PacBio unveils strategies to enhance methylation identification within HiFi chemistry
Pacific Biosciences (PacBio), a leading provider of high-quality sequencing platforms, has announced a significant advancement in its DNA methylation detection capabilities. This improvement comes from licensing advanced methylation detection methods from The Chinese University of Hong Kong (CUHK), notably enhancing their HK2 model.
The new HK2-based approach allows sensitive detection of both 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) modifications, crucial for epigenetic analyses. This enhancement supports strand-specific methylation analysis, improving resolution of methylation patterns on individual DNA strands.
CUHK's expertise in sophisticated methylation detection algorithms enables the model to discriminate 5mC from 5hmC, epigenetically distinct cytosine modifications often difficult to differentiate by traditional methods. Integrating these methods into PacBio’s Single-Molecule Real-Time (SMRT) sequencing technology expands its epigenomic profiling beyond the detection of 6mA and 4mC (common bacterial methylation marks) to a more nuanced eukaryotic methylation landscape.
The new method maintains DNA integrity and supports haplotype-resolved analysis in complex genomic regions. This contrasts with chemical-based methods like bisulfite or TAPS sequencing, which can degrade DNA or diminish phasing and structural context.
Mark Van Oene, Chief Operating Officer at PacBio, expressed excitement about the new capability, stating, "This innovation enhances our ability to provide comprehensive epigenomic data critical for research in human disease, neurobiology, and microbial epigenetics."
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. The licensed technology includes an enhanced AI deep learning framework called Holistic Kinetic Model 2 (HK2), which improves the accuracy of 5mC and N6-methyladenine (6mA) detection and introduces native 5hmC calling in single molecules.
This development is particularly useful for profiling dynamic and tissue-specific epigenetic mark 5hmC, implicated in brain development, cancer, and neurodegenerative diseases. CUHK, along with Take2 Technologies Limited, pioneered robust 5mC detection using the PacBio platform in 2021.
The new capability enables high-resolution, native detection of 5mC, 6mC, and 5hmC. 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.
Professor Dennis Lo, Scientific Director of Centre for Novostics, CUHK, expresses excitement about the technology's deployment through PacBio's global customer base. He believes this collaboration will further advance research in cancer, human development, and beyond.
Digital health advancements in science have led to the enhancement of PacBio's Single-Molecule Real-Time (SMRT) sequencing technology, thanks to licensed methylation detection methods from The Chinese University of Hong Kong (CUHK). This new HK2-based approach supports the sensitive detection of both 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC), crucial for understanding various medical-conditions, particularly in brain development, cancer, and neurodegenerative diseases. Technology plays a pivotal role in this development, improving our understanding and management of these conditions.