Plasma Proteome Profiling to Assess Human Health and Disease

TLDR

Proteins in the circulatory system reflect an individual's physiology, yet current clinical practice relies on single‑protein immunoassays, and high‑throughput mass‑spectrometry proteomics of blood would be advantageous but is hindered by the wide dynamic range of protein abundances. The study introduces a rapid and robust plasma proteome profiling pipeline. The workflow is a single‑run shotgun proteomic method that omits protein depletion, uses 1 µl finger‑prick samples and 20‑min gradients, and, with simple peptide pre‑fractionation, yields quantitative 1,000‑protein plasma proteomes. The method reproducibly quantifies over 40 FDA‑approved biomarkers, apolipoproteins, inflammatory markers such as C‑reactive protein, gender‑related proteins, and provides a functional portrait of a person's health state, suggesting large‑scale biomedical utility.

Abstract

Proteins in the circulatory system mirror an individual's physiology. In daily clinical practice, protein levels are generally determined using single-protein immunoassays. High-throughput, quantitative analysis using mass-spectrometry-based proteomics of blood, plasma, and serum would be advantageous but is challenging because of the high dynamic range of protein abundances. Here, we introduce a rapid and robust "plasma proteome profiling" pipeline. This single-run shotgun proteomic workflow does not require protein depletion and enables quantitative analysis of hundreds of plasma proteomes from 1 μl single finger pricks with 20 min gradients. The apolipoprotein family, inflammatory markers such as C-reactive protein, gender-related proteins, and >40 FDA-approved biomarkers are reproducibly quantified (CV <20% with label-free quantification). Furthermore, we functionally interpret a 1,000-protein, quantitative plasma proteome obtained by simple peptide pre-fractionation. Plasma proteome profiling delivers an informative portrait of a person's health state, and we envision its large-scale use in biomedicine.