We present an algorithm for the optimal alignment of sequences to genome graphs. It works by phrasing the edit distance minimization task as finding a shortest path on an implicit alignment graph. To find a shortest path, we instantiate the A? paradigm with a novel domain-specific heuristic function that accounts for the upcoming subsequence in the query to be aligned, resulting in a provably optimal alignment algorithm called AStarix. Experimental evaluation of AStarix shows that it is 1–2 orders of magnitude faster than state-of-the-art optimal algorithms on the task of aligning Illumina reads to reference genome graphs. Implementations and evaluations are available at https://github.com/eth-sri/astarix.

@article{ivanov2020astarix, title={AStarix: Fast and Optimal Sequence-to-Graph Alignment}, author={Ivanov, Pesho and Bichsel, Benjamin and Mustafa, Harun and Kahles, Andre and R{"a}tsch, Gunnar and Vechev, Martin}, journal={RECOMB}, year={2020}, publisher={Cold Spring Harbor Laboratory} }