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Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma

In metabolic diagnostics, there is an emerging need for a comprehensive test to acquire a complete view of metabolite status. Here, we describe a non-quantitative direct-infusion high-resolution mass spectrometry (DI-HRMS) based metabolomics method and evaluate the method for both dried blood spots...

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Autores principales: Haijes, Hanneke A., Willemsen, Marcel, van der Ham, Maria, Gerrits, Johan, Pras-Raves, Mia L., Prinsen, Hubertus C. M. T., van Hasselt, Peter M., de Sain-van der Velden, Monique G. M., Verhoeven-Duif, Nanda M., Jans, Judith J. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359237/
https://www.ncbi.nlm.nih.gov/pubmed/30641898
http://dx.doi.org/10.3390/metabo9010012
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author Haijes, Hanneke A.
Willemsen, Marcel
van der Ham, Maria
Gerrits, Johan
Pras-Raves, Mia L.
Prinsen, Hubertus C. M. T.
van Hasselt, Peter M.
de Sain-van der Velden, Monique G. M.
Verhoeven-Duif, Nanda M.
Jans, Judith J. M.
author_facet Haijes, Hanneke A.
Willemsen, Marcel
van der Ham, Maria
Gerrits, Johan
Pras-Raves, Mia L.
Prinsen, Hubertus C. M. T.
van Hasselt, Peter M.
de Sain-van der Velden, Monique G. M.
Verhoeven-Duif, Nanda M.
Jans, Judith J. M.
author_sort Haijes, Hanneke A.
collection PubMed
description In metabolic diagnostics, there is an emerging need for a comprehensive test to acquire a complete view of metabolite status. Here, we describe a non-quantitative direct-infusion high-resolution mass spectrometry (DI-HRMS) based metabolomics method and evaluate the method for both dried blood spots (DBS) and plasma. 110 DBS of 42 patients harboring 23 different inborn errors of metabolism (IEM) and 86 plasma samples of 38 patients harboring 21 different IEM were analyzed using DI-HRMS. A peak calling pipeline developed in R programming language provided Z-scores for ~1875 mass peaks corresponding to ~3835 metabolite annotations (including isomers) per sample. Based on metabolite Z-scores, patients were assigned a ‘most probable diagnosis’ by an investigator blinded for the known diagnoses of the patients. Based on DBS sample analysis, 37/42 of the patients, corresponding to 22/23 IEM, could be correctly assigned a ‘most probable diagnosis’. Plasma sample analysis, resulted in a correct ‘most probable diagnosis’ in 32/38 of the patients, corresponding to 19/21 IEM. The added clinical value of the method was illustrated by a case wherein DI-HRMS metabolomics aided interpretation of a variant of unknown significance (VUS) identified by whole-exome sequencing. In summary, non-quantitative DI-HRMS metabolomics in DBS and plasma is a very consistent, high-throughput and nonselective method for investigating the metabolome in genetic disease.
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spelling pubmed-63592372019-02-11 Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma Haijes, Hanneke A. Willemsen, Marcel van der Ham, Maria Gerrits, Johan Pras-Raves, Mia L. Prinsen, Hubertus C. M. T. van Hasselt, Peter M. de Sain-van der Velden, Monique G. M. Verhoeven-Duif, Nanda M. Jans, Judith J. M. Metabolites Article In metabolic diagnostics, there is an emerging need for a comprehensive test to acquire a complete view of metabolite status. Here, we describe a non-quantitative direct-infusion high-resolution mass spectrometry (DI-HRMS) based metabolomics method and evaluate the method for both dried blood spots (DBS) and plasma. 110 DBS of 42 patients harboring 23 different inborn errors of metabolism (IEM) and 86 plasma samples of 38 patients harboring 21 different IEM were analyzed using DI-HRMS. A peak calling pipeline developed in R programming language provided Z-scores for ~1875 mass peaks corresponding to ~3835 metabolite annotations (including isomers) per sample. Based on metabolite Z-scores, patients were assigned a ‘most probable diagnosis’ by an investigator blinded for the known diagnoses of the patients. Based on DBS sample analysis, 37/42 of the patients, corresponding to 22/23 IEM, could be correctly assigned a ‘most probable diagnosis’. Plasma sample analysis, resulted in a correct ‘most probable diagnosis’ in 32/38 of the patients, corresponding to 19/21 IEM. The added clinical value of the method was illustrated by a case wherein DI-HRMS metabolomics aided interpretation of a variant of unknown significance (VUS) identified by whole-exome sequencing. In summary, non-quantitative DI-HRMS metabolomics in DBS and plasma is a very consistent, high-throughput and nonselective method for investigating the metabolome in genetic disease. MDPI 2019-01-11 /pmc/articles/PMC6359237/ /pubmed/30641898 http://dx.doi.org/10.3390/metabo9010012 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Haijes, Hanneke A.
Willemsen, Marcel
van der Ham, Maria
Gerrits, Johan
Pras-Raves, Mia L.
Prinsen, Hubertus C. M. T.
van Hasselt, Peter M.
de Sain-van der Velden, Monique G. M.
Verhoeven-Duif, Nanda M.
Jans, Judith J. M.
Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma
title Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma
title_full Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma
title_fullStr Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma
title_full_unstemmed Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma
title_short Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients’ Dried Blood Spots and Plasma
title_sort direct infusion based metabolomics identifies metabolic disease in patients’ dried blood spots and plasma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359237/
https://www.ncbi.nlm.nih.gov/pubmed/30641898
http://dx.doi.org/10.3390/metabo9010012
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