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

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.

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Liu, Yunxi, Kearney, Joshua, Mahmoud, Medhat, et al.. "Rescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data." Nature Communications, 13, (2022) Springer Nature: https://doi.org/10.1038/s41467-022-28852-1.

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