Key result
Computational method identifies multiple coexisting SARS-CoV-2 strains in reference and California wastewater samples.
A novel computational method successfully identified multiple co-existing intra-host strains of SARS-CoV-2 in the original reference genome sample and wastewater, highlighting within-host viral diversity.
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Raises caution for assuming clonal populations in SARS-CoV-2 reference and surveillance samples; leaves open clinical relevance of intra-host diversity.
The COVID-19 pandemic caused by SARS-CoV-2 has had a severe impact on people worldwide. The reference genome of the virus has been widely used as a template for designing mRNA vaccines to combat the disease. In this study, we present a computational method aimed at identifying co-existing intra-host strains of the virus from RNA-sequencing data of short reads that were used to assemble the original reference genome. Our method consisted of five key steps: extraction of relevant reads, error correction for the reads, identification of within-host diversity, phylogenetic study, and protein binding affinity analysis. Our study revealed that multiple strains of SARS-CoV-2 can coexist in both the viral sample used to produce the reference sequence and a wastewater sample from California. Additionally, our workflow demonstrated its capability to identify within-host diversity in foot-and-mouth disease virus (FMDV). Through our research, we were able to shed light on the binding affinity and phylogenetic relationships of these strains with the published SARS-CoV-2 reference genome, SARS-CoV, variants of concern (VOC) of SARS-CoV-2, and some closely related coronaviruses. These insights have important implications for future research efforts aimed at identifying within-host diversity, understanding the evolution and spread of these viruses, as well as the development of effective treatments and vaccines against them.
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Cai et al. (2023) studied SARS-CoV-2. Computational method for identifying co-existing intra-host strains was evaluated on Identification of co-existing intra-host strains. A computational method revealed that multiple strains of SARS-CoV-2 coexisted in the viral sample used to produce the reference sequence and a California wastewater sample.
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