AI Summary: Theseus is a new algorithm designed to solve one of the biggest bottlenecks in genomics: aligning DNA sequences to complex pangenome graphs. While previous methods were either slow (if optimal) or inaccurate (if heuristic), Theseus manages to be both fast and 100% accurate.
Sequence-to-graph alignment is a cornerstone of modern pangenomics, yet current optimal algorithms suffer from high memory and computational costs. We present Theseus, a novel, fast, and optimal affine-gap alignment algorithm that leverages genomic similarities to accelerate computation. Theseus exploits a 'diagonal transition' property and a sparse-data strategy to process only a subset of dynamic programming cells without compromising optimality. We evaluate Theseus on multiple sequence alignment (MSA) and pangenome read mapping, demonstrating a 2.0x to 232.2x speed improvement over state-of-the-art optimal aligners like SPOA and POASTA. Theseus supports optimal affine-gap alignment on arbitrary directed graphs, including those with cycles.
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