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Prediction of HIV-1 Coreceptor Usage Tropism by Sequence Analysis using a Genotypic Approach
Published on: December 1, 2011
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A genotypic method for determining HIV-2 coreceptor usage enables epidemiological studies and clinical decision
Matthias Döring1, Pedro Borrego2,3, Joachim Büch4
1Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarland Informatics Campus, Campus E 1 4, 66123, Saarbrücken, Germany. mdoering@mpi-inf.mpg.de.
Retrovirology
|December 22, 2016
Summary
A new online tool, geno2pheno[coreceptor-hiv2], predicts HIV-2 coreceptor usage from the V3 loop. This tool identifies novel markers for X4-capable variants, aiding treatment decisions for HIV-2 patients.
Area of Science:
- Virology
- Computational Biology
- Genetics
Background:
- CCR5-coreceptor antagonists are used for HIV-2 treatment.
- Determining viral coreceptor usage (CCR5 or CXCR4) is crucial before treatment.
- No online tool existed for genotypic identification of HIV-2 coreceptor usage.
Purpose of the Study:
- To develop a data-driven web service for predicting HIV-2 coreceptor usage.
- To identify novel determinants of HIV-2 coreceptor usage, particularly for X4-capable variants.
Main Methods:
- Developed geno2pheno[coreceptor-hiv2], a web service using a linear support vector machine (SVM).
- Trained SVM models on V3 loop amino-acid sequences of HIV-2 glycoprotein.
- Utilized tenfold cross-validation and an independent data set for model evaluation.
Main Results:
- The linear SVM model achieved an AUC of 0.95, with 73.5% sensitivity and 96% specificity.
- geno2pheno[coreceptor-hiv2] demonstrated 100% predictive accuracy on an independent dataset.
- Identified novel amino-acid markers (27K, 15G, 8S) predictive of CXCR4 usage and found V1/V2 loop influence.
Conclusions:
- geno2pheno[coreceptor-hiv2] is the first online tool for predicting HIV-2 coreceptor usage from the V3 loop.
- The tool aids clinicians in selecting coreceptor antagonists and facilitates epidemiological studies.
- Novel amino-acid markers for X4-capable variants were discovered, expanding knowledge of HIV-2 tropism.
