Estimating the strength of selection for new SARS-CoV-2 variants

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Abstract

Controlling the SARS-CoV-2 pandemic becomes increasingly challenging as the virus adapts to human hosts through the continual emergence of more transmissible variants. Simply observing that a variant is increasing in frequency is relatively straightforward, but more sophisticated methodology is needed to determine whether a new variant is a global threat and the magnitude of its selective advantage. We present two models for quantifying the strength of selection for new and emerging variants of SARS-CoV-2 relative to the background of contemporaneous variants. These methods range from a detailed model of dynamics within one country to a broad analysis across all countries, and they include alternative explanations such as migration and drift. We find evidence for strong selection favoring the D614G spike mutation and B.1.1.7 (Alpha), weaker selection favoring B.1.351 (Beta), and no advantage of R.1 after it spreads beyond Japan. Cutting back data to earlier time horizons reveals that uncertainty is large very soon after emergence, but that estimates of selection stabilize after several weeks. Our results also show substantial heterogeneity among countries, demonstrating the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.

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  1. SciScore for 10.1101/2021.03.29.21254233: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.


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    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Each approach that we examined has its own strengths and weaknesses for how it can fit into an expanded molecular epidemiology surveillance system. The isotonic regression method is easy to compute and based on the very straightforward premise that a consistent selective advantage should produce a continually increasing frequency of the new variant in all countries where it has been observed. However, because the method is based on a hypothesis-testing framework, there is no way to determine the strength of selection relative to the background strains. Likewise, the method could be misleading in a context where the genetic background is rapidly changing (e.g., other strains under positive selection are introduced into the population during the study period). We believe that a regression-based approach is, nevertheless, very useful for rapidly evaluating evidence of selection potentially in large-scale molecular surveillance pipelines. The population genetic model is more mechanistically explicit than the regression approach and, therefore, gives a direct estimate of the selection effect. The model also allowed us to integrate a simple migration process and to jointly estimate the parameters of selection and migration. The population genetic model is also simple enough that it was coded in a popular statistical language and fit to the global data in a matter of hours on a standard laptop computer. Its framework to estimate country-level selection effects shaped by an overall g...

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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