Analysis of unusual and signature APOBEC-mutations in HIV-1 pol next-generation sequences

At low mutation-detection thresholds, next generation sequencing (NGS) for HIV-1 genotypic resistance testing is susceptible to artifactual detection of mutations arising from PCR error and APOBEC-mediated G-to-A hypermutation. We analyzed published HIV-1 pol Illumina NGS data to characterize the di...

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Bibliographic Details
Published in:PloS one 2020-02, Vol.15 (2), p.e0225352-e0225352
Main Authors: Tzou, Philip L, Kosakovsky Pond, Sergei L, Avila-Rios, Santiago, Holmes, Susan P, Kantor, Rami, Shafer, Robert W
Format: Article
Language:English
Subjects:
Amino acids
Amino Acids - genetics
Analysis
APOBEC Deaminases - genetics
Archives & records
Biology and Life Sciences
Codon - genetics
Criminal investigation
Datasets
Drug resistance
Drug Resistance, Viral - genetics
Genetic aspects
Genotype
High-Throughput Nucleotide Sequencing
HIV
HIV Infections - genetics
HIV Infections - virology
HIV-1 - genetics
HIV-1 - isolation & purification
Human immunodeficiency virus
Humans
Infectious diseases
Luminance distribution
Medicine
Medicine and Health Sciences
Mutation
Next-generation sequencing
Plasma
pol Gene Products, Human Immunodeficiency Virus - genetics
Profiling
Research and Analysis Methods
Ribonucleic acid
RNA
RNA, Viral - blood
RNA, Viral - genetics
Studies
Thresholds
Viral Load - genetics
Viruses
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Summary:At low mutation-detection thresholds, next generation sequencing (NGS) for HIV-1 genotypic resistance testing is susceptible to artifactual detection of mutations arising from PCR error and APOBEC-mediated G-to-A hypermutation. We analyzed published HIV-1 pol Illumina NGS data to characterize the distribution of mutations at eight NGS mutation detection thresholds: 20%, 10%, 5%, 2%, 1%, 0.5%, 0.2%, and 0.1%. At each threshold, we determined proportions of amino acid mutations that were unusual (defined as having a prevalence
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0225352