ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic surveillance has been vital in understanding the spread of coronavirus disease 2019 (COVID-19), the emergence of viral escape mutants, and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low-frequency variants, important in uncovering infection transmission chains. We systematically evaluated three widely adopted SARS-CoV-2 whole-genome sequencing methods for their sensitivity, specificity, and ability to reliably detect low-frequency variants. Our analyses reveal that the ARTIC v3 protocol consistently displays high sensitivity for generating complete genomes at low viral loads compared with the probe-based Illumina Respiratory Viral Oligo panel and a pooled long-amplicon method. We show substantial variability in the number and location of low-frequency variants detected using the three methods, highlighting the importance of selecting appropriate methods to obtain high-quality sequence data from low-viral-load samples for public health and genomic surveillance purposes.
【저자키워드】 public health, SARS-CoV-2, Genomics, variants, 【초록키워드】 COVID-19, coronavirus disease, severe acute respiratory syndrome coronavirus 2, whole-genome sequencing, public health, Coronavirus disease 2019, coronavirus, protocol, Genome, Genomic surveillance, variant, variants of concern, severe acute respiratory syndrome Coronavirus, variants, Spread, sensitivity, specificity, Phylogenetic analysis, Viral, Surveillance, Viral load, mutants, location, phylogenetic analyses, respiratory, Illumina, genomic, Analysis, Infection transmission, acute respiratory syndrome, acute respiratory syndrome coronavirus, Variability, sequence, specimen, viral escape, probe, Affect, Complete, detect, evaluated, adopted, highlighting, 【제목키워드】 Sample, Ability,