Discovery of potential antidiabetic peptides using deep learning

Abstract

Antidiabetic peptides (ADPs), peptides with potential antidiabetic activity, hold significant importance in the treatment and control of diabetes. Despite their therapeutic potential, the discovery and prediction of ADPs remain challenging due to limited data, the complex nature of peptide functions, and the expensive and time-consuming nature of traditional wet lab experiments. This study aims to address these challenges by exploring methods for the discovery and prediction of ADPs using advanced deep learning techniques. Specifically, we developed two models: a single-channel CNN and a three-channel neural network (CNN + RNN + Bi-LSTM). ADPs were primarily gathered from the BioDADPep database, alongside thousands of non-ADPs sourced from anticancer, antibacterial, and antiviral peptide datasets. Subsequently, data preprocessing was performed with the evolutionary scale model (ESM-2), followed by model training and evaluation through 10-fold cross-validation. Furthermore, this work collected a series of newly published ADPs as an independent test set through literature review, and found that the CNN model achieved the highest accuracy (90.48 %) in predicting the independent test set, surpassing existing ADP prediction tools. Finally, the application of the model was considered. SeqGAN was used to generate new candidate ADPs, followed by screening with the constructed CNN model. Selected peptides were then evaluated using physicochemical property prediction and structural forecasts for pharmaceutical potential. In summary, this study not only established robust ADP prediction models but also employed these models to screen a batch of potential ADPs, addressing a critical need in the field of peptide-based antidiabetic research.