variability than fasting metabolite concentrations over time.

AB - IntroductionIt is crucial to understand the factors that introduce variability before applying metabolomics to clinical and biomarker research.ObjectivesWe quantified technical and biological variability of both fasting and postprandial metabolite concentrations measured using H-1 NMR spectroscopy in plasma samples.MethodsIn the Netherlands Epidemiology of Obesity study (n = 6,671), 148 metabolite concentrations (101 metabolites belonging to lipoprotein subclasses) were measured under fasting and postprandial states (150 minutes after a mixed liquid meal). Technical variability was evaluated among 265 fasting and 851 postprandial samples, with the identical blood plasma sample being measured twice by the same laboratory protocol. Biological reproducibility was assessed by measuring 165 individuals twice across time for evaluation of short- (3 years) biological variability. Intra-class coefficients (ICCs) were used to assess variability. The ICCs of the fasting metabolites were compared with the postprandial metabolites using two-sided paired Wilcoxon test separately for short- and long-term measurements.ResultsBoth fasting and postprandial metabolite concentrations showed high technical reproducibility using H-1 NMR spectroscopy (median ICC = 0.99). Postprandial metabolite concentrations revealed slightly higher ICC scores than fasting ones in short-term repeat measures (median ICC in postprandial and fasting metabolite concentrations 0.72 versus 0.67, Wilcoxon p-value = 8.0x10(-14)). Variability did not increase further in a long-term repeat measure, with median ICC in postprandial of 0.64 and in fasting metabolite concentrations 0.66.ConclusionTechnical reproducibility is excellent. Biological reproducibility of postprandial metabolite concentrations showed a less or equal variability than fasting metabolite concentrations over time.

KW - EPIDEMIOLOGY

KW - METABOLOMICS

U2 - 10.1371/journal.pone.0218549

DO - 10.1371/journal.pone.0218549

M3 - Article

VL - 14

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

M1 - e0218549

ER -