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Bioinformatics Advance Access originally published online on February 12, 2004
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Bioinformatics 20(10) © Oxford University Press 2004; all rights reserved.

Combining partial order alignment and progressive multiple sequence alignment increases alignment speed and scalability to very large alignment problems

Catherine Grasso and Christopher Lee *

Department of Chemistry and Biochemistry, Molecular Biology Institute, Center for Genomics and Proteomics, University of California, Los Angeles, CA 90095-1570, USA

Received on May 25, 2003; revised on January 5, 2004; accepted on January 6, 2004
Advance Access Publication February 12, 2004

Motivation: Partial order alignment (POA) has been proposed as a new approach to multiple sequence alignment (MSA), which can be combined with existing methods such as progressive alignment. This is important for addressing problems both in the original version of POA (such as order sensitivity) and in standard progressive alignment programs (such as information loss in complex alignments, especially surrounding gap regions).

Results: We have developed a new Partial Order–Partial Order alignment algorithm that optimally aligns a pair of MSAs and which therefore can be applied directly to progressive alignment methods such as CLUSTAL. Using this algorithm, we show the combined Progressive POA alignment method yields results comparable with the best available MSA programs (CLUSTALW, DIALIGN2, T-COFFEE) but is far faster. For example, depending on the level of sequence similarity, aligning 1000 sequences, each 500 amino acids long, took 15 min (at 90% average identity) to 44 min (at 30% identity) on a standard PC. For large alignments, Progressive POA was 10–30 times faster than the fastest of the three previous methods (CLUSTALW). These data suggest that POA-based methods can scale to much larger alignment problems than possible for previous methods.

Availability: The POA source code is available at http://www.bioinformatics.ucla.edu/poa

Contact: leec{at}mbi.ucla.edu

* To whom correspondence should be addressed.


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