{"entity": "publication", "iuid": "e8d5450e7fa24f618378b9c3a1a15e6d", "timestamp": "2026-08-20T20:36:26.825Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e8d5450e7fa24f618378b9c3a1a15e6d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e8d5450e7fa24f618378b9c3a1a15e6d"}}, "title": "Simultaneous polyclonal antibody sequencing and epitope mapping by cryo electron microscopy and mass spectrometry.", "authors": [{"family": "Schulte", "given": "Douwe", "initials": "D"}, {"family": "\u0160iborov\u00e1", "given": "Marta", "initials": "M"}, {"family": "K\u00e4ll", "given": "Lukas", "initials": "L"}, {"family": "Snijder", "given": "Joost", "initials": "J", "orcid": "0000-0002-9310-8226", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eaf244f006c744cea77ba2addf983ff0.json"}}], "type": "journal article", "published": "2025-04-23", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "14", "issn-l": "2050-084X"}, "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.", "doi": "10.7554/eLife.101322", "pmid": "40266252", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12017766"}, {"db": "pii", "key": "101322"}], "notes": [], "created": "2026-08-20T13:50:56.173Z", "modified": "2026-08-20T13:50:56.248Z"}