A new study demonstrates the impact of HiFi long-read sequencing technology in identifying genetic causes of rare diseases, illustrating the feasibility of potentially replacing multiple diagnostic tests with a single, more comprehensive approach.
PacBio, specialists in highly accurate long-read sequencing solutions, have announced a significant publication from Radboud University Medical Center (Radboudumc) and its research partners in the American Journal of Human Genetics.
The study, led by Christian Gilissen and Lisenka Vissers of Radboudumc, used PacBio’s Revio platform and HiFi long reads to analyze 100 challenging patient samples where genetic causes of rare diseases were previously unidentified using short reads and supplementary tests.
HiFi sequencing identified 93% of pathogenic variants in these samples, potentially enhancing cost-effective diagnostics. It also detected variants missed by short-read methods.
Metrics for Clinical Genomics Momentum
In support of this study and a broader transition to HiFi long-reads, PacBio and Radboudumc are accelerating efforts to study bringing this approach into clinical practice. The collaboration is advancing rapidly, with recent milestones demonstrating measurable progress:
Nearly 1,000 samples processed: As of January 10, 2025, 981 samples have been sequenced, with 862 fully analysed since August 2024.
Operational improvements: Automated library preparation now enables 24 samples per run, with plans to scale up to 96 samples per run for even greater throughput.
Streamlined workflows: Advanced protocols and a graphical user interface are being optimized to support future diagnostics for all variant types, with the first-tier diagnostic rollout targeted for summer 2025.
Commitment to diagnostic genomes: In the fourth quarter of 2024, Radboudumc expanded its Revio instrument fleet to support an order for 5,000 genomes on SPRQ chemistry.
Christian Henry, President and CEO of PacBio, remarked: “The diagnostic capabilities demonstrated in this study represent a watershed moment for the potential of genomic medicine.
“PacBio is honored to partner with Radboudumc and other leading centers by delivering SPRQ chemistry for 5,000 genomes as we work together to study ways to simplify diagnostics, increase accuracy, and improve patient outcomes. These metrics reflect our shared commitment to advancing clinical genomics with scalable, practical solutions.”
Major advance for rare disease diagnostics
Dr. Alexander Hoischen, Professor of Genomic Technologies at Radboudumc, emphasised the significance of these advancements: “For patients and families affected by rare diseases, HiFi sequencing offers a pathway to answers.
“This study not only demonstrates the diagnostic power of long reads but also lays the groundwork for their clinical adoption. The scale and efficiency metrics from our collaboration show the potential feasibility of making these advanced diagnostics available to more patients worldwide.”
Defining moment for rare disease genomics
This study demonstrates the advantages of HiFi long reads in potentially consolidating multiple diagnostic tests into a single, highly accurate, and comprehensive solution. Researchers anticipate that continued advancements and decreasing technology costs will accelerate its potential adoption as the preferred method for rare disease diagnostics.
The study, HiFi long-read genomes for difficult-to-detect, clinically relevant variants, is available in the American Journal of Human Genetics.
