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

doi:10.15252/emmm.201910427

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

Novo Nordisk Foundation Center for Protein Research

41 Citations (Scopus)

13 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 language	English
Article number	e10427
Journal	EMBO Molecular Medicine
Volume	11
Issue number	11
ISSN	1757-4676
DOIs	https://doi.org/10.15252/emmm.201910427
Publication status	Published - 7 Nov 2019

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Plasma Proteome Profiling to detect and avoid sample-related biases in biomarker studiesFinal published version, 3.56 MBLicence: CC BY

Cite this

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title = "Plasma Proteome Profiling to detect and avoid sample-related biases in biomarker studies",

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.",

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AU - Geyer, Philipp E.

AU - Voytik, Eugenia

AU - Treit, Peter V.

AU - Doll, Sophia

AU - Kleinhempel, Alisa

AU - Niu, Lili

AU - Müller, Johannes B

AU - Buchholtz, Marie-Luise

AU - Bader, Jakob M

AU - Teupser, Daniel

AU - Holdt, Lesca M

AU - Mann, Matthias

PY - 2019/11/7

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N2 - 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.

AB - 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.

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

Abstract

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