Evidence map›Paper›PMID 40266252›Full record

ArticleeLife2025

Simultaneous polyclonal antibody sequencing and epitope mapping by cryo electron microscopy and mass spectrometry.

Douwe Schulte, Marta Šiborová, Lukas Käll, Joost Snijder

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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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

6 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

4 authors.

Douwe SchulteBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Padualaan, Utrecht, Netherlands.
Marta ŠiborováBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Padualaan, Utrecht, Netherlands.
Lukas KällScience for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, Royal Institute of Technology - KTH, Solna, Sweden.
Joost SnijderBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Padualaan, Utrecht, Netherlands.ORCID https://orcid.org/0000-0002-9310-8226

Funding

European Research Council 10.13039/100019180Nederlandse Organisatie voor Wetenschappelijk Onderzoek Gravitation 2013 BOO,Institute for Chemical Immunology (ICI; 024.002.009)
6 · The paper itself

Abstract

Antibodies are a major component of adaptive immunity against invading pathogens. Here, we explore possibilities for an analytical approach to characterize the antigen-specific antibody repertoire directly from the secreted proteins in convalescent serum. This approach aims to perform simultaneous antibody sequencing and epitope mapping using a combination of single particle cryo-electron microscopy (cryoEM) and bottom-up proteomics techniques based on mass spectrometry (LC-MS/MS). We evaluate the performance of the deep-learning tool ModelAngelo in determining de novo antibody sequences directly from reconstructed 3D volumes of antibody-antigen complexes. We demonstrate that while map quality is a critical bottleneck, it is possible to sequence antibody variable domains from cryoEM reconstructions with accuracies of up to 80-90%. While the rate of errors exceeds the typical levels of somatic hypermutation, we show that the ModelAngelo-derived sequences can be used to assign the used V-genes. This provides a functional guide to assemble de novo peptides from LC-MS/MS data more accurately and improves the tolerance to a background of polyclonal antibody sequences. Following this proof-of-principle, we discuss the feasibility and future directions of this approach to characterize antigen-specific antibody repertoires.

Indexed as

AntibodiesCryoelectron MicroscopyEpitope MappingSequence Analysis, ProteinChromatography, LiquidHumansProteomicsTandem Mass SpectrometryAntibodiesantibodycryoEMepitopehumanimmunologyinflammationmolecular biophysicsmouseproteomicsrepertoirerhesus macaquestructural biology

Identifiers

PMID40266252
PMCPMC12017766

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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 OpenQuestion graph.