TY - JOUR
T1 - Operation Moonshot
T2 - rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use
AU - Hällqvist, Jenny
AU - Lane, Dan
AU - Shapanis, Andrew
AU - Davis, Kayleigh
AU - Heywood, Wendy E.
AU - Doykov, Ivan
AU - Śpiewak, Justyna
AU - Ghansah, Nana
AU - Keevil, Brian
AU - Gupta, Pankaj
AU - Jukes-Jones, Rebekah
AU - Singh, Raj
AU - Foley, Dominic
AU - Vissers, Johannes P.C.
AU - Pattison, Rebecca
AU - Ferries, Samantha
AU - Wardle, Robert
AU - Bartlett, Amy
AU - Calton, Lisa J.
AU - Anderson, Leigh
AU - Razavi, Morteza
AU - Pearson, Terry
AU - Pope, Matt
AU - Yip, Richard
AU - Ng, Leong L.
AU - Nicholas, Benjamin I.
AU - Bailey, Alistair
AU - Noel, Dan
AU - Dalton, R. Neil
AU - Heales, Simon
AU - Hopley, Christopher
AU - Pitt, Andrew R.
AU - Barran, Perdita
AU - Jones, Donald J.L.
AU - Mills, Kevin
AU - Skipp, Paul
AU - Carling, Rachel S.
N1 - Funding Information:
Research funding: This work was funded by the UK Department of Health and Social Care (DHSC) as part of the Moonshot programme.
Publisher Copyright:
© 2023 De Gruyter. All rights reserved.
PY - 2023/1/27
Y1 - 2023/1/27
N2 - 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. Methods: 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.
AB - 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. Methods: 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.
KW - high performance liquid chromatography
KW - laboratory methods & tools
KW - mass spectrometry
KW - proteins
UR - http://www.scopus.com/inward/record.url?scp=85142930546&partnerID=8YFLogxK
U2 - 10.1515/cclm-2022-1000
DO - 10.1515/cclm-2022-1000
M3 - Article
C2 - 36395058
AN - SCOPUS:85142930546
SN - 1434-6621
VL - 61
SP - 302
EP - 310
JO - Clinical Chemistry and Laboratory Medicine
JF - Clinical Chemistry and Laboratory Medicine
IS - 2
ER -
