biostudies-literatureKlotzer KANIDDK NIH HHSNIA NIH HHSDeutsche Forschungsgemeinschaft (German Research Foundation)Österreichische Agentur für Internationale Mobilität und Kooperation in Bildung, Wissenschaft und Forschung (Austrian Agency for International Cooperation in Education and Research)U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)Marshallplan-Jubiläumsstiftung (Austrian Marshall Plan Foundation)1922-1934https://www.ebi.ac.uk/biostudies/studies/S-EPMC12415535biostudies-literatureUnknown57(8)The use of single-cell RNA sequencing in clinical and translational research is limited by the challenge of identifying cell-type-specific, targetable molecular changes in individual patients and cross-species differences. Here we created an integrated single-cell kidney atlas including over 1 million cells from 140 samples, defining more than 70 conserved cell states in human and rodent models. We developed CellSpectra, a computational tool that quantifies changes in gene expression coordination across cellular functions, which we applied to kidney and lung cancer data. This tool powers our patient-level single-cell functional profiling report, which highlights cell-type-specific changes in the coordination of pathway gene expression in individuals. Our cross-species atlas facilitates the selection of a rodent model that closely reflects the cellular and pathway-level signatures observed in patient samples, advancing the application of single-cell methodologies in clinical precision medicine. Finally, using experimental models, we demonstrate how our informatics approach can be applied for the potential selection of suitable therapeutics.Nature geneticsAnalysis of individual patient pathway coordination in a cross-species single-cell kidney atlas.PMC124155355R01DK105821-08R01 DK0876352R01DK076077-155R01DK132630-02Marietta-Blau GrantBA 6205/2-15R01DK087635-15R01 DK076077P50 DK114786Austrian Marshall Plan Foundation scholarshipR01 DK1058215P50DK114786-07R01 DK132630R56 AG081351Liang XSusztak KBalzer MSHogan JJEller KBloom RDAbedini AZhang NRHalmos BSchuller MLevinsohn JLi SDumoulin BQuinn GHa EKlotzer KAfalseAnalysis of individual patient pathway coordination in a cross-species single-cell kidney atlas.The use of single-cell RNA sequencing in clinical and translational research is limited by the challenge of identifying cell-type-specific, targetable molecular changes in individual patients and cross-species differences. Here we created an integrated single-cell kidney atlas including over 1 million cells from 140 samples, defining more than 70 conserved cell states in human and rodent models. We developed CellSpectra, a computational tool that quantifies changes in gene expression coordination across cellular functions, which we applied to kidney and lung cancer data. This tool powers our patient-level single-cell functional profiling report, which highlights cell-type-specific changes in the coordination of pathway gene expression in individuals. Our cross-species atlas facilitates the selection of a rodent model that closely reflects the cellular and pathway-level signatures observed in patient samples, advancing the application of single-cell methodologies in clinical precision medicine. Finally, using experimental models, we demonstrate how our informatics approach can be applied for the potential selection of suitable therapeutics.2025-01-01T00:00:00Z2025 Aug2026-06-04T16:14:24.832Z2026-05-13T14:24:11.845ZS-EPMC124155354077526910.1038/s41588-025-02285-0