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Sequence alignment
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===Scoring functions=== The choice of a scoring function that reflects biological or statistical observations about known sequences is important to producing good alignments. Protein sequences are frequently aligned using [[substitution matrix|substitution matrices]] that reflect the probabilities of given character-to-character substitutions. A series of matrices called [[Point accepted mutation|PAM matrices]] (Point Accepted Mutation matrices, originally defined by [[Margaret Dayhoff]] and sometimes referred to as "Dayhoff matrices") explicitly encode evolutionary approximations regarding the rates and probabilities of particular amino acid mutations. Another common series of scoring matrices, known as [[BLOSUM]] (Blocks Substitution Matrix), encodes empirically derived substitution probabilities. Variants of both types of matrices are used to detect sequences with differing levels of divergence, thus allowing users of BLAST or FASTA to restrict searches to more closely related matches or expand to detect more divergent sequences. [[Gap penalty|Gap penalties]] account for the introduction of a gap - on the evolutionary model, an insertion or deletion mutation - in both nucleotide and protein sequences, and therefore the penalty values should be proportional to the expected rate of such mutations. The quality of the alignments produced therefore depends on the quality of the scoring function. It can be very useful and instructive to try the same alignment several times with different choices for scoring matrix and/or gap penalty values and compare the results. Regions where the solution is weak or non-unique can often be identified by observing which regions of the alignment are robust to variations in alignment parameters.
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