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MUMMALS: multiple sequence alignment improved by using hidden Markov models with local structural information.

ABSTRACT: We have developed MUMMALS, a program to construct multiple protein sequence alignment using probabilistic consistency. MUMMALS improves alignment quality by using pairwise alignment hidden Markov models (HMMs) with multiple match states that describe local structural information without exploiting explicit structure predictions. Parameters for such models have been estimated from a large library of structure-based alignments. We show that (i) on remote homologs, MUMMALS achieves statistically best accuracy among several leading aligners, such as ProbCons, MAFFT and MUSCLE, albeit the average improvement is small, in the order of several percent; (ii) a large collection (>10 000) of automatically computed pairwise structure alignments of divergent protein domains is superior to smaller but carefully curated datasets for estimation of alignment parameters and performance tests; (iii) reference-independent evaluation of alignment quality using sequence alignment-dependent structure superpositions correlates well with reference-dependent evaluation that compares sequence-based alignments to structure-based reference alignments.

SUBMITTER: Pei J

PROVIDER: S-EPMC1636350 | biostudies-literature | 2006

REPOSITORIES: biostudies-literature

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MUMMALS: multiple sequence alignment improved by using hidden Markov models with local structural information.

Pei Jimin J Grishin Nick V NV

Nucleic acids research 20060826 16

We have developed MUMMALS, a program to construct multiple protein sequence alignment using probabilistic consistency. MUMMALS improves alignment quality by using pairwise alignment hidden Markov models (HMMs) with multiple match states that describe local structural information without exploiting explicit structure predictions. Parameters for such models have been estimated from a large library of structure-based alignments. We show that (i) on remote homologs, MUMMALS achieves statistically be ...[more]

PMID: 16936316

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Project description:BACKGROUND:During procedures for conducting multiple sequence alignment, that is so essential to use the substitution score of pairwise alignment. To compute adaptive scores for alignment, researchers usually use Hidden Markov Model or probabilistic consistency methods such as partition function. Recent studies show that optimizing the parameters for hidden Markov model, as well as integrating hidden Markov model with partition function can raise the accuracy of alignment. The combination of partition function and optimized HMM, which could further improve the alignment's accuracy, however, was ignored by these researches. RESULTS:A novel algorithm for MSA called ProbPFP is presented in this paper. It intergrate optimized HMM by particle swarm with partition function. The algorithm of PSO was applied to optimize HMM's parameters. After that, the posterior probability obtained by the HMM was combined with the one obtained by partition function, and thus to calculate an integrated substitution score for alignment. In order to evaluate the effectiveness of ProbPFP, we compared it with 13 outstanding or classic MSA methods. The results demonstrate that the alignments obtained by ProbPFP got the maximum mean TC scores and mean SP scores on these two benchmark datasets: SABmark and OXBench, and it got the second highest mean TC scores and mean SP scores on the benchmark dataset BAliBASE. ProbPFP is also compared with 4 other outstanding methods, by reconstructing the phylogenetic trees for six protein families extracted from the database TreeFam, based on the alignments obtained by these 5 methods. The result indicates that the reference trees are closer to the phylogenetic trees reconstructed from the alignments obtained by ProbPFP than the other methods. CONCLUSIONS:We propose a new multiple sequence alignment method combining optimized HMM and partition function in this paper. The performance validates this method could make a great improvement of the alignment's accuracy.

Dataset Information

MUMMALS: multiple sequence alignment improved by using hidden Markov models with local structural information.

Publications

MUMMALS: multiple sequence alignment improved by using hidden Markov models with local structural information.

Similar Datasets

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