In depth proteome coverage is one of the key challenges in the current biomarker field and comprehensive robust quantifications are key to any (multi-) omics approach. Plasma is the most easily accessible clinical specimen and it´s protein composition reports on a person’s well-being at the time point of collection. Results from the Munich and Germany-wide ring trials will be presented, which were performed as overarching standardization and quality assurance in the ClinspectM consortium [1] and the MSCoreSys initiative [2] aiming to successfully establish mass spectrometry for systems medicine and develop start-to-finish and fit-for purpose workflows. In brief, it is now possible to assess ~70% of the FDA approved biomarkers accessible by mass spec robustly with very low variations even between different labs.
However, the very imbalanced proportion of high abundant proteins in plasma prevent detection of low abundant proteins by mass spectrometry and thus most low abundant proteins are missed. As a complementary and alternative approach, proximity extension assays (PEA) can capture also low abundant proteins in a targeted fashion. PEA achieves very high correlation with DDA and DIA methods in overlapping proteins [3]. Most interestingly, when comparing high performing PEA (Olink ExploreHT) with latest bead-based enrichments coupled to LC-MSMS (timsTOF HT) the overlap of detected proteins is restricted to ~20% while the overall coverage expands to more than 4000 proteins robustly detected above LOD. Recent results from a cohort study comprising 422 participants analysed with Olink Explore3k and Preomics Enrich-iST coupled to timsTOF HT will be discussed.