Analytical Validation of an Annotation Tool for WGS-Based Pharmacogenomics: Preparing for Clinical Implementation

CYP2D6, CYP2C19, CYP2C9, SLCO1B1, TPMT, NUDT15, DPYD (WGS panel)

Validation of a PGx annotation tool on WGS data: concordance with dedicated genotyping panels (SNP arrays, qPCR) for CPIC Level A/B genes; sensitivity and specificity of allele calling from WGS

Analytical validation of a pharmacogenomic annotation tool from WGS (whole genome) data for clinical implementation. The tool is evaluated on the most clinically actionable CPIC Level A/B genes: CYP2D6, CYP2C19, CYP2C9, SLCO1B1, TPMT, NUDT15, DPYD. Concordance with dedicated genotyping panels (gold standard) is high for most genes. Residual challenges concern CYP2D6 duplication detection and resolution of highly polymorphic genes.

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With the generalization of WGS in diagnostics, recovering PGx data without additional testing is a major objective. This validation demonstrates feasibility for the main CPIC Level A/B genes. Limitations on CYP2D6 (multiple copies) remain to be resolved before broad implementation in clinical routine.

WGS-PGx analytical validation (major clinical challenge) +2; high concordance with dedicated panels +2; Clin Transl Sci +1; clinical implementation impact +2