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

Research output: Contribution to journalArticleAcademicpeer-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 1H 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- (<6 months) and long-term (>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 1H 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 = 8.0×10−14). 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
JournalPLoS ONE
Volume14
Issue number6
DOIs
Publication statusPublished - 2019

Cite this

Li-Gao, Ruifang ; Hughes, David A. ; le Cessie, Saskia ; de Mutsert, Renée ; den Heijer, Martin ; Rosendaal, Frits R. ; van Dijk, Ko Willems ; 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 = "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 1H 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- (<6 months) and long-term (>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 1H 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 = 8.0×10−14). 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.",
author = "Ruifang Li-Gao and Hughes, {David A.} and {le Cessie}, Saskia and {de Mutsert}, Ren{\'e}e and {den Heijer}, Martin and Rosendaal, {Frits R.} and {van Dijk}, {Ko Willems} and Timpson, {Nicholas J.} and Mook-Kanamori, {Dennis O.}",
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Li-Gao, R, Hughes, DA, le Cessie, S, de Mutsert, R, den Heijer, M, Rosendaal, FR, van Dijk, KW, 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.; le Cessie, Saskia; de Mutsert, Renée; den Heijer, Martin; Rosendaal, Frits R.; van Dijk, Ko Willems; Timpson, Nicholas J.; Mook-Kanamori, Dennis O.

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

Research output: Contribution to journalArticleAcademicpeer-review

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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 - le Cessie, Saskia

AU - de Mutsert, Renée

AU - den Heijer, Martin

AU - Rosendaal, Frits R.

AU - van Dijk, Ko Willems

AU - Timpson, Nicholas J.

AU - Mook-Kanamori, Dennis O.

PY - 2019

Y1 - 2019

N2 - 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 1H 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- (<6 months) and long-term (>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 1H 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 = 8.0×10−14). 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.

AB - 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 1H 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- (<6 months) and long-term (>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 1H 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 = 8.0×10−14). 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.

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