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
.
Tracking low frequency intra-host variants has helped understanding within-host viral population dynamics and transmission. Precise tracking, however, depends partially on the error rate of the sequencing platforms used. Here, Liu et al. present Variabel, a method to rescue low frequency intra-host variants from Oxford Nanopore Technol...

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

10.1038/s41467-022-28852-1