PacBio Announces Plans To Improve Methylation Detection in HiFi Chemistry
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PacBio (Nasdaq: PACB), announced it plans to improve on its already highly accurate methylation detection capabilities in HiFi chemistry through licensing advanced DNA methylation detection methods developed by Professor Dennis Lo and colleagues at the The Chinese University of Hong Kong (CUHK) and Centre for Novostics. The licensed technology is designed to enhance PacBio HiFi sequencing with improved detection of DNA base modifications—including 5-hydroxymethylcytosine (5hmC) and hemimethylated 5-methylcytosine (5mC)—in native DNA. PacBio plans to bring these capabilities to its Revio and Vega systems, building on its existing 5mC support to deliver even more comprehensive epigenomic insights as part of standard HiFi whole-genome sequencing workflows.
“PacBio was the first to detect native epigenetic modifications alongside accurate DNA sequencing. With the integration of the CUHK deep learning models, our technology will be able to detect many additional and biologically meaningful methylation signatures, including 5hmC and strand-specific 5mC,” said Christian Henry, President and CEO of PacBio. “Our commitment to continually improving HiFi chemistry will enable our customers to gain even deeper insights into the human genome, powering new discoveries and clinical possibilities.”
The newly licensed technology includes an enhanced AI deep learning framework known as Holistic Kinetic Model 2 (HK2), which integrates convolutional and transformer layers to model local and long-range kinetic features with extraordinary precision. HK2 is designed to significantly improve the accuracy of 5mC and N6-methyladenine (6mA) detection and introduces native 5hmC calling in single molecules—a first for HiFi sequencing.
HiFi sequencing, available on both the Revio and Vega platforms, provides a comprehensive and simultaneous readout of the genome and epigenome from native DNA without the need for chemical conversion, additional sample preparation, or parallel workflows. The new capabilities from the HK2 model will be delivered to existing customers through software updates, with no changes to sequencing protocols and no additional cost.
“I am delighted to see this technology now being deployed more broadly through PacBio’s global customer base,” said Professor Dennis Lo, Scientific Director of Centre for Novostics, CUHK. “Accurate detection of DNA methylation—particularly 5mC and 5hmC—on native molecules is important for advancing research in cancer, human development, and beyond. With the improvements enabled by HK2, methylation calling with PacBio HiFi sequencing is poised to set a new standard for accuracy in the industry, surpassing other available technologies.”
CUHK, together with Take2 Technologies Limited, a Hong Kong-based biotechnology company, pioneered robust 5mC detection in 2021 using the PacBio platform. PacBio introduced on-instrument 5mC detection in April 2022 and extended support to 6mA in December 2024 for Fiber-seq chromatin architecture studies. HK2 is designed to push detection performance to new levels of accuracy. Importantly, HK2 will also enable strand-specific 5mC analysis, which opens new opportunities to study hemimethylation—an emerging epigenetic signal.
HiFi 5-base sequencing has already been adopted by pioneering institutions such as Children’s Mercy Kansas City, the first to use comprehensive genomic and epigenomic profiling in a clinical setting. GeneDx is also leveraging this capability to investigate the diagnostic potential of epigenetic signals in neonatal care.
The ability to profile 5hmC—a dynamic and tissue-specific epigenetic mark implicated in brain development, cancer, and neurodegenerative diseases—opens new frontiers in liquid biopsy, cancer detection, and cell-free DNA analysis. Unlike chemical-based methods such as bisulfite or TAPS sequencing, which degrade DNA and diminish phasing and structural context, PacBio’s native detection maintains DNA integrity and supports haplotype-resolved analysis in complex genomic regions.
The licensing of HK2 marks another milestone in PacBio’s continued leadership in long-read epigenomics. Combined with the high accuracy and long read lengths of HiFi sequencing, HK2 delivers a uniquely powerful tool for understanding the full landscape of genome function—across both sequence and modification.
“By enabling high-resolution, native detection of 5mC, 6mA, and 5hmC, we’re empowering researchers to ask more sophisticated questions and uncover new biology,” said Mark Van Oene, Chief Operating Officer at PacBio. “And because this capability is powered entirely by software and existing sequencing signals, customers can access it with no added cost or workflow changes.”
