PacBio Licenses CUHK Deep Learning To Advance HiFi Sequencing Methylation Detection

PacBio, a leader in accurate long-read sequencing, announced plans to enhance methylation detection in HiFi chemistry by licensing novel deep learning models from Professor Dennis Lo at The Chinese University of Hong Kong (CUHK) and Centre for Novostics. The technology will improve detection of 5-hydroxymethylcytosine (5hmC), hemimethylated 5-methylcytosine (5mC), and N6-methyladenine (6mA) in native DNA during standard sequencing workflows on PacBio’s Revio and Vega systems.

Christian Henry, President and CEO of PacBio, stated, “PacBio was the first to detect native epigenetic modifications alongside accurate DNA sequencing. With the integration of CUHK deep learning models, our technology will detect additional biologically meaningful methylation signatures, including 5hmC and strand-specific 5mC. 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.”

Professor Dennis Lo, Scientific Director at the Centre for Novostics, CUHK, mentioned, “I am delighted to see this technology now being deployed more broadly through PacBio’s global customer base. 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.”

“This new capability enables high-resolution, native detection of 5mC, 6mA, and 5hmC. We’re empowering researchers to ask more sophisticated questions and uncover new biology. And because this capability is powered entirely by software and existing sequencing signals, customers can access it with no added cost or changes,” mentioned Mark Van Oene, Chief Operating Officer at PacBio. 

The licensed technology includes the Holistic Kinetic Model 2 (HK2), an enhanced AI framework combining convolutional and transformer layers to model kinetic features for higher precision. HK2 improves detection of 5mC and 6mA and introduces native 5hmC calling in single molecules, a first for HiFi sequencing. These advancements will be available through software updates at no additional cost or workflow change. PacBio had previously introduced 5mC detection in 2022 and extended support for 6mA in 2024. The new HK2 model enables strand-specific 5mC analysis, supporting research into hemimethylation.