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Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level

Development of HIV-1 drug resistance mutations (HDRMs) is one of the major reasons for the clinical failure of antiretroviral therapy. Treatment success rates can be improved by applying personalized anti-HIV regimens based on a patient’s HDRM profile. However, the sensitivity and specificity of the...

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Autores principales: Huang, Da Wei, Raley, Castle, Jiang, Min Kang, Zheng, Xin, Liang, Dun, Rehman, M Tauseef, Highbarger, Helene C., Jiao, Xiaoli, Sherman, Brad, Ma, Liang, Chen, Xiaofeng, Skelly, Thomas, Troyer, Jennifer, Stephens, Robert, Imamichi, Tomozumi, Pau, Alice, Lempicki, Richard A, Tran, Bao, Nissley, Dwight, Lane, H Clifford, Dewar, Robin L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775093/
https://www.ncbi.nlm.nih.gov/pubmed/26949565
http://dx.doi.org/10.4172/2153-0602.1000182
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author Huang, Da Wei
Raley, Castle
Jiang, Min Kang
Zheng, Xin
Liang, Dun
Rehman, M Tauseef
Highbarger, Helene C.
Jiao, Xiaoli
Sherman, Brad
Ma, Liang
Chen, Xiaofeng
Skelly, Thomas
Troyer, Jennifer
Stephens, Robert
Imamichi, Tomozumi
Pau, Alice
Lempicki, Richard A
Tran, Bao
Nissley, Dwight
Lane, H Clifford
Dewar, Robin L.
author_facet Huang, Da Wei
Raley, Castle
Jiang, Min Kang
Zheng, Xin
Liang, Dun
Rehman, M Tauseef
Highbarger, Helene C.
Jiao, Xiaoli
Sherman, Brad
Ma, Liang
Chen, Xiaofeng
Skelly, Thomas
Troyer, Jennifer
Stephens, Robert
Imamichi, Tomozumi
Pau, Alice
Lempicki, Richard A
Tran, Bao
Nissley, Dwight
Lane, H Clifford
Dewar, Robin L.
author_sort Huang, Da Wei
collection PubMed
description Development of HIV-1 drug resistance mutations (HDRMs) is one of the major reasons for the clinical failure of antiretroviral therapy. Treatment success rates can be improved by applying personalized anti-HIV regimens based on a patient’s HDRM profile. However, the sensitivity and specificity of the HDRM profile is limited by the methods used for detection. Sanger-based sequencing technology has traditionally been used for determining HDRM profiles at the single nucleotide variant (SNV) level, but with a sensitivity of only ≥ 20% in the HIV population of a patient. Next Generation Sequencing (NGS) technologies offer greater detection sensitivity (~ 1%) and larger scope (hundreds of samples per run). However, NGS technologies produce reads that are too short to enable the detection of the physical linkages of individual SNVs across the haplotype of each HIV strain present. In this article, we demonstrate that the single-molecule long reads generated using the Third Generation Sequencer (TGS), PacBio RS II, along with the appropriate bioinformatics analysis method, can resolve the HDRM profile at a more advanced quasispecies level. The case studies on patients’ HIV samples showed that the quasispecies view produced using the PacBio method offered greater detection sensitivity and was more comprehensive for understanding HDRM situations, which is complement to both Sanger and NGS technologies. In conclusion, the PacBio method, providing a promising new quasispecies level of HDRM profiling, may effect an important change in the field of HIV drug resistance research.
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spelling pubmed-47750932016-03-02 Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level Huang, Da Wei Raley, Castle Jiang, Min Kang Zheng, Xin Liang, Dun Rehman, M Tauseef Highbarger, Helene C. Jiao, Xiaoli Sherman, Brad Ma, Liang Chen, Xiaofeng Skelly, Thomas Troyer, Jennifer Stephens, Robert Imamichi, Tomozumi Pau, Alice Lempicki, Richard A Tran, Bao Nissley, Dwight Lane, H Clifford Dewar, Robin L. J Data Mining Genomics Proteomics Article Development of HIV-1 drug resistance mutations (HDRMs) is one of the major reasons for the clinical failure of antiretroviral therapy. Treatment success rates can be improved by applying personalized anti-HIV regimens based on a patient’s HDRM profile. However, the sensitivity and specificity of the HDRM profile is limited by the methods used for detection. Sanger-based sequencing technology has traditionally been used for determining HDRM profiles at the single nucleotide variant (SNV) level, but with a sensitivity of only ≥ 20% in the HIV population of a patient. Next Generation Sequencing (NGS) technologies offer greater detection sensitivity (~ 1%) and larger scope (hundreds of samples per run). However, NGS technologies produce reads that are too short to enable the detection of the physical linkages of individual SNVs across the haplotype of each HIV strain present. In this article, we demonstrate that the single-molecule long reads generated using the Third Generation Sequencer (TGS), PacBio RS II, along with the appropriate bioinformatics analysis method, can resolve the HDRM profile at a more advanced quasispecies level. The case studies on patients’ HIV samples showed that the quasispecies view produced using the PacBio method offered greater detection sensitivity and was more comprehensive for understanding HDRM situations, which is complement to both Sanger and NGS technologies. In conclusion, the PacBio method, providing a promising new quasispecies level of HDRM profiling, may effect an important change in the field of HIV drug resistance research. 2015-11-08 2016-01 /pmc/articles/PMC4775093/ /pubmed/26949565 http://dx.doi.org/10.4172/2153-0602.1000182 Text en http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Huang, Da Wei
Raley, Castle
Jiang, Min Kang
Zheng, Xin
Liang, Dun
Rehman, M Tauseef
Highbarger, Helene C.
Jiao, Xiaoli
Sherman, Brad
Ma, Liang
Chen, Xiaofeng
Skelly, Thomas
Troyer, Jennifer
Stephens, Robert
Imamichi, Tomozumi
Pau, Alice
Lempicki, Richard A
Tran, Bao
Nissley, Dwight
Lane, H Clifford
Dewar, Robin L.
Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level
title Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level
title_full Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level
title_fullStr Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level
title_full_unstemmed Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level
title_short Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level
title_sort towards better precision medicine: pacbio single-molecule long reads resolve the interpretation of hiv drug resistant mutation profiles at explicit quasispecies (haplotype) level
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775093/
https://www.ncbi.nlm.nih.gov/pubmed/26949565
http://dx.doi.org/10.4172/2153-0602.1000182
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