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TopHap: Rapid inference of key phylogenetic structures from common haplotypes in large genome collections with limited diversity

View ORCID ProfileMarcos A. Caraballo-Ortiz, Sayaka Miura, Maxwell Sanderford, Tenzin Dolker, View ORCID ProfileQiqing Tao, Steven Weaver, Sergei L. K. Pond, View ORCID ProfileSudhir Kumar
doi: https://doi.org/10.1101/2021.12.13.472454
Marcos A. Caraballo-Ortiz
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
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  • ORCID record for Marcos A. Caraballo-Ortiz
Sayaka Miura
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
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Maxwell Sanderford
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
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Tenzin Dolker
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
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Qiqing Tao
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
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Steven Weaver
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
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Sergei L. K. Pond
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
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Sudhir Kumar
1Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA
2Department of Biology, Temple University, Philadelphia, PA 19122, USA
3Center of Excellence in Genome Medicine Research, King Abdulaziz University, Saudi Arabia
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  • For correspondence: s.kumar@temple.edu
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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 SARS-CoV-2 strains exemplify these difficulties since there are only hundreds of phylogenetically informative sites and 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 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. To assess topological robustness, we develop a bootstrap resampling strategy that resamples genomes spatiotemporally. The application of TopHap to build a phylogeny of 68,057 genomes (68KG) 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 genomes reconstructed the most comprehensive evolutionary relationships of major variants, which confirmed the 68KG phylogeny and provided evolutionary origins of major variants of concern.

Availability TopHap is available on the web at https://github.com/SayakaMiura/TopHap.

Contact s.kumar{at}temple.edu

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵x Joint first authors.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted December 14, 2021.
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TopHap: Rapid inference of key phylogenetic structures from common haplotypes in large genome collections with limited diversity
Marcos A. Caraballo-Ortiz, Sayaka Miura, Maxwell Sanderford, Tenzin Dolker, Qiqing Tao, Steven Weaver, Sergei L. K. Pond, Sudhir Kumar
bioRxiv 2021.12.13.472454; doi: https://doi.org/10.1101/2021.12.13.472454
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TopHap: Rapid inference of key phylogenetic structures from common haplotypes in large genome collections with limited diversity
Marcos A. Caraballo-Ortiz, Sayaka Miura, Maxwell Sanderford, Tenzin Dolker, Qiqing Tao, Steven Weaver, Sergei L. K. Pond, Sudhir Kumar
bioRxiv 2021.12.13.472454; doi: https://doi.org/10.1101/2021.12.13.472454

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