Plasma Proteome Profiling to Assess Human Health and Disease

TY - JOUR

T1 - Plasma Proteome Profiling to Assess Human Health and Disease

AU - Geyer, Philipp E

AU - Kulak, Nils A

AU - Pichler, Garwin

AU - Holdt, Lesca M

AU - Teupser, Daniel

AU - Mann, Matthias

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/3/23

Y1 - 2016/3/23

N2 - Summary 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.

AB - Summary 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.

KW - Journal Article

U2 - 10.1016/j.cels.2016.02.015

DO - 10.1016/j.cels.2016.02.015

M3 - Journal article

C2 - 27135364

SN - 2405-4712

VL - 2

SP - 185

EP - 195

JO - Cell Systems

JF - Cell Systems

IS - 3

ER -