Ultra-low-input, tagmentation-based whole genome bisulfite sequencing

We have adapted transposase-based in vitro shotgun library construction (“tagmentation”) for whole genome bisulfite sequencing. This method, Tn5mC-seq, enables a >100-fold reduction in starting material relative to conventional protocols, such that we generate highly complex bisulfite sequencing libraries from as little as 10 nanograms of input DNA, and ample useful sequence from 1 nanogram of input DNA. We demonstrate Tn5mC-seq by sequencing the methylome of a human lymphoblastoid cell line to approximately 8.6X high quality coverage of each strand.