A pangenomic method for establishing a synthetic somatic variant resource in HapMap mixtures.

A pangenomic method creates a comprehensive somatic variant resource with over 6 million SNVs and 49,000 structural variations from HapMap mixtures.

• Why it matters: Robust benchmarks for somatic mosaicism are scarce despite its prevalence in human biology and disease, hindering the evaluation of detection technologies.
• What they did: The team developed a technology-agnostic approach that constructs pangenome graphs from assemblies of six HapMap cell lines, validated variants with ultra-deep simulated reads, and modeled coverage needs for detection.
• The result: This resource improves structural variant detection, especially in difficult regions, and enables systematic assessment of somatic variant detection methods across diverse genomic contexts.