Evidence map›Paper›PMID 40940569›Full record

ArticleEMBO molecular medicine2025

Pre-analytical drivers of bias in bead-enriched plasma proteomics.

Kathrin Korff, Johannes B Müller-Reif, Dorothea Fichtl, Vincent Albrecht, Alicia-Sophie Schebesta, Ericka C M Itang, Sebastian Virreira Winter, Lesca M Holdt, Daniel Teupser, Matthias Mann and 1 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Kathrin KorffDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID http://orcid.org/0009-0005-4971-2417
Johannes B Müller-ReifDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID http://orcid.org/0000-0003-3454-2396
Dorothea FichtlInstitute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany.
Vincent AlbrechtDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID http://orcid.org/0009-0003-1985-7733
Alicia-Sophie SchebestaDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
Ericka C M ItangDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.ORCID http://orcid.org/0000-0003-3387-2537
Sebastian Virreira Winterions.bio GmbH, Martinsried, Germany.
Lesca M HoldtInstitute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany.
Daniel TeupserInstitute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-9843-0145
Matthias MannDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. mmann@biochem.mpg.de.ORCID http://orcid.org/0000-0003-1292-4799
Philipp E GeyerDepartment of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. geyer@ions.bio.ORCID http://orcid.org/0000-0001-7980-4826

Funding

Bill and Melinda Gates Foundation (GF) INV-058348Bundesministerium für Bildung und Forschung (BMBF) 3LW0245German Center for Child and Adolescent Health (DZKJ) 01GL2406D
6 · The paper itself

Abstract

Bead-based enrichment is a promising strategy to improve depth in plasma proteomics by overcoming the dynamic range barrier. However, its robustness against pre-analytical variation has not been sufficiently characterized. Here, we systematically evaluate five plasma proteomics workflows, including three bead-based methods, a neat workflow, and a precipitation protocol using spike-ins of low-abundance proteins and defined cellular contaminants. We find that bead-based approaches enhance detection of low-abundance proteins but can be highly susceptible to systematic bias from platelet and PBMC contamination. This can inflate results by thousands of proteins, potentially explaining some of the high literature-reported numbers. A perchloric acid-based workflow shows resistance to erythrocyte and platelet-derived contamination. We investigate how centrifugation conditions, anticoagulant choice, and buffer-bead combinations modulate contamination profiles and demonstrate that bias can be mitigated by optimized sample handling. Altogether, we identify more than 13,000 different protein groups, including cellular components from the circulating proteome. Our results provide a quantitative framework for assessing workflow performance under variable sample quality and offer guidance for both biomarker discovery and quality control in clinical proteomics studies.

Indexed as

Blood ProteinsPlasmaProteomeProteomicsBlood PlateletsHumansBlood ProteinsProteomeBead-Based EnrichmentBiomarker ValidationPlasma ProteomicsPre-Analytical BiasSample Quality

Identifiers

PMID40940569
PMCPMC12603263

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.