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Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies

Mass spectrometry (MS) is increasingly used in clinical studies to obtain molecular evidence of chemical exposures, such as tobacco smoke, alcohol, and drugs. This evidence can help verify clinical data retrieved through anamnesis or questionnaires and may provide insights into unreported exposures,...

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Autores principales: Klont, Frank, Sosnowski, Piotr, Kremer, Daan, Knobbe, Tim J., Bonner, Ron, Blokzijl, Hans, Weersma, Rinse K., Bakker, Stephan J. L., Investigators, TransplantLines, Hak, Eelko, Touw, Daan J., Hopfgartner, Gérard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611019/
https://www.ncbi.nlm.nih.gov/pubmed/36295843
http://dx.doi.org/10.3390/metabo12100942
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author Klont, Frank
Sosnowski, Piotr
Kremer, Daan
Knobbe, Tim J.
Bonner, Ron
Blokzijl, Hans
Weersma, Rinse K.
Bakker, Stephan J. L.
Investigators, TransplantLines
Hak, Eelko
Touw, Daan J.
Hopfgartner, Gérard
author_facet Klont, Frank
Sosnowski, Piotr
Kremer, Daan
Knobbe, Tim J.
Bonner, Ron
Blokzijl, Hans
Weersma, Rinse K.
Bakker, Stephan J. L.
Investigators, TransplantLines
Hak, Eelko
Touw, Daan J.
Hopfgartner, Gérard
author_sort Klont, Frank
collection PubMed
description Mass spectrometry (MS) is increasingly used in clinical studies to obtain molecular evidence of chemical exposures, such as tobacco smoke, alcohol, and drugs. This evidence can help verify clinical data retrieved through anamnesis or questionnaires and may provide insights into unreported exposures, for example those classified as the same despite small but possibly relevant chemical differences or due to contaminants in reported exposure compounds. Here, we aimed to explore the potential of untargeted SWATH metabolomics to differentiate such closely related exposures. This data-independent acquisition MS-based profiling technique was applied to urine samples of 316 liver and 570 kidney transplant recipients from the TransplantLines Biobank and Cohort Study (NCT03272841), where we focused on the immunosuppressive drug mycophenolate, which is either supplied as a morpholino-ester prodrug or as an enteric-coated product, the illicit drug cocaine, which is usually supplied as an adulterated product, and the proton pump inhibitors omeprazole and esomeprazole. Based on these examples, we found that untargeted SWATH metabolomics has considerable potential to identify different (unreported) exposure or co-exposure metabolites and may determine variations in their abundances. We also found that these signals alone may sometimes be unable to distinguish closely related exposures, and enhancement of differentiation, for example by integration with pharmacogenomics data, is needed.
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spelling pubmed-96110192022-10-28 Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies Klont, Frank Sosnowski, Piotr Kremer, Daan Knobbe, Tim J. Bonner, Ron Blokzijl, Hans Weersma, Rinse K. Bakker, Stephan J. L. Investigators, TransplantLines Hak, Eelko Touw, Daan J. Hopfgartner, Gérard Metabolites Article Mass spectrometry (MS) is increasingly used in clinical studies to obtain molecular evidence of chemical exposures, such as tobacco smoke, alcohol, and drugs. This evidence can help verify clinical data retrieved through anamnesis or questionnaires and may provide insights into unreported exposures, for example those classified as the same despite small but possibly relevant chemical differences or due to contaminants in reported exposure compounds. Here, we aimed to explore the potential of untargeted SWATH metabolomics to differentiate such closely related exposures. This data-independent acquisition MS-based profiling technique was applied to urine samples of 316 liver and 570 kidney transplant recipients from the TransplantLines Biobank and Cohort Study (NCT03272841), where we focused on the immunosuppressive drug mycophenolate, which is either supplied as a morpholino-ester prodrug or as an enteric-coated product, the illicit drug cocaine, which is usually supplied as an adulterated product, and the proton pump inhibitors omeprazole and esomeprazole. Based on these examples, we found that untargeted SWATH metabolomics has considerable potential to identify different (unreported) exposure or co-exposure metabolites and may determine variations in their abundances. We also found that these signals alone may sometimes be unable to distinguish closely related exposures, and enhancement of differentiation, for example by integration with pharmacogenomics data, is needed. MDPI 2022-10-04 /pmc/articles/PMC9611019/ /pubmed/36295843 http://dx.doi.org/10.3390/metabo12100942 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Klont, Frank
Sosnowski, Piotr
Kremer, Daan
Knobbe, Tim J.
Bonner, Ron
Blokzijl, Hans
Weersma, Rinse K.
Bakker, Stephan J. L.
Investigators, TransplantLines
Hak, Eelko
Touw, Daan J.
Hopfgartner, Gérard
Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies
title Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies
title_full Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies
title_fullStr Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies
title_full_unstemmed Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies
title_short Assessing the Potential of Untargeted SWATH Mass Spectrometry-Based Metabolomics to Differentiate Closely Related Exposures in Observational Studies
title_sort assessing the potential of untargeted swath mass spectrometry-based metabolomics to differentiate closely related exposures in observational studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611019/
https://www.ncbi.nlm.nih.gov/pubmed/36295843
http://dx.doi.org/10.3390/metabo12100942
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