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November 15, 2023  |  Pharmacogenomics

Empowering the pharmacogenomics research community with long-read sequencing

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The power of pharmacogenomics (PGx) panel testing


PGx aims to understand how individual genetic differences influence drug response, enabling personalized medicine research. While several amplicon studies have shown the advantages of HiFi sequencing for single gene tests in PGx, panel testing is gaining traction for a variety of scientific, clinical, and economic reasons. Target enrichment panels allow PGx researchers to focus on specific genes with clinical evidence for implementation, such as genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines or FDA biomarkers, which are involved in drug safety and efficacy. By leveraging Twist Bioscience long read panels with PacBio sequencing, labs can consolidate multiple assays, reducing per-gene costs and labor. Additionally, reimbursement for panel testing is increasing, making testing more broadly accessible.

With standardized workflows from Twist Bioscience and PacBio®, hybrid capture-based panel sequencing can be done at a higher throughput and lower cost than whole genome sequencing, while still providing all the benefits of long reads. Long-read HiFi sequencing with PacBio allows for high accuracy and more comprehensive variant calling. With direct phasing across gene targets, HiFi reads allow for unambiguous star (*) allele assignment and unbiased, ancestry-agnostic coverage. A study by van der Lee, et al. shows that a targeted panel approach with HiFi sequencing for PGx research is “superior for both accuracy and phasing” when compared to short-read sequencing-based panels.
 

Funding opportunity

Apply now to the PacBio Twist Long-read PGx Sequencing Grant hosted by the Phamacogenomics Global Research Network

Apply now

Apply PGx panel testing to your research


In collaboration with Twist Bioscience and researchers at Stanford University, we designed a comprehensive 49-gene PGx panel for long-read HiFi sequencing that includes all 20 current genes with CPIC guidelines, as well as FDA PGx genes, and genes research interest (Figure 1). This 2 Mb panel is available off-the-shelf as the Twist Alliance Long-Read PGx Panel with sample data for 10 selected GeT-RM samples available online. Thirty-nine genes on the panel have full-gene coverage, enabling more complete phasing, and the panel can be ordered or easily customized through Twist. Preliminary panel performance shows high accuracy and coverage of clinically relevant PGx variants (Figure 2), with phasing to enable accurate star (*)-allele assignment.

Forty-nine  gene targets included in the Twist Alliance Long-Read PGx Panel
Figure 1. Forty-nine gene targets included in the Twist Alliance Long-Read PGx Panel. *Bold denotes full-gene coverage. +Underline denotes inclusion in a CPIC Level A guideline. **full length mtDNA coverage is available for spike-in separately through Twist.

To increase accessibility, highlight the utility of long-read sequencing in PGx research, and support diversity in genomics research, PacBio is excited to announce the sponsorship of a sequencing grant with the Pharmacogenomics Global Research Network (PGRN): PacBio Twist Long-read PGx Sequencing Grant – Apply Now! One grant will be awarded on a competitive basis to a PGRN member who proposes a PGx project that utilizes PacBio sequencing of pharmacogenes and targets an under-represented population.

PacBio will provide long-read targeted sequencing of 288 samples (four Revio™ SMRT® Cells) using the Twist Alliance Long-Read PGx panel. The program will be organized and judged by PGRN and will consider a submission of proposals on a wide range of drug-related phenotypes, particularly those with direct relevance to potential clinical implementation. Applicants are encouraged to leverage the panel to study more than one pharmacogene in their population of interest. PacBio and PGRN organizers also support public data release (with proper consent) and submission of novel haplotypes to PharmVar. If interested, please apply directly through PGRN, please note a membership is required. Additional contributions (probes and reagents) will be provided by Twist Bioscience, and sequencing services will be provided by Sampled, a PacBio Certified Service Provider and Twist ProLab.

HiFi reads coverage of CPIC variants
Figure 2. HiFi reads coverage of CPIC variants. Distribution of CPIC variant coverage across 10 publicly-available GeT-RM samples, summarized by gene.

Learn more about pharmacogenomics and targeted sequencing with PacBio, or see what we did at ASHG 2023.
 

About PGRN:


PGRN logoThe mission of the Pharmacogenomics Global Research Network (PGRN) is to catalyze and lead research in precision medicine for the discovery and translation of genomic variation influencing therapeutic and adverse drug effects. Membership is required for this grant – Learn more and apply at www.pgrn.org. Follow PGRN at @pgrnhub or LinkedIn.
 

About Twist Bioscience:


Twist bioscience logoTwist Bioscience is a leading and rapidly growing synthetic biology and genomics company that has developed a disruptive DNA synthesis platform to industrialize the engineering of biology. The core of the platform is a proprietary technology that pioneers a new method of manufacturing synthetic DNA by “writing” DNA on a silicon chip. Twist is leveraging its unique technology to manufacture a broad range of synthetic DNA-based products, including synthetic genes, tools for next-generation sequencing (NGS) preparation, and antibody libraries for drug discovery and development. Twist is also pursuing longer-term opportunities in digital data storage in DNA and biologics drug discovery. Twist makes products for use across many industries including healthcare, industrial chemicals, agriculture and academic research.

Follow Twist on Twitter | Facebook | LinkedIn | YouTube
 

About Sampled:


Sampled logoSampled enables their clients to advance human health by leveraging active biological samples through preservation, immortalization and utilization in comprehensive multiomics research within the only leading-edge Global Integrated Analytical Biorepository. For more information, please visit www.sampled.com or follow them on LinkedIn.

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