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Sequence Comparison.pdf

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Chapter 3<br />

Pairwise <strong>Sequence</strong> Alignment<br />

Pairwise alignment is often used to reveal similarities between sequences, determine<br />

the residue-residue correspondences, locate patterns of conservation, study<br />

gene regulation, and infer evolutionary relationships.<br />

This chapter is divided into eight sections. It starts with a brief introduction in<br />

Section 3.1, followed by the dot matrix representation of pairwise sequence comparison<br />

in Section 3.2.<br />

Using alignment graph, we derive a dynamic-programming method for aligning<br />

globally two sequences in Section 3.3. An example is used to illustrate the tabular<br />

computation for computing the optimal alignment score as well as the backtracking<br />

procedure for delivering an optimal global alignment.<br />

Section 3.4 describes a method for delivering an optimal local alignment, which<br />

involves only a segment of each sequence. The recurrence for an optimal local alignment<br />

is quite similar to that for global alignment. To reflect the flexibility that an<br />

alignment can start at any position of the two sequences, an additional entry “zero”<br />

is added.<br />

In Section 3.5, we address some flexible strategies for coping with various scoring<br />

schemes. Affine gap penalties are considered more appropriate for aligning DNA<br />

and protein sequences. To favor longer gaps, constant gap penalties or restricted<br />

affine gap penalties could be the choice.<br />

Straightforward implementations of the dynamic-programming algorithms consume<br />

quadratic space for alignment. For certain applications, such as careful analysis<br />

of a few long DNA sequences, the space restriction is more important than the<br />

time constraint. Section 3.6 introduces Hirschberg’s linear-space approach.<br />

Section 3.7 discusses several advanced topics such as constrained sequence alignment,<br />

similar sequence alignment, suboptimal alignment, and robustness measurement.<br />

Finally, we conclude the chapter with the bibliographic notes in Section 3.8.<br />

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