Chemical, or epigenetic, modifications made to the DNA base cytosine play an important role in the regulation of gene expression across the genome. The base is chemically modified with four chemically and functionally distinct “marks”, with 5-methylcytosine (5mC) being the most common and most frequently disordered in cancer. The others are 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5-fC) and 5-carboxycytosine (5caC). The Ludwig Oxford laboratory of Chunxiao Song reported in 2019 a sensitive, cost-effective and efficient method for the whole-genome sequencing of 5mC named TET-assisted pyridine borane sequencing (TAPS). Now the gold standard of such technologies, TAPS was at the heart of a biotech spin-off that was bought late last year by Exact Sciences, which will use the method in novel cancer diagnostics. In January, researchers led by Chunxiao and his University of Oxford colleague Ahmed Ahmed reported in Nature Communications an expanded toolkit for the direct and quantitative sequencing of all four cytosine epigenetic marks—a new version of TAPS for 5mC (named TAPSβ) and brand new methods for the other three.
This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).