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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
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Sierra SARS-CoV-2 sequence and antiviral resistance analysis program.

Philip L Tzou1, Kaiming Tao1, Malaya K Sahoo2

  • 1Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA.

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology
|November 5, 2022
PubMed
Summary

Sierra SARS-CoV-2 is a new program that improves the quality control of viral genomic data and assesses the clinical significance of mutations impacting antiviral therapy effectiveness for SARS-CoV-2.

Keywords:
Antiviral resistanceGenomic sequencingMutationsSARS-CoV-2

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Area of Science:

  • Genomic surveillance
  • Virology
  • Bioinformatics

Background:

  • Full-genome sequencing of SARS-CoV-2 is common, but analyzing sequence quality and mutation impact on antiviral therapy is challenging.
  • Laboratories need tools to assess sequence quality, set mutation thresholds, and understand clinical significance of mutations.

Purpose of the Study:

  • To introduce and benchmark Sierra SARS-CoV-2, a program for analyzing SARS-CoV-2 genomic data.
  • To assess sequence quality, detect mutations, and annotate their potential impact on antiviral drug susceptibility.

Main Methods:

  • Sierra SARS-CoV-2 processes FASTQ and FASTA sequence files and lists of Spike mutations.
  • The program identifies sequences with unusual mutations and those affecting susceptibility to monoclonal antibodies (mAbs), remdesivir, and nirmatrelvir.

Main Results:

  • Performance on FASTQ files was benchmarked against the COVID-19 EDGE program using 600 sequences.
  • Analysis of nearly one million FASTA sequences was compared to GISAID mutation annotation.
  • 88% of 13,578 Spike RBD mutation patterns had matching annotations, validating the program's accuracy.

Conclusions:

  • Sierra SARS-CoV-2 enhances viral genomic data quality control.
  • It provides functional annotation on the impact of mutations on SARS-CoV-2 antiviral targets.
  • The program is available online for researchers to improve SARS-CoV-2 variant analysis.