PacBio discloses objectives for enhancing methylation identification in HiFi chemistry
PacBio's HiFi sequencing technology, with its recent chemistry updates such as SPRQ on the Revio system, is making waves in the scientific community. The enhanced capabilities of this technology now include the detection of DNA methylation, including 5mC and 6mA, alongside variant detection and transcript sequencing—all from a single library preparation with as little as 500 ng DNA.
At the heart of these methylation detection advances is the Holistic Kinetic Model 2 (HK2). Although the search results do not explicitly detail the HK2, it is known that this advanced kinetic model was developed by PacBio to improve the accuracy of DNA base modifications detection by analysing polymerase kinetics data from the single-molecule real-time (SMRT) sequencing.
HK2 leverages subtle changes in DNA polymerase kinetics during sequencing caused by DNA modifications. By modelling these kinetics more holistically, HK2 enhances methylation detection resolution and distinguishes among different types of DNA modifications with greater confidence, compared to earlier kinetic models. This improvement translates into a more sensitive and accurate methylation calling capability embedded within PacBio HiFi workflows.
The applications of HK2 and the HiFi chemistry's enhanced methylation detection are far-reaching. They include epigenetic studies where high-fidelity methylation profiling at base resolution is critical, analysis of complex epigenetic marks like 5-methylcytosine (5mC) and N6-methyladenine (6mA) simultaneously, detection of methylation states in phased genomes, and integration with transcript isoform data for holistic epigenome-transcriptome analyses.
The new capability from PacBio allows high-resolution, native detection of 5mC, 6mA, and 5hmC. Unlike chemical-based methods such as bisulfite or TAPS sequencing, PacBio's native detection does not degrade DNA and diminish phasing and structural context.
This advancement is expected to be a significant step forward in the field of epigenetics research and diagnostics, with the potential to revolutionize the understanding and diagnosis of various diseases such as cancer and neurodegenerative diseases. PacBio plans to bring these capabilities to its Revio and Vega systems.
Institutions like Children's Mercy Kansas City are already using PacBio's technology for clinical use, and GeneDx is leveraging this capability to investigate the diagnostic potential of epigenetic signals in neonatal care. The new technology includes an enhanced AI deep learning framework known as Holistic Kinetic Model 2 (HK2), which will significantly improve the accuracy of 5mC and 6mA detection and introduce native 5hmC calling in single molecules.
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). This new capability opens new frontiers in liquid biopsy, cancer detection, and cell-free DNA analysis, particularly for profiling 5hmC, a dynamic and tissue-specific epigenetic mark implicated in brain development, cancer, and neurodegenerative diseases.
Mark Van Oene, Chief Operating Officer at PacBio, expressed that the technology empowers researchers to ask more sophisticated questions and uncover new biology. 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. PacBio's native detection maintains DNA integrity and supports haplotype-resolved analysis in complex genomic regions, making it a valuable tool in the ongoing quest to unravel the mysteries of the genome.
In the realm of digital health and medical-conditions, the recent advancements in PacBio's HiFi sequencing technology, namely the Holistic Kinetic Model 2 (HK2), are poised to revolutionize epigenetics research and diagnostics. By enhancing methylation detection resolution and introducing native 5hmC calling in single molecules, this technology offers potential breakthroughs in understanding and diagnosing diseases such as cancer and neurodegenerative diseases. The incorporation of this technology into clinical settings, like Children's Mercy Kansas City, and its utilization by institutions like GeneDx underscores its significant value in the medical field, enabled by technology and science.
