Evolution of drug resistance in HIV protease.
BMC Bioinformatics
; 21(Suppl 18): 497, 2020 Dec 30.
Article
em En
| MEDLINE
| ID: mdl-33375936
ABSTRACT
BACKGROUND:
Drug resistance is a critical problem limiting effective antiviral therapy for HIV/AIDS. Computational techniques for predicting drug resistance profiles from genomic data can accelerate the appropriate choice of therapy. These techniques can also be used to identify protease mutants for experimental studies of resistance and thereby assist in the development of next-generation therapies. Few studies, however, have assessed the evolution of resistance from genotype-phenotype data.RESULTS:
The machine learning produced highly accurate and robust classification of resistance to HIV protease inhibitors. Genotype data were mapped to the enzyme structure and encoded using Delaunay triangulation. Estimates of evolutionary relationships, based on this encoding, and using Minimum Spanning Trees, showed clusters of mutations that closely resemble the wild type. These clusters appear to evolve uniquely to more resistant phenotypes.CONCLUSIONS:
Using the triangulation metric and spanning trees results in paths that are consistent with evolutionary theory. The majority of the paths show bifurcation, namely they switch once from non-resistant to resistant or from resistant to non-resistant. Paths that lose resistance almost uniformly have far lower levels of resistance than those which either gain resistance or are stable. This strongly suggests that selection for stability in the face of a rapid rate of mutation is as important as selection for resistance in retroviral systems.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Protease de HIV
/
Evolução Molecular
/
Farmacorresistência Viral
/
Aprendizado de Máquina
Limite:
Humans
Idioma:
En
Revista:
BMC Bioinformatics
Assunto da revista:
INFORMATICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos