Mining complex genotypic features for predicting HIV-1 drug resistance

摘要

Motivation: Human immunodeficiency virus type 1 (HIV-1) evolves in human body, and its exposure to a drug often causes mutations that enhance the resistance against the drug. To design an effective pharmacotherapy for an individual patient, it is important to accurately predict the drug resistance based on genotype data. Notably, the resistance is not just the simple sum of the effects of all mutations. Structural biological studies suggest that the association of mutations is crucial: even if mutations A or B alone do not affect the resistance, a significant change might happen when the two mutations occur together. Linear regression methods cannot take the associations into account, while decision tree methods can reveal only limited associations. Kernel methods and neural networks implicitly use all possible associations for prediction, but cannot select salient associations explicitly.