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

• Topic: A systematic benchmarking and technical evaluation of the current landscape of plasma proteomics, directly comparing different affinity-based and mass spectrometry platforms.
• Method: Eight state-of-the-art proteomics platforms were applied to the same human plasma cohort to compare performance across over 13,000 proteins, assessing metrics like coverage, sensitivity, and reproducibility.
• Impact: The study provides a critical resource for researchers, detailing the trade-offs in protein coverage and identifying the complementary strengths and limitations of each platform to guide informed decision-making for biomarker discovery.

PubMed: 40999057 DOI: 10.1038/s42004-025-01665-1 Overview generated by: Gemini 2.5 Flash, 27/11/2025

Background and Objective

Plasma proteins are critical biomolecules that reflect health and disease states, driving the rapidly expanding field of plasma proteome profiling for biomarker discovery. However, researchers often lack comprehensive, head-to-head comparisons of the diverse and evolving plasma proteomics platforms available.

The objective of this study was to address this gap by conducting a direct, systematic comparison of multiple state-of-the-art proteomics platforms to assess their performance, identify key differences, and provide valuable guidance for researchers in selecting appropriate technologies for biomarker discovery and clinical applications.

Methods: Platform Benchmarking on a Shared Cohort

The study performed a rigorous technical evaluation of plasma proteomics technologies:

1. Platform Selection: Eight different plasma proteomics platforms were directly compared. These platforms represented both affinity-based methods (e.g., proximity extension assays) and various mass spectrometry (MS) approaches.
2. Coverage: The platforms collectively covered over 13,000 proteins.
3. Experimental Design: All platforms were applied to the same human cohort to ensure a direct and unbiased assessment of performance, allowing for systematic comparison of their capabilities, including protein coverage, dynamic range, and reproducibility.

Key Results and Significance

The systematic assessment provided critical insights into the performance characteristics and trade-offs of the different technologies:

• Key Differences and Complementary Strengths: The comparison identified significant differences in platform performance, as well as complementary strengths, highlighting that different platforms are best suited for different research goals.
• Trade-offs in Coverage: The findings specifically illustrated the trade-offs in protein coverage—the number of quantifiable proteins—versus other performance metrics like sensitivity and throughput.
• Essential Resource: This study serves as an essential resource for the research community, offering both technical evaluation and biological insights to support the development of novel diagnostics and therapeutics by informing the critical choice of technology for plasma proteomics profiling.