Position-specific automated processing of V3 env ultra-deep pyrosequencing data for predicting HIV-1 tropism

Jeanne, Nicolas, Saliou, Adrien, Carcenac, Romain, Lefebvre, Caroline, Dubois, Martine, Cazabat, Michelle, Nicot, Florence, Loiseau, Claire, Raymond, Stéphanie, Izopet, Jacques, and Delobel, Pierre (2015) Position-specific automated processing of V3 env ultra-deep pyrosequencing data for predicting HIV-1 tropism. Scientific Reports, 5. 16944. pp. 1-10.

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Abstract

HIV-1 coreceptor usage must be accurately determined before starting CCR5 antagonist-based treatment as the presence of undetected minor CXCR4-using variants can cause subsequent virological failure. Ultra-deep pyrosequencing of HIV-1 V3 env allows to detect low levels of CXCR4-using variants that current genotypic approaches miss. However, the computation of the mass of sequence data and the need to identify true minor variants while excluding artifactual sequences generated during amplification and ultra-deep pyrosequencing is rate-limiting. Arbitrary fixed cut-offs below which minor variants are discarded are currently used but the errors generated during ultra-deep pyrosequencing are sequence-dependant rather than random. We have developed an automated processing of HIV-1 V3 env ultra-deep pyrosequencing data that uses biological filters to discard artifactual or non-functional V3 sequences followed by statistical filters to determine position-specific sensitivity thresholds, rather than arbitrary fixed cut-offs. It allows to retain authentic sequences with point mutations at V3 positions of interest and discard artifactual ones with accurate sensitivity thresholds.

Item ID: 46286
Item Type: Article (Research - C1)
ISSN: 2045-2322
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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Funders: French National Institute for Health and Medical Research-French National Agency for Aids and Viral Hepatitis Research (Inserm-ANRS)
Date Deposited: 10 Nov 2016 23:25
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060506 Virology @ 50%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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