Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis

Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-aff...

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Autores principales:	Andreas Hober, Khue Hua Tran-Minh, Dominic Foley, Thomas McDonald, Johannes PC Vissers, Rebecca Pattison, Samantha Ferries, Sigurd Hermansson, Ingvar Betner, Mathias Uhlén, Morteza Razavi, Richard Yip, Matthew E Pope, Terry W Pearson, Leigh N Andersson, Amy Bartlett, Lisa Calton, Jessica J Alm, Lars Engstrand, Fredrik Edfors
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	SARS CoV-2 COVID-19 SISCAPA proteomics diagnostics mass spectrometry Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b86beb7f359342dfa0a6a2b4f3d48930
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spelling	oai:doaj.org-article:b86beb7f359342dfa0a6a2b4f3d489302021-12-02T15:22:32ZRapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis10.7554/eLife.708432050-084Xe70843https://doaj.org/article/b86beb7f359342dfa0a6a2b4f3d489302021-11-01T00:00:00Zhttps://elifesciences.org/articles/70843https://doaj.org/toc/2050-084XReliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct ≤ 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.Andreas HoberKhue Hua Tran-MinhDominic FoleyThomas McDonaldJohannes PC VissersRebecca PattisonSamantha FerriesSigurd HermanssonIngvar BetnerMathias UhlénMorteza RazaviRichard YipMatthew E PopeTerry W PearsonLeigh N AnderssonAmy BartlettLisa CaltonJessica J AlmLars EngstrandFredrik EdforseLife Sciences Publications LtdarticleSARS CoV-2COVID-19SISCAPAproteomicsdiagnosticsmass spectrometryMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS CoV-2 COVID-19 SISCAPA proteomics diagnostics mass spectrometry Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	SARS CoV-2 COVID-19 SISCAPA proteomics diagnostics mass spectrometry Medicine R Science Q Biology (General) QH301-705.5 Andreas Hober Khue Hua Tran-Minh Dominic Foley Thomas McDonald Johannes PC Vissers Rebecca Pattison Samantha Ferries Sigurd Hermansson Ingvar Betner Mathias Uhlén Morteza Razavi Richard Yip Matthew E Pope Terry W Pearson Leigh N Andersson Amy Bartlett Lisa Calton Jessica J Alm Lars Engstrand Fredrik Edfors Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
description	Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct ≤ 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.
format	article
author	Andreas Hober Khue Hua Tran-Minh Dominic Foley Thomas McDonald Johannes PC Vissers Rebecca Pattison Samantha Ferries Sigurd Hermansson Ingvar Betner Mathias Uhlén Morteza Razavi Richard Yip Matthew E Pope Terry W Pearson Leigh N Andersson Amy Bartlett Lisa Calton Jessica J Alm Lars Engstrand Fredrik Edfors
author_facet	Andreas Hober Khue Hua Tran-Minh Dominic Foley Thomas McDonald Johannes PC Vissers Rebecca Pattison Samantha Ferries Sigurd Hermansson Ingvar Betner Mathias Uhlén Morteza Razavi Richard Yip Matthew E Pope Terry W Pearson Leigh N Andersson Amy Bartlett Lisa Calton Jessica J Alm Lars Engstrand Fredrik Edfors
author_sort	Andreas Hober
title	Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
title_short	Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
title_full	Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
title_fullStr	Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
title_full_unstemmed	Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
title_sort	rapid and sensitive detection of sars-cov-2 infection using quantitative peptide enrichment lc-ms analysis
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/b86beb7f359342dfa0a6a2b4f3d48930
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Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis

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