Wednesday 25 December 2013

Needleman and Wunsch algorithm

Needleman and Wunsch (1970) performed progressive building of an alignment by comparing two amino acids at a time. They started at the end of each sequence and then moved ahead one amino acid pair at a time, allowing for various combinations of matched pairs, mismatched pairs, or extra amino acids in one sequence (insertion or deletion). In computer science, this approach is called dynamic programming.
The Needleman and Wunsch approach generated :
(1) every possible alignment, each one including every possible combination of match, mismatch, and single
insertion or deletion, and
(2) a scoring system to score the alignment. The object was to
determine which was the best alignment of all by determining the highest score.
Thus, every match in a trial alignment was given a score of 1, every mismatch a score of 0, and individual gaps a penalty score. These numbers were then added across the alignment to obtain a total score for the alignment. The alignment with the highest possible score was
defined as the optimal alignment.



The procedure for generating all of the possible alignments is to move sequentially through all of the matched positions within a matrix, much like the dot matrix graph (see above), starting at those positions that correspond to the end of one of the sequences, as shown in Figure 1.4. At each position in the matrix, the highest possible score that can be achieved up to that point is placed in that position, allowing for all possible starting points
in either sequence and any combination of matches, mismatches, insertions, and deletions.
The best alignment is found by finding the highest-scoring position in the graph, and then tracing back through the graph through the path that generated the highest-scoring positions. The sequences are then aligned so that the sequence characters corresponding to this path are matched.





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