Plasma Proteome Profiling to detect and avoid sample-related biases in biomarker studies

Philipp E. Geyer, Eugenia Voytik, Peter V. Treit, Sophia Doll, Alisa Kleinhempel, Lili Niu, Johannes B Müller, Marie-Luise Buchholtz, Jakob M Bader, Daniel Teupser, Lesca M Holdt, Matthias Mann

Research output: Contribution to journalJournal articleResearchpeer-review

170 Citations (Scopus)
224 Downloads (Pure)

Abstract

Plasma and serum are rich sources of information regarding an individual's health state, and protein tests inform medical decision making. Despite major investments, few new biomarkers have reached the clinic. Mass spectrometry (MS)-based proteomics now allows highly specific and quantitative readout of the plasma proteome. Here, we employ Plasma Proteome Profiling to define quality marker panels to assess plasma samples and the likelihood that suggested biomarkers are instead artifacts related to sample handling and processing. We acquire deep reference proteomes of erythrocytes, platelets, plasma, and whole blood of 20 individuals (> 6,000 proteins), and compare serum and plasma proteomes. Based on spike-in experiments, we determine sample quality-associated proteins, many of which have been reported as biomarker candidates as revealed by a comprehensive literature survey. We provide sample preparation guidelines and an online resource ( www.plasmaproteomeprofiling.org) to assess overall sample-related bias in clinical studies and to prevent costly miss-assignment of biomarker candidates.

Original languageEnglish
Article numbere10427
JournalEMBO Molecular Medicine
Volume11
Issue number11
ISSN1757-4676
DOIs
Publication statusPublished - 2019

Cite this