Local multiple sequence alignment using dead-end elimination.
BACKGROUND
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.


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


BACKGROUND
alex_lukashin@biogen.com.
Lukashin
A V
AV
Biogen, Inc., Cambridge, MA 02142, USA.
Rosa
J J
JJ
D000465:Algorithms; D019295:Computational Biology / Q000379:methods; D005069:Evaluation Studies as Topic; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors