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The Song group at Ludwig Oxford has adapted TAPS to measure DNA modifications on much longer sections of DNA at a whole-genome scale.

Most high-throughput DNA sequencing is currently performed using short-read sequencing, which fragments and processes DNA in short sections of roughly 300 base pairs. However, the more recent advance of long-read sequencing has allowed the mapping of repetitive and complex genomic regions, which can reveal new information about the genome.

Researchers have also devised novel sequencing technologies to study epigenetic modifications to DNA, such as cytosine methylation, which are altered across the genome in cancer. Epigenetic sequencing has been shown to be a promising tool for sophisticated, minimally invasive cancer diagnostics.

In 2019, Ludwig Oxford’s Chunxiao Song and Benjamin Schuster-Böckler and their groups published the TAPS  (for Tet-assisted pyridine borane sequencing) method 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 2020, the Song lab adapted TAPS for targeted long-read sequencing.

In a new paper published in Nucleic Acids Research, Jinfeng Chen and Jingfei Cheng have now added whole-genome long-read TAPS to the suite of TAPS methods. This new method has uncovered many sites for methylation that were not present in data from short-read TAPS. Whole-genome long-read TAPS was also able to detect allele-specific methylation in imprinting genes.

Whole-genome long-read TAPS will enhance the use of long-read sequencing technologies for the study of DNA epigenetics at a whole genome scale.

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