Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards

National Institute of Standards and Technology; Federico Torta; Nils Hoffmann; Bo Burla; Irina Alecu; Makoto Arita; Takeshi Bamba; Steffany A.L. Bennett; Justine Bertrand-Michel; Britta Brügger; Mónica P. Cala; Dolores Camacho-Muñoz; Antonio Checa; Michael Chen; Michaela Chocholoušková; Michelle Cinel; Emeline Chu-Van; Benoit Colsch; Cristina Coman; Lisa Connell; Bebiana C. Sousa; Alex M. Dickens; Maria Fedorova; Finnur Freyr Eiríksson; Hector Gallart-Ayala; Mohan Ghorasaini; Martin Giera; Xue Li Guan; Mark Haid; Thomas Hankemeier; Amy Harms; Marcus Höring; Michal Holčapek; Thorsten Hornemann; Chunxiu Hu; Andreas J. Hülsmeier; Kevin Huynh; Christina M. Jones; Julijana Ivanisevic; Yoshihiro Izumi; Harald C. Köfeler; Sin Man Lam; Mike Lange; Jong Cheol Lee; Gerhard Liebisch; Katrice Lippa; Andrea F. Lopez-Clavijo; Malena Manzi; Manuela R. Martinefski; Denise Wolrab; Robert Ahrends; Markus R. Wenk

doi:10.1038/s41467-024-52087-x

Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards

National Institute of Standards and Technology
, Federico Torta
, Nils Hoffmann
, Bo Burla
, Irina Alecu
, Makoto Arita
, Takeshi Bamba
, Steffany A.L. Bennett
, Justine Bertrand-Michel
, Britta Brügger
, Mónica P. Cala
, Dolores Camacho-Muñoz
, Antonio Checa
, Michael Chen
, Michaela Chocholoušková
, Michelle Cinel
, Emeline Chu-Van
, Benoit Colsch
, Cristina Coman
, Lisa Connell

Bebiana C. Sousa, Alex M. Dickens, Maria Fedorova, Finnur Freyr Eiríksson, Hector Gallart-Ayala, Mohan Ghorasaini, Martin Giera, Xue Li Guan, Mark Haid, Thomas Hankemeier, Amy Harms, Marcus Höring, Michal Holčapek, Thorsten Hornemann, Chunxiu Hu, Andreas J. Hülsmeier, Kevin Huynh, Christina M. Jones, Julijana Ivanisevic, Yoshihiro Izumi, Harald C. Köfeler, Sin Man Lam, Mike Lange, Jong Cheol Lee, Gerhard Liebisch, Katrice Lippa, Andrea F. Lopez-Clavijo, Malena Manzi, Manuela R. Martinefski, Denise Wolrab, Robert Ahrends (Corresponding author), Markus R. Wenk (Corresponding author)

Department of Analytical Chemistry

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

Original language	English
Article number	8562
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-52087-x
Publication status	Published - Dec 2024

