slides-alignment-2 - String Alignment II Computational...

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String Alignment II Computational Biology, Department Informatik ETH Zentrum Computational Biology – p.1/26
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Review of Last Week Mutation Matrices Dynamic programming Tabular computation - Matches, Mismatches, or Spaces (gaps, indels, deletions, insertions) Traceback Global Align Global Align Cost-free end gaps Local Align Computational Biology – p.2/26
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Organization Gaps Dyanmic programming - Formal definition - follows Gusfiled Algorithms on Strings, Trees and Sequences Chapter 11 Gap Placement- the unsolved problem Gap Penalties and dynamic programming constant arbitrary linear (Affine) convex Time analysis Linear space dynamic programming Computational Biology – p.3/26
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Gaps Random sequence mutated 200 PAM units with deletions default - gap open penalty - 10.00, gap extension penalty .10 one TLTKEATQMIVLNNIGLGAETEENNEVLAQPGHDDCERTTETVMVCIAKLYDCSE two TGAGHNLFMIFLDHHNGTVKEGEKYMNAVVTGSDHLVENSVVLMI----LYRYGA * . ** * . . * * * .. .*. ** one YAMYWVSTLKFTNGLQDQITRKLIVKQPSTEVPSVLSYLS two ----NISPLWFSDTRGNIPKLSVWLDDPQGSEPDMFNHFA gap open penalty 1.0, gap extension penalty .05 one TLTKEATQMIVLNN-IGLGAETEE-NNEVLAQPGHDDCERTTETVMVCIAKLYDC two TGAGHNLFMIFLDHHNGTVKEGEKYMNAVVT--GSDHLVENSVVLMI----LYRY * . ** * . * * * * *.. * * .. .*. ** one SRYAMYWVSTLKFTNGLQDQITRKLIVKQPSTEVPSVLSYLS two SNISPLWFSD---TRGNIPKLSVWLDDPQ-GSE-PDMFNHFA gap open penalty 0, gap extension penalty 0 one TLTKEATQMIVLNN-IGLGAETEE-NNEVLAQPGHDDCERTTETVMVCIAKLYDC two TGAGHNLFMIFLDHHNGTVKEGEKYMNAVVT--GSDHLVENSVVLMI----LYRY * . ** * . * * * * *.. * * .. .*. ** one SRYAMYWVSTLKFTNGLQDQITRKLIVKQ--PS-TEVPSVLSYLS two SNISPLWFSD---TRG---NIP-KLSVWLDDPQGSE-PDMFNHFA Computational Biology – p.4/26
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Gap Weights A constant Gap Penalty implies that the cost of aligning -_---_ and -----__ -H---Y -----HY are the same. A better model of gap placement says that it is easier to add a second space to an existing gap than to open a new gap. mechanisms of insertion-deletion events more likely to happen in loops slippage of DNA machinery It is more likely that 1 strand of 6 spaces is deleted than 6 strands of 1 space. A gap of more than one space can be created by one mutational event. A more plausible model treats the spaces in a gap not as separate events. Computational Biology – p.5/26
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Review of Dynamic Programming 1) recurrence relation -establishes a recursive relationship between D(i,j) and values of D with index pairs smaller than i and j. When there are no smaller indices then the value of D(i,j) must be stated explicitly in the base conditions for D(i,j). 2) base conditions - Cost to transform the first i characters of one string into zero characters of the other string. Cost of deleting the first i characters.
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