An Improved Search Algorithm for Optimal Multiple-Sequence
Alignment
Paper by: Stefan SchroedlPresentation by: Bryan Franklin
Outline
Multiple-Sequence Alignment (MSA)
Graph Representation
Computing Path Costs
Heuristics
Experimental Results
Other Optimizations
Multiple-Sequence-Alignment
Sequence:
DNA: String over alphabet {A,C,G,T}
Protein: String with |Σ|=20 (one symbol for each amino acid)
Alignment:
Insert gaps (_) into sequences to line up matching characters.
Multiple-Sequence-Alignment
Indel: Insertion, Deletion, Point mutation (single symbol replacement)
Find a minimum set of indels between two or more sequences.
NP-Hard for an arbitrary number of sequences
Multiple-Sequence-Alignment
Applications
Common ancestry between species
Locating useful portions of DNA
Predicting structure of folded proteins
Computing G(n)
ConsiderationsBiological MeaningCost of computation
Sum-of-pairs
Substitution matrix ((|Σ|+1)2)Sum alignment costs for all pairsCosts can depend on neighbors
Optimizations
Sparse Path Representation
Curve fitting for predicting threshold values
Sub-optimal paths periodically deleted
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