Engineering & Technologyarticle2026-08-14

Anchors for Homology-Based Scaffolding

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Abstract

Homology-based scaffolding orders contigs based on conserved collinearity of homologous sequences across related species. Existing methods often rely on costly whole-genome alignments or show limited robustness when integrating multiple references. Here, we introduce an anchor-based scaffolding framework that adapts synteny anchors to efficiently infer contig order and orientation relative to one or more reference genomes. Our approach leverages precomputed, sufficiently unique anchors and their respective high-confidence homology matches in a greedy approach, combining single-reference to multi-reference scaffolds using a maximum matching. Across simulated and real datasets, anchor-based scaffolding achieves accuracy comparable to state-of-the-art methods. Notably, the approach shows particular strengths in multi-reference settings. These results demonstrate that synteny-anchor-based scaffolding provides an additional tool for homology-based scaffolding with robust accuracy and superior performance in multi-reference scenarios.

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View paper (DOI)Open access versionOpenAlexJournal of Bioinformatics and Computational BiologyPublished 2026-08-14

Authors: Karl K. Käther, Steffen Lemke, Peter F. Stadler

Institutions: Technical University of Denmark, University of Vienna, Universidad Nacional de Colombia, University of Hohenheim, Max Planck Institute for Mathematics, Telstra (Australia)