Advancements in DNA sequencing have changed how we study genetics. Scientists can now explore the genetic changes behind complex diseases and understand genetic diversity better. Long-read sequencing technologies are very useful, but high costs and specific sample requirements have slowed their use in big studies.
PacBio has introduced SPRQ chemistry, which aims to tackle these issues. This technology enhances sequencing efficiency and accuracy, bringing the cost of sequencing a human genome down to under $500.
In a recent chat, Dr. Aaron Wenger, senior director at PacBio, shared insights about SPRQ chemistry. He discussed its unique benefits, how it’s helping with rare diseases, and ongoing efforts to make HiFi sequencing more accessible for researchers and clinicians worldwide.
Anna MacDonald (AM):
Senior Science Editor
Technology Networks
Anna is a senior science editor at Technology Networks. She has a degree in biological sciences from the University of East Anglia and previously helped organize scientific conferences.
Can you give us an overview of the new SPRQ chemistry and the benefits it can bring to researchers?
Aaron Wenger, PhD (AW):
Senior Director, Product Management
PacBio
Aaron oversees the long-read sequencing portfolio at PacBio. His interests include using genome sequencing to improve human health. He holds a BS in computer engineering from the University of Notre Dame and a PhD in computer science from Stanford University.
The SPRQ chemistry offers key advantages: it requires four times less DNA, increases sequencing yield by 33%, and allows for more accurate detection of methylation. With just 500 ng of DNA, HiFi sequencing can now work with tough samples such as saliva and tumors. It also lets researchers sequence two human genomes at once, reducing costs to $500 and improving throughput to 2,500 genomes per year.
Since its launch, SPRQ has transformed sequencing with better chemistry and polymerase engineering. This has vastly improved DNA loading and the quality of HiFi reads, making it a game changer in the field.
AM:
Senior Science Editor
Technology Networks
Anna is a senior science editor at Technology Networks. She has a degree in biological sciences from the University of East Anglia and previously helped organize scientific conferences.
Reducing the cost of a HiFi human genome to under $500 is a major milestone. How might this price reduction accelerate large-scale genomic studies and what impact could this have on our understanding of complex diseases and their genetic underpinnings?
AW:
Senior Director, Product Management
PacBio
Aaron oversees the long-read sequencing portfolio at PacBio. His interests include using genome sequencing to improve human health. He holds a BS in computer engineering from the University of Notre Dame and a PhD in computer science from Stanford University.
With the introduction of the Revio system in 2023, HiFi sequencing supports large projects like the All of Us program in the U.S., the Estonia Biobank in Europe, and the PRECISE project in Singapore. It’s also vital in networks studying rare diseases, like GREGoR, that analyze the complete genome, including structural variants and gene methylation. Moreover, this technology allows for pangenomes, which reflect genetic diversity across populations rather than relying solely on one reference genome.
The lower cost and improved efficiency from SPRQ chemistry will allow these projects to include more samples. This growth will enhance our understanding of critical genetic features involved in complex diseases, which are often difficult to study.
AM:
Senior Science Editor
Technology Networks
Anna is a senior science editor at Technology Networks. She has a degree in biological sciences from the University of East Anglia and previously helped organize scientific conferences.
What unique advantages does HiFi sequencing offer in helping diagnose rare diseases compared to traditional short-read sequencing? How might these advantages impact patient outcomes and treatment options?
AW:
Senior Director, Product Management
PacBio
Aaron oversees the long-read sequencing portfolio at PacBio. His interests include using genome sequencing to improve human health. He holds a BS in computer engineering from the University of Notre Dame and a PhD in computer science from Stanford University.
HiFi sequencing allows for a detailed look at genetic changes and variations all in one process. Rare diseases often arise from specific genetic or epigenetic changes. HiFi sequencing uncovers variations in regions that shorter technologies can’t reach. Importantly, it also differentiates maternal and paternal genomes.
Research from institutes like Children’s Mercy Kansas City and Radboud University shows that HiFi sequencing finds harmful variants that other methods miss in about 10% of cases. Finding these variants is crucial for discovering the genetic basis of rare diseases, leading to better targeted treatments and patient outcomes.
AM:
Senior Science Editor
Technology Networks
Anna is a senior science editor at Technology Networks. She has a degree in biological sciences from the University of East Anglia and previously helped organize scientific conferences.
What are some of the key logistical and technical challenges you foresee in implementing HiFi sequencing broadly across clinical settings for rare disease genomics? What approaches are being taken to overcome these barriers?
AW:
Senior Director, Product Management
PacBio
Aaron oversees the long-read sequencing portfolio at PacBio. His interests include using genome sequencing to improve human health. He holds a BS in computer engineering from the University of Notre Dame and a PhD in computer science from Stanford University.
For HiFi sequencing to be widely adopted, smart workflows are essential from DNA collection to data analysis. We’re working with partners to automate processes like DNA extraction and library preparation. This has cut costs and improved scalability. Recent developments, such as using saliva samples, also broaden the types of samples we can analyze.
Data handling is another challenge. We’ve created standardized workflows, like the HiFi WGS variant pipeline, available in the cloud and locally. This simplifies data processing and transfer through tools like SMRT Link.
Lastly, building comprehensive genetic variation databases is crucial. HiFi sequencing reveals more variations, making it vital to expand our reference datasets. With initiatives like CoLoRS and HiFi Solves, PacBio is collaborating with global partners to create these resources.
AM:
