Journal article
Quantitative in-vitro diagnostic NMR spectroscopy for lipoprotein and metabolite measurements in plasma and serum: Recommendations for analytical artifact minimization with special reference to COVID-19/SARS-CoV-2 Samples
Journal of Proteome Research, Vol.19(11), pp.4428-4441
2020
Abstract
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.
Details
- Title
- Quantitative in-vitro diagnostic NMR spectroscopy for lipoprotein and metabolite measurements in plasma and serum: Recommendations for analytical artifact minimization with special reference to COVID-19/SARS-CoV-2 Samples
- Authors/Creators
- R.L. Loo (Author/Creator)S. Lodge (Author/Creator)T. Kimhofer (Author/Creator)S-H Bong (Author/Creator)S. Begum (Author/Creator)L. Whiley (Author/Creator)N. Gray (Author/Creator)J.C. Lindon (Author/Creator)P. Nitschke (Author/Creator)N.G. Lawler (Author/Creator)H. Schäfer (Author/Creator)M. Spraul (Author/Creator)T. Richards (Author/Creator)J.K. Nicholson (Author/Creator)E. Holmes (Author/Creator)
- Publication Details
- Journal of Proteome Research, Vol.19(11), pp.4428-4441
- Publisher
- American Chemical Society
- Identifiers
- 991005541262507891
- Copyright
- © 2020 American Chemical Society
- Murdoch Affiliation
- Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 2 Chemistry
- 2.211 Mass Spectrometry
- 2.211.990 Metabolomics
- Web Of Science research areas
- Biochemical Research Methods
- ESI research areas
- Biology & Biochemistry