Progressive multiple sequence alignment with indel evolution

BMC Bioinformatics
Massimo MaioloMaria Anisimova

Abstract

Sequence alignment is crucial in genomics studies. However, optimal multiple sequence alignment (MSA) is NP-hard. Thus, modern MSA methods employ progressive heuristics, breaking the problem into a series of pairwise alignments guided by a phylogeny. Changes between homologous characters are typically modelled by a Markov substitution model. In contrast, the dynamics of indels are not modelled explicitly, because the computation of the marginal likelihood under such models has exponential time complexity in the number of taxa. But the failure to model indel evolution may lead to artificially short alignments due to biased indel placement, inconsistent with phylogenetic relationship. Recently, the classical indel model TKF91 was modified to describe indel evolution on a phylogeny via a Poisson process, termed PIP. PIP allows to compute the joint marginal probability of an MSA and a tree in linear time. We present a new dynamic programming algorithm to align two MSAs -represented by the underlying homology paths- by full maximum likelihood under PIP in polynomial time, and apply it progressively along a guide tree. We have corroborated the correctness of our method by simulation, and compared it with competitive methods on an ill...Continue Reading

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Citations

Feb 13, 2021·NAR Genomics and Bioinformatics·Massimo MaioloMaria Anisimova
Apr 20, 2021·Computational and Structural Biotechnology Journal·Federico Scossa, Alisdair R Fernie
Mar 8, 2021·Bioinformatics·Benjamin D Redelings
Aug 24, 2021·Computational Biology and Chemistry·Anderson Rici AmorimLiria Matsumoto Sato

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Software Mentioned

PRANK
PIP
Coffee
MUSCLE
ClustalW
MAFFT
PhyML

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