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

Area of Science:

• Biochemistry
• Proteomics
• Analytical Chemistry

Background:

• Plasma and serum proteomics are crucial for disease characterization, biomarker identification, and diagnostic technology advancement.
• Current proteomic workflows require improvements in accuracy, reproducibility, cost-effectiveness, and cross-platform transferability.

Purpose of the Study:

• To develop an open, versatile peptide internal standard for mass spectrometry-based plasma and serum proteomics.
• To improve the accuracy, reproducibility, and cross-platform compatibility of proteomic analyses.

Main Methods:

• Generation of the Charité Open Peptide Standard for Plasma Proteomics (OSPP) using 211 concentration-matched stable-isotope-labeled peptides.
• Validation of OSPP quantification across serum and various plasma types (EDTA, citrate, heparin) using multiple LC-MS platforms.
• Demonstration of OSPP utility in a COVID-19 cohort study.

Main Results:

• OSPP peptides were consistently quantified across different sample types and LC-MS platforms.
• OSPP peptides represent proteins involved in diverse biological processes, clinical tests, and drug targets, enabling its use as a clinical marker panel.
• OSPP improved analytical performance, facilitated cross-platform data alignment, and aided disease stratification and biomarker discovery in a COVID-19 study.

Conclusions:

• The OSPP is a valuable, open-access tool for enhancing plasma and serum proteomics.
• OSPP improves analytical performance and enables cross-platform data harmonization.
• OSPP facilitates biomarker discovery and clinical applications in disease research, including infectious diseases like COVID-19.