When cells die, they release cell-free DNA into the body. Cell-free circulating DNA (ctDNA) is an attractive diagnostic target because it is obtained through non-invasive blood draws, and could be applied to a wide variety of diseases with characteristic cell death, including cancer, autoimmune diseases, and myocardial infarction. However, identifying the ctDNA of interest remains challenging due to the large amount of circulating DNA that is irrelevant for detecting the disease. For example, in cancer less than 1% of the total circulating DNA arises from cancerous cells. Due to this high level of background noise, it is imperative that the tissue-of-origin of the ctDNA is correctly identified. Epigenetic modifications, such as nucleosome positioning or methylation patterns, are highly cell-type specific, but detecting these modifications in very small amounts of ctDNA is impractical with current technologies.