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In bioinformatics, a sequence alignment is a way of arranging the sequences of
DNA,
RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences.[1] Aligned sequences of nucleotide or amino acid residues are typically represented as rows within a matrix.
Gaps are inserted between the residues so that identical or similar characters are aligned in successive columns.
Sequence alignments are also used for non-biological sequences, such as those present in natural language or in financial data.
Very short or very similar sequences can be aligned by hand. However, most interesting problems require the alignment of lengthy, highly variable or extremely numerous sequences that cannot be aligned solely by human effort.
Instead, human knowledge is applied in constructing algorithms to produce high-quality sequence alignments, and occasionally in adjusting the final results to reflect patterns that are difficult to represent algorithmically (especially in the case of nucleotide sequences). Computational approaches to sequence alignment generally fall into two categories: global alignments and local alignments. Calculating a global alignment is a form of global optimization that "forces" the alignment to span the entire length of all query sequences. By contrast, local alignments identify regions of similarity within long sequences that are often widely divergent overall. Local alignments are often preferable, but can be more difficult to calculate because of the additional challenge of identifying the regions of similarity. A variety of computational algorithms have been applied to the sequence alignment problem. These include slow but formally correct methods like dynamic programming. These also include efficient, heuristic algorithms or probabilistic methods designed for large-scale database search, that do not guarantee to find best matches.
Global alignments, which attempt to align every residue in every sequence, are most useful when the sequences in the query set are similar and of roughly equal size. (This does not mean global alignments cannot end in gaps.) A general global alignment technique is the Needleman--Wunsch algorithm, which is based on dynamic programming. Local alignments are more useful for dissimilar sequences that are suspected to contain regions of similarity or similar sequence motifs within their larger sequence context. The Smith--Waterman algorithm is a general local alignment method also based on dynamic programming.
Hybrid methods, known as semiglobal or "glocal" (short for global-local) methods, attempt to find the best possible alignment that includes the start and end of one or the other sequence. This can be especially useful when the downstream part of one sequence overlaps with the upstream part of the other sequence. In this case, neither global nor local alignment is entirely appropriate: a global alignment would attempt to force the alignment to extend beyond the region of overlap, while a local alignment might not fully cover the region of overlap.[5] Another case where semiglobal alignment is useful is when one sequence is short (for example a gene sequence) and the other is very long (for example a chromosome sequence). In that case, the short sequence should be globally aligned but only a local alignment is desired for the long sequence.
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- published: 29 Oct 2013
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