ChIP-seq of urine cell-free nucleosomes deliniates sources of renal cell-free DNA in health and disease
2School of Computer Science and Engineering, Hebrew University of Jerusalem, Israel
Cell-free DNA (cfDNA) in human urine is used to gain insight into the biology of organs or tumors in the renal pathway. This cfDNA originates from the fragmented chromatin of dying cells which was shown to maintain several histone modifications still intact. Here we applied chromatin immunoprecipitation of cell-free nucleosomes in urine followed by DNA sequencing (urine cfChIP-seq) to the urine of healthy individuals and the urines of patients with bladder cancer. We show urine cfChIP-seq identifies the major contributing organs to urinary cfDNA in the renal pathway including the cfDNA from the kidneys, the bladder-urothelium and neutrophils. We explore factors contributing to inter- and intrapersonal variance in urine cfChIP such as sex differences and variations in sequential urinations. Finally we use urine cfChiP-seq to detect pathology-related differences between healthy individuals and patients with bladder cancer. Taken together, these results mark urine cfChIP-seq as a powerful tool for interrogating biological processes in the renal pathway and a method for non-invasive liquid-biopsy.