MUSCLE: multiple sequence alignment with high accuracy and high throughput - PubMed (original) (raw)

Comparative Study

. 2004 Mar 19;32(5):1792-7.

doi: 10.1093/nar/gkh340. Print 2004.

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Comparative Study

MUSCLE: multiple sequence alignment with high accuracy and high throughput

Robert C Edgar. Nucleic Acids Res. 2004.

Abstract

We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the log-expectation score, and refinement using tree-dependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5\. com/muscle.

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Figures

Figure 1

Figure 1

Motifs misaligned by a progressive method. A set of 41 sequences containing SH2 domains (44) were aligned by the progressive method T-Coffee (above), and by MUSCLE (below). The N-terminal region of a subset of five sequences is shown. The highlighted columns (upper case) are conserved within this family but are misaligned by T-Coffee. It should be noted that T-Coffee aligns these motifs correctly when given these five sequences alone; the problem arises in the context of the other sequences. Complete alignments are available at

http://www.drive5.com/muscle

.

Figure 2

Figure 2

This diagram summarizes the flow of the MUSCLE algorithm. There are three main stages: Stage 1 (draft progressive), Stage 2 (improved progressive) and Stage 3 (refinement). A multiple alignment is available at the completion of each stage, at which point the algorithm may terminate.

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References

    1. Wang L. and Jiang,T. (1994) On the complexity of multiple sequence alignment. J. Comput. Biol., 1, 337–348. - PubMed
    1. Waterman M.S., Smith,T.F. and Beyer,W.A. (1976) Some biological sequence metrics. Adv. Math., 20, 367–387.
    1. Hogeweg P. and Hesper,B. (1984) The alignment of sets of sequences and the construction of phyletic trees: an integrated method. J. Mol. Evol., 20, 175–186. - PubMed
    1. Feng D.F. and Doolittle,R.F. (1987) Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J. Mol. Evol., 25, 351–360. - PubMed
    1. Notredame C., Higgins,D.G. and Heringa,J. (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol., 302, 205–217. - PubMed

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