Browsing by Author "Phillippy, Adam M"

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    Minmers are a generalization of minimizers that enable unbiased local Jaccard estimation
    (Oxford University Press, 2023) Kille, Bryce; Garrison, Erik; Treangen, Todd J; Phillippy, Adam M
    The Jaccard similarity on k-mer sets has shown to be a convenient proxy for sequence identity. By avoiding expensive base-level alignments and comparing reduced sequence representations, tools such as MashMap can scale to massive numbers of pairwise comparisons while still providing useful similarity estimates. However, due to their reliance on minimizer winnowing, previous versions of MashMap were shown to be biased and inconsistent estimators of Jaccard similarity. This directly impacts downstream tools that rely on the accuracy of these estimates.To address this, we propose the minmer winnowing scheme, which generalizes the minimizer scheme by use of a rolling minhash with multiple sampled k-mers per window. We show both theoretically and empirically that minmers yield an unbiased estimator of local Jaccard similarity, and we implement this scheme in an updated version of MashMap. The minmer-based implementation is over 10 times faster than the minimizer-based version under the default ANI threshold, making it well-suited for large-scale comparative genomics applications.MashMap3 is available at https://github.com/marbl/MashMap.
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    Parsnp 2.0: scalable core-genome alignment for massive microbial datasets
    (Oxford University Press, 2024) Kille, Bryce; Nute, Michael G; Huang, Victor; Kim, Eddie; Phillippy, Adam M; Treangen, Todd J
    Since 2016, the number of microbial species with available reference genomes in NCBI has more than tripled. Multiple genome alignment, the process of identifying nucleotides across multiple genomes which share a common ancestor, is used as the input to numerous downstream comparative analysis methods. Parsnp is one of the few multiple genome alignment methods able to scale to the current era of genomic data; however, there has been no major release since its initial release in 2014.To address this gap, we developed Parsnp v2, which significantly improves on its original release. Parsnp v2 provides users with more control over executions of the program, allowing Parsnp to be better tailored for different use-cases. We introduce a partitioning option to Parsnp, which allows the input to be broken up into multiple parallel alignment processes which are then combined into a final alignment. The partitioning option can reduce memory usage by over 4× and reduce runtime by over 2×, all while maintaining a precise core-genome alignment. The partitioning workflow is also less susceptible to complications caused by assembly artifacts and minor variation, as alignment anchors only need to be conserved within their partition and not across the entire input set. We highlight the performance on datasets involving thousands of bacterial and viral genomes.Parsnp v2 is available at https://github.com/marbl/parsnp.
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    RefSeq database growth influences the accuracy of k-mer-based lowest common ancestor species identification
    (BioMed Central, 10/30/2018) Nasko, Daniel J; Koren, Sergey; Phillippy, Adam M; Treangen, Todd J
    Abstract In order to determine the role of the database in taxonomic sequence classification, we examine the influence of the database over time on k-mer-based lowest common ancestor taxonomic classification. We present three major findings: the number of new species added to the NCBI RefSeq database greatly outpaces the number of new genera; as a result, more reads are classified with newer database versions, but fewer are classified at the species level; and Bayesian-based re-estimation mitigates this effect but struggles with novel genomes. These results suggest a need for new classification approaches specially adapted for large databases.