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Influence of preanalytical sampling conditions on the 1H NMR metabolic profile of human blood plasma and introduction of the Standard PREanalytical Code used in biobanking

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Abstract

Variations in sample collection, processing and storage within the field of clinical metabolomics might hamper its effective implementation. In this study, the impact of relevant preanalytical conditions on the plasma 1H NMR metabolic profile was examined. The biobanking community recently developed a method for coding preanalytical conditions called the Standard PREanalytical Code (SPREC). It is envisaged that SPREC will ultimately identify which samples are fit for a particular analysis, based on prior validation by a panel of experts in the respective field. In an effort to validate SPREC for 1H NMR plasma metabolomics, we have coded the conditions used here, when possible, according to SPREC and evaluated its power to identify preanalytical conditions that affect the plasma 1H NMR metabolic profile. From all preanalytical conditions studied, only prolonged processing delays (3 and 8 h) have a significant impact on the plasma 1H NMR metabolic profile as compared to the reference condition (30 min). Principal component analysis shows a clear systematic shift as a function of increasing processing delay. Nevertheless, the inter-individual variation is clearly much larger than this preanalytical variation, indicating that the impact on multivariate group classification will be minimal. Nonetheless, we recommend to keep the time gap between blood collection and centrifugation similar for all samples within a study. The implementation of SPREC within clinical metabolomics allows for an appropriate sample encoding and exclusion of samples that were subjected to unwanted, interfering preanalytical conditions. Without doubt, it will contribute to the validation of 1H NMR metabolomics in clinical, biobank and multicenter research settings.

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Abbreviations

1H:

Proton

CPMG:

Carr-Purcell-Meiboom-Gill

D2O:

Deuterium oxide

EDTA:

Ethylenediaminetetraacetic acid

FID:

Free induction decay

LC:

Liquid chromatography

LiHe:

Lithium-heparin

LN2 :

Liquid nitrogen

MHz:

Megahertz

MS:

Mass spectrometry

NMR:

Nuclear magnetic resonance

PC:

Principal component

PCA:

Principal component analysis

ppm:

Parts per million

RT:

Room temperature

SOP:

Standard operating procedure

SPREC:

Standard PREanalytical Code

TSP:

Trimethylsilyl-2,2,3,3-tetradeuteropropionic acid

VAR:

Variable

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Acknowledgments

This study is part of the ‘Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa’, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. We thank the Research Foundation Flanders for supporting via the MULTIMAR project. We thank Bogaers A., Pousset V., Rutten I., Penders J. and Reynders C. for their assistance.

Conflict of interest

All authors ‘Liene Bervoets, Evelyne Louis, Gunter Reekmans, Liesbet Mesotten, Michiel Thomeer, Peter Adriaensens and Loes Linsen’ declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Correspondence to Peter Adriaensens.

Additional information

Liene Bervoets and Evelyne Louis contributed equally to this work.

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Bervoets, L., Louis, E., Reekmans, G. et al. Influence of preanalytical sampling conditions on the 1H NMR metabolic profile of human blood plasma and introduction of the Standard PREanalytical Code used in biobanking. Metabolomics 11, 1197–1207 (2015). https://doi.org/10.1007/s11306-015-0774-y

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