Funding

1,2 Work in the MRW laboratory is supported by grants from the National University of Singapore via the Life Sciences Institute (LSI) and A*STAR IAF-ICP I1901E0040. 4 N.H. acknowledges support by de.NBI and the de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI) and ELIXIR-DE (Forschungszentrum J\u00FClich and W-de.NBI-001, W-de.NBI-004, W-de.NBI-008, W-de.NBI-010, W-de.NBI-013, W-de.NBI-014, W-de.NBI-016, W-de.NBI-022). 5 Bundesministerium fu\u0308r Bildung, Wissenschaft und Forschung\u201D BMBFW within the project DigiOmics4Austria. 6 Work in the SALB laboratory is supported by grants from the Canadian Institutes of Health Research and the Canadian Consortium on Neurodegeneration and Aging CAN-CIHR 163902 and PJT 183604. 7,8,55,56 H.T. was supported by JSPS KAKENHI (21K18216 to Hiroshi T.), the National Cancer Centre Research and Development Fund (2020-A-9, H.T.), and JST ERATO Grant (JPMJER2101 to H.T.). 9 This research is partly supported by AMED-BINDS (JP23ama121055), JST A-STEP (JPMJTR204J), JST-NBDC (JPMJND2305), and the MEXT Cooperative Research Project Program, Medical Research Center Initiative for High Depth Omics, and CURE:JPMXP1323015486 for the Medical Institute of Bioregulation, Kyushu University. 10 Work in MetaToul (Toulouse metabolomics & fluxomics facilities, www.mth-metatoul.com ) part of the French National Infrastructure for Metabolomics and Fluxomics is supported by MetaboHUB-ANR-11-INBS-0010 and Inserm (French National Institut for Research in Health). 13 Work at the University of Manchester supported in part by grants from the British Heart Foundation (PG/2019/34923) and BBSRC (BB/W006022/1). 16 Work at University of Pardubice was supported by grant No. 21-20238S (Czech Science Foundation) and ERC Adv grant No. 101095860 (European Research Council). 19 Work in the MTS department is supported by the MetaboHUB infrastructure (ANR-11-INBS-0010 grant). 21 BBSRC for funding to the Babraham Institute and to Michael Wakelam\u2019s memory for his life of contribution to the lipidomics world. 23 Mass spectrometeric analysis was performed at the Turku Metabolomics Centre with the support of Biocenter Finland. 24,25,26 This publication is based upon work from COST Action EpiLipidNET, Pan-European Network in Lipidomics and Epilipidomics (CA19105; https://www.epilipid.net ), supported by COST (European Cooperation in Science and Technology).\u201D 30 M.G. is an early-stage researcher supported by the H2020 ITN consortium ArthritisHeal (#812890). M.G. was partially supported by the NWO XOmics project #184.034.019. 31 Nanyang Assistant Professorship, Lee Kong Chian School of Medicine, Nanyang Technological University. 36 Supported by grants from the National Natural Science Foundation of China (21934006 and 22074144). 48 Ser Cymru Project Sepsis grant funded by Welsh Government/EU-ERDF (VJT, VBO). 51,52 Supported by the Tohoku Medical Megabank Project from MEXT, the Japan Agency for Medical Research and Development (AMED; under grant numbers JP20km0105001 and JP21tm0124005) and KAKENHI Grant Number JP23H02625 [D.S.]. 54 The Christian Doppler Laboratory for Innovative Gut Health Concepts of Livestock has been funded by the Austrian Federal Ministry for Digital and Economic Affairs, the Austrian National Foundation for Research, Technology and Development as well as BIOMIN Holding GmbH, which is part of DSM. The authors also thank Marco Reiter for technical support. The participants would like to acknowledge Clay Davis from the National Institute of Standards and Technology. B.B. would like to acknowledge Christian Luechtenborg for his contribution to this project. 1,2 Work in the MRW laboratory is supported by grants from the National University of Singapore via the Life Sciences Institute (LSI) and A*STAR IAF-ICP I1901E0040. 4 N.H. acknowledges support by de.NBI and the de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI) and ELIXIR-DE (Forschungszentrum J\u00FClich and W-de.NBI-001, W-de.NBI-004, W-de.NBI-008, W-de.NBI-010, W-de.NBI-013, W-de.NBI-014, W-de.NBI-016, W-de.NBI-022). 5\u00A0Bundesministerium fu\u0308r Bildung, Wissenschaft und Forschung\u201D BMBFW within the project DigiOmics4Austria. 6 Work in the SALB laboratory is supported by grants from the Canadian Institutes of Health Research and the Canadian Consortium on Neurodegeneration and Aging CAN-CIHR 163902 and PJT 183604. 7,8,55,56 H.T. was supported by JSPS KAKENHI (21K18216 to Hiroshi T.), the National Cancer Centre Research and Development Fund (2020-A-9, H.T.), and JST ERATO Grant (JPMJER2101 to H.T.). 9 This research is partly supported by AMED-BINDS (JP23ama121055), JST A-STEP (JPMJTR204J), JST-NBDC (JPMJND2305), and the MEXT Cooperative Research Project Program, Medical Research Center Initiative for High Depth Omics, and CURE:JPMXP1323015486 for the Medical Institute of Bioregulation, Kyushu University. 10 Work in MetaToul (Toulouse metabolomics & fluxomics facilities, www.mth-metatoul.com) part of the French National Infrastructure for Metabolomics and Fluxomics is supported by MetaboHUB-ANR-11-INBS-0010 and Inserm (French National Institut for Research in Health). 13 Work at the University of Manchester supported in part by grants from the British Heart Foundation (PG/2019/34923) and BBSRC (BB/W006022/1). 16 Work at University of Pardubice was supported by grant No. 21-20238S (Czech Science Foundation) and ERC Adv grant No. 101095860 (European Research Council). 19 Work in the MTS department is supported by the MetaboHUB infrastructure (ANR-11-INBS-0010 grant). 21 BBSRC for funding to the Babraham Institute and to Michael Wakelam\u2019s memory for his life of contribution to the lipidomics world.\u00A023 Mass spectrometeric analysis was performed at the Turku Metabolomics Centre with the support of Biocenter Finland. 24,25,26 This publication is based upon work from COST Action EpiLipidNET, Pan-European Network in Lipidomics and Epilipidomics (CA19105; https://www.epilipid.net), supported by COST (European Cooperation in Science and Technology).\u201D 30 M.G. is an early-stage researcher supported by the H2020 ITN consortium ArthritisHeal (#812890). M.G. was partially supported by the NWO XOmics project #184.034.019. 31 Nanyang Assistant Professorship, Lee Kong Chian School of Medicine, Nanyang Technological University. 36 Supported by grants from the National Natural Science Foundation of China (21934006 and 22074144).\u00A048 Ser Cymru Project Sepsis grant funded by Welsh Government/EU-ERDF (VJT, VBO). 51,52 Supported by the Tohoku Medical Megabank Project from MEXT, the Japan Agency for Medical Research and Development (AMED; under grant numbers JP20km0105001 and JP21tm0124005) and KAKENHI Grant Number JP23H02625 [D.S.]. 54 The Christian Doppler Laboratory for Innovative Gut Health Concepts of Livestock has been funded by the Austrian Federal Ministry for Digital and Economic Affairs, the Austrian National Foundation for Research, Technology and Development as well as BIOMIN Holding GmbH, which is part of DSM. The authors also thank Marco Reiter for technical support. The participants would like to acknowledge Clay Davis from the National Institute of Standards and Technology. B.B. would like to acknowledge Christian Luechtenborg for his contribution to this project.

