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

Liu, YunxiKearney, JoshuaMahmoud, MedhatKille, BryceSedlazeck, Fritz J.Treangen, Todd J.2022-04-152022-04-152022Liu, Yunxi, Kearney, Joshua, Mahmoud, Medhat, et al.. "Rescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data." <i>Nature Communications,</i> 13, (2022) Springer Nature: https://doi.org/10.1038/s41467-022-28852-1.https://hdl.handle.net/1911/112097Infectious 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.engThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.Rescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing dataJournal articles41467-022-28852-1https://doi.org/10.1038/s41467-022-28852-1