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. 2020 Jan 15;36(2):416-421.
doi: 10.1093/bioinformatics/btz585.

THETA: a new genotypic approach for predicting HIV-1 CRF02-AG coreceptor usage

Chloé Dimeglio  1 , Stéphanie Raymond  1   2 , Nicolas Jeanne  1 , Christelle Reynes  3   4   5 , Romain Carcenac  1 , Caroline Lefebvre  1 , Michelle Cazabat  1 , Florence Nicot  1 , Pierre Delobel  6 , Jacques Izopet  1   2
Affiliations

THETA: a new genotypic approach for predicting HIV-1 CRF02-AG coreceptor usage

Chloé Dimeglio et al. Bioinformatics. .

Abstract

Motivation: The circulating recombinant form of HIV-1 CRF02-AG is the most frequent non-B subtype in Europe. Anti-HIV therapy and pathophysiological studies on the impact of HIV-1 tropism require genotypic determination of HIV-1 tropism for non-B subtypes. But genotypic approaches based on analysis of the V3 envelope region perform poorly when used to determine the tropism of CRF02-AG. We, therefore, designed an algorithm based on information from the gp120 and gp41 ectodomain that better predicts the tropism of HIV-1 subtype CRF02-AG.

Results: We used a bio-statistical method to identify the genotypic determinants of CRF02-AG coreceptor use. Toulouse HIV Extended Tropism Algorithm (THETA), based on a Least Absolute Shrinkage and Selection Operator method, uses HIV envelope sequence from phenotypically characterized clones. Prediction of R5X4/X4 viruses was 86% sensitive and that of R5 viruses was 89% specific with our model. The overall accuracy of THETA was 88%, making it sufficiently reliable for predicting the tropism of subtype CRF02-AG sequences.

Availability and implementation: Binaries are freely available for download at https://github.com/viro-tls/THETA. It was implemented in Matlab and supported on MS Windows platform. The sequence data used in this work are available from GenBank under the accession numbers MK618182-MK618417.

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