Abstract
Due to the unnecessary immune responses induced by therapeutic antibodies in clinical applications, immunogenicity is an important factor to be considered in the development of antibody therapeutics. To a certain extent, there is a lag in using wet-lab experiments to test the immunogenicity in the development process of antibody therapeutics. Developing a computational method to predict the immunogenicity at once the antibody sequence is designed, is of great significance for the screening in the early stage and reducing the risk of antibody therapeutics development. In this study, a computational immunogenicity prediction method was proposed on the basis of AntiBERTy-based features of amino sequences in the antibody variable region. The AntiBERTy-based sequence features were first calculated using the AntiBERTy pre-trained model. Principal component analysis (PCA) was then applied to reduce the extracted feature to two dimensions to obtain the final features. AutoGluon was then used to train multiple machine learning models and the best one, the weighted ensemble model, was obtained through 5-fold cross-validation on the collected data. The data contains 199 commercial therapeutic antibodies, of which 177 samples were used for model training and 5-fold cross-validation, and the remaining 22 samples were used as an independent test dataset to evaluate the performance of the constructed model and compare it with other prediction methods. Test results show that the proposed method outperforms the comparison method with 0.7273 accuracy on the independent test dataset, which is 9.09% higher than the comparison method. The corresponding web server is available through the official website of GenScript Co., Ltd., https://www.genscript.com/tools/antibody-immunogenicity.