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Bioinformatics Vol. 15 no. 11 1999
Pages 947-953
© 1999 Oxford University Press

Local multiple sequence alignment using dead-end elimination

Alexander V.Lukashin 1 and Joseph J.Rosa 1

1 Biogen, Inc., 14 Cambridge Center, Cambridge, MA 02142, USA

Alexander V. Lukashin

Motivation: Local multiple sequence alignment is a basic tool for extracting functionally important regions shared by a family of protein sequences. We present an effectively polynomial-time algorithm for rigorously solving the local multiple alignment problem.

Results: The algorithm is based on the dead-end elimination procedure that makes it possible to avoid an exhaustive search. In the framework of the sum-of-pairs scoring system, certain rejection criteria are derived in order to eliminate those sequence segments and segment pairs that can be mathematically shown to be inconsistent (dead-ending) with the globally optimal alignment. Iterative application of the elimination criteria results in a rapid reduction of combinatorial possibilities without considering them explicitly. In the vast majority of cases, the procedure converges to a unique globally optimal solution. In contrast to the exhaustive search, whose computational complexity is combinatorial, the algorithm is computationally feasible because the number of operations required to eliminate the dead-ending segments and segment pairs grows quadratically and cubically, respectively, with the total number of sequence elements. The method is illustrated on a set of protein families for which the globally optimal alignments are well recognized.

Availability: The source code of the program implementing the algorithm is available upon request from the authors.

Contact: alex\|[dot ]\|lukashin{at}biogen.com


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