BRIEF RESEARCH REPORT article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1653999
Comparative evaluation of Oxford Nanopore Technologies' adaptive sampling and the Twist long-read PGx panel for pharmacogenomic profiling
Provisionally accepted
- Ghent University, Ghent, Belgium
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Clinical pharmacogenomics (PGx) testing strategies are mainly based on targeted PCR, microarrays, or short-read sequencing. These methods perform well for detecting known single nucleotide variants (SNVs), small insertions/deletions (indels), and certain copy number variants (CNVs), but they fall short in resolving complex structural variants (SVs), particularly in complex pharmacogenes such as CYP2D6. Therefore, we previously developed a targeted PGx test based on long-read Oxford Nanopore Technologies (ONT) sequencing. Harnessing adaptive sampling (AS) to in silico enrich a panel of PGx genes, we illustrated superior performance in star-allele calling compared to the Genetic Testing Reference Materials Program (GeT-RM) truth set. However, accurate diplotyping of CYP2D6 remained challenging. In this work, we adopted the latest basecalling, variant calling, phasing and star-allele calling tools on our pre-existing data from the HG001, HG01190, NA19785, HG002 and HG005 reference samples. Additionally, we benchmarked the results to public data obtained using the long-read compatible Twist Alliance PGx panel. The re-analyzed ONT AS data demonstrated correct CYP2D6 star-alleles compared to (GeT-RM) truth set. Upon benchmarking to the Twist Alliance PGx panel, perfect star-allele matching was obtained between our panel and the Twist PGx panel for all included Clinical Pharmacogenomics Implementation Consortium (CPIC) Level A genes. However, our ONT AS panel demonstrated superior variant phasing, resulting in three times more variants per phasing block. These findings confirm the robustness of ONT AS for targeted long-read PGx applications and highlight its potential to support more accurate pharmacogenomic testing, particularly for structurally complex genes like CYP2D6.
Keywords: pharmacogenomics, Long-read sequencing, Adaptive sampling, CYP2D6, Twist Alliance PGx panel
Received: 25 Jun 2025; Accepted: 12 Aug 2025.
Copyright: © 2025 Deserranno, Tilleman, Deforce and Van Nieuwerburgh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Koen Deserranno, Ghent University, Ghent, Belgium
Filip Van Nieuwerburgh, Ghent University, Ghent, Belgium
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