title: Multilabel classification for exploiting cross-resistance information in HIV-1 drug resistance prediction.
abstract: BACKGROUND
  Antiretroviral treatment regimens can sufficiently suppress viral replication in human immunodeficiency virus (HIV)-infected patients and prevent the progression of the disease. However, one of the factors contributing to the progression of the disease despite ongoing antiretroviral treatment is the emergence of drug resistance. The high mutation rate of HIV can lead to a fast adaptation of the virus under drug pressure, thus to failure of antiretroviral treatment due to the evolution of drug-resistant variants. Moreover, cross-resistance phenomena have been frequently found in HIV-1, leading to resistance not only against a drug from the current treatment, but also to other not yet applied drugs. Automatic classification and prediction of drug resistance is increasingly important in HIV research as well as in clinical settings, and to this end, machine learning techniques have been widely applied. Nevertheless, cross-resistance information was not taken explicitly into account, yet.
  
  
  RESULTS
  In our study, we demonstrated the use of cross-resistance information to predict drug resistance in HIV-1. We tested a set of more than 600 reverse transcriptase sequences and corresponding resistance information for six nucleoside analogues. Based on multilabel classification models and cross-resistance information, we were able to significantly improve overall prediction accuracy for all drugs, compared with single binary classifiers without any additional information. Moreover, we identified drug-specific patterns within the reverse transcriptase sequences that can be used to determine an optimal order of the classifiers within the classifier chains. These patterns are in good agreement with known resistance mutations and support the use of cross-resistance information in such prediction models.
  
  
  BACKGROUND
  dominik.heider@uni-due.de
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Bioinformatics, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Heider
authors.forename: Robin
authors.initials: R
authors.lastname: Senge
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cheng
authors.forename: Eyke
authors.initials: E
authors.lastname: Hüllermeier
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D017421:Sequence Analysis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase