Performance of amplicon and capture based next-generation sequencing approaches for the epidemiological surveillance of Omicron SARS-CoV-2 and other variants of concern

PLoS One. 2024 Apr 29;19(4):e0289188. doi: 10.1371/journal.pone.0289188. eCollection 2024.

Abstract

To control the SARS-CoV-2 pandemic, healthcare systems have focused on ramping up their capacity for epidemiological surveillance through viral whole genome sequencing. In this paper, we tested the performance of two protocols of SARS-CoV-2 nucleic acid enrichment, an amplicon enrichment using different versions of the ARTIC primer panel and a hybrid-capture method using KAPA RNA Hypercap. We focused on the challenge of the Omicron variant sequencing, the advantages of automated library preparation and the influence of the bioinformatic analysis in the final consensus sequence. All 94 samples were sequenced using Illumina iSeq 100 and analysed with two bioinformatic pipelines: a custom-made pipeline and an Illumina-owned pipeline. We were unsuccessful in sequencing six samples using the capture enrichment due to low reads. On the other hand, amplicon dropout and mispriming caused the loss of mutation G21987A and the erroneous addition of mutation T15521A respectively using amplicon enrichment. Overall, we found high sequence agreement regardless of method of enrichment, bioinformatic pipeline or the use of automation for library preparation in eight different SARS-CoV-2 variants. Automation and the use of a simple app for bioinformatic analysis can simplify the genotyping process, making it available for more diagnostic facilities and increasing global vigilance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / epidemiology
  • COVID-19* / virology
  • Computational Biology / methods
  • Epidemiological Monitoring
  • Genome, Viral
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Mutation
  • RNA, Viral / genetics
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / isolation & purification
  • Whole Genome Sequencing / methods

Substances

  • RNA, Viral

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work has been funded by: the European Centre for disease Prevention and Control under the GA ECDC/HERA/2021/024 ECD.12241, the Aid for the consolidation and structuring of competitive research units and other promotion actions of the Galician Innovation Agency, code IN607B-2022/19, and the Consellería de Sanidade, Galicia, Spain The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.