Algorithms Dr. Nancy Warter-Perez June 19, 2003

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms2 Outline Programming workshop 2 solutions – 2 algorithms References for sequence alignment algorithms Discussion of Needleman-Wunsch iterative algorithm for global alignment Programming workshop 3

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms3 Programming Workshop 2 Solutions Solution 1 – Nested For Loops Solution 2 – Use dynamic programming concept of building on partial solution

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms4 Classic Papers Needleman, S.B. and Wunsch, C.D. A General Method Applicable to the Search for Similarities in Amino Acid Sequence of Two Proteins. J. Mol. Biol., 48, pp , ( ssicArticlesArchive/needlemanandwunsch1970.pdf) Needleman, S.B. and Wunsch, C.D. A General Method Applicable to the Search for Similarities in Amino Acid Sequence of Two Proteins. J. Mol. Biol., 48, pp , Smith, T.F. and Waterman, M.S. Identification of Common Molecular Subsequences. J. Mol. Biol., 147, pp , 1981.( sicArticlesArchive/smithandwaterman1981.pdf) Smith, T.F. and Waterman, M.S. Identification of Common Molecular Subsequences. J. Mol. Biol., 147, pp , Smith, T.F. The History of the Genetic Sequence Databases. Genomics, 6, pp , ( iclesArchive/smith1990.pdf) Smith, T.F. The History of the Genetic Sequence Databases. Genomics, 6, pp , 1990.

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms5 Needleman-Wunsch (1 of 3) Match = 1 Mismatch = 0 Gap = 0

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms6 Needleman-Wunsch (2 of 3)

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms7 Needleman-Wunsch (3 of 3) From page 446: It is apparent that the above array operation can begin at any of a number of points along the borders of the array, which is equivalent to a comparison of N-terminal residues or C-terminal residues only. As long as the appropriate rules for pathways are followed, the maximum match will be the same. The cells of the array which contributed to the maximum match, may be determined by recording the origin of the number that was added to each cell when the array was operated upon.

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms8 Programming Workshop #3 Write a program to determine the score of 2 globally aligned sequences using fixed scoring with affine gap penalty. A gap in an aligned sequence will be represented by a period (“.”). Your program should read the sequences from standard input and display the score to standard output. You should test your program with different sequences.

May 20, 2003 Developing Pairwise Sequence Alignment Algorithms9 Globally Aligned Sequences (Is this the Needleman-Wunsch Method?) The sequences abcdefghajklm abbdhijk are aligned and scored like this a b c d e f g h a j k l m | | | | | | a b b d... h i j k match mismatch gap_open -2 gap_extend for a total score of = 13