London Calling 2023: Advancing targeted haplotyping in pharmacogenomics using adaptive sampling

Pharmacogenomics (PGx) encompasses the personalisation of a patient’s drug therapy based on their genomic blueprint. However, current genotyping techniques are still limited in terms of the relevance of the information they provide. Therefore, we applied the recently unrolled adaptive sampling feature on the PromethION device to characterize relevant PGx genes. We targeted a panel of over 1,056 pharmacogenes, including challenging genes such as CYP2D6, from the Pharmacogenomics Knowledge Base. Using the latest R10.4.1 Flow Cells and Native Barcoding Kit V14, we multiplexed reference DNA standards, including the well-characterized GIAB NA12878 sample and performed PromethION sequencing. After superhigh accuracy basecalling, we evaluated variant calling, structural variant detection, and haplotype phasing with respect to the published references and earlier Oxford Nanopore sequencing data from R9.4.1 Flow Cells. Our results confirm the potential added value of the latest Oxford Nanopore sequencing chemistry to inform haplotype-guided pharmacological treatment.