SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission

Sapoval, Nicolae; Mahmoud, Medhat; Jochum, Michael D.; Liu, Yunxi; Elworth, R. A. Leo; Wang, Qi; Albin, Dreycey; Ogilvie, Huw A.; Lee, Michael; Villapol, Sonia; Hernandez, Kyle M.; Berry, Irina Maljkovic; Foox, Jonathan; Beheshti, Afshin; Ternus, Krista; Aagaard, Kjersti M.; Posada, David; Mason, Christopher E.; Sedlazeck, Fritz J.; Treangen, Todd J.

doi:10.1101/gr.268961.120

Cited by 43 publications

(35 citation statements)

References 54 publications

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“…Among 12 single nucleotide polymorphisms types, A > G, G > A, T > C, and G > T were most common. The ratio of C > T was 40% in our SNPs datasets, which is lower than 50% C > T for GISAID SNPs datasets but similar to 40% C > T iSNV for Houston samples in a recent survey [ 58 ] (Figure S1). In humans and many other species, the rate of C > T substitutions is higher than that of other types of substitutions, as methylated Cytosine (C) can be replaced by thymine (T) during DNA replication if the amino group is removed from the methylated cytosine.…”

Section: Resultssupporting

confidence: 71%

Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis

Gao

Liu

et al. 2021

Virulence

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New SARS-CoV-2 mutants have been continuously indentified with enhanced transmission ever since its outbreak in early 2020. As an RNA virus, SARS-CoV-2 has a high mutation rate due to the low fidelity of RNA polymerase. To study the single nucleotide polymorphisms (SNPs) dynamics of SARS-CoV-2, 158 SNPs with high confidence were identified by deep meta-transcriptomic sequencing, and the most common SNP type was C > T. Analyses of intra-host population diversity revealed that intra-host quasispecies' composition varies with time during the early onset of symptoms, which implicates viral evolution during infection. Network analysis of co-occurring SNPs revealed the most abundant non-synonymous SNP 22,638 in the S glycoprotein RBD region and 28,144 in the ORF8 region. Furthermore, SARS-CoV-2 variations differ in an individual's respiratory tissue (nose, throat, BALF, or sputum), suggesting independent compartmentalization of SARS-CoV-2 populations in patients. The positive selection analysis of the SARS-CoV-2 genome uncovered the positive selected amino acid G251V on ORF3a. Alternative allele frequency spectrum (AAFS) of all variants revealed that ORF8 could bear alternate alleles with high frequency. Overall, the results show the quasispecies' profile of SARS-CoV-2 in the respiratory tract in the first two months after the outbreak.

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Section: Resultssupporting

confidence: 71%

Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis

Gao

Liu

et al. 2021

Virulence

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“…Accelerated evolution has been described for coronaviruses, e.g., those carrying a mutator polymerase or exposed to a mutating drug 15 . Accelerated evolution can also be achieved by sequential bottlenecks, such as generated during persistent low-level infection where the host immune responses dramatically decimate, but never fully eradicate the virus 25,31,32 . Even under the conservative assumptions of (a) the one most divergent sample in our study being due to reinfection with an unrelated strain and (b) the other persistently positive patients in the cohort, for which a second genome sample was incomplete, having no SNVs, we estimate that highly divergent variants of SARS-CoV-2 emerge at a frequency of 2/94 (2%) among hospitalized COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Intra-host evolution provides for continuous emergence of SARS-CoV-2 variants

Moorad

Pluta

et al. 2021

Preprint

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Variants of concern (VOC) in SARS-CoV-2 refer to viral genomes that differ significantly from the ancestor virus and that show the potential for higher transmissibility and/or worse clinical progression. VOC have the potential to disrupt ongoing public health measures and vaccine efforts. Yet, little is known regarding how frequently different viral variants emerge and under what circumstances. We report a longitudinal study to determine the degree of SARS-CoV-2 sequence evolution in 94 COVID-19 cases and to estimate the frequency at which highly diverse variants emerge. 2 cases accumulated 9 single-nucleotide variants (SNVs) over a two-week period and 1 case accumulated 23 SNVs over a three-week period, including three non-synonymous mutations in the Spike protein (D138H, E554D, D614G). We estimate that in 2% of COVID cases, viral variants with multiple mutations, including in the Spike glycoprotein, can become the dominant strains in as little as one month of persistent in patient virus replication. This suggests the continued local emergence of VOC independent of travel patterns. Surveillance by sequencing for (i) viremic COVID-19 patients, (ii) patients suspected of re-infection, and (iii) patients with diminished immune function may offer broad public health benefits.

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“…The inversions are likely related to the transcriptional landscape of SARS-CoV-2. 66 These inversions are small (less than 1Kb), and five of them were found in ORF1ab and one on ORF M.…”

Section: Cnv2svmentioning

confidence: 98%

An international virtual hackathon to build tools for the analysis of structural variants within species ranging from coronaviruses to vertebrates

Cartney¹,

Mahmoud

Jochum

et al. 2021

F1000Res

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In October 2020, 62 scientists from nine nations worked together remotely in the Second Baylor College of Medicine & DNAnexus hackathon, focusing on different related topics on Structural Variation, Pan-genomes, and SARS-CoV-2 related research. The overarching focus was to assess the current status of the field and identify the remaining challenges. Furthermore, how to combine the strengths of the different interests to drive research and method development forward. Over the four days, eight groups each designed and developed new open-source methods to improve the identification and analysis of variations among species, including humans and SARS-CoV-2. These included improvements in SV calling, genotyping, annotations and filtering. Together with advancements in benchmarking existing methods. Furthermore, groups focused on the diversity of SARS-CoV-2. Daily discussion summary and methods are available publicly at https://github.com/collaborativebioinformatics provides valuable insights for both participants and the research community.

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SARS-CoV-2 genomic diversity and the implications for qRT-PCR diagnostics and transmission

Cited by 43 publications

References 54 publications

Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis

Quasispecies of SARS-CoV-2 revealed by single nucleotide polymorphisms (SNPs) analysis

Intra-host evolution provides for continuous emergence of SARS-CoV-2 variants

An international virtual hackathon to build tools for the analysis of structural variants within species ranging from coronaviruses to vertebrates

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