Austrian Fields of Science 2012

301302 Lipidomics research
104002 Analytical chemistry

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10.1038/s41467-024-52087-x

Cite this

National Institute of Standards and Technology, Torta, F., Hoffmann, N., Burla, B., Alecu, I., Arita, M., Bamba, T., Bennett, S. A. L., Bertrand-Michel, J., Brügger, B., Cala, M. P., Camacho-Muñoz, D., Checa, A., Chen, M., Chocholoušková, M., Cinel, M., Chu-Van, E., Colsch, B., Coman, C., ... Wenk, M. R. (2024). Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards. Nature Communications, 15(1), Article 8562. https://doi.org/10.1038/s41467-024-52087-x

@article{054ad9ba670a477589c7f49775ff013d,

title = "Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards",

abstract = "In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2\%) and concordant (inter-laboratory CVs < 14\%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.",

author = "\{National Institute of Standards and Technology\} and Federico Torta and Nils Hoffmann and Bo Burla and Irina Alecu and Makoto Arita and Takeshi Bamba and Bennett, \{Steffany A.L.\} and Justine Bertrand-Michel and Britta Br{\"u}gger and Cala, \{M{\'o}nica P.\} and Dolores Camacho-Mu{\~n}oz and Antonio Checa and Michael Chen and Michaela Chocholou{\v s}kov{\'a} and Michelle Cinel and Emeline Chu-Van and Benoit Colsch and Cristina Coman and Lisa Connell and Sousa, \{Bebiana C.\} and Dickens, \{Alex M.\} and Maria Fedorova and Eir{\'i}ksson, \{Finnur Freyr\} and Hector Gallart-Ayala and Mohan Ghorasaini and Martin Giera and Guan, \{Xue Li\} and Mark Haid and Thomas Hankemeier and Amy Harms and Marcus H{\"o}ring and Michal Hol{\v c}apek and Thorsten Hornemann and Chunxiu Hu and H{\"u}lsmeier, \{Andreas J.\} and Kevin Huynh and Jones, \{Christina M.\} and Julijana Ivanisevic and Yoshihiro Izumi and K{\"o}feler, \{Harald C.\} and Lam, \{Sin Man\} and Mike Lange and Lee, \{Jong Cheol\} and Gerhard Liebisch and Katrice Lippa and Lopez-Clavijo, \{Andrea F.\} and Malena Manzi and Martinefski, \{Manuela R.\} and Denise Wolrab and Robert Ahrends and Wenk, \{Markus R.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024. Accession Number WOS:001328657100031 PubMed ID 39362843 ",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-52087-x",

