Fig. 1.

Study methodology and cell type specificity of genome-wide methylation profiles. (A) Schematic of single-stranded library preparation method. cfDNA is denatured and treated with sodium bisulfite, which converts unmethylated cytosines (dark blue) into uracils (light blue) but not methylated cytosines (green). Bisulfite-treated DNA is first ligated to single-stranded adapters and bound to magnetic beads. Second-strand synthesis, and double-stranded adapter ligation are performed on the beads. The final step is a PCR, which converts uracils to thymines (red). (B) Pie chart with summary of samples included in this study, colored by pathology. (C) Schematic of WGBS analysis workflow. (D) PCA of reference whole-genome methylation profiles from human tissues. (E) UMAP of reference methylation profiles. Ellipses in D and E are normal 95% confidence ellipses (K means, 4 centers).