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SVkhor: a unified framework for structural variant integration across long-read, short-read, and optical genome mapping data

Sharif Rahmani, E.; Thomas, Q.; Tisserant, E.; Vautrot, V.; Auclair, A.; Hounnondaho, F.-Z.; Castillon, E.; Faivre, L.; THAUVIN-ROBINET, C.; Vitobello, A.; Duffourd, Y.

2026-08-02 genetic and genomic medicine
10.64898/2026.07.30.26359319 medRxiv
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Summary Multi-technology human genome structural variant (SV) discovery is challenged by differences in breakpoint resolution, allele representation, SV annotation, and VCF structure across various callers and platforms. Here, we present SVkhor, a software framework designed to merge outputs from multiple callers within each technology and integrate SV callsets across available short-read sequencing, long-read sequencing, and optical genome mapping data. SVkhor addresses these challenges through caller-aware normalization, within-technology merging, and cross-technology integration, producing compact, source-annotated SV catalogs suitable for benchmarking and downstream interpretation. Benchmarking using HG002 and analysis of a clinical trio demonstrate that SVkhor reduces redundant caller-level complexity while preserving technology-specific evidence, enabling the transition from heterogeneous SV callsets to interpretable sample- and family-level SV catalogs.

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