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Plasma Proteome Profiling to Assess Human Health and Disease

2016; Elsevier BV; Volume: 2; Issue: 3 Linguagem: Inglês

10.1016/j.cels.2016.02.015

2639-5460

Philipp E. Geyer, Nils A. Kulak, Garwin Pichler, Lesca M. Holdt, Daniel Teupser, Matthias Mann,

Metabolomics and Mass Spectrometry Studies

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.