Current landscape of plasma proteomics from technical innovations to biological insights and biomarker discovery

Plasma is a rich source of biomolecules, including proteins, that reflect both health and disease. Due to their key roles in biological processes, proteins hold significant potential as biomarkers, fueling the rise of plasma proteome profiling in recent years. However, comprehensive comparisons of the performance of different plasma proteomics platforms are limited. Our study addresses this gap by conducting a direct comparison of eight platforms, representing both affinity-based and diverse mass spectrometry approaches, and covering over 13,000 proteins. By applying these platforms to the same cohort, we systematically assess their performance, identifying key differences and complementary strengths. Our findings offer valuable insights for researchers, highlighting trade-offs in coverage and their implications for biomarker discovery and clinical applications. This study serves as an essential resource, offering both technical evaluation and biological insights to support the development of novel diagnostics and therapeutics through plasma proteomics. Plasma proteome profiling has surged as a promising avenue for biomarker discovery, yet comprehensive platform comparisons remain scarce. Here, the authors evaluate eight proteomics platforms, revealing key differences and complementary strengths, providing crucial insights for researchers into coverage trade-offs and implicating biomarker discovery and clinical applications.