The Maximum Weight Trace Problem in Multiple Sequence Alignment

Abs t rac t . We define a new problem in multiple sequence alignment, called maximum weight trace. The problem formalizes in a natural way the common practice of merging pairwise alignments to form multiple sequence alignments, and contains a version of the minimum sum of pairs alignment problem as a special case. Informally, the input is a set of pairs of matched characters from the sequences; each pair has an associated weight. The output is a subset of the pairs of maximum total weight that satisfies the following property: there is a multiple alignment that places each pair of characters selected by the subset together in the same column. A set of pairs with this property is called a trace. Intuitively a trace of maximum weight specifies a multiple alignment that agrees as much as possible with the character matches of the input. We develop a branch and bound algorithm for maximum weight trace. Though the problem is NP-complete, an implementation of the algorithm shows we can solve instances on as many as 6 sequences of length 250 in a few minutes. These are among the largest instances that have been solved to optimality to date for any formulation of multiple sequence alignment.