Investigating and Annotating the Human Peptidome Profile from Urine under Normal Physiological Conditions

Examining the composition of the typical urinary peptidome and identifying the enzymes responsible for its formation holds significant importance, as it mirrors the normal physiological state of the human body. Any deviation from this normal profile could serve as an indicator of pathological processes occurring in vivo. Consequently, this study focuses on characterizing the normal urinary peptidome and investigating the various catalytic enzymes that are involved in generating these native peptides in urine. Our findings reveal that 1503 endogenous peptides, corresponding to 436 precursor proteins, were consistently identified robustly in at least 10 samples out of a total of 19 samples. Notably, the liver and kidneys exhibited the highest number of tissue-enriched or enhanced genes in the analyzed urinary peptidome. Furthermore, among the catalytic types, CTSD (cathepsin D) and MMP2 (matrix metalloproteinase-2) emerged as the most prominent peptidases in the aspartic and metallopeptidases categories, respectively. A comparison of our dataset with two of the most comprehensive urine peptidome datasets to date indicates a consistent relative abundance of core endogenous peptides for different proteins across all three datasets. These findings can serve as a foundational reference for the discovery of biomarkers in various human diseases.