PhyLAT: a phylogenetic local alignment tool.

MOTIVATION: The expansion of DNA sequencing capacity has enabled the sequencing of whole genomes from a number of related species. These genomes can be combined in a multiple alignment that provides useful information about the evolutionary history at each genomic locus. One area in which evolutionary information can productively be exploited is in aligning a new sequence to a database of existing, aligned genomes. However, existing high-throughput alignment tools are not designed to work effectively with multiple genome alignments. RESULTS: We introduce PhyLAT, the phylogenetic local alignment tool, to compute local alignments of a query sequence against a fixed multiple-genome alignment of closely related species. PhyLAT uses a known phylogenetic tree on the species in the multiple alignment to improve the quality of its computed alignments while also estimating the placement of the query on this tree. It combines a probabilistic approach to alignment with seeding and expansion heuristics to accelerate discovery of significant alignments. We provide evidence, using alignments of human chromosome 22 against a five-species alignment from the UCSC Genome Browser database, that PhyLAT's alignments are more accurate than those of other commonly used programs, including BLAST, POY, MAFFT, MUSCLE and CLUSTAL. PhyLAT also identifies more alignments in coding DNA than does pairwise alignment alone. Finally, our tool determines the evolutionary relationship of query sequences to the database more accurately than do POY, RAxML, EPA or pplacer.