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Journal Article
Review
Next-generation sequencing in pharmacogenomics - fit for clinical decision support?
Expert Review of Clinical Pharmacology 2024 January 23
INTRODUCTION: The technological advances of sequencing methods during the past 20 years have fuelled the generation of large amounts of sequencing data that comprise common variations, as well as millions of rare and personal variants that would not be identified by conventional genotyping. While comprehensive sequencing is technically feasible, its clinical utility for guiding personalized treatment decisions remains controversial.
AREAS COVERED: We discuss the opportunities and challenges of comprehensive sequencing compared to targeted genotyping for pharmacogenomic applications. Current pharmacogenomic sequencing panels are heterogeneous and clinical actionability of the included genes is not a major focus. We provide a current overview and critical discussion of how current studies utilize sequencing data either retrospectively from biobanks, databases or repurposed diagnostic sequencing, or prospectively using pharmacogenomic sequencing.
EXPERT OPINION: While sequencing-based pharmacogenomics has provided important insights into genetic variations underlying the safety and efficacy of a multitude pharmacological treatments, important hurdles for the clinical implementation of pharmacogenomic sequencing remain. We identify gaps in the interpretation of pharmacogenetic variants, technical challenges pertaining to complex loci and variant phasing, as well as unclear cost-effectiveness and incomplete reimbursement. It is critical to address these challenges in order to realize the promising prospects of pharmacogenomic sequencing.
AREAS COVERED: We discuss the opportunities and challenges of comprehensive sequencing compared to targeted genotyping for pharmacogenomic applications. Current pharmacogenomic sequencing panels are heterogeneous and clinical actionability of the included genes is not a major focus. We provide a current overview and critical discussion of how current studies utilize sequencing data either retrospectively from biobanks, databases or repurposed diagnostic sequencing, or prospectively using pharmacogenomic sequencing.
EXPERT OPINION: While sequencing-based pharmacogenomics has provided important insights into genetic variations underlying the safety and efficacy of a multitude pharmacological treatments, important hurdles for the clinical implementation of pharmacogenomic sequencing remain. We identify gaps in the interpretation of pharmacogenetic variants, technical challenges pertaining to complex loci and variant phasing, as well as unclear cost-effectiveness and incomplete reimbursement. It is critical to address these challenges in order to realize the promising prospects of pharmacogenomic sequencing.
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