A Targeted LC-MRM 3 Proteomic Approach for the Diagnosis of SARS-CoV-2 Infection in Nasopharyngeal Swabs.

Autor:	Drouin N; Metabolomics and Analytics Centre, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: n.f.p.drouin@lacdr.leidenuniv.nl., Elfrink HL; Metabolomics and Analytics Centre, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands., Boers SA; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands., van Hugten S; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands., Wessels E; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands., de Vries JJC; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands., Groeneveld GH; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, The Netherlands; Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands., Miggiels P; Metabolomics and Analytics Centre, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands., Van Puyvelde B; ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium., Dhaenens M; ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium., Budding AE; Inbiome, Amsterdam, The Netherlands., Ran L; Eurofins, Amsterdam, The Netherlands., Masius R; Eurofins, Amsterdam, The Netherlands., Takats Z; Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom., Boogaerds A; DSM, Geleen, The Netherlands., Bulters M; DSM, Geleen, The Netherlands., Muurlink W; TSE, Haarlem, The Netherlands., Oostvogel P; Regional Laboratory, Municipal Health Service (GGD) Amsterdam, Amsterdam, The Netherlands., Harms AC; Metabolomics and Analytics Centre, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands., van der Lubben M; Regional Laboratory, Municipal Health Service (GGD) Amsterdam, Amsterdam, The Netherlands., Hankemeier T; Metabolomics and Analytics Centre, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands. Electronic address: hankemeier@lacdr.leidenuniv.nl.
Jazyk:	angličtina
Zdroj:	Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2024 Jul; Vol. 23 (7), pp. 100805. Date of Electronic Publication: 2024 Jun 17.
DOI:	10.1016/j.mcpro.2024.100805
Abstrakt:	Since its first appearance, severe acute respiratory syndrome coronavirus 2 quickly spread around the world and the lack of adequate PCR testing capacities, especially during the early pandemic, led the scientific community to explore new approaches such as mass spectrometry (MS). We developed a proteomics workflow to target several tryptic peptides of the nucleocapsid protein. A highly selective multiple reaction monitoring-cubed (MRM 3 ) strategy provided a sensitivity increase in comparison to conventional MRM acquisition. Our MRM 3 approach was first tested on an Amsterdam public health cohort (alpha-variant, 760 participants) detecting viral nucleocapsid protein peptides from nasopharyngeal swabs samples presenting a cycle threshold value down to 35 with sensitivity and specificity of 94.2% and 100.0%, without immunopurification. A second iteration of the MS-diagnostic test, able to analyze more than 400 samples per day, was clinically validated on a Leiden-Rijswijk public health cohort (delta-variant, 2536 participants) achieving 99.9% specificity and 93.1% sensitivity for patients with cycle threshold values up to 35. In this manuscript, we also developed and brought the first proof of the concept of viral variant monitoring in a complex matrix using targeted MS. Competing Interests: Conflict of interest The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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