Imperial researchers demonstratedܾٲٲԻrobustnessofspecialisedspectroscopy formolecularanalysisof humansamples in a multi-laboratory trial.

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Robust clinical utility of molecular phenotyping

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Imperial researchers demonstratedܾٲٲԻrobustnessofspecialisedspectroscopy formolecularanalysisof humansamples in a multi-laboratory trial.

The Imperial College Phenome Centre (IPC) – the core facility of the ݮƵ Imperial BRC Molecular Phenomics Theme – led a multi-centre laboratory study to assess the precision and accuracy of measuring lipoprotein concentrations by NMR spectroscopy in human samples.

Lipoproteins are classified based on their density and size, into high-, low- and very low-density lipoproteins, and chylomicrons, which are composed of dietary fat triglycerides. Circulating lipoproteinsin blood, more commonly known as ‘cholesterol levels’, areroutinely measured in clinic and are used as an indicator of cardiovascular and other disorders. However standard examination has limitations with respect to turnaround time and the depth of information it provides.

Dr Beatriz Jiménez

Dr Beatriz Jiménez, NMR Manager at the IPC and lead author of the study, explained further: “NMR provides a more detailed picture than the routine laboratory analysis. It is also quick and relatively cheap. In a routine clinical lab only 3 parameters are measured. Alternatively,aspecialisedlab can provide a similarin-depthanalysis to the one obtained by NMR, however it takes almost 1 week per sample and is quite laborious. NMR allows the measurement of 112 relevant lipoprotein subfractions, orcholesterol levels’,with only a 4-minute experiment.”

Scientistsfrom five laboratories in three institutionsanalysed98blood serum and plasmasamplesusing 11 NMR spectrometersfollowingthe same protocols, while operators were not exchanged betweenlabs, even within same institutions.Study results,published in ,demonstratedexceptionalreproducibility of lipoproteinquantificationmeasured by NMR, compliantwith NCEPrequirements(National Cholesterol Education Program) for the measurement of lipids in certified clinical laboratories. In addition to lipoproteinamounts, quantification of 26 metabolites,including glucose, lactate, several aminoacids and creatinine,wasalso possible by using the same 4minute NMR measurement,with negligible analyticalvariation. However, the authors do caution that lower molecular weight metabolites would need to be considered on individual basis.

Extract from Figure 1, Jiménez et al, Anal. Chem. 90, 11962-11971 (2018)

As with most medical tests, inter-institutional reproducibility is crucial to avoid operator bias and to ensure wider NHS implementation.This work provides important evidence for reliable and reproducible use ofNMR spectroscopy in clinic, which can provide informative in-depth biochemical informationto aid clinical decision-making at patient level in most disorders where lipid metabolism is deregulated.


MolecularPhenomicsis anݮƵ Imperial BRC Cross-cutting Theme and forms part of ITMAT.

Publications
  • Analytical Chemistry