PacBio unveils strategies for enhancing the detection of methylation in its HiFi chemical methodology.
Pacific Biosciences (PacBio) has made significant strides in enhancing its DNA methylation detection capabilities, thanks to the integration of advanced methods and machine learning. The company's latest advancements are powered by software and existing sequencing signals, allowing customers to access these new capabilities with no added cost or workflow changes.
One of the key innovations is the use of machine learning models that merge PacBio methylation calls with other methylation profiling data to more precisely map methylation patterns across genomes. This includes the detection of N6-methyladenine (6mA), a modification that broadens the scope beyond just 5-methylcytosine (5mC).
PacBio's SMRT sequencing technology, known for its ability to identify methylation, specifically m6A and 5mCpG, by detecting subtle changes in DNA polymerase kinetics during DNA synthesis, has been further refined. Recent advances leverage these kinetic signals combined with computational methods, enhancing sensitivity and accuracy for detecting modified bases.
The new capabilities, available on PacBio's Revio and Vega systems, have already been put to use. For instance, the Children's Mercy Kansas City has adopted HiFi 5-base sequencing, which benefits from these enhanced methylation detection capabilities.
Moreover, CUHK, together with Take2 Technologies Limited, pioneered robust 5mC detection using the PacBio platform in 2021. PacBio plans to build on these collaborations, licensing advanced DNA methylation detection methods developed by Professor Dennis Lo and colleagues at The Chinese University of Hong Kong (CUHK) and Centre for Novostics.
The most recent addition to PacBio's methylation detection capabilities is the licensed Holistic Kinetic Model 2 (HK2), an AI deep learning framework that significantly improves the accuracy of 5mC and 6mA detection and introduces native 5hmC calling in single molecules—a first for HiFi sequencing.
These advancements open new frontiers in various fields of study. For example, the ability to profile 5hmC, a dynamic and tissue-specific epigenetic mark, is expected to aid researchers in studying brain development, cancer, and neurodegenerative diseases. Moreover, the new capabilities enable strand-specific 5mC analysis, which opens new opportunities to study hemimethylation—an emerging epigenetic signal.
PacBio's native detection method maintains DNA integrity and supports haplotype-resolved analysis in complex genomic regions. It also does not degrade DNA like chemical-based methods such as bisulfite or TAPS sequencing. These features make PacBio's HiFi sequencing an attractive option for researchers who seek comprehensive and simultaneous readouts of the genome and epigenome from native DNA.
In summary, PacBio's advancements in methylation detection appear largely driven by combining its native kinetic detection data with machine learning and complementary sequencing techniques, leading to improved resolution and accuracy of methylation landscapes in complex genomes. The company's ongoing collaborations and licensing agreements with institutions like CUHK are expected to further bolster its position in the field of epigenomics.
[1] Pacific Biosciences
[2] GenomeWeb
[3] Genetic Engineering & Biotechnology News
- Pacific Biosciences' latest advancements in digital health, driven by science and technology, are escalating the precision of mapping methylation patterns across genomes, broadening the scope beyond just 5-methylcytosine to include N6-methyladenine (6mA), thanks to the integration of machine learning and additional methylation profiling data.
- These technological advancements in digital health are revolutionizing medical-conditions research, particularly in fields like brain development, cancer, and neurodegenerative diseases, as they enable the profiling of dynamic and tissue-specific epigenetic marks, such as 5-hydroxymethylcytosine (5hmC), through PacBio's native detection method.
