Exact global alignment using A* with chaining seed heuristic and match pruning.

Abstract

Sequence alignment has been at the core of computational biology for half a century. Still, it is an open problem to design a practical algorithm for exact alignment of a pair of related sequences in linear-like time. We solve exact global pairwise alignment with respect to edit distance by using the A* shortest path algorithm. In order to efficiently align long sequences with high divergence, we extend the recently proposed seed heuristic with match chaining, gap costs, and inexact matches. We additionally integrate the novel match pruning technique and diagonal transition to improve the A* search. We prove the correctness of our algorithm, implement it in the A*PA aligner, and justify our extensions intuitively and empirically. github.com/RagnarGrootKoerkamp/astar-pairwise-aligner.