Ab-amy 2.0: Predicting light chain amyloidogenic risk of therapeutic antibodies based on antibody language model.

Abstract

Therapeutic antibodies have emerged as a promising treatment option for a wide range of diseases. However, the light chain of antibodies can potentially induce amyloidosis, a condition characterized by protein misfolding and aggregation, posing a significant safety concern. Therefore, it is crucial to assess the amyloidogenic risk of therapeutic antibodies during the early stages of drug development. In this study, we introduce AB-Amy 2.0, a new computational model with enhanced performance for assessing the light chain amyloidogenic risk of therapeutic antibodies. By employing pretrained protein language models (PLMs) embeddings, AB-Amy 2.0 achieves higher accuracy in amyloidogenic risk prediction compared with traditional features offering a crucial tool for early-stage identification of antibodies with low aggregation propensity. The AB-Amy 2.0 was trained on antiBERTy embeddings and utilizes the SVM algorithm, resulting in superior performance metrics. On an independent test dataset, the model achieved high sensitivity, specificity, ACC, MCC and AUC of 93.47%, 89.23%, 91.92%, 0.8261 and 0.9739, respectively. These results highlight the effectiveness and robustness of AB-Amy 2.0 in predicting light chain amyloidogenic risk accurately. To facilitate user-friendly access, we have developed an online web server (http://i.uestc.edu.cn/AB-Amy2) and a command line tool (https://github.com/zzyywww/ABAmy2). These resources enable the broader application of this advanced model and promise to enhance the development of safer therapeutic antibodies.