X-Mapper: fast and accurate sequence alignment via gapped x-mers

• Main Authors: Gaston, Jeffry M., Alm, Eric J., Zhang, An-Ni
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2025
• Subjects: Medicine, Health and Life Sciences; Bioinformatics; Sequence alignment algorithms
• Online Access: https://hdl.handle.net/10356/182567
• Institution: Nanyang Technological University

Sequence alignment is foundational to many bioinformatic analyses. Many aligners start by splitting sequences into contiguous, fixed-length seeds, called k-mers. Alignment is faster with longer, unique seeds, but more accurate with shorter seeds avoiding mutations. Here, we introduce X-Mapper, aiming to offer high speed and accuracy via dynamic-length seeds containing gaps, called gapped x-mers. We observe 11–24-fold fewer suboptimal alignments analyzing a human reference and 3–579-fold lower inconsistency across bacterial references than other aligners, improving on 53% and 30% of reads aligned to non-target strains and species, respectively. Other seed-based analysis algorithms might benefit from gapped x-mers too.