Charoenkwan P.Chumnanpuen P.Schaduangrat N.Shoombuatong W.Mahidol University2025-01-232025-01-232025-02-01Methods Vol.234 (2025) , 131-14010462023https://repository.li.mahidol.ac.th/handle/20.500.14594/102826Identifying angiotensin-I-converting enzyme (ACE) inhibitory peptides accurately is crucial for understanding the primary factor that regulates the renin-angiotensin system and for providing guidance in developing new potential drugs. Given the inherent experimental complexities, using computational methods for in silico peptide identification could be indispensable for facilitating the high-throughput characterization of ACE inhibitory peptides. In this paper, we propose a novel deep stacking-based ensemble learning framework, termed Deepstack-ACE, to precisely identify ACE inhibitory peptides. In Deepstack-ACE, the input peptide sequences are fed into the word2vec embedding technique to generate sequence representations. Then, these representations were employed to train five powerful deep learning methods, including long short-term memory, convolutional neural network, multi-layer perceptron, gated recurrent unit network, and recurrent neural network, for the construction of base-classifiers. Finally, the optimized stacked model was constructed based on the best combination of selected base-classifiers. Benchmarking experiments showed that Deepstack-ACE attained a more accurate and robust identification of ACE inhibitory peptides compared to its base-classifiers and several conventional machine learning classifiers. Remarkably, in the independent test, our proposed model significantly outperformed the current state-of-the-art methods, with a balanced accuracy of 0.916, sensitivity of 0.911, and Matthews correlation coefficient scores of 0.826. Moreover, we developed a user-friendly web server for Deepstack-ACE, which is freely available at https://pmlabqsar.pythonanywhere.com/Deepstack-ACE. We anticipate that our proposed Deepstack-ACE model can provide a faster and reasonably accurate identification of ACE inhibitory peptides.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1016/j.ymeth.2024.12.0052-s2.0-8521321897410959130