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CAPS+, a new procedure for epigenetic mapping, improves on a gold standard

Chunxiao Song, Ludwig Cancer Research Oxford
Chunxiao Song

Selective, efficient and controllable oxidation of cytosine modifications is valuable for epigenetic analysis. Researchers co-led by Ludwig Oxford’s Chunxiao Song reported in a March paper in the Journal of the American Chemical Society a new method for that purpose. Their method integrates two new modular chemical oxidation reactions with borane reduction to develop a method they call CAPS+ for the direct and quantitative sequencing of hydroxymethylcytosine modifications on DNA. CAPS+ is an improvement on the chemical-assisted pyridine borane sequencing (CAPS) procedure for epigenetic mapping developed in Chunxiao’s lab. Chunxiao and his colleagues showed that the oxidation reactions they employ cause very little damage to DNA, an asset in applying such methods to extremely small samples, such as those of liquid biopsies and single cells. The researchers tested the CAPS+ procedure by mapping 5hmC on DNA from mouse embryonic stem cells as well as tissues taken from normal human brain and glioblastoma tumors. Their studies confirmed previous findings that the 5hmC modification, which plays a role in multiple biological processes and is especially abundant in nervous system tissues, declines some seven-fold in abundance in glioblastoma tumors. Their analysis shows that CAPS+ generates fewer false positives and is more efficient than CAPS, which is already an extremely sensitive and efficient procedure for epigenetic sequencing.

Modular oxidation of cytosine modifications and their application in direct and quantitative sequencing of 5-hydroxy-methylcytosine
Journal of the American Chemical Society, 2023 March 24

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