Accordingly, it has been difficult to use urine (or non-invasive biopsies besides blood, such as saliva or stool samples) to detect cancer or other diseases. The proportional contribution of each tissue source to the total urinary cfDNA is unknown, and in some studies, the concentration of cfDNA from the source of interest is extremely low, or even undetectable (15,16,18). Previous studies focus on detecting cfDNA from a single source of interest at a time, and there is a large variation in the quantity of urinary cfDNA derived from a particular source. Using blood transfusion (9), pregnancy (9-11), hematopoietic stem cell transplantation (12), non-urologic malignancies (13,14), renal transplantation (15), and bladder cancer (16,17) as model systems, a number of groups have demonstrated that a proportion of urinary cfDNA is derived from the systemic circulation, the kidney, and from the post-renal urothelium. DNA isolated from the cell-free supernatant of urine can be broadly categorized as arising from the pre-renal, renal, or post-renal system. Urine analysis is truly noninvasive and understanding the origin of urinary cfDNA is useful for guiding its clinical use as a form of ‘liquid biopsy’. Analyses of cell-free (cf) DNA in circulating plasma originating from the fetus (2), tumor cells (3) and transplant allograft (4) have enabled the development of noninvasive prenatal testing (5), ‘liquid biopsy’ for assessing tumors (6,7), and the monitoring of the clinical status of transplanted organs (8). Short fragments of extracellular DNA found in human body fluids are released during apoptosis and necrosis from dying cells (1). 30, 2016, the entire contents of which are herein incorporated by reference for all purposes. 62/427,999, entitled “Analysis of Cell-Free DNA in Urine and Other Samples” filed Nov. The present application claims priority from U.S. Cell-free DNA in a blood sample and organ-associated sample can both be analyzed to identify chromosomal regions exhibiting a copy number aberration. In other embodiments, two different samples can be analyzed to determine whether a particular organ has cancer. A statistical measure of the size profile may indicate that cell-free DNA fragments are collectively longer than expected for subjects with healthy tissue compared to non-healthy tissue. In other embodiments, sizes of organ-associated cell-free DNA can be measured. Tissue-specific methylation patterns can be used to determine fractional contributions from different tissue types. In some embodiments, methylation levels of cell-free DNA can be measured in a sample. Some embodiments may use an organ-associated sample that is from a particular organ or passes through the particular organ, as may occur, for example, in urine, saliva, blood, and stool samples. Diseases (e.g., cancer) of a particular organ can be detected by analyzing cell-free DNA.
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