Multicenter Longitudinal Quality Assessment of MS-Based Proteomics in Plasma and Serum

Advancing MS-based proteomics toward clinical applications evolves around developing standardized start-to-finish and fit-for-purpose workflows for clinical specimens. Steps along the method design involve the determination and optimization of several bioanalytical parameters such as selectivity, sensitivity, accuracy, and precision. In a joint effort, eight proteomics laboratories belonging to the MSCoreSys initiative including the CLINSPECT-M, MSTARS, DIASyM, and SMART-CARE consortia performed a longitudinal round-robin study to assess the analysis performance of plasma and serum as clinically relevant samples. A variety of LC-MS/MS setups including mass spectrometer models from ThermoFisher and Bruker as well as LC systems from ThermoFisher, Evosep, and Waters Corporation were used in this study. As key performance indicators, sensitivity, precision, and reproducibility were monitored over time. Protein identifications range between 300 and 400 IDs across different state-of-the-art MS instruments, with timsTOF Pro, Orbitrap Exploris 480, and Q Exactive HF-X being among the top performers. Overall, 71 proteins are reproducibly detectable in all setups in both serum and plasma samples, and 22 of these proteins are FDA-approved biomarkers, which are reproducibly quantified (CV < 20% with label-free quantification). In total, the round-robin study highlights a promising baseline for bringing MS-based measurements of serum and plasma samples closer to clinical utility.

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Publication Details

Journal
Journal of Proteome Research
Published
2025-02-07
DOI
https://doi.org/10.1021/acs.jproteome.4c00644
Citations
8
Primary Topic
Advanced Proteomics Techniques and Applications
Type
article
Field-Weighted Citation Impact
6.05

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article

Multicenter Longitudinal Quality Assessment of MS-Based Proteomics in Plasma and Serum

Stephan Breimann, Juliane Merl‐Pham, Ute Distler, Stefanie M. Hauck et al.
8 citations
Journal of Proteome Research
Advanced Proteomics Techniques and Applications
6.05
article

Multicenter Longitudinal Quality Assessment of MS-Based Proteomics in Plasma and Serum

Stephan Breimann, Juliane Merl‐Pham, Ute Distler, Stefanie M. Hauck, Christine von Toerne, Philipp Mertins, Johanna Tüshaus, Jüergen Cox, Thomas Gronauer, Julia Mergner, Pieter Giesbertz, Teresa K. Barth, Stefan Tenzer, Bernhard Küster, David Gómez-Zepeda, Stefan F. Lichtenthaler, Oliver Popp, Lisa Schweizer, Daniel Teupser, Axel Imhof, Jeroen Krijgsveld, Christina Ludwig, Fabian Coscia, Oliver Kardell, Di Qin, Ann‐Christine König, Torsten Müller, Georg Kliewer
article en
8 citations

Abstract

Advancing MS-based proteomics toward clinical applications evolves around developing standardized start-to-finish and fit-for-purpose workflows for clinical specimens. Steps along the method design involve the determination and optimization of several bioanalytical parameters such as selectivity, sensitivity, accuracy, and precision. In a joint effort, eight proteomics laboratories belonging to the MSCoreSys initiative including the CLINSPECT-M, MSTARS, DIASyM, and SMART-CARE consortia performed a longitudinal round-robin study to assess the analysis performance of plasma and serum as clinically relevant samples. A variety of LC-MS/MS setups including mass spectrometer models from ThermoFisher and Bruker as well as LC systems from ThermoFisher, Evosep, and Waters Corporation were used in this study. As key performance indicators, sensitivity, precision, and reproducibility were monitored over time. Protein identifications range between 300 and 400 IDs across different state-of-the-art MS instruments, with timsTOF Pro, Orbitrap Exploris 480, and Q Exactive HF-X being among the top performers. Overall, 71 proteins are reproducibly detectable in all setups in both serum and plasma samples, and 22 of these proteins are FDA-approved biomarkers, which are reproducibly quantified (CV < 20% with label-free quantification). In total, the round-robin study highlights a promising baseline for bringing MS-based measurements of serum and plasma samples closer to clinical utility.

Journal of Proteome ResearchVol. 24(3)
German Cancer Research Center (DE), Johannes Gutenberg University Mainz (DE), Max Delbrück Center (DE), Heidelberg University (DE), German Center for Neurodegenerative Diseases (DE), University Hospital Heidelberg (DE), TUM Klinikum (DE), Center for Environmental Health (US), Helmholtz Zentrum München (DE), LMU Klinikum (DE), Faculty (United Kingdom) (GB), Bioanalytica (Switzerland) (CH), University Medical Center of the Johannes Gutenberg University Mainz (DE), Protein Express (United States) (US), Munich Cluster for Systems Neurology (DE), Helmholtz Institute Mainz (DE), Institute of Immunology (HR), Max Planck Institute of Biochemistry (DE), Immunomedics (Germany) (DE), Technical University of Munich (DE), Ludwig-Maximilians-Universität München (DE)
Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung
Openalex Percentile: Top 4%
Advanced Proteomics Techniques and Applications
6.05
DOIOpen Access PDFOpenAlex
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