language = "English",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "NATURE PUBLISHING GROUP",

number = "1",

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National Institute of Standards and Technology, Torta, F, Hoffmann, N, Burla, B, Alecu, I, Arita, M, Bamba, T, Bennett, SAL, Bertrand-Michel, J, Brügger, B, Cala, MP, Camacho-Muñoz, D, Checa, A, Chen, M, Chocholoušková, M, Cinel, M, Chu-Van, E, Colsch, B, Coman, C, Connell, L, Sousa, BC, Dickens, AM, Fedorova, M, Eiríksson, FF, Gallart-Ayala, H, Ghorasaini, M, Giera, M, Guan, XL, Haid, M, Hankemeier, T, Harms, A, Höring, M, Holčapek, M, Hornemann, T, Hu, C, Hülsmeier, AJ, Huynh, K, Jones, CM, Ivanisevic, J, Izumi, Y, Köfeler, HC, Lam, SM, Lange, M, Lee, JC, Liebisch, G, Lippa, K, Lopez-Clavijo, AF, Manzi, M, Martinefski, MR, Wolrab, D, Ahrends, R & Wenk, MR 2024, 'Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards', Nature Communications, vol. 15, no. 1, 8562. https://doi.org/10.1038/s41467-024-52087-x

TY - JOUR

T1 - Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards

AU - National Institute of Standards and Technology

AU - Torta, Federico

AU - Hoffmann, Nils

AU - Burla, Bo

AU - Alecu, Irina

AU - Arita, Makoto

AU - Bamba, Takeshi

AU - Bennett, Steffany A.L.

AU - Bertrand-Michel, Justine

AU - Brügger, Britta

AU - Cala, Mónica P.

AU - Camacho-Muñoz, Dolores

AU - Checa, Antonio

AU - Chen, Michael

AU - Chocholoušková, Michaela

AU - Cinel, Michelle

AU - Chu-Van, Emeline

AU - Colsch, Benoit

AU - Coman, Cristina

AU - Connell, Lisa

AU - Sousa, Bebiana C.

AU - Dickens, Alex M.

AU - Fedorova, Maria

AU - Eiríksson, Finnur Freyr

AU - Gallart-Ayala, Hector

AU - Ghorasaini, Mohan

AU - Giera, Martin

AU - Guan, Xue Li

AU - Haid, Mark

AU - Hankemeier, Thomas

AU - Harms, Amy

AU - Höring, Marcus

AU - Holčapek, Michal

AU - Hornemann, Thorsten

AU - Hu, Chunxiu

AU - Hülsmeier, Andreas J.

AU - Huynh, Kevin

AU - Jones, Christina M.

AU - Ivanisevic, Julijana

AU - Izumi, Yoshihiro

AU - Köfeler, Harald C.

AU - Lam, Sin Man

AU - Lange, Mike

AU - Lee, Jong Cheol

AU - Liebisch, Gerhard

AU - Lippa, Katrice

AU - Lopez-Clavijo, Andrea F.

AU - Manzi, Malena

AU - Martinefski, Manuela R.

AU - Wolrab, Denise

AU - Ahrends, Robert

AU - Wenk, Markus R.

PY - 2024/12

Y1 - 2024/12

N2 - In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

AB - In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

UR - https://www.scopus.com/pages/publications/85205605136

U2 - 10.1038/s41467-024-52087-x

DO - 10.1038/s41467-024-52087-x

M3 - Article

C2 - 39362843

AN - SCOPUS:85205605136

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 8562

ER -

Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards

Abstract

Funding

Austrian Fields of Science 2012

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