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Multicenter longitudinal quality assessment of MS-based proteomics in plasma and serum

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Item Type:Article
Title:Multicenter longitudinal quality assessment of MS-based proteomics in plasma and serum
Creators Name:Kardell, O., Gronauer, T., von Toerne, C., Merl-Pham, J., König, A.C., Barth, T.K., Mergner, J., Ludwig, C., Tüshaus, J., Giesbertz, P., Breimann, S., Schweizer, L., Müller, T., Kliewer, G., Distler, U., Gomez-Zepeda, D., Popp, O., Qin, D., Teupser, D., Cox, J., Imhof, A., Küster, B., Lichtenthaler, S.F., Krijgsveld, J., Tenzer, S., Mertins, P., Coscia, F. and Hauck, S.M.
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.
Keywords:Longitudinal Round-Robin Study, Clinical Specimen, Plasma, Serum, LC-MS/MS, R Package MpwR
Source:Journal of Proteome Research
ISSN:1535-3893
Publisher:American Chemical Society
Date:7 February 2025
Official Publication:https://doi.org/10.1021/acs.jproteome.4c00644
PubMed:View item in PubMed

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