Stack-AAgP: Computational prediction and interpretation of anti-angiogenic peptides using a meta-learning framework

Background: Angiogenesis plays a vital role in the pathogenesis of several human diseases, particularly in the case of solid tumors. In the realm of cancer treatment, recent investigations into peptides with anti-angiogenic properties have yielded encouraging outcomes, thereby creating a hopeful therapeutic avenue for the treatment of cancer. Therefore, correctly identifying the anti-angiogenic peptides is extremely important in comprehending their biophysical and biochemical traits, laying the groundwork for uncovering novel drugs to combat cancer. Methods: In this work, we present a novel ensemble-learning-based model, Stack-AAgP, specifically designed for the accurate identification and interpretation of anti-angiogenic peptides (AAPs). Initially, a feature representation approach is employed, generating 24 baseline models through six machine learning algorithms (random forest [RF], extra tree classifier [ETC], extreme gradient boosting [XGB], light gradient boosting machine [LGBM], CatBoost, and SVM) and four feature encodings (pseudo-amino acid composition [PAAC], amphiphilic pseudo-amino acid composition [APAAC], composition of k-spaced amino acid group pairs [CKSAAP], and quasi-sequence-order [QSOrder]). Subsequently, the output (predicted probabilities) from 24 baseline models was inputted into the same six machine-learning classifiers to generate their respective meta-classifiers. Finally, the meta-classifiers were stacked together using the ensemble-learning framework to construct the final predictive model. Results: Findings from the independent test demonstrate that Stack-AAgP outperforms the state-of-the-art methods by a considerable margin. Systematic experiments were conducted to assess the influence of hyperparameters on the proposed model. Our model, Stack-AAgP, was evaluated on the independent NT15 dataset, revealing superiority over existing predictors with an accuracy improvement ranging from 5% to 7.5% and an increase in Matthews Correlation Coefficient (MCC) from 7.2% to 12.2%.