The method produces genome-wide mappings of in vivo nucleosome occupancy to detect the tissue-of-origin of cfDNA molecules. The method uses reads' endpoint position aligned which are expected to be close to nucleosome core particle (NCP) sites. Windowed Protection Score (WPS) is proposed to quantify the cfDNA density close to NCPs using the frequency of cfDNA particles that cover 120 base pairs centred at a given location minus the frequency of fragments with an endpoint at the same interval. Then, the peaks are called heuristically for WPS to identify footprints. The cells contributing to cfDNA are then predicted from the footprints. These footprints can be used for identifying non-malignant epigenetic or genetic sites like transcription factor binding sites, and detection of malignancy-related biomarkers based on the extent of tissue damage and cell deaths.