Sequencing of DNA using high-throughput methods has a wide range of applications in many fields, including cancer research. Over the last 15 years, the optimisation of short-read sequencing, the current mainstream technology, has made DNA sequencing much cheaper, allowing this method to be used more routinely. However, one drawback of short-read sequencing is that, by fragmenting and processing the DNA in short sections of roughly 300 base pairs, the subsequent computational assembly of the short sequences into the longer, original sequence can be challenging, especially for complex and repetitive regions. In an effort to overcome this issue, several companies have developed technologies that can sequence longer sections of DNA, with average lengths ~40-fold longer.
A parallel strand of research is the study of DNA chemical epigenetic modifications, such as cytosine methylation. In 2019, Chunxiao Song’s and Benjamin Schuster-Böckler’s groups published the TAPS method (Tet-assisted pyridine borane sequencing) for the detection of cytosine methylation and hydroxymethylation. Unlike other DNA methylation sequencing methods, TAPS does not rely on the harsh chemical bisulphite, which degrades a lot of the DNA sample. This allows TAPS to be used on much smaller amounts of DNA, such as those found in blood samples. In a new paper published in Genome Biology, Yibin Liu and Jingfei Cheng from Chunxiao Song’s laboratory have developed TAPS for the long-read sequencing applications mentioned above. This method now allows the study of long-range epigenetic phasing such as in cancer samples and genomic imprinting.