Original author(s) Development status Active | Developer(s) drive5 Operating system | |
Initial release 2004; 13 years ago (2004) Stable release 3.8.31 / 18 August 2016; 6 months ago (2016-08-18) | ||
MUltiple Sequence Comparison by Log-Expectation (MUSCLE) is computer software for multiple sequence alignment of protein and nucleotide sequences. It is licensed as public domain. The method was published by Robert C. Edgar in two papers in 2004. The first paper, published in Nucleic Acids Research, introduced the sequence alignment algorithm. The second paper, published in BMC Bioinformatics, presented more technical details.
Contents
Algorithm
The MUSCLE algorithm proceeds in three stages: the draft progressive, improved progressive, and refinement stages. In the draft progressive stage, the algorithm produces a draft multiple alignment, emphasising speed over accuracy. In the improved progressive stage, the Kimura distance is used to reestimate the binary tree used to create the draft alignment, in turn producing a more accurate multiple alignment. The final refinement stage refines the improved alignment made in step two. Multiple alignments are available at the end of each stage. In the first two stages of the algorithm, the time complexity is O(N2L + NL2), the space complexity is O(N2 + NL + L2). The refinement stage adds to the time complexity another term, O(N3L). MUSCLE is often used as a replacement for Clustal, since it usually (but not always) gives better sequence alignments, depending on the chosen options. Also, MUSCLE is significantly faster than Clustal, more so for larger alignments.
Integration
MUSCLE is integrated into DNASTAR's Lasergene software, Geneious, and MacVector and is available in Sequencher, MEGA, and UGENE as a plug-in. MUSCLE is also available as a web service via the European Molecular Biology Laboratory (EMBL)-European Bioinformatics Institute (EBI). As of September 2016, the two papers describing MUSCLE have been cited more than 19,000 times in total.