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Nucleic Acids Research, 2003, Vol. 31, No. 13 3850-3855
© 2003 Oxford University Press

Geno2pheno: estimating phenotypic drug resistance from HIV-1 genotypes

Niko Beerenwinkel*, Martin Däumer1, Mark Oette2, Klaus Korn3, Daniel Hoffmann4, Rolf Kaiser1, Thomas Lengauer, Joachim Selbig5 and Hauke Walter3

Max Planck Institute for Informatics, Stuhlsatzenhausweg 85, D-66115 Saarbrücken, Germany 1 Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, D-50935 Köln, Germany 2 Clinic for Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany 3 Institute of Clinical and Molecular Virology, German National Reference Center for Retroviruses, University of Erlangen-Nürnberg, Schlossgarten 4, D-91054 Erlangen, Germany 4 Center of Advanced European Studies and Research, Friedensplatz 16, D-53111 Bonn, Germany 5 Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, D-14476 Golm, Germany

*To whom correspondence should be addressed. Tel: +49 6819325304; Fax: +49 6819325399; Email: beerenwinkel{at}mpi-sb.mpg.de

Therapeutic success of anti-HIV therapies is limited by the development of drug resistant viruses. These genetic variants display complex mutational patterns in their pol gene, which codes for protease and reverse transcriptase, the molecular targets of current antiretroviral therapy. Genotypic resistance testing depends on the ability to interpret such sequence data, whereas phenotypic resistance testing directly measures relative in vitro susceptibility to a drug. From a set of 650 matched genotype–phenotype pairs we construct regression models for the prediction of phenotypic drug resistance from genotypes. Since the range of resistance factors varies considerably between different drugs, two scoring functions are derived from different sets of predicted phenotypes. Firstly, we compare predicted values to those of samples derived from 178 treatment-naive patients and report the relative deviance. Secondly, estimation of the probability density of 2000 predicted phenotypes gives rise to an intrinsic definition of a susceptible and a resistant subpopulation. Thus, for a predicted phenotype, we calculate the probability of membership in the resistant subpopulation. Both scores provide standardized measures of resistance that can be calculated from the genotype and are comparable between drugs. The geno2pheno system makes these genotype interpretations available via the Internet (http://www.genafor.org/).


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