Consider pairwise alignments between 3 sequences Carillo and lipman-sum of Pairs method A-B-C Do we need to Score each node? moco o B-C A-B A-C Sequence A Get the multiple alignment score within the cubic lattice by Adding together the scores of the pairwise alignments
Consider pairwise alignments between 3 sequences Carillo and Lipman – Sum of Pairs method Sequence B CecneuqeS A-C A-B B-C A-B-C Do we need to Score each node? Sequence A Get the multiple alignment score within the cubic lattice by Adding together the scores of the pairwise alignments…
In practice, doesn't give optimal alignment. But were close Seems reasonable that the optimal alignment won't be far from the diagonal we were on, so we just set bounds on the location of the msa within the cube based on each pairwise-alignment Then just do dynamic programing within the volume defined by the pre-imposed bounds
In practice, doesn’t give optimal alignment…But we’re close! Seems reasonable that the optimal alignment won’t be far from the diagonal we were on…so we just set bounds on the location of the msa within the cube based on each pairwise-alignment. Then just do dynamic programing within the volume defined by the pre-imposed bounds
the volume is broken into polyhedra and the borders of the polyhedra are defined by paths through possible alignments
Still takes too long for more than three sequences. need a better way! Progressive Methods of Multiple Sequence Alignment Concept- simple: 1-Use DP to build pairwise alignments of most closely related sequences 2-Then progressively add less related sequences or groups of sequences
Still takes too long for more than three sequences…need a better way! • Progressive Methods of Multiple Sequence Alignment Concept – simple: 1-Use DP to build pairwise alignments of most closely related sequences 2- Then progressively add less related sequences or groups of sequences…
Clustalw Higgins and Sharp 1988 1-Do pairwise analysis of all the sequences (you choose similarity matrix) 2Use the alignment scores to make a phylogenetic tree 3- Align the sequences to each other guided by the phylogenetic relationships in the tree New features: Clustal E ClustalW (allows weights)L ClustalX(GUI-based Weighting is important to avoid biasing an alignment by many sequence Members that are closely related to each other evolutionarily
ClustalW Higgins and Sharp 1988 • 1- Do pairwise analysis of all the sequences (you choose similarity matrix). • 2- Use the alignment scores to make a phylogenetic tree. • 3- Align the sequences to each other guided by the phylogenetic relationships in the tree. New features: Clustal ⌦ClustalW (allows weights) ⌦ ClustalX (GUI-based Weighting is important to avoid biasing an alignment by many sequence Members that are closely related to each other evolutionarily!