CyriPanel for CYP2D6 Genotyping from Targeted Capture Panels Using Assay-Matched Diploid References

CYP2D6

Paralog-aware framework (Cyrius, BCyrius) adapted with assay-matched diploid references and a spacer interval downstream of CYP2D7 for structural inference

CyriPanel adapts the paralog-aware framework of Cyrius and BCyrius to CYP2D6 genotyping from targeted capture panels, where assay-specific coverage affects copy-number estimation and sequence similarity with CYP2D7 obscures hybrid structures. The tool relies on assay-matched diploid references and a spacer interval downstream of CYP2D7. Evaluated in 116 Human Pangenome Reference Consortium cell lines sequenced with a custom panel, with assembly-derived diplotypes as the reference standard, it reached with five references a mean concordance of 94.7% (BWA-MEM) and 94.5% (DRAGEN), compared with 88.7% and 92.2% for Aldy 4. Among 28 hybrid samples, concordance was 88.8% and 88.6% versus 67.7% and 71.6% for Aldy 4, with differences concentrated in haplotypes carrying three or more gene copies. The software, evaluation records and raw reads are publicly available.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Preprint, not peer reviewed. The comparison with Aldy 4 is favourable but asymmetric: CyriPanel counts as correct as soon as any of its candidates matches, and requiring a single candidate lowers its concordance to 91.3% and 91.1%, the authors themselves describing the comparison as descriptive. For a panel-based PGx laboratory, the tool is open and testable, but clinical validity was not assessed and the result holds only for the capture design studied.

Analysis by Dr Thibaut Benquey