StackAHTPs: An explainable antihypertensive peptides identifier based on heterogeneous features and stacked learning approach

Abstract

Hypertension, often known as high blood pressure, is a major concern to millions of individuals globally. Recent studies have demonstrated the significant efficacy of naturally derived peptides in reducing blood pressure. Hypertension is one of the risks associated with cardiovascular disorders and other health problems. Naturally sourced bioactive peptides possessing antihypertensive properties provide considerable potential as viable substitutes for conventional pharmaceutical medications. Currently, thorough examination of antihypertensive peptide (AHTPs), by using traditional wet-lab methods is highly expensive and labours. Therefore, in-silico approaches especially machine-learning (ML) algorithms are favourable due to saving time and cost in the discovery of AHTPs. In this study, a novel ML-based predictor, called StackAHTP was developed for predicting accurate AHTPs from sequence only. The proposed method, utilise two types of feature descriptors Pseudo-Amino Acid Composition and Dipeptide Composition to encode the local and global hidden information from peptide sequences. Furthermore, the encoded features are serially merged and ranked through SHapley Additive explanations (SHAP) algorithm. Then, the top ranked are fed into three different ensemble classifiers (Bagging, Boosting, and Stacking) for enhancing the prediction performance of the model. The StackAHTPs method achieved superior performance compare to other ML classifiers (AdaBoost, XGBoost and Light Gradient Boosting (LightGBM), Bagging and Boosting) on 10-fold cross validation and independent test. The experimental outcomes demonstrate that our proposed method outperformed the existing methods and achieved an accuracy of 92.25% and F1-score of 89.67% on independent test for predicting AHTPs and non-AHTPs. The authors believe this research will remarkably contribute in predicting large-scale characterisation of AHTPs and accelerate the drug discovery process. At https://github.com/ali-ghulam/StackAHTPs you may find datasets features used.