Figure 1. Experimental paradigm using cell-free methylated DNA in blood to identify cellular origins of radiation-induced tissue damage.

Serial serum samples were collected from breast cancer patients treated with radiation. In parallel, paired serum and tissue samples were collected from mice receiving 3 Gy or 8 Gy of radiation compared to sham control. Cell-free DNA (cfDNA) methylome profiling of serum samples was performed using hybridization capture-sequencing of bisulfite-treated cfDNA. Cell-type-specific methylation blocks were identified from whole-genome bisulfite sequencing (WGBS) reference data of healthy tissues and used to identify the cellular origins of the serum cfDNA.