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      MS-based lipidomics of human blood plasma: a community-initiated position paper to develop accepted guidelines 1

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      * , , †† , § , , * , || , # , $ , ** , , †† , §§ , || , ‡‡ , |||| , ## , $$ , 2 , *** , || , ††† , §§§ , 2 , * , ||
      Journal of Lipid Research
      The American Society for Biochemistry and Molecular Biology
      clinical trials, diagnostic tools, lipids, mass spectrometry, absolute concentrations, clinical research, data sharing, National Institute of Standards and Technology Standard Reference Material 1950, quality control

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          Abstract

          Human blood is a self-regenerating lipid-rich biological fluid that is routinely collected in hospital settings. The inventory of lipid molecules found in blood plasma (plasma lipidome) offers insights into individual metabolism and physiology in health and disease. Disturbances in the plasma lipidome also occur in conditions that are not directly linked to lipid metabolism; therefore, plasma lipidomics based on MS is an emerging tool in an array of clinical diagnostics and disease management. However, challenges exist in the translation of such lipidomic data to clinical applications. These relate to the reproducibility, accuracy, and precision of lipid quantitation, study design, sample handling, and data sharing. This position paper emerged from a workshop that initiated a community-led process to elaborate and define a set of generally accepted guidelines for quantitative MS-based lipidomics of blood plasma or serum, with harmonization of data acquired on different instrumentation platforms across independent laboratories as an ultimate goal. We hope that other fields may benefit from and follow such a precedent.

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          A rapid method of total lipid extraction and purification.

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            Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics.

            Accurate profiling of lipidomes relies upon the quantitative and unbiased recovery of lipid species from analyzed cells, fluids, or tissues and is usually achieved by two-phase extraction with chloroform. We demonstrated that methyl-tert-butyl ether (MTBE) extraction allows faster and cleaner lipid recovery and is well suited for automated shotgun profiling. Because of MTBE's low density, lipid-containing organic phase forms the upper layer during phase separation, which simplifies its collection and minimizes dripping losses. Nonextractable matrix forms a dense pellet at the bottom of the extraction tube and is easily removed by centrifugation. Rigorous testing demonstrated that the MTBE protocol delivers similar or better recoveries of species of most all major lipid classes compared with the "gold-standard" Folch or Bligh and Dyer recipes.
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              MassBank: a public repository for sharing mass spectral data for life sciences.

              MassBank is the first public repository of mass spectra of small chemical compounds for life sciences (<3000 Da). The database contains 605 electron-ionization mass spectrometry (EI-MS), 137 fast atom bombardment MS and 9276 electrospray ionization (ESI)-MS(n) data of 2337 authentic compounds of metabolites, 11 545 EI-MS and 834 other-MS data of 10,286 volatile natural and synthetic compounds, and 3045 ESI-MS(2) data of 679 synthetic drugs contributed by 16 research groups (January 2010). ESI-MS(2) data were analyzed under nonstandardized, independent experimental conditions. MassBank is a distributed database. Each research group provides data from its own MassBank data servers distributed on the Internet. MassBank users can access either all of the MassBank data or a subset of the data by specifying one or more experimental conditions. In a spectral search to retrieve mass spectra similar to a query mass spectrum, the similarity score is calculated by a weighted cosine correlation in which weighting exponents on peak intensity and the mass-to-charge ratio are optimized to the ESI-MS(2) data. MassBank also provides a merged spectrum for each compound prepared by merging the analyzed ESI-MS(2) data on an identical compound under different collision-induced dissociation conditions. Data merging has significantly improved the precision of the identification of a chemical compound by 21-23% at a similarity score of 0.6. Thus, MassBank is useful for the identification of chemical compounds and the publication of experimental data. 2010 John Wiley & Sons, Ltd.
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                Author and article information

