From gene to dose: Long-read sequencing and *-allele tools to refine phenotype predictions of CYP2C19

• DOI: 10.3389/fphar.2023.1076574
• Publication Date: 2023-03-01T07:15:12Z
• Authors: Lonneke J. Graansma; Qinglian Zhai; Loes Busscher; Roberta Menafra; Redmar R. van den...; Susan L. Kloet; Maaike van der Lee
• Keywords: Pharmacogenomics

Background: Inter-individual differences in drug response based on genetic variations can lead to toxicity and treatment inefficacy. A large part of this variability is caused by variants pharmacogenes. Unfortunately, the Single Nucleotide Variant arrays currently used clinical pharmacogenomic (PGx) testing are unable detect all these genes. Long-read sequencing, other hand, has been shown be able resolve complex (pharmaco) In study we aimed assess value long-read sequencing for research PGx focusing important highly polymorphic CYP2C19 gene. Methods Results: With a capture-based panel were characterize entire region assign their allele origin (phasing), resulting identification 813 unique 37 samples. To utility data have compared performance three different *-allele tools (Aldy, PharmCat PharmaKU) which specifically designed haplotypes pharmacogenes input variants. Conclusion: We conclude that improve our ability locus, help identify novel useful asset phenotype prediction. Ultimately, approach could better predict an individual's therapy outcomes. However, added might limited.