Background: Drug resistance in HIV is the major problem limiting effective antiviral therapy. Computational techniques for predicting drug resistance profiles from genomic data can accelerate the appropriate choice of therapy. These techniques can also be used to select protease mutants for experimental studies of resistance and thereby assist in the development of next-generation therapies.
Results: The machine learning produced highly accurate and robust classification of HIV protease resistance. Genotype data were mapped to the enzyme structure and encoded using Delaunay triangulation. Generative machine learning models trained on one inhibitor could classify resistance from other inhibitors with varying levels of accuracy. Generally, the accuracy was best when the inhibitors were chemically similar.
Conclusions: Restricted Boltzmann Machines are an effective machine learning tool for classification of genomic and structural data. They can also be used to compare resistance profiles of different protease inhibitors.
Keywords: Drug resistance; HIV protease; Machine learning; RBM; Structure-based.