Phylogeny Reconstruction with Alignment-Free Method That Corrects for Horizontal Gene Transfer

Abstract

Advances in sequencing have generated a large number of complete genomes. Traditionally, phylogenetic analysis relies on alignments of orthologs, but defining orthologs and separating them from paralogs is a complex task that may not always be suited to the large datasets of the future. An alternative to traditional, alignment-based approaches are whole-genome, alignment-free methods. These methods are scalable and require minimal manual intervention. We developed SlopeTree, a new alignment-free method that estimates evolutionary distances by measuring the decay of exact substring matches as a function of match length. SlopeTree corrects for horizontal gene transfer, for composition variation and low complexity sequences, and for branch-length nonlinearity caused by multiple mutations at the same site. We tested SlopeTree on 495 bacteria, 73 archaea, and 72 strains of Escherichia coli and Shigella. We compared our trees to the NCBI taxonomy, to trees based on concatenated alignments, and to trees produced by other alignment-free methods. The results were consistent with current knowledge about prokaryotic evolution. We assessed differences in tree topology over different methods and settings and found that the majority of bacteria and archaea have a core set of proteins that evolves by descent. In trees built from complete genomes rather than sets of core genes, we observed some grouping by phenotype rather than phylogeny, for instance with a cluster of sulfur-reducing thermophilic bacteria coming together irrespective of their phyla. The source-code for SlopeTree is available at: http://prodata.swmed.edu/download/pub/slopetree_v1/slopetree.tar.gz.

The number of spaced-word matches between twoDNAsequences as a function of the underlying pattern weight

“…Therefore, in order to ensure that the lower bound given by (7) is smaller than the upper bound in (8), we must require…”

“…Recently, Bromberg et al published an interesting new approach to alignment-free protein sequence comparison that they called Slope Tree [7]. They defined a distance measure using the decay of the number of k-mer matches between two sequences, as a function of k. Trees reconstructed with this distance measure were in accordance to known phylogenetic trees for various sets of prokaryotes.…”

Genetic Distance Calculation based on Locality Sensitive Hashing

“…In current state word frequency approach is widely used to calculate genetic distances and phylogenetic applications other than alignment-based approaches [13] because of their less computational power requirement than alignment-based approach [14]. Use feature frequency profile (FFP) of whole genomes for comparison is one approach in the alignment-free method.…”

Multi-SpaM: A Maximum-Likelihood Approach to Phylogeny Reconstruction Using Multiple Spaced-Word Matches and Quartet Trees

“…In recent years, a number of alignment-free approaches to genome-based phylogeny reconstruction have been published which are very fast in comparison to alignment-based methods [49,57,5,7,40,42]. Another advantage of these new methods is that they circumvent some well-known problems in genome alignment such as genome rearrangements and duplications.…”