Cost Partitioning for Multiple Sequence Alignment

Multiple Sequence Alignment (MSA) is a fundamental problem in computational biology that is used to understand the evolutionary history of protein, DNA, or RNA sequences. An optimal alignment for two sequences can efficiently be found using dynamic programming, but computing optimal alignments for more sequences continues to be a hard problem. A common method to solve MSA problems is A* search with admissible heuristics, computed from subsets of the input sequences. In this paper, we consider MSA from the perspective of cost partitioning and relate the existing heuristics for MSA to uniform cost partitioning and post-hoc optimization, two well-known techniques from the automated planning literature. We show that the MSA heuristics are bounded by uniform cost partitioning and that post-hoc optimization yields strictly dominating heuristics. For a common benchmark set of protein sequences and a set of DNA sequences, we show that the theoretical dominance relations between the heuristics carry over to practical instances.