Institut für Medizintechnik und Medizininformatik

Dauerhafte URI für die Sammlunghttps://irf.fhnw.ch/handle/11654/23

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  • Publikation
    Unconstrained generation of synthetic antibody–antigen structures to guide machine learning methodology for antibody specificity prediction
    (Nature, 19.12.2022) Robert, Philippe A.; Akbar, Rahmad; Frank, Robert; Pavlović, Milena; Widrich, Michael; Snapkov, Igor; Slabodkin, Andrei; Chernigovskaya, Maria; Scheffer, Lonneke; Smorodina, Eva; Rawat, Puneet; Mehta, Brij Bhushan; Vu, Mai Ha; Mathisen, Ingvild Frøberg; Prósz, Aurél; Abram, Krzysztof; Olar, Alex; Miho, Enkelejda; Haug, Dag Trygve Tryslew; Lund-Johansen, Fridtjof; Hochreiter, Sepp; Haff, Ingrid Hobæk; Klambauer, Günter; Sandve, Geir Kjetil; Greiff, Victor
    Machine learning (ML) is a key technology for accurate prediction of antibody–antigen binding. Two orthogonal problems hinder the application of ML to antibody-specificity prediction and the benchmarking thereof: the lack of a unified ML formalization of immunological antibody-specificity prediction problems and the unavailability of large-scale synthetic datasets to benchmark real-world relevant ML methods and dataset design. Here we developed the Absolut! software suite that enables parameter-based unconstrained generation of synthetic lattice-based three-dimensional antibody–antigen-binding structures with ground-truth access to conformational paratope, epitope and affinity. We formalized common immunological antibody-specificity prediction problems as ML tasks and confirmed that for both sequence- and structure-based tasks, accuracy-based rankings of ML methods trained on experimental data hold for ML methods trained on Absolut!-generated data. The Absolut! framework has the potential to enable real-world relevant development and benchmarking of ML strategies for biotherapeutics design.
    01A - Beitrag in wissenschaftlicher Zeitschrift