Imperial College London
Alternate

ProfessorElaineHolmes

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lodge:2021:10.1021/acs.analchem.0c04952,
author = {Lodge, S and Nitschke, P and Kimhofer, T and Wist, J and Bong, S-H and Loo, RL and Masuda, R and Begum, S and Richards, T and Lindon, JC and Bermel, W and Reinsperger, T and Schaefer, H and Spraul, M and Holmes, E and Nicholson, JK},
doi = {10.1021/acs.analchem.0c04952},
journal = {Analytical Chemistry},
pages = {3976--3986},
title = {Diffusion and relaxation edited proton NMR spectroscopy of plasma reveals a high-fidelity supramolecular biomarker signature of SARS-CoV-2 infection},
url = {http://dx.doi.org/10.1021/acs.analchem.0c04952},
volume = {93},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - We have applied nuclear magnetic resonance spectroscopy based plasma phenotyping to reveal diagnostic molecular signatures of SARS-CoV-2 infection via combined diffusional and relaxation editing (DIRE). We compared plasma from healthy age-matched controls (n = 26) with SARS-CoV-2 negative non-hospitalized respiratory patients and hospitalized respiratory patients (n = 23 and 11 respectively) with SARS-CoV-2 rRT-PCR positive respiratory patients (n = 17, with longitudinal sampling time-points). DIRE data were modelled using principal component analysis and orthogonal projections to latent structures discriminant analysis (O-PLS-DA), with statistical cross-validation indices indicating excellent model generalization for the classification of SARS-CoV-2 positivity for all comparator groups (area under the receiver operator characteristic curve = 1). DIRE spectra show biomarker signal combinations conferred by differential concentrations of metabolites with selected molecular mobility properties. These comprise the following: (a) composite N-acetyl signals from α-1-acid glycoprotein and other glycoproteins (designated GlycA and GlycB) that were elevated in SARS-CoV-2 positive patients [p = 2.52 × 10–10 (GlycA) and 1.25 × 10–9 (GlycB) vs controls], (b) two diagnostic supramolecular phospholipid composite signals that were identified (SPC-A and SPC-B) from the –+N–(CH3)3 choline headgroups of lysophosphatidylcholines carried on plasma glycoproteins and from phospholipids in high-density lipoprotein subfractions (SPC-A) together with a phospholipid component of low-density lipoprotein (SPC–B). The integrals of the summed SPC signals (SPCtotal) were reduced in SARS-CoV-2 positive patients relative to both controls (p = 1.40 × 10–7) and SARS-CoV-2 negative patients (p = 4.52 × 10–8) but were not significantly different between controls and SARS-CoV-2 negative patients. The identity of the SPC signal comp
AU  - Lodge,S
AU  - Nitschke,P
AU  - Kimhofer,T
AU  - Wist,J
AU  - Bong,S-H
AU  - Loo,RL
AU  - Masuda,R
AU  - Begum,S
AU  - Richards,T
AU  - Lindon,JC
AU  - Bermel,W
AU  - Reinsperger,T
AU  - Schaefer,H
AU  - Spraul,M
AU  - Holmes,E
AU  - Nicholson,JK
DO  - 10.1021/acs.analchem.0c04952
EP  - 3986
PY  - 2021///
SN  - 0003-2700
SP  - 3976
TI  - Diffusion and relaxation edited proton NMR spectroscopy of plasma reveals a high-fidelity supramolecular biomarker signature of SARS-CoV-2 infection
T2  - Analytical Chemistry
UR  - http://dx.doi.org/10.1021/acs.analchem.0c04952
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000626269400040&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://pubs.acs.org/doi/10.1021/acs.analchem.0c04952
UR  - http://hdl.handle.net/10044/1/91209
VL  - 93
ER  -
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