Towards Better Precision Medicine: PacBio Single-Molecule Long Reads Resolve the Interpretation of HIV Drug Resistant Mutation Profiles at Explicit Quasispecies (Haplotype) Level
| Autor: | Helene C Highbarger, Dwight V. Nissley, Xiaofeng Chen, Jennifer L. Troyer, Xiaoli Jiao, Liang Ma, Tomozumi Imamichi, Dun Liang, Thomas Skelly, Xin Zheng, Bao Tran, Robert M. Stephens, Richard A. Lempicki, Robin L. Dewar, Min Kang Jiang, Castle Raley, H. Clifford Lane, Alice Pau, Da-Wei Huang, Brad T. Sherman, M Tauseef Rehman |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Genetics PacBio education.field_of_study Linkage Haplotype Population Genomics Drug resistance Viral quasispecies Biology Precision medicine DNA sequencing Article Single nucleotide variant 03 medical and health sciences Quasispecies 030104 developmental biology Tag-sequence Next generation sequencing HIV-1 drug resistance mutation Third generation sequencing education HIV drug resistance |
| Zdroj: | Journal of data mining in genomics & proteomics |
| ISSN: | 2153-0602 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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