Prediction of HIV-1 protease cleavage site from octapeptide sequence information using selected classifiers and hybrid descriptors

Abstract

Background In most parts of the world, especially in underdeveloped countries, acquired immunodeficiency syndrome (AIDS) still remains a major cause of death, disability, and unfavorable economic outcomes. This has necessitated intensive research to develop effective therapeutic agents for the treatment of human immunodeficiency virus (HIV) infection, which is responsible for AIDS. Peptide cleavage by HIV-1 protease is an essential step in the replication of HIV-1. Thus, correct and timely prediction of the cleavage site of HIV-1 protease can significantly speed up and optimize the drug discovery process of novel HIV-1 protease inhibitors. In this work, we built and compared the performance of selected machine learning models for the prediction of HIV-1 protease cleavage site utilizing a hybrid of octapeptide sequence information comprising bond composition, amino acid binary profile (AABP), and physicochemical properties as numerical descriptors serving as input variables for some selected machine learning algorithms. Our work differs from antecedent studies exploring the same subject in the combination of octapeptide descriptors and method used. Instead of using various subsets of the dataset for training and testing the models, we combined the dataset, applied a 3-way data split, and then used a "stratified" 10-fold cross-validation technique alongside the testing set to evaluate the models. Results Among the 8 models evaluated in the “stratified” 10-fold CV experiment, logistic regression, multi-layer perceptron classifier, linear discriminant analysis, gradient boosting classifier, Naive Bayes classifier, and decision tree classifier with AUC, F-score, and B. Acc. scores in the ranges of 0.91–0.96, 0.81–0.88, and 80.1–86.4%, respectively, have the closest predictive performance to the state-of-the-art model (AUC 0.96, F-score 0.80 and B. Acc. ~ 80.0%). Whereas, the perceptron classifier and the K-nearest neighbors had statistically lower performance (AUC 0.77–0.82, F-score 0.53–0.69, and B. Acc. 60.0–68.5%) at p < 0.05. On the other hand, logistic regression, and multi-layer perceptron classifier (AUC of 0.97, F-score > 0.89, and B. Acc. > 90.0%) had the best performance on further evaluation on the testing set, though linear discriminant analysis, gradient boosting classifier, and Naive Bayes classifier equally performed well (AUC > 0.94, F-score > 0.87, and B. Acc. > 86.0%). Conclusions Logistic regression and multi-layer perceptron classifiers have comparable predictive performances to the state-of-the-art model when octapeptide sequence descriptors consisting of AABP, bond composition and standard physicochemical properties are used as input variables. In our future work, we hope to develop a standalone software for HIV-1 protease cleavage site prediction utilizing the linear regression algorithm and the aforementioned octapeptide sequence descriptors.

Meta-2OM: A multi-classifier meta-model for the accurate prediction of RNA 2′-O-methylation sites in human RNA

“…A NB classifier is the probabilistic ML model built based on the principles of Bayes’ theorem, with the foundational assumption of conditional independence among all pairs of input features. This model is extensively applied across various bioinformatics challenges, especially sequence-based function prediction [ 75 ]. Among the different variants of Naive Bayes classifiers, we implemented here the Gaussian Naive Bayes classifier.…”

Comprehending the Structure, Dynamics, and Mechanism of Action of Drug-Resistant HIV Protease

“…Red: negatively charged residues, blue: positively charged residues, green: polar uncharged residues, black: hydrophobic residues. Figure adapted with permission from ref ( 63 ). Onah et al CC BY license.…”

“… 62 A comprehensive bioinformatics study evaluated the performance of different machine learning models for predicting HIV PR cleavage sites for octapeptide sequences using descriptors such as bond composition, amino acid binary profile (AABP), and physicochemical properties. 63 The study suggested that the predictive performances of the logistic regression model and multilayer perceptron classifiers model are on par with the state-of-the-art linear support vector machine model. The authors also plotted a sequence logo from multiple sequence alignment of cleavable octapeptide sequences to predict the frequency of amino acids at each cleavable subsite ( Figure 4 c).…”

“…In a recent work, from the kinetic measurements of 150 distinct HIV PR substrate variants, two motifs for the cleavage site of the substrates are proposed, namely, NΩ/PI (N: Asn, Ω: aromatic Phe or Tyr, P: Pro, I: Ile) and βΦ/ΦE (β: β-branched aliphatic, Φ: hydrophobic, Φ: hydrophobic, E: Glu) . A comprehensive bioinformatics study evaluated the performance of different machine learning models for predicting HIV PR cleavage sites for octapeptide sequences using descriptors such as bond composition, amino acid binary profile (AABP), and physicochemical properties . The study suggested that the predictive performances of the logistic regression model and multilayer perceptron classifiers model are on par with the state-of-the-art linear support vector machine model.…”

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“…A NB classifier is the probabilistic ML model built based on the principles of Bayes' theorem, with the foundational assumption of conditional independence among all pairs of input features. This model is extensively applied across various bioinformatics challenges, especially sequence-based function prediction [75]. Among the different variants of Naive Bayes classifiers, we implemented here the Gaussian Naive Bayes classifier.…”