ClipKIT: A multiple sequence alignment trimming software for accurate phylogenomic inference

Antonis Rokas,Xing-Xing Shen,Andreas Hejnol,Yuanning Li,Jacob L. Steenwyk,Thomas J. Buida

doi:10.1371/journal.pbio.3001007

Antonis Rokas, Xing-Xing Shen

Open Access

https://doi.org/10.1371/journal.pbio.3001007

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Abstract

Highly divergent sites in multiple sequence alignments (MSAs), which can stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Thus, several different trimming strategies have been developed for identifying and removing these sites prior to phylogenetic inference. However, a recent study reported that doing so can worsen inference, underscoring the need for alternative alignment trimming strategies. Here, we introduce ClipKIT, an alignment trimming software that, rather than identifying and removing putatively phylogenetically uninformative sites, instead aims to identify and retain parsimony-informative sites, which are known to be phylogenetically informative. To test the efficacy of ClipKIT, we examined the accuracy and support of phylogenies inferred from 14 different alignment trimming strategies, including those implemented in ClipKIT, across nearly 140,000 alignments from a broad sampling of evolutionary histories. Phylogenies inferred from ClipKIT-trimmed alignments are accurate, robust, and time saving. Furthermore, ClipKIT consistently outperformed other trimming methods across diverse datasets, suggesting that strategies based on identifying and retaining parsimony-informative sites provide a robust framework for alignment trimming.

Highlights

Multiple sequence alignment (MSA) of a set of homologous sequences is an essential step of molecular phylogenetics, the science of inferring evolutionary relationships from molecular sequence data
To test the efficacy of ClipKIT, we examined the accuracy and support of single-gene and species-level phylogenetic trees inferred from untrimmed MSAs and MSAs trimmed using 14 different strategies (Table 1) across 4 empirical genome-scale datasets and 4 simulated datasets
A previous analysis suggested that MSA trimming strategies often decreased the accuracy of phylogenetic inference [7], highlighting the need for new strategies

Summary

Introduction

Multiple sequence alignment (MSA) of a set of homologous sequences is an essential step of molecular phylogenetics, the science of inferring evolutionary relationships from molecular sequence data. Errors in phylogenetic analysis can be caused by erroneously inferring site homology or saturation of multiple substitutions [1], which often present as highly divergent sites in MSAs. To remove errors and phylogenetically uninformative sites, several methods “trim” or filter highly divergent sites using calculations of site/region dissimilarity from MSAs [1,2,3,4]. A beneficial by-product of MSA trimming, especially for studies that analyze hundreds of MSAs from thousands of taxa [5], is that trimming MSAs reduces the computational time. ClipKIT, the alignment trimming toolkit provided for review purposes only https://figshare.

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