Evidence map›Paper›PMID 38232633›Full record

ArticleEBioMedicine2024

Integrating artificial intelligence-based epitope prediction in a SARS-CoV-2 antibody discovery pipeline: caution is warranted.

Delphine Diana Acar, Wojciech Witkowski, Magdalena Wejda, Ruifang Wei, Tim Desmet, Bert Schepens, Sieglinde De Cae, Koen Sedeyn, Hannah Eeckhaut, Daria Fijalkowska and 15 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
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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

25 authors at 8 institutions in 2 countries.

Delphine Diana AcarHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, Ghent 9000, Belgium.
Wojciech WitkowskiHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, Ghent 9000, Belgium.
Magdalena WejdaHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, Ghent 9000, Belgium.
Ruifang WeiHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, Ghent 9000, Belgium.
Tim DesmetDepartment of Basic and Applied Medical Sciences, Ghent University, Ghent 9000, Belgium.
Bert SchepensVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Sieglinde De CaeVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Koen SedeynVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Hannah EeckhautVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Daria FijalkowskaVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Kenny RooseVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Sandrine VanmarckeVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Anne PouponMAbSilico, Tours 37000, France.
Dirk JochmansLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven 3000, Belgium.
Xin ZhangLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven 3000, Belgium.
Rana AbdelnabiLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven 3000, Belgium.
Caroline S FooLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven 3000, Belgium.
Birgit WeynandDepartment of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven 3000, Belgium.
Dirk ReiterDepartment of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels 1050, Belgium.
Nico CallewaertVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Han RemautDepartment of Bioengineering Sciences, Vrije Universiteit Brussel, Brussels 1050, Belgium; VIB-VUB Center for Structural Biology, VIB, Brussels 1050, Belgium.
Johan NeytsLaboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven 3000, Belgium.
Xavier SaelensVIB-UGent Center for Medical Biotechnology, VIB, Ghent 9052, Belgium; Department of Biochemistry and Microbiology, Ghent University, Ghent 9052, Belgium.
Sarah GerloHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, Ghent 9000, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent 9000, Belgium.
Linos VandekerckhoveHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, Ghent 9000, Belgium. Electronic address: linos.vandekerckhove@ugent.be.
Vlaams Instituut voor Biotechnologie · BEGhent University Hospital · BERega Institute for Medical Research · BECentre National de la Recherche Scientifique · FRGhent University · BEUniversité de Tours · FRUniversité Libre de Bruxelles · BEVrije Universiteit Brussel · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSARS-CoV-2-neutralizing antibodies (nABs) showed great promise in the early phases of the COVID-19 pandemic. The emergence of resistant strains, however, quickly rendered the majority of clinically approved nABs ineffective. This underscored the imperative to develop nAB cocktails targeting non-overlapping epitopes.

methodsUndertaking a nAB discovery program, we employed a classical workflow, while integrating artificial intelligence (AI)-based prediction to select non-competing nABs very early in the pipeline. We identified and in vivo validated (in female Syrian hamsters) two highly potent nABs.

findingsDespite the promising results, in depth cryo-EM structural analysis demonstrated that the AI-based prediction employed with the intention to ensure non-overlapping epitopes was inaccurate. The two nABs in fact bound to the same receptor-binding epitope in a remarkably similar manner.

interpretationOur findings indicate that, even in the Alphafold era, AI-based predictions of paratope-epitope interactions are rough and experimental validation of epitopes remains an essential cornerstone of a successful nAB lead selection.

fundingFull list of funders is provided at the end of the manuscript.

Indexed as

COVID-19SARS-CoV-2AnimalsAntibodies, NeutralizingAntibodies, ViralArtificial IntelligenceCricetinaeEpitopesFemaleHumansMesocricetusPandemicsAntibodies, NeutralizingAntibodies, ViralEpitopesCovid-19Epitope mappingIn silico predictionNeutralizing antibodySARS-CoV-2

Identifiers

PMID38232633
PMCPMC10803917
OpenAlexW4390988621

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.