Large multiple sequence alignments with a root-to-leaf regressive method

Edgar Garriga, Paolo Di Tommaso, Cedrik Magis, Ionas Erb, Leila Mansouri, Athanasios Baltzis, Hafid Laayouni, Fyodor Kondrashov, Evan Floden, Cedric Notredame
2019 Nature Biotechnology  
Multiple sequence alignments (MSAs) are used for structural1,2 and evolutionary predictions1,2, but the complexity of aligning large datasets requires the use of approximate solutions3, including the progressive algorithm4. Progressive MSA methods start by aligning the most similar sequences and subsequently incorporate the remaining sequences, from leaf to root, based on a guide tree. Their accuracy declines substantially as the number of sequences is scaled up5. We introduce a regressive
more » ... ithm that enables MSA of up to 1.4 million sequences on a standard workstation and substantially improves accuracy on datasets larger than 10,000 sequences. Our regressive algorithm works the other way around from the progressive algorithm and begins by aligning the most dissimilar sequences. It uses an efficient divide-and-conquer strategy to run third-party alignment methods in linear time, regardless of their original complexity. Our approach will enable analyses of extremely large genomic datasets such as the recently announced Earth BioGenome Project, which comprises 1.5 million eukaryotic genomes6.
doi:10.1038/s41587-019-0333-6 pmid:31792410 pmcid:PMC6894943 fatcat:h3pgl3fwqnbszfvud6sfsl4pzq