Misdetection of frameshifts in SARS-CoV-2 genomes: need for additional harmonisation and efficient monitoring of data workflows

Abstract Five years after the outbreak of the SARS-CoV-2 pandemic in 2020, diagnostic laboratories have moved from massive sequencing of thousands of samples to routine surveillance of SARS-CoV-2 cases, as with all other respiratory viruses. Surveillance remains of paramount importance to prevent a...

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Bibliographic Details
Published in:Bioinformatics (Oxford, England) Vol. 41; no. 10
Main Authors: Kogoj, Rok, Petrillo, Mauro, Zakotnik, Samo, Suljič, Alen, Korva, Miša, Leoni, Gabriele
Format: Journal Article
Language:English
Published: England Oxford University Press 01.10.2025
Oxford Publishing Limited (England)
Subjects:
Bioinformatics
Computational Biology - methods
Conserved sequence
COVID-19
COVID-19 - virology
Frameshift mutation
Frameshifting, Ribosomal
Genome, Viral
High-Throughput Nucleotide Sequencing
Humans
Laboratories
Mutation
Nucleocapsids
Pandemics
SARS-CoV-2 - genetics
Sequences
Severe acute respiratory syndrome coronavirus 2
Surveillance
Viral diseases
Workflow
ISSN:1367-4803, 1367-4811, 1367-4811
Online Access:Get full text
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Summary:Abstract Five years after the outbreak of the SARS-CoV-2 pandemic in 2020, diagnostic laboratories have moved from massive sequencing of thousands of samples to routine surveillance of SARS-CoV-2 cases, as with all other respiratory viruses. Surveillance remains of paramount importance to prevent a further SARS-CoV-2 surge, as the virus has been shown to mutate rapidly and can render available drugs and vaccines ineffective. During the pandemic, several bioinformatics pipelines and workflows have been developed to streamline analysis, shorten turnaround time and ensure reproducibility. As the number of samples decreases, laboratories are moving towards more flexible sequencing strategies and optimizing the cost per sample. However, workflow redesigns, even if individual steps have proven successful time and time again, can lead to challenges when changes in a bioinformatics pipeline are introduced (e.g. version updates, implementation of new features, etc.), a new combination of viral mutations emerge or a change in wet-lab procedures leads to unpredictable results. Here, we present a report of misidentified frameshift mutations in the consensus sequence of SARS-CoV-2, which led to an incorrect assumption of mutations in the spike and nucleocapsid viral proteins with the potential to affect PCR detection or even antigen testing. This investigation exemplifies the need for better awareness of the challenges that can occur even when using routinely applied protocols and analytical workflows and highlights the need for cooperation between experts of NGS, bioinformaticians and decision-makers towards more harmonized data workflows.
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ISSN:1367-4803
1367-4811
1367-4811
DOI:10.1093/bioinformatics/btaf516