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.