DNA 5-methylcytosine specific profiling with limited input

DNA methylation 5mC specific detection has been limited by the mixed signals from traditional bisulfite sequencing or by the severe degradation of input during oxBS-seq pretreatment. Here, we presented a 5mC specific whole genome amplification method (5mC-WGA), with which we achieved whole genome bisulfite sequencing with 5mC retention from limited input down to 10 pg scale without 5hmC signals, presenting DNA 5mC methylome with high producibility and great accuracy. Overall design: We compared our 5mC-WGA method with well-established TAB-Seq and oxBS-Seq methods.