CPPred-FL: a sequence-based predictor for large-scale identification of cell-penetrating peptides by feature representation learning.

Cell-penetrating peptides (CPPs) have been shown to be a transport vehicle for delivering cargoes into live cells, offering great potential as future therapeutics. It is essential to identify CPPs for better understanding of their functional mechanisms. Machine learning-based methods have recently emerged as a main approach for computational identification of CPPs. However, one of the main challenges and difficulties is to propose an effective feature representation model that sufficiently exploits the inner difference and relevance between CPPs and non-CPPs, in order to improve the predictive performance. In this paper, we have developed CPPred-FL, a powerful bioinformatics tool for fast, accurate and large-scale identification of CPPs. In our predictor, we introduce a new feature representation learning scheme that enables one to learn feature representations from totally 45 well-trained random forest models with multiple feature descriptors from different perspectives, such as compositional information, position-specific information and physicochemical properties, etc. We integrate class and probabilistic information into our feature representations. To improve the feature representation ability, we further remove redundant and irrelevant features by feature space optimization. Benchmarking experiments showed that CPPred-FL, using 19 informative features only, is able to achieve better performance than the state-of-the-art predictors. We anticipate that CPPred-FL will be a powerful tool for large-scale identification of CPPs, facilitating the characterization of their functional mechanisms and accelerating their applications in clinical therapy.