DeepForest-HTP: A novel deep forest approach for predicting antihypertensive peptides

Hypertension is a major preventable risk factor for cardiovascular disease, affecting over 1.5 billion adults worldwide. Antihypertensive peptides (AHTPs) have gained attention as a natural therapeutic option with minimal side effects. This study proposes a Deep Forest-based machine learning framework for AHTP prediction, leveraging a multi-granularity cascade structure to enhance classification accuracy. We integrated data from BIOPEP-UWM and three previously used datasets, totaling 2000 peptide sequences, and introduced novel feature extraction methods to build a comprehensive dataset for model training. This study represents the first application of Deep Forest for AHTP identification, demonstrating substantial classification performance advantages over traditional methods (e.g., SVM, CNN, and XGBoost) as well as recent mainstream prediction models (Ensemble-AHTPpred, CNN-SVM Ensemble, and mAHTPred). Requiring no complex manual feature engineering, the model adapts flexibly to various data needs, offering a novel perspective for efficient AHTP prediction and promising utility in hypertension management. On the benchmark dataset, the model achieved high accuracy, sensitivity, and AUC, providing a robust tool for identifying safe and effective AHTPs. However, future efforts should incorporate larger and more diverse independent validation datasets to further improve the model and enhance its generalizability. Additionally, the model's predictive accuracy relies on known AHTP targets and sequence features, potentially limiting its ability to detect AHTPs with uncharacterized or atypical properties.