Improved tagmentation-based whole-genome bisulfite sequencing for input DNA from less than 100 mammalian cells

Aim: To develop a whole-genome methylation sequencing method that fulfills the needs for studies using ultra-low-input DNA. Materials & methods: The tagmentationbased whole-genome bisulfite sequencing (T-WGBS) technology is modified, enabling stable library construction with complexity from minimally 0.5 ng of initial genomic DNA, which equals less than 100 mammalian cells. Results: We thoroughly assessed the performance of this T-WGBS method by sequencing the methylomes of a rice strain and pre-implantation embryos of rhesus monkey and compare to traditional WGBS approach, thereby demonstrating the efficacy of this new approach. Conclusion: This new approach is highly attractive for the complete methylome analysis of very few cells, for example, mammalian pre-implantation embryos, or tiny human biopsy specimens.