alexa Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level | Abstract
ISSN: 2153-0602

Journal of Data Mining in Genomics & Proteomics
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Research Article

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

Da Wei Huang1,7#, Castle Raley3#, Min Kang Jiang1#, Xin Zheng1, Dun Liang1, M Tauseef Rehman1, Helene C Highbarger1, Xiaoli Jiao1, Brad Sherman1, Liang Ma5, Xiaofeng Chen2, Thomas Skelly2, Jennifer Troyer3,6, Robert Stephens3, Tomozumi Imamichi1, Alice Pau4, Richard A Lempicki1, Bao Tran3, Dwight Nissley3, H Clifford Lane4 and Robin L Dewar1*

1Applied and Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, MD 21702, USA

2Advanced Biomedical Computing Center, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, MD 21702, USA

3Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, MD 21702, USA

4Division of Clinical Research, National Institute of Allergy & Infectious Diseases, USA

5Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, 20892, USA

6National Human Genome Research Institute, National Institutes of Health, Rockville, MD, 20852, USA

7National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

#Authors contribution

*Corresponding Author:
Robin Dewar & Da Wei Huan
Applied and Developmental Research Directorate, USA
Tel: 301-846-1268
Fax: 301-846-5145
E-mail: [email protected] [email protected] & [email protected]

Received date: October 14, 2015; Accepted date: November 02, 2015; Published date: November 08, 2015

Citation: Huang DW, Raley C, Jiang MK, Zheng X, Liang D, et al. (2015) Towards Better Precision Medicine: Pacbio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level. J Data Mining Genomics Proteomics 7:182. doi:10.4172/2153- 0602.1000182

Copyright: © 2015 Huang DW, et al. 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.

Abstract

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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