Targeted haplotyping in pharmacogenomics using Oxford Nanopore Technologies’ adaptive sampling

The primary aim of this study was to explore the use of Oxford Nanopore Technologies (ONT) adaptive sampling for targeted haplotyping in pharmacogenomics (PGx). The researchers sought to improve the identification of complex genetic variations and structural variants relevant to drug response. The study addressed the limitations of traditional methods like microarrays and short-read sequencing, which struggle to detect large structural variants and haplotype phasing. The researchers developed an enrichment strategy to target a panel of 1,036 genes associated with PGx using adaptive sampling.

Oxford Nanopore sequencing, specifically using the PromethION platform, was employed to carry out the targeted sequencing and enrichment. The study demonstrated that adaptive sampling improved the sequencing depth of targeted regions without additional sample preparation steps. They also showcased that three samples could be multiplexed on a single flow cell without significant drops in variant calling performance, achieving high recall (99.35%) and precision (99.84%) for targeted PGx variants.

Key findings of the study highlighted the advantages of long nanopore reads in accurately detecting single nucleotide variants (SNVs), indels, structural variants, and phasing haplotypes. The Oxford Nanopore-based method outperformed traditional short-read sequencing in identifying complex PGx regions. This approach is more flexible, allowing updates to the gene panel as new pharmacogenetic markers are discovered, potentially making it a cost-effective solution for clinical PGx applications.