Cells throughout the body release fragmented chromatin into the bloodstream during cell death. These cell-free chromatin fragments carry genetic and epigenetic information that reflects both their tissue of origin and the physiological state of the tissues from which they arise.

Cell-free DNA-based liquid biopsy has already shown substantial promise in cancer detection. However, most current approaches focus mainly on tumour-specific DNA methylation patterns or mutations, which can limit unbiased inference of tissue origin and often provide only a partial view of tissue state.