Plasma Proteome Profiling to Assess Human Health and Disease

• Published in: Cell systems Vol. 2; no. 3; pp. 185 - 195
• Main Authors: Geyer, Philipp E., Kulak, Nils A., Pichler, Garwin, Holdt, Lesca M., Teupser, Daniel, Mann, Matthias
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.03.2016
• Subjects: apolipoproteins; Biomarkers; blood analysis; Blood Proteins; Chromatography, Liquid; clinic; disease; Gene Expression Profiling; human; Humans; Mass Spectrometry; plasma proteome profile; Proteome; Proteomics; Tandem Mass Spectrometry; apolipoproteins; disease; mass spectrometry; clinic; plasma proteome profile; human; blood analysis
• ISSN: 2405-4712; 2405-4720
• DOI: 10.1016/j.cels.2016.02.015

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. [Display omitted] •Automated, highly reproducible, 3-hr proteomic workflow from blood droplet to results•Plasma protein data reflecting allele differences, metabolic risk, and inflammatory status•Quantitative 1,000-protein plasma proteome•The plasma proteome profile as a proteomic portrait of a person’s health state A rapid and highly reproducible proteomic workflow delivers a systemic-view proteomic portrait of a person’s health state from a single drop of blood.