BackgroundDrug 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.ResultsThe 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.ConclusionsRestricted 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.
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.
Network based attacks are the major threat to security on the Internet. The volume of traffic and the high variability of the attacks place threat detection squarely in the domain of big data. Conventional approaches are mostly based on signatures. While these are relatively inexpensive computationally, they are inflexible and insensitive to small variations in the attack vector. Therefore we explored the use of machine learning techniques on real flow data. We found that benign traffic could be identified with high accuracy.
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