title: Plasma Proteome Profiling to Assess Human Health and Disease.
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.
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Geyer
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Nils A
authors.initials: NA
authors.lastname: Kulak
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Garwin
authors.initials: G
authors.lastname: Pichler
authors.affiliation: Institute of Laboratory Medicine, Ludwig-Maximilians University Munich, 80539 Munich, Germany.
authors.forename: Lesca M
authors.initials: LM
authors.lastname: Holdt
authors.affiliation: Institute of Laboratory Medicine, Ludwig-Maximilians University Munich, 80539 Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany; NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: mmann@biochem.mpg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D015415:Biomarkers; D001798:Blood Proteins; D002853:Chromatography, Liquid; D020869:Gene Expression Profiling; D006801:Humans; D013058:Mass Spectrometry; D020543:Proteome; D040901:Proteomics; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome
keywords: apolipoproteins; blood analysis; clinic; disease; human; mass spectrometry; plasma proteome profile