PacBio, a leader in high-quality, long-read sequencing, is proud to announce its critical role in a study to be published in Nature Genetics. The study, titled Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition, showcases how researchers leveraged PacBio’s advanced sequencing solutions, including the synchronized Fiber-seq and Kinnex (formerly MAS-seq) multiomic approach, to uncover the genetic and molecular basis of a rare and complex Mendelian condition.

In collaboration with the University of Washington and the Undiagnosed Diseases Network (UDN), the study applied PacBio’s state-of-the-art Revio™ sequencing system to integrate long-read genomic, transcriptomic, methylomic, and epigenomic data in a synchronized analysis to analyze a 9-month-old patient with an unsolved condition involving bilateral retinoblastomas, developmental delays, and additional symptoms. Previous diagnostic methods, including short-read sequencing, were unable to provide an answer. With PacBio’s innovative multiomic solutions, researchers identified a chromosome X;13 balanced translocation disrupting four key genes—each through a unique molecular mechanism.

“This study highlights the power of highly accurate long-read multiomic sequencing in understanding the genetic mechanisms behind complex rare diseases,” said Andrew B. Stergachis, MD, PhD, senior author and associate professor at the University of Washington. “By integrating genomic, transcriptomic, epigenomic, and methylomic data in a single analysis, we were able to pinpoint multiple molecular disruptions contributing to this rare Mendelian condition—findings that would have been impossible with traditional approaches.”

Key Findings Enabled by PacBio Technology:

• Synchronized Multiomic Sequencing: For the first time, a single sequencing run provided simultaneous insights into genome, methylome, epigenome, and transcriptome data, eliminating the need for redundant experiments.
• Resolution of Complex Mechanisms: PacBio’s long-read accuracy uncovered a range of pathogenic events, including fusion transcripts, enhancer adoption, transcriptional readthrough silencing, and epigenetic disruptions—offering a complete genomic picture of the disease.
• Haplotype-Specific Insights: The technology allowed precise phasing of genetic, epigenetic, and transcriptomic features, crucial for understanding the functional impact of rare variants.

“This is the kind of transformative research we’re passionate about enabling,” said David Miller, Vice President of Global Marketing at PacBio. “The ability to replace multiple legacy assays and simultaneously analyze the genome, methylome, epigenome, and transcriptome in high resolution is a testament to how far HiFi sequencing technology has come. With the latest Revio system and SPRQ chemistry updates launched at ASHG, scientists now have the tools to uncover answers that were previously out of reach. It’s thrilling to see this technology driving real-world impact.”

This study, spearheaded by a team of renowned researchers including Mitchell R. Vollger, Andrew B. Stergachis, and others, highlights the collaboration between leading institutions such as the University of Washington Center for Mendelian Genomics (UW-CMG) and the Undiagnosed Diseases Network (UDN). Their collective expertise is helping shape the future of genomics, advancing the ability of health care providers to diagnose and treat rare genetic diseases.

Source – Globe Newswire