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Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation

Specific plasma proteins serve as valuable markers for various diseases and are in many cases routinely measured in clinical laboratories by fully automated systems. For safe diagnostics and monitoring using these markers, it is important to ensure an analytical quality in line with clinical needs....

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Detalles Bibliográficos
Autores principales: Andersen, Lou-Ann C., Palstrøm, Nicolai Bjødstrup, Diederichsen, Axel, Lindholt, Jes Sanddal, Rasmussen, Lars Melholt, Beck, Hans Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707687/
https://www.ncbi.nlm.nih.gov/pubmed/34941812
http://dx.doi.org/10.3390/proteomes9040047
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author Andersen, Lou-Ann C.
Palstrøm, Nicolai Bjødstrup
Diederichsen, Axel
Lindholt, Jes Sanddal
Rasmussen, Lars Melholt
Beck, Hans Christian
author_facet Andersen, Lou-Ann C.
Palstrøm, Nicolai Bjødstrup
Diederichsen, Axel
Lindholt, Jes Sanddal
Rasmussen, Lars Melholt
Beck, Hans Christian
author_sort Andersen, Lou-Ann C.
collection PubMed
description Specific plasma proteins serve as valuable markers for various diseases and are in many cases routinely measured in clinical laboratories by fully automated systems. For safe diagnostics and monitoring using these markers, it is important to ensure an analytical quality in line with clinical needs. For this purpose, information on the analytical and the biological variation of the measured plasma protein, also in the context of the discovery and validation of novel, disease protein biomarkers, is important, particularly in relation to for sample size calculations in clinical studies. Nevertheless, information on the biological variation of the majority of medium-to-high abundant plasma proteins is largely absent. In this study, we hypothesized that it is possible to generate data on inter-individual biological variation in combination with analytical variation of several hundred abundant plasma proteins, by applying LC-MS/MS in combination with relative quantification using isobaric tagging (10-plex TMT-labeling) to plasma samples. Using this analytical proteomic approach, we analyzed 42 plasma samples prepared in doublets, and estimated the technical, inter-individual biological, and total variation of 265 of the most abundant proteins present in human plasma thereby creating the prerequisites for power analysis and sample size determination in future clinical proteomics studies. Our results demonstrated that only five samples per group may provide sufficient statistical power for most of the analyzed proteins if relative changes in abundances >1.5-fold are expected. Seventeen of the measured proteins are present in the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Biological Variation Database, and demonstrated remarkably similar biological CV’s to the corresponding CV’s listed in the EFLM database suggesting that the generated proteomic determined variation knowledge is useful for large-scale determination of plasma protein variations.
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spelling pubmed-87076872021-12-25 Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation Andersen, Lou-Ann C. Palstrøm, Nicolai Bjødstrup Diederichsen, Axel Lindholt, Jes Sanddal Rasmussen, Lars Melholt Beck, Hans Christian Proteomes Article Specific plasma proteins serve as valuable markers for various diseases and are in many cases routinely measured in clinical laboratories by fully automated systems. For safe diagnostics and monitoring using these markers, it is important to ensure an analytical quality in line with clinical needs. For this purpose, information on the analytical and the biological variation of the measured plasma protein, also in the context of the discovery and validation of novel, disease protein biomarkers, is important, particularly in relation to for sample size calculations in clinical studies. Nevertheless, information on the biological variation of the majority of medium-to-high abundant plasma proteins is largely absent. In this study, we hypothesized that it is possible to generate data on inter-individual biological variation in combination with analytical variation of several hundred abundant plasma proteins, by applying LC-MS/MS in combination with relative quantification using isobaric tagging (10-plex TMT-labeling) to plasma samples. Using this analytical proteomic approach, we analyzed 42 plasma samples prepared in doublets, and estimated the technical, inter-individual biological, and total variation of 265 of the most abundant proteins present in human plasma thereby creating the prerequisites for power analysis and sample size determination in future clinical proteomics studies. Our results demonstrated that only five samples per group may provide sufficient statistical power for most of the analyzed proteins if relative changes in abundances >1.5-fold are expected. Seventeen of the measured proteins are present in the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Biological Variation Database, and demonstrated remarkably similar biological CV’s to the corresponding CV’s listed in the EFLM database suggesting that the generated proteomic determined variation knowledge is useful for large-scale determination of plasma protein variations. MDPI 2021-12-01 /pmc/articles/PMC8707687/ /pubmed/34941812 http://dx.doi.org/10.3390/proteomes9040047 Text en © 2021 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
Andersen, Lou-Ann C.
Palstrøm, Nicolai Bjødstrup
Diederichsen, Axel
Lindholt, Jes Sanddal
Rasmussen, Lars Melholt
Beck, Hans Christian
Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation
title Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation
title_full Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation
title_fullStr Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation
title_full_unstemmed Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation
title_short Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation
title_sort determining plasma protein variation parameters as a prerequisite for biomarker studies—a tmt-based lc-msms proteome investigation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707687/
https://www.ncbi.nlm.nih.gov/pubmed/34941812
http://dx.doi.org/10.3390/proteomes9040047
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