title: A simple structure-based model for the prediction of HIV-1 co-receptor tropism.
abstract: BACKGROUND
  Human Immunodeficiency Virus 1 enters host cells through interaction of its V3 loop (which is part of the gp120 protein) with the host cell receptor CD4 and one of two co-receptors, namely CCR5 or CXCR4. Entry inhibitors binding the CCR5 co-receptor can prevent viral entry. As these drugs are only available for CCR5-using viruses, accurate prediction of this so-called co-receptor tropism is important in order to ensure an effective personalized therapy. With the development of next-generation sequencing technologies, it is now possible to sequence representative subpopulations of the viral quasispecies.
  
  
  RESULTS
  Here we present T-CUP 2.0, a model for predicting co-receptor tropism. Based on our recently published T-CUP model, we developed a more accurate and even faster solution. Similarly to its predecessor, T-CUP 2.0 models co-receptor tropism using information of the electrostatic potential and hydrophobicity of V3-loops. However, extracting this information from a simplified structural vacuum-model leads to more accurate and faster predictions. The area-under-the-ROC-curve (AUC) achieved with T-CUP 2.0 on the training set is 0.968±0.005 in a leave-one-patient-out cross-validation. When applied to an independent dataset, T-CUP 2.0 has an improved prediction accuracy of around 3% when compared to the original T-CUP.
  
  
  CONCLUSIONS
  We found that it is possible to model co-receptor tropism in HIV-1 based on a simplified structure-based model of the V3 loop. In this way, genotypic prediction of co-receptor tropism is very accurate, fast and can be applied to large datasets derived from next-generation sequencing technologies. The reduced complexity of the electrostatic modeling makes T-CUP 2.0 independent from third-party software, making it easy to install and use.
authors.affiliation: Research Group Bioinformatics, Center of Medical Biotechnology, University of Duisburg-Essen, Universitaetsstr. 2, 45117 Essen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Heider
authors.affiliation: Research Group Bioinformatics, Center of Medical Biotechnology, University of Duisburg-Essen, Universitaetsstr. 2, 45117 Essen, Germany.
authors.forename: Jan Nikolaj
authors.initials: JN
authors.lastname: Dybowski
authors.affiliation: Research Group Bioinformatics, Center of Medical Biotechnology, University of Duisburg-Essen, Universitaetsstr. 2, 45117 Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wilms
authors.affiliation: Research Group Bioinformatics, Center of Medical Biotechnology, University of Duisburg-Essen, Universitaetsstr. 2, 45117 Essen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoffmann