| Autor: |
Szabolcs Éliás, Clemens Wrzodek, Charlotte M. Deane, Alain C. Tissot, Stefan Klostermann, Francesca Ros |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Frontiers in Bioinformatics, Vol 3 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2673-7647 |
| DOI: |
10.3389/fbinf.2023.1286883 |
| Popis: |
Antibodies are generated with great diversity in nature resulting in a set of molecules, each optimized to bind a specific target. Taking advantage of their diversity and specificity, antibodies make up for a large part of recently developed biologic drugs. For therapeutic use antibodies need to fulfill several criteria to be safe and efficient. Polyspecific antibodies can bind structurally unrelated molecules in addition to their main target, which can lead to side effects and decreased efficacy in a therapeutic setting, for example via reduction of effective drug levels. Therefore, we created a neural-network-based model to predict polyspecificity of antibodies using the heavy chain variable region sequence as input. We devised a strategy for enriching antibodies from an immunization campaign either for antigen-specific or polyspecific binding properties, followed by generation of a large sequencing data set for training and cross-validation of the model. We identified important physico-chemical features influencing polyspecificity by investigating the behaviour of this model. This work is a machine-learning-based approach to polyspecificity prediction and, besides increasing our understanding of polyspecificity, it might contribute to therapeutic antibody development. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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