Multiomics characterization of cell type repertoires for urine liquid biopsies

Urine is assayed alongside blood in medicine, yet current clinical diagnostic tests utilize only a small fraction of its total biomolecular repertoire, potentially foregoing high-resolution insights into human health and disease. In this work, we characterized the joint landscapes of transcriptomic and metabolomic signals in human urine. We also compared the urine transcriptome to plasma cell-free RNA, identifying a distinct cell type repertoire and enrichment for metabolic signal. Untargeted metabolomic measurements identified a complementary set of pathways to the transcriptomic analysis. Our findings suggest that urine is a promising biofluid yielding prognostic and detailed insights for hard-to-biopsy tissues with low representation in the blood, offering promise for a new generation of liquid biopsies. ### Competing Interest Statement SRQ is a founder and shareholder of Molecular Stethoscope and Mirvie. SKV, GBL, SRQ are inventors on a patent application submitted by the Chan Zuckerberg Biohub and Stanford University. CRB is a co-founder and scientific advisory board member of Grace Science LLC, Lycia therapeutics, Palleon Pharmaceuticals, Enable Bioscience, Redwood Biosciences (a subsidiary of Catalent), OliLux Bio, InterVenn Bio, GanNA Bio, Firefly Bio, Neuravid Therapeutics, Valora Therapeutics, and is a member of the Board of Directors of Alnylam Pharmaceuticals and OmniAb.