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BCB 597

Fall, 2007

Multiple Base Insertion/Deletion Mutation Event .

Constant Gap Penalty • Each gap character is penalized a constant amount: γ • Not a good gap penalty for our mutation event model • What if we had a more general gap penalty function? .

j k ] W (k ) k 1 .0] 0 • O(n3) running time S[i.0] W (i ) • Cannot directly apply space saving S[0. j 1] (i 1. j ] max max S [i k . j ] W ( j ) • O(nm) space S [i 1. j 1) i S[i. j ] W (k ) k 1 j max S [i. General Gap Penalty Function • Gap penalty function: W (g ) • Each entry in the dynamic programming table now takes O(n) time to fill. S[0.

– Small g. Affine Gap Penalty • W(i)=g+hi (for i >= 1) • g: gap opening penalty • h: gap extension penalty • The ratio between g and h affects how much we view the size of the gap. Small h: size less important . Large h: size more important – Large g.

BA) = E(AA[0.L]. BA [0.i]) + E(AA[i+1.L]) . BA[i+1. Remember our “What if?” • E(AA.i].

TCT---GAGGTAGA optimal AGCTAGAGACCAGC TATCTAGAGGTAGA 1. this was a sufficient condition. h 1 However. --TCT-GAGGTAGA not optimal AGCTAGAGACCAGC TATCTAGAGGTAGA optimal AGCTAGAGACCAG. Alignment Decomposition No Longer Behaves optimal AGCTAGAGACCAG---TCT-GAGGTAGA AGCTAGAGACCAGCTATCTAGAGGTAGA optimal AGCTAGAGACCAG. g 3. not a necessary condition! . 1.

Amortize the cost of opening AGCTAAGGAA • Consider filling out the dynamic AGCTAAGGAC programming table > • The cost of g is eventually spread AGCTAAGGA- out over the length of the gap AGCTAAGGAC once the gap is closed.” AGCTAAGGACT • We cannot predict ahead to know how much the gap opening AGCTAAGGAAAA will cost per gap character. > • However. or we AGCTAAGGACTT would directly know if the gap < opening will be worth it. the one time loss might AGCTAAGGA-- eventually become “worth it. AGCTAAGGA--- AGCTAAGGACTT . • While gap opening might initially AGCTAAGGAAA cause the alignment score to be AGCTAAGGACT less than a mismatch.

under the restriction that the last character in BA be aligned with a gap. . • Table GB: Stores the best alignment score. under the restriction that the last character in AA be aligned with a gap.” • Table GA: Stores the best alignment. in case they might eventually become “worth it. we simple store the best possible alignments that end in gaps. Three Dynamic Programming Tables • Instead of looking to the future. • Table S: Stores the best alignment score with no restrictions.

j 1] g h S [i. Three Recursions G A [i 1. j ] . j ] max G A [i. j ] GB [i. j ] h G A [i.0] g ih S [i 1. j ] g h GB [i. j ] g jh GB [i.0] GB [i. j ] S [i 1. j 1) S [0.0] 0 S[i. j ] max G A [0. j ] max S [i. j 1] h S [0. j 1] (i 1.

j].” • Paths through GA must move up • Paths through GB must move left .j] = GA[i.j] or GB[i. without making a “move. Traceback • The path can now travel • Start in table S • If S[i. jump to the corresponding table.

j ] h G A [i. j 1] h S [0. j 1] g h S [i.0] GB [i. j ] . j ] 0 GB [i. j ] max S [i. j ] GB [i. j 1) S [0. j ] S [i 1. j ] max G A [i. j ] max G A [0.0] 0 S [i 1. Semiglobal Alignment G A [i 1. j 1] (i 1. j ] g h GB [i.0] 0 S[i.

Local Alignment • The key to Local Alignment is that the aligning region must still start and end with a matching character. • This means that a local alignment path must start and end in table S. • Thus finding local alignment is very similar to local alignment for constant gap penalty. .

j ] g h GB [i. j ] GB [i. Local Alignment G A [i 1. j ] max S [0. j 1] h GB [i. j ] max G A [i. j ] S [i 1.0] 0 S [0. j 1] (i 1. j ] max G A [0. j ] 0 S [i. j 1) S[i. j ] h G A [i. j ] 0 .0] 0 S [i 1. j 1] g h S [i.0] GB [i.

Applying Space Saving To Affine Gap Alignment .

j ] h j j G [i. j ] G A [i 1. Finding the Intersection S[i. j ] g h j j A A max S[i. j ) j j 1 . j 1] (i. j ] S[i 1. j ] g h j j G [i. j ] h j j j A S[i. j ] S[i 1. j ] S [i 1. j ] G [i 1.

j ) … g+2h g+h g+3h g+2h g+h … g+3h g+2h g+h … g+h g+2h … .Diagonal Intersection (i.

Vertical Intersection gh … 2h h g+3h g+2h g+h … g+3h g+2h g+h … h 2h … .

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