                Journal
                J Lipid Res
                J. Lipid Res
                jlr
                jlr
                jlr
                Journal of Lipid Research
                The American Society for Biochemistry and Molecular Biology
                0022-2275
                1539-7262
                October 2018
                16 August 2018
                16 August 2018
                : 59
                : 10
                : 2001-2017
                Affiliations
                Singapore Lipidomics Incubator (SLING), Life Sciences Institute, [* ] National University of Singapore , Singapore
                Department of Biochemistry, YLL School of Medicine, [|| ] National University of Singapore , Singapore
                Laboratory for Metabolomics, [] RIKEN Center for Integrative Medical Sciences , Yokohama, Japan
                Cellular and Molecular Epigenetics Laboratory, [†† ] Graduate School of Medical Life Science, Yokohama City University , Yokohama, Japan
                Division of Physiological Chemistry and Metabolism, [§ ] Keio University Faculty of Pharmacy, Tokyo, Japan
                National Institute of Genetics , [] Shizuoka, Japan and RIKEN Center for Sustainable Resource Science , Yokohama, Japan
                Departments of Pharmacology and Chemistry and Biochemistry, [# ] School of Medicine, University of California at San Diego , La Jolla, CA
                Lipidomics Consulting Ltd. , [$ ] Esbo, Finland
                Barshop Institute for Longevity and Aging Studies and Department of Medicine-Diabetes, [** ] University of Texas Health Science Center at San Antonio , San Antonio, TX
                Institute of Clinical Chemistry and Laboratory Medicine, [§§ ] University of Regensburg , Regensburg, Germany
                Department of Laboratory Medicine, [‡‡ ] National University Hospital , Singapore
                Baker Heart and Diabetes Institute , [|||| ] Melbourne, Victoria, Australia
                Turku Centre for Biotechnology, [## ] University of Turku and Åbo Akademi University , Turku, Finland and School of Medical Sciences, Örebro University , Örebro, Sweden
                Departments of Pharmacology and Medicine, [$$ ] School of Medicine, University of California at San Diego , La Jolla, CA
                Max Planck Institute of Molecular Cell Biology and Genetics , [*** ] Dresden, Germany
                Babraham Institute , [††† ] Cambridge, United Kingdom
                Division of Physiological Chemistry 2, [§§§ ] Department of Medical Biochemistry and Biophysics, Karolinska Institute , Stockholm, Sweden
                Author notes
                [1]

                Guest editor for this article was Arthur A. Spector, the National Institutes of Health, Bethesda, MD.

                [2 ]To whom correspondence should be addressed. e-mail: bchmrw@ 123456nus.edu.sg (M.R.W.); shevchenko@ 123456mpi-cbg.de (A.S.)
                Author information
                http://orcid.org/0000-0002-5918-3249
                http://orcid.org/0000-0001-8198-6104
                http://orcid.org/0000-0002-3050-634X
                http://orcid.org/0000-0003-3738-3140
                http://orcid.org/0000-0001-6810-4736
                http://orcid.org/0000-0002-8615-2413
                http://orcid.org/0000-0003-4886-0811
                http://orcid.org/0000-0002-2593-4665
                http://orcid.org/0000-0002-2856-9165
                http://orcid.org/0000-0001-8950-9169
                http://orcid.org/0000-0002-5079-1109
                http://orcid.org/0000-0001-7545-7484
                http://orcid.org/0000-0002-8113-0653
                http://orcid.org/0000-0001-5447-7881
                Article
                s087163
                10.1194/jlr.S087163
                6168311
                30115755
                47926ffc-5b41-4ab9-9d42-bcfb4feece41
                Copyright © 2018 Burla et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.

                Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license.

                History
                : 26 May 2018
                : 11 August 2018
                Funding
                Funded by: National University of Singapore, open-funder-registry 10.13039/501100001352;
                Funded by: National Research Foundation Singapore, open-funder-registry 10.13039/501100001381;
                Award ID: NRFI2015-05
                Funded by: Deutsche Forschungsgemeinschaft, open-funder-registry 10.13039/501100001659;
                Funded by: Bundesministerium für Bildung und Forschung, open-funder-registry 10.13039/501100002347;
                Funded by: Swedish Heart-Lung Foundation, open-funder-registry 10.13039/501100003793;
                Award ID: 20170734
                Award ID: 20170603
                Funded by: Swedish Research Council, open-funder-registry 10.13039/501100004359;
                Award ID: 2016-02798
                Funded by: Foundation for the National Institutes of Health, open-funder-registry 10.13039/100000009;
                Award ID: U54 GM069338
                Award ID: RO1 GM20501-41
                Funded by: Japan Agency for Medical Research and Development
                Award ID: JP18gm5910001
                Funded by: Japan Society for the Promotion of Science, open-funder-registry 10.13039/501100000646;
                Award ID: 15H05897
                Award ID: 15H05898
                Funded by: Japan Society for the Promotion of Science, open-funder-registry 10.13039/501100000646;
                Award ID: 15H05897
                Award ID: 17H03621
                Funded by: Japan Agency for Medical Research and Development, open-funder-registry 10.13039/100009619;
                Award ID: 17gm0910005h0403
                Award ID: 17gm1010006h0001
                Funded by: National Bioscience Database Center, open-funder-registry 10.13039/501100004696;
                Funded by: Biotechnology and Biological Sciences Research Council, open-funder-registry 10.13039/501100000268;
                Award ID: BB/P013384/1
                Funded by: Medical Research Council, open-funder-registry 10.13039/501100000265;
                Award ID: MR/M004821/1
                Funded by: Academy of Finland, open-funder-registry 10.13039/501100002341;
                Award ID: 292568
                Funded by: European Commission, open-funder-registry 10.13039/501100000780;
                Award ID: 777377
                Funded by: National Institute of General Medical Sciences, open-funder-registry 10.13039/100000057;
                Award ID: R01 GM105724
                Categories
                Patient-Oriented and Epidemiological Research

                Biochemistry
                clinical trials,diagnostic tools,lipids,mass spectrometry,absolute concentrations,clinical research,data sharing,national institute of standards and technology standard reference material 1950,quality control

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