pairwise-alignment-clean

pairwise-alignment-clean - Pairwise Sequence Alignment...

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Pairwise Sequence Alignment BMI/CS 576 bmi576 Colin Dewey [email protected] Fall 2016
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Overview What does it mean to align sequences? How do we cast sequence alignment as a computational problem? What algorithms exist for solving this computational problem? 2
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What is sequence alignment? Optimization problem Pattern matching ...CATCG ATG ACT A T CCG ... ATG ACT G T Database searching . . . CATG CATG CTG CGTAC CATG GTTG CTCACAAGTAC CATG CCTG CTG CGTAA TACGTG CCTG ACCTG CGTAC CATG CCG AATG CTG . . . CATG CTTG CTG G CGTAAA Statistical problem suffix trees, locality-sensitive hashing,... BLAST Needleman-Wunsch, Smith-Waterman,... Pair HMMs, TKF, Karlin-Altschul statistic... 3
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DNA sequence edits Substitutions: A C GA A G GA Insertions: ACGA AC CGGA GA Deletions: A CGGA GA AGA Transpositions: A CGG AGA AAG CGG A Inversions: AC GGA GA AC TCC GA 4
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Alignment scales For proteins and short DNA sequences (gene scale) we will generally only consider Substitutions: cause mismatches in alignments Insertions/Deletions: cause gaps in alignments For long DNA sequences (genome scale) we will consider additional events Transposition Inversion In this course we will focus on the case of short sequences 5
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What is a pairwise alignment? We will focus on evolutionary alignment matching of homologous positions in two sequences positions with no homologous pair are matched with a space ‘ - A group of consecutive spaces is a gap CA--GATTCGAAT CGCCGATT---AT gap 6
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The Role of Homology character : some feature of an organism (could be molecular, structural, behavioral, etc.) homology : the relationship of two characters that have descended from a common ancestor homologous characters tend to be similar due to their common ancestry and evolutionary pressures thus we often infer homology from similarity thus we can sometimes infer structure/function from sequence similarity 7
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Homology Example: Evolution of the Globins 8
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Dot plots Not technically an “alignment” But gives picture of correspondence between pairs of sequences Dot represents similarity between segments of the two sequences 9
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Insertions/Deletions and Protein Structure loop structures : insertions/deletions here not so significant Why is it that two “similar” sequences may have large insertions/deletions? some insertions and deletions may not significantly affect the structure of a protein 10
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Example Alignment: Globins figure at right shows prototypical structure of globins figure below shows part of alignment for 8 globins (-’s indicate gaps) 11
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Issues in Sequence Alignment the sequences we’re comparing probably differ in length there may be only a relatively small region in the sequences that matches we want to allow partial matches (i.e. some amino acid pairs are more substitutable than others) variable length regions may have been inserted/deleted from the common ancestral sequence 12
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Two main classes of pairwise
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