Using minor variant genomes and machine learning to study the genome biology of SARS-CoV-2 over time
In infected individuals, viruses are present as a population consisting of dominant and minor variant genomes. Most databases contain information on the dominant genome sequence. Since the emergence of SARS-CoV-2 in late 2019, variants have been selected that are more transmissible and capable of partial immune escape. Currently, models for projecting the evolution of SARS-CoV-2 are based on using dominant genome sequences to forecast whether a known mutation will be prevalent in the future. However, novel variants of SARS-CoV-2 (and other viruses) are driven by evolutionary pressure acting on minor variant genomes, which then become dominant and form a potential next wave of infection. In this study, sequencing data from 96 209 patients, sampled over a 3-year period, were used to analyse patterns of minor variant genomes. These data were used to develop unsupervised machine learning clusters to identify amino acids that had a greater potential for mutation than others in the Spike protein. Being able to identify amino acids that may be present in future variants would better inform the design of longer-lived medical countermeasures and allow a risk-based evaluation of viral properties, including assessment of transmissibility and immune escape, thus providing candidates with early warning signals for when a new variant of SARS-CoV-2 emerges.
Authors
- Giulia Gallo (ORCID: https://orcid.org/0000-0002-3269-142X)
- Alistair C. Darby (ORCID: https://orcid.org/0000-0002-3786-6209)
- Robert D. Orr (ORCID: https://orcid.org/0000-0001-9008-7696)
- Julian A. Hiscox (ORCID: https://orcid.org/0000-0002-6582-0275)
- Xiaofeng Dong (ORCID: https://orcid.org/0000-0003-1438-4079)
- David A. Matthews (ORCID: https://orcid.org/0000-0003-4611-8795)
- Hannah Goldswain (ORCID: https://orcid.org/0000-0003-4194-8714)
- I’ah Donovan-Banfield (ORCID: https://orcid.org/0000-0002-5124-2427)
- Miles W. Carroll (ORCID: https://orcid.org/0000-0002-7026-7187)
- Todd Myers
- Tracy MacGill
- Dalan Bailey
Institutions
- Agency for Science, Technology and Research (SG)
- The Pirbright Institute (GB)
- United States Food and Drug Administration (US)
- Centre for Human Genetics (GB)
- University of Liverpool (GB)
- University of Bristol (GB)
- University of Oxford (GB)
- Health & Life (Taiwan) (TW)
- Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool (GB)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1093/nar/gkaf077
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- Liverpool School of Tropical Medicine
- National Institute for Health Research Health Protection Research Unit
- National Institute for Health and Care Research
- University of Oxford
- University of Liverpool
- U.S. Food and Drug Administration
- Musculoskeletal Research Center, Washington University in St. Louis
- Medical Research Council
- Biotechnology and Biological Sciences Research Council