title: PASS-based approach to predict HIV-1 reverse transcriptase resistance.
abstract: HIV reverse transcriptase (RT) inhibitors targeting the early stages of virus-host interactions are of great interest to scientists. Acquired HIV RT resistance happens due to mutations in a particular region of the pol gene encoding the HIV RT amino acid sequence. We propose an application of the previously developed PASS algorithm for prediction of amino acid substitutions potentially involved in the resistance of HIV-1 based on open data. In our work, we used more than 3200 HIV-1 RT variants from the publicly available Stanford HIV RT and protease sequence database already tested for 10 anti-HIV drugs including both nucleoside and non-nucleoside RT inhibitors. We used a particular amino acid residue and its position to describe primary structure-resistance relationships. The average balanced accuracy of the prediction obtained in 20-fold cross-validation for the Phenosense dataset was about 88% and for the Antivirogram dataset was about 79%. Thus, the PASS-based algorithm may be used for prediction of the amino acid substitutions associated with the resistance of HIV-1 based on open data. The computational approach for the prediction of HIV-1 associated resistance can be useful for the selection of RT inhibitors for the treatment of HIV infected patients in the clinical practice. Prediction of the HIV-1 RT associated resistance can be useful for the development of new anti-HIV drugs active against the resistant variants of RT. Therefore, we propose that this study can be potentially useful for anti-HIV drug development.
authors.affiliation: 1 Department for Bioinformatics, Institute of Biomedical Chemistry, 10 building 8, Pogodinskaya street, 119121, Moscow, Russia.
authors.forename: Olga
authors.identifier: http://orcid.org/0000-0002-3723-7832
authors.initials: O
authors.lastname: Tarasova
authors.affiliation: 1 Department for Bioinformatics, Institute of Biomedical Chemistry, 10 building 8, Pogodinskaya street, 119121, Moscow, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Filimonov
authors.affiliation: 1 Department for Bioinformatics, Institute of Biomedical Chemistry, 10 building 8, Pogodinskaya street, 119121, Moscow, Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Poroikov
mesh_terms: D000465:Algorithms; D019380:Anti-HIV Agents / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D024882:Drug Resistance, Viral / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1 resistance; PASS; amino acid sequences; open data; reverse transcriptase