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

Kardell, Oliver ; Gronauer, Thomas; Toerne, Christine von; Merl-Pham, Juliane; König, Ann-Christine; Barth, Teresa K.; Mergner, Julia; Ludwig, Christina ; Tüshaus, Johanna; Giesbertz, Pieter; Breimann, Stephan ; Schweizer, Lisa ; Müller, Torsten; Kliewer, Georg; Distler, Ute ; Gomez-Zepeda, David ; Popp, Oliver ; Qin, Di; Teupser, Daniel ; Cox, Jürgen ; Imhof, Axel ; Küster, Bernhard ; Lichtenthaler, Stefan F. ; Krijgsveld, Jeroen; Tenzer, Stefan ; Mertins, Philipp ; Coscia, Fabian und Hauck, Stefanie M. (2025): Multicenter Longitudinal Quality Assessment of MS-Based Proteomics in Plasma and Serum. In: Journal of Proteome Research, Vol. 24, No. 3: pp. 1017-1029

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.

• Item Type: Journal article
• Faculties: Medicine; Medicine > Adolf Butenandt Institute; Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Institute for Stroke and Dementia Research (ISD); Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute; Medicine > Medical Center of the University of Munich > Institute of Laboratory Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1535-3893
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198