PR002086 (Project)

Description:Background: Early detection of the cell type changes underlying several genitourinary tract diseases largely remains an unmet clinical need, whereas existing assays, if available, lack the cellular resolution afforded by an invasive biopsy. While messenger RNA in urine could reflect dynamic signal that facilitates early detection, current measurements primarily detect single genes and thus do not capture the full spectrum of cell type specific contributions. Methods: We isolated and sequenced the cellular and cell-free RNA from urine samples (n = 6healthy controls and n = 12 kidney stones) alongside the metabolome. We analyzed the resulting urine transcriptomes and metabolomes by comparing the bulk gene expression, deconvolving the noninvasively measurable cell type contributions, and comparing to the plasma cell-free transcriptome. Results: We primarily observed signal originating from genitourinary tract cell types in addition to cell types from high-turnover solid tissues beyond the genitourinary tract. Integration of urinary transcriptomic and metabolomic measurements identified various metabolic pathways involved in amino acid metabolism overlap with metabolic subsystems associated with proximal tubule function. Conclusions: Noninvasive whole transcriptome measurements of human urine reflect signal from hard-to-biopsy tissues exhibiting low representation in the blood at cell type resolution.