Cross-Laboratory Standardization of Preclinical Lipidomics Using Differential Mobility Spectrometry and Multiple Reaction Monitoring

Mohan Ghorasaini, Yassene Mohammed, Jerzy Adamski, Lisa Bettcher, John A. Bowden, Matias Cabruja, Kévin Contrepois, Mathew Ellenberger, Bharat Gajera, Mark Haid, Daniel Hornburg, Christie Hunter, Christina M. Jones, Theo Klein, Oleg Mayboroda, Mina Mirzaian, Ruin Moaddel, Luigi Ferrucci, Jacqueline Lovett, Kenneth NazirMackenzie Pearson, Baljit K. Ubhi, Daniel Raftery, Fabien Riols, Rebekah Sayers, Eric J.G. Sijbrands, Michael P. Snyder, Baolong Su, Vidya Velagapudi, Kevin J. Williams, Yolanda B. De Rijke, Martin Giera*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

Modern biomarker and translational research as well as personalized health care studies rely heavily on powerful omics' technologies, including metabolomics and lipidomics. However, to translate metabolomics and lipidomics discoveries into a high-throughput clinical setting, standardization is of utmost importance. Here, we compared and benchmarked a quantitative lipidomics platform. The employed Lipidyzer platform is based on lipid class separation by means of differential mobility spectrometry with subsequent multiple reaction monitoring. Quantitation is achieved by the use of 54 deuterated internal standards and an automated informatics approach. We investigated the platform performance across nine laboratories using NIST SRM 1950-Metabolites in Frozen Human Plasma, and three NIST Candidate Reference Materials 8231-Frozen Human Plasma Suite for Metabolomics (high triglyceride, diabetic, and African-American plasma). In addition, we comparatively analyzed 59 plasma samples from individuals with familial hypercholesterolemia from a clinical cohort study. We provide evidence that the more practical methyl-tert-butyl ether extraction outperforms the classic Bligh and Dyer approach and compare our results with two previously published ring trials. In summary, we present standardized lipidomics protocols, allowing for the highly reproducible analysis of several hundred human plasma lipids, and present detailed molecular information for potentially disease relevant and ethnicity-related materials.

Original languageEnglish
Pages (from-to)16369-16378
Number of pages10
JournalAnalytical Chemistry
Volume93
Issue number49
DOIs
Publication statusPublished - 14 Dec 2021

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