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Shetab Boushehri, S. ; Essig, K.* ; Chlis, N.K.* ; Herter, S.* ; Bacac, M.* ; Theis, F.J. ; Glasmacher, E.* ; Marr, C. ; Schmich, F.*

Explainable machine learning for profiling the immunological synapse and functional characterization of therapeutic antibodies.

Nat. Commun. 14:7888 (2023)

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Therapeutic antibodies are widely used to treat severe diseases. Most of them alter immune cells and act within the immunological synapse; an essential cell-to-cell interaction to direct the humoral immune response. Although many antibody designs are generated and evaluated, a high-throughput tool for systematic antibody characterization and prediction of function is lacking. Here, we introduce the first comprehensive open-source framework, scifAI (single-cell imaging flow cytometry AI), for preprocessing, feature engineering, and explainable, predictive machine learning on imaging flow cytometry (IFC) data. Additionally, we generate the largest publicly available IFC dataset of the human immunological synapse containing over 2.8 million images. Using scifAI, we analyze class frequency and morphological changes under different immune stimulation. T cell cytokine production across multiple donors and therapeutic antibodies is quantitatively predicted in vitro, linking morphological features with function and demonstrating the potential to significantly impact antibody design. scifAI is universally applicable to IFC data. Given its modular architecture, it is straightforward to incorporate into existing workflows and analysis pipelines, e.g., for rapid antibody screening and functional characterization.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords T-cells; Colocalization

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 14, Issue: 1, Article Number: 7888

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of AI for Health (AIH)
Institute of Computational Biology (ICB)

Grants Hightech Agenda Bayern
European Research Council (ERC)
F. Hoffmann-La Roche Ltd