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Trees, Stars, and Multiple Biological Sequence Alignment Jesse Wolfgang CSE 497 February 19, 2004 * Importance? RNA folding (Trifonov, Bolshoi) Gene regulation (Galas et al.) Protein structure-function relationships(Wu, Kabat) Molecular evolution (Dayhoff) * Introduction Original sequence unknown Must consider all possible transformations Including insertions, deletions, and replacements Choose the most likely set of transformations With a given model of protein evolution * Sequences and Alignments An alignment of the sequences is written as K-sequence: sequence of k characters Each is obtained from Blanks are inserted in positions where some of the other sequences have a nonblank character At least one must be nonblank for each is the length of the aligned sequences * Alignments D Q L F D N V QQ G L D - - Q – L F D N V Q - - - - - - Q G L - Ex: sequences DQLF, DNVQ, QGL * Lattices and Paths Cartesian product of strings of squares A path between the sequences is a set of connected line segments (connected broken line) A lattice of sequences with lengths n Consists of -dimensional hypercubes Forms an -dimensional parallelepiped * Paths 2 dimensions 3 dimensions 3 possible paths 7 possible paths = 2n-1 = O(2n) * Paths D Q G L N V Q D Q L F 3-dimensional parallelepiped sublattice Sequences DQLF, DNVQ, QGL D D - - N - Q Q Q - - G L - L F - - - V - * Sequences: ABCD, ABD, BCD Paths and Sequence Length Note: Where is the length of A B C D A B – D - B C D A B C D A B D B C D * Sequences: ABCD, EFGH, IJK Paths and Sequence Length Note: Where is the length of E I J K F G H A B C D A B C D – - - - - - - - - - - E F G H - - - - - - - - - - - I J K * Sequences DQLF, DNVQ, QGL Projections D Q G L N V Q D Q L F denotes an alignment of and D Q – L F - Q G L - D Q L F Q G L * Optimal Paths is a measure assigned to Measure
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