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Biology subjects

Bevers, J.

Publications and source records attributed to Bevers, J..

2 recordsLinked to original sources

Property Enhancer - a data efficient multi-objective approach for functional antibody optimization

In-silico antibody lead optimization remains challenging due to scarce high-quality data, costly experimental validation, and the need to jointly optimize multiple developability properties. Discovery workflows often rely on high-throughput phage, ribosome or yeast display experiments, which yield large but noisy datasets; as leads emerge, strategies shift to low-throughput assays which are precise, yet unscalable. Deep-learning and language-model approaches are hindered by such limited, unreliable measurements. We introduce Property Enhancer (PropEn), a data-efficient framework for low-data, heterogeneous regimes that can simultaneously optimize multiple antibody properties. PropEn proposes a matching-based augmentation that expands the training data with sequence pairs differing by only a few mutations; within each pair the second sequence improves the target value, providing an implicit optimization signal. Extensive in silico and in vitro tests show 10-39x affinity gains across four targets and nine leads, and enable joint multi-property optimization, positioning PropEn as a scalable, general solution.

molecular biology↗

Lab-in-the-loop therapeutic antibody design with deep learning

Therapeutic antibody design is a complex multi-property optimization problem with substantial promise for improvement with the application of machine-learning methods. Towards realizing that promise, we introduce "Lab-in-the-loop," a new approach that orchestrates state-of-the-art repertoire mining methods, generative machine learning models, multi-task property predictors, active learning ranking and selection, and in vitro experimentation in a semi-autonomous, iterative optimization loop. By automating the design of antibody variants, property prediction, ranking and selection of designs to assay in the lab, and ingestion of in vitro data, we enable an end-to-end approach to developing computationally-informed therapeutic antibody design pipelines. We apply lab-in-the-loop to eleven seed antibodies obtained via animal immunization with four clinically relevant antigen targets: EGFR, IL-6, HER2, and OSM. Over 1,800 unique antibody variants are tested throughout four rounds of iterative optimization identifying 3-100x better binding variants for all targets and 10/11 seeds, with the best binders exceeding 100 pM affinity, demonstrating a process by which end-to-end machine learning can be developed for therapeutic antibody development.

bioengineering↗