CPPCGM: A Highly Efficient Sequence-Based Tool for Simultaneously Identifying and Generating Cell-Penetrating Peptides.

Abstract

Cell-penetrating peptides (CPPs) are usually short oligopeptides with 5-30 amino acid residues. CPPs have been proven as important drug delivery vehicles into cells through different mechanisms, demonstrating their potential as therapeutic candidates. However, experimental screening and synthesis of CPPs could be time-consuming and expensive. Recently, numerous attempts have been made to develop computational methods as a cost-effective way for screening a number of potential CPP candidates. Despite significant advancements, current methods exhibit limited feature representation capabilities, thereby constraining the potential for further performance enhancements. In this study, we developed a deep learning framework called CPPCGM, which uses protein language models (PLMs) to identify and generate novel CPPs. There are two separate blocks in this framework: CPPClassifier and CPPGenerator. The former utilizes three pretrained models for simple voting, thereby accurately categorizing CPPs and non-CPPs. The latter, similar to a generative adversarial network, including a discriminator and a generator, generates peptides that are not present in the training data set. Our proposed CPPCGM has achieved remarkably high Matthews correlation coefficient scores of 0.876, 0.923, and 0.664 on three data sets based on the classification results. Compared with the state-of-the-art methods, the performance of our method is significantly improved. The results also demonstrated the generating potential of CPPCGM through qualitative and quantitative evaluation of the generated samples. Significantly, using PLM-based methods can optimize peptides for biochemical functions, benefiting drug delivery and biomedical applications. Materials related are publicly available at https://github.com/QiufenChen/CPPCGM.