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. 2024 Apr 4;19(4):e0298164.
doi: 10.1371/journal.pone.0298164. eCollection 2024.

Unveiling hidden structural patterns in the SARS-CoV-2 genome: Computational insights and comparative analysis

Alison Ziesel  1 , Hosna Jabbari  1
Affiliations

Unveiling hidden structural patterns in the SARS-CoV-2 genome: Computational insights and comparative analysis

Alison Ziesel et al. PLoS One. .

Abstract

SARS-CoV-2, the causative agent of COVID-19, is known to exhibit secondary structures in its 5' and 3' untranslated regions, along with the frameshifting stimulatory element situated between ORF1a and 1b. To identify additional regions containing conserved structures, we utilized a multiple sequence alignment with related coronaviruses as a starting point. We applied a computational pipeline developed for identifying non-coding RNA elements. Our pipeline employed three different RNA structural prediction approaches. We identified forty genomic regions likely to harbor structures, with ten of them showing three-way consensus substructure predictions among our predictive utilities. We conducted intracomparisons of the predictive utilities within the pipeline and intercomparisons with four previously published SARS-CoV-2 structural datasets. While there was limited agreement on the precise structure, different approaches seemed to converge on regions likely to contain structures in the viral genome. By comparing and combining various computational approaches, we can predict regions most likely to form structures, as well as a probable structure or ensemble of structures. These predictions can be used to guide surveillance, prophylactic measures, or therapeutic efforts. Data and scripts employed in this study may be found at https://doi.org/10.5281/zenodo.8298680.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. UCSC genome browser rendering of the SARS-CoV-2 genome and genes.
Fig 2
Fig 2. Phylogenetic tree describing the relationship between viruses as developed by MUSCLE from a MAFFT multiple sequence alignment.
Fig 3
Fig 3. Modified pipeline employed in this study.
Fig 4
Fig 4. Positions of the 40 likely RNA structures (top) aligned against the SARS-CoV-2 genome (bottom).
The location of the sequence block with both high confidence RNA structure and covariant bases, which overlaps with the FSE, is indicated with a red box.
Fig 5
Fig 5. Structures of the 10 predicted RNA structures with agreed upon elements highlighted in green.
Fig 6
Fig 6. Part one of the distance matrices describing edit distance between this work, the predictive work of Andrews and Li, and the SHAPE data of the Huston and Manfredonia papers.
Fig 7
Fig 7. Part two of the distance matrices describing edit distance between this work, the predictive work of Andrews and Li, and the SHAPE data of the Huston and Manfredonia papers.
Fig 8
Fig 8. The mean edit distances as measured for each of the five data sets analyzed in this work.
See this image and copyright information in PMC

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References

    1. Hu B, Guo H, Zhou P, Shi Z-L. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2020. 19:141–154. doi: 10.1038/s41579-020-00459-7 - DOI - PMC - PubMed
    1. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med. 2020. 26:450–452. doi: 10.1038/s41591-020-0820-9 - DOI - PMC - PubMed
    1. Domingo JL. An updated review of the scientific literature on the origin of SARS-CoV-2. Environmental Research 2022. 215:114131. doi: 10.1016/j.envres.2022.114131 - DOI - PMC - PubMed
    1. Nicholson BL, White KA. Exploring the architecture of viral RNA genomes. Curr Opin Virol. 2015. 12:66–74. doi: 10.1016/j.coviro.2015.03.018 - DOI - PubMed
    1. Huang X, Yang Y, Wang G, Cheng Q, Du Z. Highly conserved RNA pseudoknots at the gag-pol junction of HIV-1 suggest a novel mechanism of -1 ribosomal frameshifting. RNA 2014. 20(5):587–593. doi: 10.1261/rna.042457.113 - DOI - PMC - PubMed

Grants and funding

This study was financially supported by Microsoft Azure AI for Health (https://www.microsoft.com/en-us/research/project/ai-for-health) in the form of an award received by HJ. This study was also financially supported by Natural Sciences and Engineering Research Council of Canada (https://www.nserc-crsng.gc.ca) in the form of a NSERC Discovery grant (RGPIN-2020-04243) received by HJ. This study was also financially supported by National Research Council of Canada (https://nrc.canada.ca) in the form of a DHGA grant (DHGA-110-1) received by HJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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