Analysis of individual patient pathway coordination in a cross-species single-cell kidney atlas
Cite
Klötzer, K.A., Abedini, A., Li, S., Balzer, M.S., Liang, X., Levinsohn, J., Ha, E., Dumoulin, B., Hogan, J.J., Quinn, G. and Bloom, R.D., 2025. Analysis of individual patient pathway coordination in a cross-species single-cell kidney atlas. Nature genetics, 57(8), pp.1922-1934.
https://doi.org/10.1038/s41588-025-02285-0
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.
Datasets
1. Species Integrated Single cell Kidney Atlas
ExploreSample source
Sample ID
Cell type (level 1)
Cell type
Cell type (KPMP)
Reference genome
Disease group
Disease
Treatment
Assay
Tissue
Sex
Age
Sample collection method
Primary adjudicated category
Race
Age group
m_humphreys_DKD275,636 cells m_humphrey_IRI112,219 cells mouse_susztak59,644 cells custom pre-mRNA GTF built from the ENSEMBL rn6 genome 127,668 cells Chronic kidney disease (CKD)583,767 cells Acute kidney injury (AKI)163,290 cells Control_diseased452,172 cells Control_healthy279,405 cells Rosiglitazone46,346 cells Spironolactone41,673 cells Chromium Next GEM Single Nuclei 3ʹ GEM Kit v3.1440,827 cells 10x Genomics Chromium Single Nuclei Kit v3413,772 cells 10X chromium Single Nuclei 3' v2171,863 cells Percutaneous Needle Biopsy61,365 cells Intra-operative Biopsy20,456 cells Deceased Donor Nephrectomy18,355 cells Total Tumor Nephrectomy18,063 cells Tumor Nephrectomy17,657 cells Partial Tumor Nephrectomy2,240 cells Acute Tubular Injury20,523 cells Diabetic Kidney Disease8,788 cells Hypertensive Kidney Disease4,469 cells Black or African-American11,312 cells 
2. Human-only Single cell Kidney Atlas
ExploreSample source
Sample ID
Cell type (level 1)
Cell type
Cell type (KPMP)
Disease group
Disease
Treatment
Assay
Tissue
Sex
Age
Sample collection method
Primary adjudicated category
Race
Age group
Subject ID
Chronic kidney disease (CKD)133,745 cells Acute kidney injury (AKI)24,152 cells Control_diseased157,897 cells Control_healthy141,505 cells Chromium Next GEM Single Nuclei 3ʹ GEM Kit v3.1161,266 cells 10x Genomics Chromium Single Nuclei Kit v3138,136 cells Percutaneous Needle Biopsy61,365 cells Intra-operative Biopsy20,456 cells Deceased Donor Nephrectomy18,355 cells Total Tumor Nephrectomy18,063 cells Tumor Nephrectomy17,657 cells Partial Tumor Nephrectomy2,240 cells Acute Tubular Injury20,523 cells Diabetic Kidney Disease8,788 cells Hypertensive Kidney Disease4,469 cells Black or African-American11,312 cells 
3. Mouse-only Single cell Kidney Atlas
ExploreSample source
Sample ID
Cell type (level 1)
Cell type
Disease group
Disease
Treatment
Assay
Tissue
m_humphreys_DKD275,636 cells m_humphrey_IRI112,219 cells mouse_susztak59,644 cells Chronic kidney disease (CKD)243,413 cells Acute kidney injury (AKI)139,138 cells Control_diseased236,782 cells Control_healthy64,948 cells Rosiglitazone46,346 cells 10x Genomics Chromium Single Nuclei Kit v3275,636 cells 10X chromium Single Nuclei 3' v2171,863 cells 
4. Rat-only Single cell Kidney Atlas
