2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Highly Scalable Pharmacogenomic Panel Testing with Hybrid Capture and Long-Read Sequencing

Pdf Summary

This document discusses the use of hybrid capture and long-read sequencing technology for highly scalable pharmacogenomic panel testing in precision medicine research. The goal of pharmacogenomics (PGx) is to create assays that are comprehensive, high-throughput, and able to cover difficult-to-sequence and difficult-to-map regions in clinically actionable PGx loci. The document highlights the limitations of legacy low-cost technologies and their potential to produce incomplete or difficult-to-phase data.<br /><br />The authors describe a pre-designed PGx panel comprising 49 gene targets, including all 20 current genes with CPIC guidelines, FDA PGx genes, and genes of PGx research interest. Probes in the panel are optimized using a proprietary algorithm to enable balanced capture of complex regions. The panel is available as a ready-made Twist Alliance Long-Read PGx Panel.<br /><br />The workflow for sample preparation involves steps from PacBio, Twist Bioscience, and a third party. The panel design, data analysis, and results are also discussed in the document. The authors used published tools and reference materials to analyze the data, including the PharmCAT tool for allele calling, Pangu for CYP2D6 diplotypes, and publicly available GeT-RM reference samples. They reported high concordance between the PharmCAT calls and GeT-RM consensus calls for selected genes.<br /><br />The authors concluded that the described PGx panel for long-read HiFi sequencing provides unbiased coverage of medically-actionable pharmacogenes and shows high accuracy in detecting key loci for pharmacogenomics research. They mention that HiFi sequencing data enables full-gene phasing across targets, which could impact star allele calls, phenotype prediction, and overall clinical utility. They also highlighted the need for future work to assess the impact of phasing on clinical predictions.<br /><br />In summary, this document presents the use of hybrid capture and long-read sequencing technology for scalable pharmacogenomic panel testing. The authors provide details about the panel design, sample preparation workflow, data analysis, and results, highlighting the accuracy and potential impact of this approach in precision medicine research.

Asset Subtitle

Presenting Author - Nina Gonzaludo, PhD; Co-Author - Sarah Kingan, PhD; Co-Author - John R. Harting, MS; Co-Author - Primo Baybayan, PhD; Co-Author - Siyuan Zhang, PhD; Co-Author - Tina Han, PhD; Co-Author - Leonardo Arbiza, PhD; Co-Author - Yao Yang, PhD, FACMG; Co-Author - Nathan Hammond, PhD; Co-Author - Stuart A. Scott, PhD, FACMG;

Meta Tag

Genetic Testing

Genome sequencing

NextGen Sequencing

Pharmacogenomics

Sequencing

Co-Author Sarah Kingan, PhD

Co-Author John R. Harting, MS

Co-Author Primo Baybayan, PhD

Co-Author Siyuan Zhang, PhD

Co-Author Tina Han, PhD

Co-Author Leonardo Arbiza, PhD

Co-Author Yao Yang, PhD, FACMG

Co-Author Nathan Hammond, PhD

Co-Author Stuart A. Scott, PhD, FACMG

Presenting Author Nina Gonzaludo, PhD

Keywords

hybrid capture

long-read sequencing

pharmacogenomic panel testing

precision medicine research

pharmacogenomics

PGx loci

legacy low-cost technologies

Twist Alliance Long-Read PGx Panel

sample preparation

HiFi sequencing