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Open Access Highly Accessed Open Badges Research article

Grammar-based distance in progressive multiple sequence alignment

David J Russell1*, Hasan H Otu2 and Khalid Sayood1

Author Affiliations

1 Department of Electrical Engineering, University of Nebraska-Lincoln, 209N WSEC, Lincoln, NE, 68588-0511, USA

2 New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center Genomics Center, Harvard Medical School, Boston, MA 02215, USA

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BMC Bioinformatics 2008, 9:306  doi:10.1186/1471-2105-9-306

Published: 10 July 2008



We propose a multiple sequence alignment (MSA) algorithm and compare the alignment-quality and execution-time of the proposed algorithm with that of existing algorithms. The proposed progressive alignment algorithm uses a grammar-based distance metric to determine the order in which biological sequences are to be pairwise aligned. The progressive alignment occurs via pairwise aligning new sequences with an ensemble of the sequences previously aligned.


The performance of the proposed algorithm is validated via comparison to popular progressive multiple alignment approaches, ClustalW and T-Coffee, and to the more recently developed algorithms MAFFT, MUSCLE, Kalign, and PSAlign using the BAliBASE 3.0 database of amino acid alignment files and a set of longer sequences generated by Rose software. The proposed algorithm has successfully built multiple alignments comparable to other programs with significant improvements in running time. The results are especially striking for large datasets.


We introduce a computationally efficient progressive alignment algorithm using a grammar based sequence distance particularly useful in aligning large datasets.