Quantitative In-Vitro Diagnostic NMR Spectroscopy for Lipoprotein and Metabolite Measurements in Plasma and Serum: Recommendations for Analytical Artefact Minimization with Special Reference to COVID-19/SARS-CoV-2 Samples.,Journal of Proteome Research

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Quantitative In-Vitro Diagnostic NMR Spectroscopy for Lipoprotein and Metabolite Measurements in Plasma and Serum: Recommendations for Analytical Artefact Minimization with Special Reference to COVID-19/SARS-CoV-2 Samples.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-08-27 , DOI: 10.1021/acs.jproteome.0c00537
Ruey Leng Loo _{1,

2} , Samantha Lodge _{1,

2} , Torben Kimhofer _{1,

2} , Sze-How Bong ₁ , Sofina Begum ₃ , Luke Whiley _{1,

2,

4} , Nicola Gray _{1,

2} , John C Lindon _{2,

5} , Philipp Nitschke _{1,

2} , Nathan G Lawler _{1,

2} , Hartmut Schäfer ₆ , Manfred Spraul ₆ , Toby Richards _{7,

8} , Jeremy K Nicholson _{1,

2,

7,

9} , Elaine Holmes _{1,

2,

3}

Affiliation

Australian National Phenome Centre, Health Futures Institute, Murdoch University, Harry Perkins Building, Perth, WA 6150, Australia.
Center for Computational and Systems Medicine, Health Futures Institute, Murdoch University, Murdoch, Perth, WA 6150, Australia.
Section for Nutrition Research, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW72AZ, U.K.
Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia.
Department of Metabolism, Nutrition and Reproduction, Imperial College London, Sir Alexander Fleming Building, London SW72AZ, U.K.
Biospin GmbH, Silberstreifen, 76287 Rheinstetten, Germany.
Division of Surgery, Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Harry Perkins Building, Robert Warren Drive, Murdoch, Perth, WA 6150, Australia.
Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Harry Perkins Building, Murdoch, Perth, WA 6150, Australia.
Institute of Global Health Innovation, Imperial College London, Level 1, Faculty Building, South Kensington Campus, London SW72NA, U.K.

Quantitative nuclear magnetic resonance (NMR) spectroscopy of blood plasma is widely used to investigate perturbed metabolic processes in human diseases. The reliability of biochemical data derived from these measurements is dependent on the quality of the sample collection and exact preparation and analysis protocols. Here, we describe systematically, the impact of variations in sample collection and preparation on information recovery from quantitative proton (¹H) NMR spectroscopy of human blood plasma and serum. The effects of variation of blood collection tube sizes and preservatives, successive freeze–thaw cycles, sample storage at −80 °C, and short-term storage at 4 and 20 °C on the quantitative lipoprotein and metabolite patterns were investigated. Storage of plasma samples at 4 °C for up to 48 h, freezing at −80 °C and blood sample collection tube choice have few and minor effects on quantitative lipoprotein profiles, and even storage at 4 °C for up to 168 h caused little information loss. In contrast, the impact of heat-treatment (56 °C for 30 min), which has been used for inactivation of SARS-CoV-2 and other viruses, that may be required prior to analytical measurements in low level biosecurity facilities induced marked changes in both lipoprotein and low molecular weight metabolite profiles. It was conclusively demonstrated that this heat inactivation procedure degrades lipoproteins and changes metabolic information in complex ways. Plasma from control individuals and SARS-CoV-2 infected patients are differentially altered resulting in the creation of artifactual pseudo-biomarkers and destruction of real biomarkers to the extent that data from heat-treated samples are largely uninterpretable. We also present several simple blood sample handling recommendations for optimal NMR-based biomarker discovery investigations in SARS CoV-2 studies and general clinical biomarker research.

中文翻译：

用于血浆和血清中脂蛋白和代谢物测量的定量体外诊断 NMR 波谱分析：分析伪影最小化的建议，特别参考 COVID-19/SARS-CoV-2 样本。

血浆定量核磁共振（NMR）波谱广泛用于研究人类疾病中的代谢过程扰动。从这些测量中得出的生化数据的可靠性取决于样品采集的质量以及精确的制备和分析方案。在这里，我们系统地描述了样品采集和制备过程中的变化对人血浆和血清定量质子 ( ^{1 H) NMR 光谱信息恢复的影响。}研究了采血管尺寸和防腐剂的变化、连续冻融循环、-80°C 样品储存以及 4 和 20°C 短期储存对定量脂蛋白和代谢物模式的影响。血浆样本在 4 °C 下保存长达 48 小时、-80 °C 冷冻以及血液样本采集管的选择对定量脂蛋白谱的影响很小且很小，甚至在 4 °C 下保存长达 168 小时也几乎没有造成什么影响。信息丢失。相比之下，在低水平生物安全设施中进行分析测量之前可能需要的热处理（56°C，30 分钟）已用于灭活 SARS-CoV-2 和其他病毒，其影响引起了显着变化脂蛋白和低分子量代谢物谱。最终证明，这种热灭活过程会降解脂蛋白并以复杂的方式改变代谢信息。对照个体和 SARS-CoV-2 感染患者的血浆发生了差异性改变，导致人为的伪生物标志物的产生和真实生物标志物的破坏，以至于热处理样本的数据在很大程度上无法解释。我们还提出了一些简单的血液样本处理建议，用于 SARS CoV-2 研究和一般临床生物标志物研究中基于 NMR 的最佳生物标志物发现研究。

更新日期：2020-08-27

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