Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use.
Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use.
Objectives: during 2020, the UK’s Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity.
Method: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study.
Results: analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7–39.1) demonstrated diagnostic sensitivity of 92.4% (87.4–95.5), specificity of 97.4% (94.0–98.9) and near total concordance with RT-qPCR (Cohen’s Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1–99.3), specificity 97.4% (94.0–98.9) and Cohen’s Kappa 0.95.Conclusions: this unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory.
clinical, covid-19, proteomics, high performance liquid chromatography, proteins, mass spectrometry, laboratory methods & tools
302-310
Hällqvist, Jenny
fdc2ef15-8b19-4759-845c-904270b201b8
Lane, Dan
63c76b9b-3fc0-49a5-a066-8a07a33fe214
Shapanis, Andrew
98b07884-92a9-4c00-afad-12194e339cbc
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Nicholas, Benjamin
785c44fb-6536-4189-803b-4545425e9385
Bailey, Alistair
19a50642-79ab-4760-b367-fafd3fccdf01
14 December 2022
Hällqvist, Jenny
fdc2ef15-8b19-4759-845c-904270b201b8
Lane, Dan
63c76b9b-3fc0-49a5-a066-8a07a33fe214
Shapanis, Andrew
98b07884-92a9-4c00-afad-12194e339cbc
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Nicholas, Benjamin
785c44fb-6536-4189-803b-4545425e9385
Bailey, Alistair
19a50642-79ab-4760-b367-fafd3fccdf01
Hällqvist, Jenny, Lane, Dan and Shapanis, Andrew
,
et al.
(2022)
Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use.
Clinical Chemistry and Laboratory Medicine, 61 (2), .
(doi:10.1515/cclm-2022-1000).
Abstract
Objectives: during 2020, the UK’s Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity.
Method: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study.
Results: analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7–39.1) demonstrated diagnostic sensitivity of 92.4% (87.4–95.5), specificity of 97.4% (94.0–98.9) and near total concordance with RT-qPCR (Cohen’s Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1–99.3), specificity 97.4% (94.0–98.9) and Cohen’s Kappa 0.95.Conclusions: this unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory.
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draft_Proof_CCLM_revised
- Accepted Manuscript
Text
10.1515_cclm-2022-1000
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More information
Accepted/In Press date: 4 November 2022
e-pub ahead of print date: 17 November 2022
Published date: 14 December 2022
Additional Information:
Funding Information: Research funding: this work was funded by the UK Department of Health and Social Care (DHSC) as part of the Moonshot programme.
Keywords:
clinical, covid-19, proteomics, high performance liquid chromatography, proteins, mass spectrometry, laboratory methods & tools
Identifiers
Local EPrints ID: 472469
URI: http://eprints.soton.ac.uk/id/eprint/472469
ISSN: 1434-6621
PURE UUID: dc049d60-f8a7-49e9-9028-571643d77080
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Date deposited: 06 Dec 2022 17:35
Last modified: 02 May 2024 04:01
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Author:
Jenny Hällqvist
Author:
Dan Lane
Author:
Benjamin Nicholas
Author:
Alistair Bailey
Corporate Author: et al.
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