Biomedical Engineering Reference
In-Depth Information
It's important to realize that picking arbitrary gap opening and extension costs typically has no real
relationship to the underlying biology of the protein or DNA involved. One solution is to use gap
penalty values that relate to biologically relevant data, as described in the "
Substitution Matrices
"
section later in this chapter.
Local Versus Global Alignment
Sequence pair (E)-(F) is an example of a global alignment—that is, an attempt to line up the two
sequences matching as many characters as possible, for the entire length of each segment. Global
alignment considers all characters in a sequence, and bases alignment on the total score, even at the
expense of stretches in the sequence that share obvious similarity (see
Figure 8-2
, top). Global
alignment is used to help determine whether two protein sequences are in the same family, for
example.
Figure 8-2. Local (top) versus Global (bottom) Alignment. In local
alignment, the alignment of local, high-scoring sequences takes precedence
over the overall alignment. In global alignment, the best overall alignment
is sought, regardless of whether local, high-scoring subsequences are in
alignment or not.
There are several methods of performing local sequence alignment, each of which has particular
uses, advantages, and computational overhead. For example, the Smith-Waterman dynamic
programming method, which uses a scoring system that penalizes the total score for a mismatch, is a
computationally intensive sequence alignment method that favors local over global alignment.
Multiple Sequence Alignment
