Efforts in this JRA are focused on making translational proteome profiling a more routine technology in the clinical setting. Although, translational proteomics has made substantial progress in the last decade, it has not yet delivered what had been promised initially. EPIC-XS feels that now is the right time to seriously invest into clinical proteomics, as jointly we have the means to address some of the most important bottlenecks in clinical proteomics, which require novel proteomics technologies. In this project we will develop robust, reproducible and high-throughput proteomics workflows to sample large sample cohorts starting with for instance small sample volumes of blood (single droplets); tackle the dynamic range in the plasma proteome by analyzing directly circulating soluble proteins, targeted proteomics approaches, as well as analyse extracellular vesicles; and focus on protein post-translational modifications (PTMs) and epigenetics as biomarkers for diseases states. Bioinformatics tools required for statistical analysis, working with large cohorts and biodiversity will be co-developed with the computational proteomics and cross-omics integration joint research project.