%0 Journal Article %T Grammar-based distance in progressive multiple sequence alignment %A David J Russell %A Hasan H Otu %A Khalid Sayood %J BMC Bioinformatics %D 2008 %I BioMed Central %R 10.1186/1471-2105-9-306 %X 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.Generation of meaningful multiple sequence alignments (MSAs) of biological sequences is a well-studied NP-complete problem, which has significant implications for a wide spectrum of applications [1,2]. In general, the challenge is aligning N sequences of varying lengths by inserting gaps in the sequences so that in the end all sequences have the same length. Of particular interest to computational biology are DNA/RNA sequences and amino acid sequences, which are comprised of nucleotide and amino acid residues, respectively.MSAs are generally used in studying phylogeny of organisms, structure prediction, and identifying segments of interest among many other applications in computational biology [3].Given a scoring scheme to evaluate the fitness of an MSA, calculating the best MSA is an NP-complete problem [1]. Variances in scoring schemes, need for expert-hand analysis in most applications, and many-to-one mapping governing elements-to-functionality (codon mapping and function) make MSA a more challenging problem when considered from a biological context as well [4].Generally, three approaches are used to automate the generation of MSAs. The first offers a brute-force method of multidimensional dynamic programming [5], which may find a good alignment but is generally computat %U http://www.biomedcentral.com/1471-2105/9/306