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

doi:10.1371/journal.pone.0218549

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

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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 language	English
Article number	e0218549
Number of pages	14
Journal	PLoS ONE
Volume	14
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0218549
Publication status	Published - 20 Jun 2019

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Bristol Population Health Science Institute

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Li-Gao, R., Hughes, D. A., le Cessie, S., de Mutsert, R., den Heijer, M., Rosendaal, F. R., Willems van Dijk, K., Timpson, N. J., & 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

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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 {Willems van Dijk}, Ko and Timpson, {Nicholas J} and Mook-Kanamori, {Dennis O}",

year = "2019",

month = jun,

day = "20",

doi = "10.1371/journal.pone.0218549",

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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 - Willems van Dijk, Ko

AU - Timpson, Nicholas J

AU - Mook-Kanamori, Dennis O

PY - 2019/6/20

Y1 - 2019/6/20

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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DO - 10.1371/journal.pone.0218549

M3 - Article (Academic Journal)

C2 - 31220183

VL - 14

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

M1 - e0218549

ER -

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

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

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