AUTHOR=Liu Xuemei , Cheng Ziqi , Xu Guohao , Xie Jiemin , Liu Xudong , Ren Bozhen , Ai Dongmei , Chen Yangxin , Xia Li Charlie 

TITLE=Ksak: A high-throughput tool for alignment-free phylogenetics

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1050130

DOI=10.3389/fmicb.2023.1050130

ISSN=1664-302X

ABSTRACT=<p>Phylogenetic tools are fundamental to the studies of evolutionary relationships. In this paper, we present <italic>Ksak</italic>, a novel high-throughput tool for alignment-free phylogenetic analysis. <italic>Ksak</italic> computes the pairwise distance matrix between molecular sequences, using seven widely accepted <italic>k</italic>-mer based distance measures. Based on the distance matrix, <italic>Ksak</italic> constructs the phylogenetic tree with standard algorithms. When benchmarked with a golden standard 16S rRNA dataset, <italic>Ksak</italic> was found to be the most accurate tool among all five tools compared and was 19% more accurate than <italic>ClustalW2</italic>, a high-accuracy multiple sequence aligner. Above all, <italic>Ksak</italic> was tens to hundreds of times faster than <italic>ClustalW2</italic>, which helps eliminate the computation limit currently encountered in large-scale multiple sequence alignment. <italic>Ksak</italic> is freely available at <ext-link xlink:href="https://github.com/labxscut/ksak" xmlns:xlink="http://www.w3.org/1999/xlink">https://github.com/labxscut/ksak</ext-link>.</p>