Ultrafast topological data analysis reveals pandemic-scale dynamics of convergent evolution

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Abstract

Genome variants which re-occur independently across evolutionary lineages are key molecular signatures of adaptation. Inferring the dynamics of such genetic changes from pandemic-scale genomic datasets is now possible, which opens up unprecedented insight into evolutionary processes. However, existing approaches depend on the construction of accurate phylogenetic trees, which remains challenging at scale. Here we present EVOtRec, an organism-agnostic, fast and scalable Topological Data Analysis approach that enables the inference of convergently evolving genomic variants over time directly from topological patterns in the dataset, without requiring the construction of a phylogenetic tree. Using data from both simulations and published experiments, we show that EVOtRec can robustly identify variants under positive selection and performs orders of magnitude faster than state-of-the-art phylogeny-based approaches, with comparable results. We apply EVOtRec to three large viral genome datasets: SARS-CoV-2, influenza virus A subtype H5N1 and HIV-1. We identify key convergent genome variants and demonstrate how EVOtRec facilitates the real-time tracking of high fitness variants in large datasets with millions of genomes, including effects modulated by varying genomic backgrounds. We envision our Topological Data Analysis approach as a new framework for efficient comparative genomics.

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  1. SciScore for 10.1101/2021.06.10.21258550: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Second, a subset of 128,347 sequences that deviated from the reference sequence in genome length, or whose genetic distance to the reference sequence was greater than 20nt, was aligned with MUSCLE [8], iteratively in blocks of 20 sequences each.
    MUSCLE
    suggested: (MUSCLE, RRID:SCR_011812)
    Ancestral state reconstruction analysis: For the study of the evolutionary histories of topologically highly recurrent mutations, we performed ancestral state reconstruction analyses using Mesquite Version 3.61 [26].
    Mesquite
    suggested: (Mesquite, RRID:SCR_017994)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    Results from scite Reference Check: We found no unreliable references.


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