ExploreSample source
Sample ID
Cell type (level 1)
Cell type
Disease group
Disease
Treatment
Assay
Tissue
Chronic kidney disease (CKD)206,609 cells Control_healthy72,952 cells Control_diseased57,493 cells Spironolactone41,673 cells Chromium Next GEM Single Nuclei 3ʹ GEM Kit v3.1279,561 cells 
5. Human extended disease-centered atlas
ExploreSubject ID
Cell type (level 1)
Cell type (SISKA)
Cell type
Cell type (KPMP)
Sample ID
Sample source
Sex
Age
Race
Disease
Disease (level 2)
GFR
Diabetes
Hypertension
Age group
Tissue
Reference genome
Assay
Sample collection method
Leiden clustering
PKD6_humphreys_ADPKD9,760 cells PKD2_humphreys_ADPKD9,487 cells control2_humphreys_ADPKD8,661 cells PKD4_humphreys_ADPKD8,449 cells PKD1_humphreys_ADPKD8,406 cells control4_humphreys_ADPKD8,275 cells PKD3_humphreys_ADPKD7,766 cells PKD5_humphreys_ADPKD7,280 cells healthy_6_humphreys_DKD7,279 cells control5_humphreys_ADPKD7,050 cells control3_humphreys_ADPKD6,117 cells control1_humphreys_ADPKD5,908 cells diabetic_1_humphreys_DKD2,863 cells PKD8_humphreys_ADPKD2,353 cells diabetic_4_humphreys_DKD2,304 cells PKD7_humphreys_ADPKD2,240 cells diabetic_3_humphreys_DKD2,183 cells diabetic_2_humphreys_DKD2,008 cells diabetic_5_humphreys_DKD829 cells PKD6_humphreys_ADPKD9,760 cells PKD2_humphreys_ADPKD9,487 cells control2_humphreys_ADPKD8,661 cells PKD4_humphreys_ADPKD8,449 cells PKD1_humphreys_ADPKD8,406 cells control4_humphreys_ADPKD8,275 cells PKD3_humphreys_ADPKD7,766 cells PKD5_humphreys_ADPKD7,280 cells healthy_6_humphreys_DKD7,279 cells control5_humphreys_ADPKD7,050 cells control3_humphreys_ADPKD6,117 cells control1_humphreys_ADPKD5,908 cells diabetic_1_humphreys_DKD2,863 cells PKD8_humphreys_ADPKD2,353 cells diabetic_4_humphreys_DKD2,304 cells PKD7_humphreys_ADPKD2,240 cells diabetic_3_humphreys_DKD2,183 cells diabetic_2_humphreys_DKD2,008 cells diabetic_5_humphreys_DKD829 cells humphreys_ADPKD55,741 cells humphreys_DKD53,477 cells Chronic kidney disease (CKD)391,874 cells Acute kidney injury (AKI)61,293 cells Chronic kidney disease (CKD)113,167 cells Hypertension associated kidney disease (H-CKD)90,850 cells Diabetic kidney disease (DKD)80,480 cells Acute kidney injury (AKI)61,293 cells Polycystic kidney disease (PKD)55,741 cells IgA nephropathy3,764 cells 50-59 ml/min/1.73m2115,727 cells 60-69 ml/min/1.73m280,419 cells 40-49 ml/min/1.73m271,552 cells 70-79 ml/min/1.73m260,811 cells 30-39 ml/min/1.73m250,034 cells 10-19 ml/min/1.73m247,724 cells 100-109 ml/min/1.73m224,757 cells 80-89 ml/min/1.73m224,443 cells 20-29 ml/min/1.73m222,279 cells 120-129 ml/min/1.73m222,170 cells 90-99 ml/min/1.73m216,669 cells 110-119 ml/min/1.73m216,600 cells 0-9 ml/min/1.73m212,949 cells 10x Genomics Chromium Single Nuclei Kit v3576,945 cells Chromium Next GEM Single Nuclei 3ʹ GEM Kit v3.1143,979 cells Percutaneous Needle Biopsy54,179 cells Intra-operative Biopsy19,276 cells Deceased Donor Nephrectomy17,398 cells Total Tumor Nephrectomy16,886 cells Tumor Nephrectomy16,692 cells Partial Tumor Nephrectomy2,050 cells 