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TopHap: rapid inference of key phylogenetic structures from common haplotypes in large genome collections with limited diversity
Caraballo-Ortiz, Marcos A. Miura, Sayaka Sanderford, Maxwell Dolker, Tenzin Tao, Qiqing Pond, Sergei L. Kosakovsky Kumar, Sudhir
Caraballo-Ortiz, Marcos A.
Miura, Sayaka
Sanderford, Maxwell
Dolker, Tenzin
Tao, Qiqing
Pond, Sergei L. Kosakovsky
Kumar, Sudhir
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Journal article
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2022-03-24
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Biology
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http://dx.doi.org/10.1093/bioinformatics/btac186
Abstract
Motivation: Building reliable phylogenies from very large collections of sequences with a limited number of phylogenetically informative sites is challenging because sequencing errors and recurrent/backward mutations interfere with the phylogenetic signal, confounding true evolutionary relationships. Massive global efforts of sequencing genomes and reconstructing the phylogeny of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains exemplify these difficulties since there are only hundreds of phylogenetically informative sites but millions of genomes. For such datasets, we set out to develop a method for building the phylogenetic tree of genomic haplotypes consisting of positions harboring common variants to improve the signal-to-noise ratio for more accurate and fast phylogenetic inference of resolvable phylogenetic features. Results: We present the TopHap approach that determines spatiotemporally common haplotypes of common variants and builds their phylogeny at a fraction of the computational time of traditional methods. We develop a bootstrap strategy that resamples genomes spatiotemporally to assess topological robustness. The application of TopHap to build a phylogeny of 68 057 SARS-CoV-2 genomes (68KG) from the first year of the pandemic produced an evolutionary tree of major SARS-CoV-2 haplotypes. This phylogeny is concordant with the mutation tree inferred using the co-occurrence pattern of mutations and recovers key phylogenetic relationships from more traditional analyses. We also evaluated alternative roots of the SARS-CoV-2 phylogeny and found that the earliest sampled genomes in 2019 likely evolved by four mutations of the most recent common ancestor of all SARS-CoV-2 genomes. An application of TopHap to more than 1 million SARS-CoV-2 genomes reconstructed the most comprehensive evolutionary relationships of major variants, which confirmed the 68KG phylogeny and provided evolutionary origins of major and recent variants of concern. Availability and implementation: TopHap is available at https://github.com/SayakaMiura/TopHap. Supplementary information: Supplementary data are available at Bioinformatics online.
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Marcos A Caraballo-Ortiz, Sayaka Miura, Maxwell Sanderford, Tenzin Dolker, Qiqing Tao, Steven Weaver, Sergei L K Pond, Sudhir Kumar, TopHap: rapid inference of key phylogenetic structures from common haplotypes in large genome collections with limited diversity, Bioinformatics, Volume 38, Issue 10, May 2022, Pages 2719–2726, https://doi.org/10.1093/bioinformatics/btac186
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Oxford University Press (OUP)
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Bioinformatics, Vol. 38, Iss. 10
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