ArticleProceedings of the National Academy of Sciences of the United States of America2011
Accurate sampling and deep sequencing of the HIV-1 protease gene using a Primer ID.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
254 citing papers in PubMed, 2 syntheses or guidelines pooled it, 384 citations in OpenAlex.
- A beginner's guide for FMDV quasispecies analysis: sub-consensus variant detection and haplotype reconstruction using next-generation sequencing.Briefings in bioinformatics · 2020Guideline
- Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals: A Systematic Review of Detection Methods, Prevalence, and Clinical Impact.The Journal of infectious diseases · 2020Pooled it
- Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C.Antiviral therapy · 2015Trial
- Trial
- Ultrasensitive single-genome sequencing reveals strong purifying selection in acute HIV-1 infection.bioRxiv : the preprint server for biology · 2026Article
- Extensive diversity and impact of drug-resistant HIV-1 variants in individuals with prior virologic failure.PLoS pathogens · 2026Article
- Advancing Precision Public Health: an implementation science framework for HIV Cluster Detection and Response driven by molecular epidemiology.Frontiers in public health · 2026Article
- Nonhomologous end-joining uses distinct mechanisms to repair each strand of a double strand break.Nature communications · 2025Article
- A bibliometric analysis of HIV-1 drug-resistant minority variants from 1999 to 2024.AIDS research and therapy · 2025Article
- HIV-1 Rebound Virus Consists of a Small Number of Lineages That Entered the Reservoir Close to ART Initiation.bioRxiv : the preprint server for biology · 2025Article
- Next-Generation Sequencing Methods to Determine the Accuracy of Retroviral Reverse Transcriptases: Advantages and Limitations.Viruses · 2025Review
- An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis.Nucleic acids research · 2025Article
- Performance of the Applied Biosystems HIV-1 Genotyping Kit with Integrase.Journal of clinical microbiology · 2024Article
- Portable Nanopore sequencing solution for next-generation HIV drug resistance testing.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2024Article
- Article
- Optimized SMRT-UMI protocol produces highly accurate sequence datasets from diverse populations-Application to HIV-1 quasispecies.Virus evolution · 2024Article
- Use of Next-Generation Sequencing in a State-Wide Strategy of HIV-1 Surveillance: Impact of the SARS-COV-2 Pandemic on HIV-1 Diagnosis and Transmission.The Journal of infectious diseases · 2023Observational
- Loss of West Nile virus genetic diversity during mosquito infection due to species-dependent population bottlenecks.iScience · 2023Article
- Cell-free circulating RAS mutation concentrations significantly impact the survival of metastatic colorectal cancer patients.Journal of cancer research and clinical oncology · 2023Article
- Full-spectrum HIV drug resistance mutation detection by high-resolution complete pol gene sequencing.Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2023Article
194 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Viruses can create complex genetic populations within a host, and deep sequencing technologies allow extensive sampling of these populations. Limitations of these technologies, however, potentially bias this sampling, particularly when a PCR step precedes the sequencing protocol. Typically, an unknown number of templates are used in initiating the PCR amplification, and this can lead to unrecognized sequence resampling creating apparent homogeneity; also, PCR-mediated recombination can disrupt linkage, and differential amplification can skew allele frequency. Finally, misincorporation of nucleotides during PCR and errors during the sequencing protocol can inflate diversity. We have solved these problems by including a random sequence tag in the initial primer such that each template receives a unique Primer ID. After sequencing, repeated identification of a Primer ID reveals sequence resampling. These resampled sequences are then used to create an accurate consensus sequence for each template, correcting for recombination, allelic skewing, and misincorporation/sequencing errors. The resulting population of consensus sequences directly represents the initial sampled templates. We applied this approach to the HIV-1 protease (pro) gene to view the distribution of sequence variation of a complex viral population within a host. We identified major and minor polymorphisms at coding and noncoding positions. In addition, we observed dynamic genetic changes within the population during intermittent drug exposure, including the emergence of multiple resistant alleles. These results provide an unprecedented view of a complex viral population in the absence of PCR resampling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.