TET-assisted pyridine borane sequencing

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TET-assisted pyridine borane sequencing (TAPS) is a method for mapping DNA methylation at single-base resolution. It uses enzymes to convert methylated cytosines (5mC) and hydroxymethylcytosines (5hmC) into a signal that is read as thymine during sequencing, while unmodified cytosine stays as cytosine. Specifically, TET enzymes turn 5mC and 5hmC into 5-carboxylcytosine (5caC), and pyridine borane then reduces 5caC to dihydrouracil (DHU), which is read as thymine. Unmodified C remains C, so methylated sites appear as C-to-T changes in the reads. This enzymatic approach avoids the DNA damage of bisulfite sequencing and can offer improved sensitivity and specificity.

TAPS was developed in 2019 by Chunxiao Song and Benjamin Schuster-Böckler and colleagues at Ludwig Cancer Research and the University of Oxford. It is patented in the United States and licensed to Exact Sciences with exclusive partner Watchmaker Genomics.

Two main variants exist:

- Standard TAPS: cannot distinguish 5mC from 5hmC; both are read as T.
- TAPSβ: adds a glucosylation step to protect 5hmC, allowing selective mapping of 5hmC.

A related approach, CAPS, can detect 5fC and 5caC by reducing these marks to DHU directly on DNA without the TET step, while leaving C, 5mC, and 5hmC unchanged.