Population-based nanopore sequencing of the HIV-1 pangenome to identify drug resistance mutations

Autor: Hirotaka Ode, Masakazu Matsuda, Urara Shigemi, Mikiko Mori, Yoshimi Yamamura, Yoshihiro Nakata, Reiko Okazaki, Mai Kubota, Yuka Setoyama, Mayumi Imahashi, Yoshiyuki Yokomaku, Yasumasa Iwatani
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-63054-3
Popis: Abstract HIV-1 drug resistance genotypic tests have primarily been performed by Sanger sequencing of gene segments encoding different drug target proteins. Since the number of targets has increased with the addition of a new class of antiretroviral drugs, a simple high-throughput system for assessing nucleotide sequences throughout the HIV-1 genome is required. Here, we developed a new solution using nanopore sequencing of viral pangenomes amplified by PCR. Benchmark tests using HIV-1 molecular clones demonstrated an accuracy of up to 99.9%. In addition, validation tests of our protocol in 106 clinical samples demonstrated high concordance of drug resistance and tropism genotypes (92.5% and 98.1%, respectively) between the nanopore sequencing-based results and archived clinical determinations made based on Sanger sequencing data. These results suggest that our new approach will be a powerful solution for the comprehensive survey of HIV-1 drug resistance mutations in clinical settings.
Databáze: Directory of Open Access Journals
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