The optimization of short-read sequencing—in which DNA strands about 300 bases in length are sequenced and then computationally reassembled—has made DNA sequencing much cheaper and revolutionized genomic profiling. But the computational assembly of short sequences into the full sequence can sometimes prove difficult, especially when those strands encode repeating sequences of bases. Similar challenges have complicated the sequencing of chemical, or epigenetic, modifications to DNA that play a critical role in an array of biological processes, especially cancer. In 2019, Ludwig Oxford’s Chunxiao Song’s and Benjamin Schuster-Böckler’s groups published the TAPS (Tet-assisted pyridine borane sequencing) method for the detection of the epigenetic modifications 5-methylcytosine and 5-hydroxymethylcytosine. The new method, now at the heart of a recently-launched startup named Base Genomics, is gentler, cheaper and far more efficient than the prevalent standard for such sequencing. This permits its use in sequencing epigenetic marks on even vanishingly tiny samples, potentially including circulating tumor DNA. In a new paper published in Genome Biology in March, Chunxiao and his colleagues describe their adaptation of TAPS for long-read sequencing applications and demonstrate its use on embryonic stem cells and the hepatitis B virus.
This article appeared in the August 2020 issue of Ludwig Link. Click here to download a PDF (2 MB).