Cross-platform clinical proteomics using the Charité open standard for plasma proteomics (OSPP)

Abstract

The role of plasma and serum proteomics in characterizing human disease, identifying biomarkers, and advancing diagnostic technologies is rapidly increasing. However, there is an ongoing need to improve proteomic workflows in terms of accuracy, reproducibility, and cost-effectiveness, and to achieve cross-platform transferability. Based on large serum and plasma proteome studies, we generate the Charité Open Peptide Standard for Plasma Proteomics (OSPP), an open, versatile peptide internal standard for targeted and untargeted mass spectrometry-based proteomic studies. The OSPP includes 211 concentration-matched stable-isotope-labeled peptides selected for consistent quantification across a large number of plasma and serum proteome studies, and synthetic accessibility. We show they are consistently quantified across serum and EDTA, citrate, and heparin plasma using multiple LC-MS platforms. Despite being selected for technical parameters, the OSPP peptides represent proteins that function in a wide range of biological processes, are used in routine clinical tests, or are targets of FDA-approved drugs, making OSPP able to serve as an expandable clinical marker panel. We demonstrate the utility of OSPP in a COVID-19 inpatient cohort study for improving analytical performances, for cross-platform alignment of proteomic data, disease stratification, and biomarker discovery.