Pangenomes aid accurate detection of large insertions and deletions from targeted sequencing: the case of cardiomyopathies.

Pangenome-based workflow GRAF achieves higher accuracy (F1 0.86) in detecting large pathogenic variants (≥20 bp) from targeted sequencing in cardiomyopathy cases.

• Why it matters: Accurate detection of large genetic variants remains challenging with traditional linear reference genomes, limiting diagnostic precision for Mendelian disorders like cardiomyopathies.
• What they did: Researchers analyzed nearly 2,000 cardiomyopathy cases and controls using a pangenome approach (GRAF) alongside five conventional methods, validating variants with PCR and Sanger sequencing.
• The result: GRAF outperformed other tools in sensitivity and precision, also excelling in detecting small variants, suggesting pangenome workflows can enhance clinical genetic testing for all variant sizes.