Prediction of HIV-1 protease cleavage site using a combination of sequence, structural, and physicochemical features.
BACKGROUND
The human immunodeficiency virus type 1 (HIV-1) aspartic protease is an important enzyme owing to its imperative part in viral development and a causative agent of deadliest disease known as acquired immune deficiency syndrome (AIDS). Development of HIV-1 protease inhibitors can help understand the specificity of substrates which can restrain the replication of HIV-1, thus antagonize AIDS. However, experimental methods in identification of HIV-1 protease cleavage sites are generally time-consuming and labor-intensive. Therefore, using computational methods to predict cleavage sites has become highly desirable.


RESULTS
In this study, we propose a prediction method in which sequence, structural, and physicochemical features are incorporated in various machine learning algorithms. Then, a bidirectional stepwise selection algorithm is incorporated in feature selection to identify discriminative features. Further, only the selected features are calculated by various encoding schemes and used as input for decision trees, logistic regression, and artificial neural networks. Moreover, a more rigorous three-way data split procedure is applied to evaluate the objective performance of cleavage site prediction. Four benchmark datasets collected from previous studies are used to evaluate the predictive performance.


CONCLUSIONS
Experiment results showed that combinations of sequence, structure, and physicochemical features performed better than single feature type for identification of HIV-1 protease cleavage sites. In addition, incorporation of stepwise feature selection is effective to identify interpretable biological features to depict specificity of the substrates. Moreover, artificial neural networks perform significantly better than the other two classifiers. Finally, the proposed method achieved 80.0% ~ 97.4% in accuracy and 0.815 ~ 0.995 evaluated by independent test sets in a three-way data split procedure.
Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Onkar
O
Singh
Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. emilysu@tmu.edu.tw.
Emily Chia-Yu
EC
Su
D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D000068598:Data Accuracy; D003663:Decision Trees; D015658:HIV Infections; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D016571:Neural Networks, Computer; D011487:Protein Conformation; D013379:Substrate Specificity
D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1
Cleavage sites; HIV-1 protease; Machine learning; Physicochemical properties; Pseudo amino acid composition; Sequence features; Structural features