TopHap: Rapid inference of key phylogenetic structures from common haplotypes in large genome collections with limited diversity.
Bioinformatics
; 2022 Mar 24.
Article
in English
| MEDLINE | ID: covidwho-1758638
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 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 resampling 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 variants of concern.AVAILABILITY:
TopHap is available at https//github.com/SayakaMiura/TopHap.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Experimental Studies
Topics:
Variants
Language:
English
Journal subject:
Medical Informatics
Year:
2022
Document Type:
Article
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