PacBio reveals intentions to enhance methylation identification in HiFi chemistry processes
PacBio Enhances DNA Methylation Detection Capabilities with Advanced Methods
Pacific Biosciences (PacBio), a leading provider of sequencing platforms, has announced significant improvements in its DNA methylation detection capabilities. The new capabilities are powered by software and existing sequencing signals, meaning customers can access them with no added cost or workflow changes.
The advancements are the result of PacBio's collaboration with the Chinese University of Hong Kong (CUHK) and Take2 Technologies Limited. CUHK's methods, integrated with PacBio's HiFi sequencing, leverage long, highly accurate reads to detect 5-methylcytosine (5mC) DNA methylation marks with improved precision and resolution.
Key details of the improvement include the use of PacBio HiFi reads, which produce long reads (15–25 kb) with high base accuracy (>Q30). This enables more comprehensive coverage of complex genomic regions, including repetitive and GC-rich areas where methylation is critical. Advanced methylation calling models, likely incorporating enhanced probabilistic modeling for methylation detection differentiated by specific methylation signatures present in the long-read kinetic signals, improve methylation site identification sensitivity and specificity beyond standard approaches.
Integration with pangenome and methylation analysis pipelines allows for gene-level methylation quantification and richer epigenomic insights. PacBio data aligned to reference genomes (e.g., GRCh38) using optimized mappers (pbmm2) combined with methylation-aware analysis pipelines make this possible.
The functional significance of these advancements lies in their ability to facilitate better interpretation of epigenetic regulation in complex diseases, the identification of active/inactive genomic regions, and studies into structural variants and repetitive region methylation patterns that were previously challenging with short-read data.
Mark Van Oene, Chief Operating Officer at PacBio, stated that the new capability empowers researchers to ask more sophisticated questions and uncover new biology. The new capabilities are already available on both the Revio and Vega platforms, providing 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 licensed technology includes an enhanced AI deep learning framework called Holistic Kinetic Model 2 (HK2), which is designed to significantly improve the accuracy of 5mC and N6-methyladenine (6mA) detection and introduce native 5hmC calling in single molecules. The technology is designed to improve detection of DNA base modifications, including 5-hydroxymethylcytosine (5hmC) and hemimethylated 5-methylcytosine (5mC).
5hmC is implicated in brain development, cancer, and neurodegenerative diseases. The ability to profile 5hmC, a dynamic and tissue-specific epigenetic mark, opens new frontiers in liquid biopsy, cancer detection, and cell-free DNA analysis. The new method also enables strand-specific 5mC analysis, opening new opportunities to study hemimethylation.
PacBio's commitment to improving HiFi chemistry aims to provide customers with even deeper insights into the human genome, powering new discoveries and clinical possibilities. HiFi 5-base sequencing has already been adopted by institutions like Children's Mercy Kansas City and GeneDx for clinical and diagnostic purposes.
In summary, CUHK’s advanced methods complement PacBio HiFi sequencing by enhancing methylation call accuracy using sophisticated models and integrative pipelines, which improves the detection of 5mC modifications genome-wide, including in difficult genomic contexts like repetitive centromeric arrays. This represents a substantial leap forward in epigenomic research using long-read sequencing technology.
- The integration of PacBio HiFi sequencing with advanced methods from the Chinese University of Hong Kong (CUHK) has the potential to revolutionize digital health and medical-conditions research, particularly in the field of health-and-wellness, by offering improved precision and resolution in detecting DNA methylation marks.
- By leveraging technologies such as PacBio's HiFi sequencing, science and technology are collaborating to enhance our understanding of complex medical-conditions, especially those relating to epigenetic regulation in areas like brain development, cancer, and neurodegenerative diseases, through more accurate detection of DNA base modifications like 5-hydroxymethylcytosine (5hmC) and hemimethylated 5-methylcytosine (5mC).
