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bioRxiv · 10.1101/513903

The effect of pre-analytical conditions on blood metabolomics in epidemiological studies

Santos Ferreira, D. L.·Maple, H.·Goodwin, M.·Brand, J. S.·Yip, V.·Min, J. L.·Groom, A.·Lawlor, D. A.·Ring, S.
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Abstract

BackgroundSerum and plasma are commonly used biofluids for large-scale metabolomic-epidemiology studies. Their metabolomic profile is susceptible to changes due to variability in pre-analytical conditions and the impact of this is unclear.\n\nMethodsParticipant-matched EDTA-plasma and serum samples were collected from 37 non-fasting volunteers and profiled using a targeted nuclear magnetic resonance (NMR) metabolomics platform (N=151 traits). Metabolic concentrations were compared between reference (pre-storage: 4{degrees}C, 1.5h; post-storage: no sample preparation or NMR-analysis delays) and four, pre-storage, blood processing conditions, where samples were incubated at (i) 4{degrees}C, 24h; (ii) 4{degrees}C, 48h; (iii) 21{degrees}C, 24h; (iv) 21{degrees}C, 48h, before centrifugation; and two, post-storage, sample processing conditions in which samples (i) thawed overnight, then left for 24h before addition of sodium buffer followed by immediate NMR analysis; (ii) thawed overnight, addition of sodium buffer, then left for 24h before profiling. Linear regression models with random-intercepts were used to assess the impact of these six pre-analytical conditions on EDTA-plasma/serum metabolome.\n\nResultsFatty acids, beta-hydroxybutyrate, glycoprotein-acetyls and most lipid-related traits, in serum and plasma, were robust to the tested pre and post-storage conditions. Pre-storage conditions impacted concentrations of glycolysis metabolites, acetate, albumin and amino-acids by levels that could potentially bias research results (up to 1.4SD difference compared with reference). Post-storage conditions affected histidine, phenylalanine and LDL-particle-size, with differences up to 1.4SD.\n\nConclusionsMost metabolic traits are robust to the pre- and post-storage conditions tested here and that may commonly occur in large-scale cohorts. However, concentrations of glycolysis metabolites, and amino-acids may be compromised.\n\nKey messagesO_LIIn large scale epidemiological studies, blood processing delays, incubation at high temperature prior to long term storage, and NMR profiling delays after long term storage, may occur.\nC_LIO_LIConcentrations of fatty acids, beta-hydroxybutyrate, glycoprotein acetyls and most lipid-related traits are robust to variations in pre-storage temperature and duration of incubation (4{degrees}C or 21{degrees}C for up to 48h prior to centrifugation) and post-storage sample handling (24h delay in sample preparation or NMR profiling).\nC_LIO_LIGlycolytic metabolite concentrations are altered by pre-storage conditions and amino-acids, particularly histidine and phenylalanine, by both, pre and post-storage conditions.\nC_LI

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Santos Ferreira, D. L., Maple, H., Goodwin, M., Brand, J. S., Yip, V., Min, J. L., Groom, A., Lawlor, D. A., Ring, S.. 2019-01-08. The effect of pre-analytical conditions on blood metabolomics in epidemiological studies. https://doi.org/10.1101/513903

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