Sierra SARS-CoV-2 sequence and antiviral resistance analysis program

ElsevierVolume 157, December 2022, 105323Journal of Clinical VirologyHighlights•

Sierra SARS-CoV-2 provides quality control and annotation for viral genomic data.

Sierra SARS-CoV-2 is highly concordant with established sequence analysis programs.

300 SARS-CoV-2 Spike mutations reduce susceptibility to monoclonal antibodies.

Approximately 20 RdRP and Mpro mutations reduce antiviral susceptibility in vitro.

Sierra SARS-CoV-2 has susceptibility data for 88% of Spike RBD mutation patterns.

AbstractIntroduction

Although most laboratories are capable of employing established protocols to perform full-genome SARS-CoV-2 sequencing, many are unable to assess sequence quality, select appropriate mutation-detection thresholds, or report on the potential clinical significance of mutations in the targets of antiviral therapy

Methods

We describe the technical aspects and benchmark the performance of Sierra SARS-CoV-2, a program designed to perform these functions on user-submitted FASTQ and FASTA sequence files and lists of Spike mutations. Sierra SARS-CoV-2 indicates which sequences contain an unexpectedly large number of unusual mutations and which mutations are associated with reduced susceptibility to clinical stage mAbs, the RdRP inhibitor remdesivir, or the Mpro inhibitor nirmatrelvir

Results

To assess the performance of Sierra SARS-CoV-2 on FASTQ files, we applied it to 600 representative FASTQ sequences and compared the results to the COVID-19 EDGE program. To assess its performance on FASTA files, we applied it to nearly one million representative FASTA sequences and compared the results to the GISAID mutation annotation. To assess its performance on mutations lists, we applied it to 13,578 distinct Spike RBD mutation patterns and showed that exactly or partially matching annotations were available for 88% of patterns

Keywords

SARS-CoV-2

Genomic sequencing

Mutations

Antiviral resistance

© 2022 The Author(s). Published by Elsevier B.V.

留言 (0)

沒有登入
gif