Identification of placenta hypomethylated domains (PHDs). (a) Mean methylation per 50 kbp genomic bin on chromosome 16 with non-pregnant ccf DNA (NP ccf DNA) and placenta shown. CpG sites (blue) and genes (orange) were summed per 50kbp genomic bin. (b) Genomic methylation level by CpG density at 50 kbp bin level. Values on the x-axis represent the number of CpG sites per 50 kbp bin. Numbers along the top indicate the number of genomic bins analyzed. (c) Differential methylation between placenta and non-pregnant plasma as a function of CpG density at 50 kbp bin level. A negative value on the y-axis is indicative of placenta hypomethylation. The red line corresponds to a loess smoothed fit.