PacBio unveils strategies to enhance methylation identification in its HiFi technology
PacBio, a leading provider of high-quality sequencing platforms, has announced a significant advancement in epigenetic sequencing with the introduction of the Holistic Kinetic Model 2 (HK2). This new analytical approach refines the direct detection and discrimination of epigenetic marks, such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), without the need for chemical conversion methods like bisulfite sequencing.
The HK2 model enhances the accuracy of 5mC and 5hmC detection by refining the kinetic signal analysis derived from PacBio's circular consensus sequencing (CCS) data. Leveraging the polymerase kinetics during sequencing, HK2 allows more precise calling of these modifications, increasing sensitivity and specificity compared to earlier methods or bisulfite sequencing, which can struggle to differentiate 5hmC from 5mC.
The improvements brought by HK2 impact methylation detection in several ways:
- Detection accuracy: HK2 allows more precise calling of 5mC and 5hmC modifications, increasing sensitivity and specificity compared to earlier methods or bisulfite sequencing.
- Direct detection without chemical conversion: PacBio HiFi sequencing combined with HK2 reads DNA modifications directly during sequencing, avoiding DNA damage or biases that chemical treatments can introduce.
- Broader epigenetic insight: Since 5hmC plays distinct biological roles different from 5mC, the ability to separately identify both modifications enhances understanding of epigenetic regulation in health and disease.
The new capability from PacBio is powered entirely by software and existing sequencing signals, with no added cost or workflow changes. It is already being adopted by institutions like Children's Mercy Kansas City and GeneDx for clinical and diagnostic purposes. CUHK, together with Take2 Technologies Limited, pioneered robust 5mC detection in 2021 using the PacBio platform.
PacBio plans to bring these capabilities to its Revio and Vega systems. The improvements will be achieved through licensing advanced DNA methylation detection methods developed by Professor Dennis Lo and colleagues at CUHK and Centre for Novostics. The new technology includes an enhanced AI deep learning framework known as Holistic Kinetic Model 2 (HK2), which is designed to significantly improve the accuracy of 5mC and N6-methyladenine (6mA) detection and introduces native 5hmC calling in single molecules.
The new capability from PacBio is aimed at profiling 5hmC, a dynamic and tissue-specific epigenetic mark implicated in brain development, cancer, and neurodegenerative diseases. This advance marks a shift from indirect methods to direct, kinetics-based epigenetic modification detection. Mark Van Oene, Chief Operating Officer at PacBio, stated that the new capability empowers researchers to ask more sophisticated questions and uncover new biology.
References:
- PacBio
- Children's Mercy Kansas City
- GeneDx
- CUHK
- Take2 Technologies Limited
- Professor Dennis Lo
- Centre for Novostics
Digital health advancements, driven by science and technology, are now being applied to medical-conditions through the use of PacBio's newest tool, the Holistic Kinetic Model 2 (HK2). This ingenious software solution refines the detection of epigenetic marks, such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), in DNA sequences, providing a more accurate understanding of epigenetic regulation in health and disease.
