Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry

Sei Harada, Akiyoshi Hirayama, Queenie Chan, Ayako Kurihara, Kota Fukai, Miho Iida, Suzuka Kato, Daisuke Sugiyama, Kazuyo Kuwabara, Ayano Takeuchi, Miki Akiyama, Tomonori Okamura, Timothy M.D. Ebbels, Paul Elliott, Masaru Tomita, Asako Sato, Chizuru Suzuki, Masahiro Sugimoto, Tomoyoshi Soga, Toru Takebayashi

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Abstract

Background Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. Methods Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. Results and conclusions In QC samples, coefficient of variation was less than 20% for 64 metabolites, and less than 30% for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20% for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95% confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.

Original languageEnglish
Article numbere0191230
JournalPLoS One
Volume13
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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Capillary electrophoresis
capillary electrophoresis
Capillary Electrophoresis
Metabolites
cohort studies
Mass spectrometry
Mass Spectrometry
Cohort Studies
mass spectrometry
metabolites
Plasmas
Metabolomics
Quality Control
metabolomics
Uric Acid
quality control
Quality control
Creatinine
uric acid
Independent Living

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry. / Harada, Sei; Hirayama, Akiyoshi; Chan, Queenie; Kurihara, Ayako; Fukai, Kota; Iida, Miho; Kato, Suzuka; Sugiyama, Daisuke; Kuwabara, Kazuyo; Takeuchi, Ayano; Akiyama, Miki; Okamura, Tomonori; Ebbels, Timothy M.D.; Elliott, Paul; Tomita, Masaru; Sato, Asako; Suzuki, Chizuru; Sugimoto, Masahiro; Soga, Tomoyoshi; Takebayashi, Toru.

In: PLoS One, Vol. 13, No. 1, e0191230, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry",
abstract = "Background Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. Methods Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. Results and conclusions In QC samples, coefficient of variation was less than 20{\%} for 64 metabolites, and less than 30{\%} for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20{\%} for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95{\%} confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.",
author = "Sei Harada and Akiyoshi Hirayama and Queenie Chan and Ayako Kurihara and Kota Fukai and Miho Iida and Suzuka Kato and Daisuke Sugiyama and Kazuyo Kuwabara and Ayano Takeuchi and Miki Akiyama and Tomonori Okamura and Ebbels, {Timothy M.D.} and Paul Elliott and Masaru Tomita and Asako Sato and Chizuru Suzuki and Masahiro Sugimoto and Tomoyoshi Soga and Toru Takebayashi",
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T1 - Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry

AU - Harada, Sei

AU - Hirayama, Akiyoshi

AU - Chan, Queenie

AU - Kurihara, Ayako

AU - Fukai, Kota

AU - Iida, Miho

AU - Kato, Suzuka

AU - Sugiyama, Daisuke

AU - Kuwabara, Kazuyo

AU - Takeuchi, Ayano

AU - Akiyama, Miki

AU - Okamura, Tomonori

AU - Ebbels, Timothy M.D.

AU - Elliott, Paul

AU - Tomita, Masaru

AU - Sato, Asako

AU - Suzuki, Chizuru

AU - Sugimoto, Masahiro

AU - Soga, Tomoyoshi

AU - Takebayashi, Toru

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. Methods Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. Results and conclusions In QC samples, coefficient of variation was less than 20% for 64 metabolites, and less than 30% for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20% for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95% confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.

AB - Background Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. Methods Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. Results and conclusions In QC samples, coefficient of variation was less than 20% for 64 metabolites, and less than 30% for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20% for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95% confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.

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