Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug;57(8):1922-1934.
doi: 10.1038/s41588-025-02285-0. Epub 2025 Aug 7.

Analysis of individual patient pathway coordination in a cross-species single-cell kidney atlas

Affiliations

Analysis of individual patient pathway coordination in a cross-species single-cell kidney atlas

Konstantin A Klötzer et al. Nat Genet. 2025 Aug.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The Susztak lab is supported by Gilead, Novo Nordisk, Novartis, GSK, BIPI, Regeneron, Genentech, ONO and Calico. K.S. is on the scientific advisory boards of Pfizer and Otsuka. The other authors declare no competing interests.

References

    1. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England) 395, 709–733 (2020). - PMC - PubMed
    1. Kidney disease: a global health priority. Nature Reviews Nephrology (2024). - PubMed
    1. Kalantar-Zadeh K, Jafar TH, Nitsch D, Neuen BL & Perkovic V Chronic kidney disease. The Lancet 398, 786–802 (2021). - PubMed
    1. Muntner P Longitudinal measurements of renal function. Seminars in nephrology 29, 650–657 (2009). - PubMed
    1. Zuk A & Bonventre JV Acute Kidney Injury. Annu Rev Med 67, 293–307 (2016). - PMC - PubMed

Grants and funding

LinkOut - more resources