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Minimum variance rooting of phylogenetic trees and implications for species tree reconstruction.

ABSTRACT: Phylogenetic trees inferred using commonly-used models of sequence evolution are unrooted, but the root position matters both for interpretation and downstream applications. This issue has been long recognized; however, whether the potential for discordance between the species tree and gene trees impacts methods of rooting a phylogenetic tree has not been extensively studied. In this paper, we introduce a new method of rooting a tree based on its branch length distribution; our method, which minimizes the variance of root to tip distances, is inspired by the traditional midpoint rerooting and is justified when deviations from the strict molecular clock are random. Like midpoint rerooting, the method can be implemented in a linear time algorithm. In extensive simulations that consider discordance between gene trees and the species tree, we show that the new method is more accurate than midpoint rerooting, but its relative accuracy compared to using outgroups to root gene trees depends on the size of the dataset and levels of deviations from the strict clock. We show high levels of error for all methods of rooting estimated gene trees due to factors that include effects of gene tree discordance, deviations from the clock, and gene tree estimation error. Our simulations, however, did not reveal significant differences between two equivalent methods for species tree estimation that use rooted and unrooted input, namely, STAR and NJst. Nevertheless, our results point to limitations of existing scalable rooting methods.

SUBMITTER: Mai U

PROVIDER: S-EPMC5553649 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Minimum variance rooting of phylogenetic trees and implications for species tree reconstruction.

Mai Uyen U Sayyari Erfan E Mirarab Siavash S

PloS one 20170811 8

Phylogenetic trees inferred using commonly-used models of sequence evolution are unrooted, but the root position matters both for interpretation and downstream applications. This issue has been long recognized; however, whether the potential for discordance between the species tree and gene trees impacts methods of rooting a phylogenetic tree has not been extensively studied. In this paper, we introduce a new method of rooting a tree based on its branch length distribution; our method, which min ...[more]

PMID: 28800608

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Project description:B cell receptor (BCR) genes exposed to an antigen undergo somatic hypermutations and Darwinian antigen selection, generating a large BCR-antibody diversity. This process, known as B cell affinity maturation, increases antibody affinity, forming a specific B cell lineage that includes the unmutated ancestor and mutated variants. In a B cell lineage, cells with a higher antigen affinity will undergo clonal expansion, while those with a lower affinity will not proliferate and probably be eliminated. Therefore, cellular (genotype) abundance provides a valuable perspective on the ongoing evolutionary process. Phylogenetic tree inference is often used to reconstruct B cell lineage trees and represents the evolutionary dynamic of BCR affinity maturation. However, such methods should process B-cell population data derived from experimental sampling that might contain different cellular abundances. There are a few phylogenetic methods for tracing the evolutionary events occurring in B cell lineages; best-performing solutions are time-demanding and restricted to analysing a reduced number of sequences, while time-efficient methods do not consider cellular abundances. We propose ClonalTree, a low-complexity and accurate approach to construct B-cell lineage trees that incorporates genotype abundances into minimum spanning tree (MST) algorithms. Using both simulated and experimental data, we demonstrate that ClonalTree outperforms MST-based algorithms and achieves a comparable performance to a method that explores tree-generating space exhaustively. Furthermore, ClonalTree has a lower running time, being more convenient for building B-cell lineage trees from high-throughput BCR sequencing data, mainly in biomedical applications, where a lower computational time is appreciable. It is hundreds to thousands of times faster than exhaustive approaches, enabling the analysis of a large set of sequences within minutes or seconds and without loss of accuracy. The source code is freely available at github.com/julibinho/ClonalTree.

Dataset Information

Minimum variance rooting of phylogenetic trees and implications for species tree reconstruction.

Publications

Minimum variance rooting of phylogenetic trees and implications for species tree reconstruction.

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