Whole‐genome single molecule real‐time sequencing of SARS‐CoV‐2 Omicron

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Nicot, Florence | Trémeaux, Pauline | Latour, Justine | Carcenac, Romain | Demmou, Sofia | Jeanne, Nicolas | Ranger, Noémie | de Smet, Clémentine | Raymond, Stéphanie | Dimeglio, Chloé | Izopet, Jacques

Edité par CCSD ; Wiley-Blackwell -

International audience. New variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome can only be identified using accurate sequencing methods. Single molecule real-time (SMRT) sequencing has been used to characterize Alpha and Delta variants, but not Omicron variants harboring numerous mutations in the SARS-CoV-2 genome. This study assesses the performance of a target capture SMRT sequencing protocol for whole genome sequencing (WGS) of SARS-CoV-2 Omicron variants and compared it to that of an amplicon SMRT sequencing protocol optimized for Omicron variants. The failure rate of the target capture protocol (6%) was lower than that of the amplicon protocol (34%, p < 0.001) on our data set, and the median genome coverage with the target capture protocol (98.6% [interquartile range (IQR): 86–99.4]) was greater than that with the amplicon protocol (76.6% [IQR: 66–89.6], [p < 0.001]). The percentages of samples with >95% whole genome coverage were 64% with the target capture protocol and 19% with the amplicon protocol (p < 0.05). The clades of 96 samples determined with both protocols were 93% concordant and the lineages of 59 samples were 100% concordant. Thus, target capture SMRT sequencing appears to be an efficient method for WGS, genotyping and detecting mutations of SARS-CoV-2 Omicron variants.

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