Rescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data.

TitleRescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data.
Publication TypeJournal Article
Year of Publication2022
AuthorsLiu, Y, Kearney, J, Mahmoud, M, Kille, B, Sedlazeck, FJ, Treangen, TJ
JournalNat Commun
Volume13
Issue1
Pagination1321
Date Published2022 Mar 14
ISSN2041-1723
Abstract

Infectious disease monitoring on Oxford Nanopore Technologies (ONT) platforms offers rapid turnaround times and low cost. Tracking low frequency intra-host variants provides important insights with respect to elucidating within-host viral population dynamics and transmission. However, given the higher error rate of ONT, accurate identification of intra-host variants with low allele frequencies remains an open challenge with no viable computational solutions available. In response to this need, we present Variabel, a novel approach and first method designed for rescuing low frequency intra-host variants from ONT data alone. We evaluate Variabel on both synthetic data (SARS-CoV-2) and patient derived datasets (Ebola virus, norovirus, SARS-CoV-2); our results show that Variabel can accurately identify low frequency variants below 0.5 allele frequency, outperforming existing state-of-the-art ONT variant callers for this task. Variabel is open-source and available for download at: www.gitlab.com/treangenlab/variabel .

DOI10.1038/s41467-022-28852-1
Alternate JournalNat Commun
PubMed ID35288552
Grant List1P01AI152999-01 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
1U19AI144297 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
75D30121C11180 / / U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC) /