Deep learning–based molecular morphometrics for kidney biopsies
JCI Insight, vol. 6
Abstract
Morphologic examination of tissue biopsies is essential for histopathological diagnosis. However, accurate and scalable cellular quantification in human samples remains challenging. Here, we present a deep learning-based approach for antigen-specific cellular morphometrics in human kidney biopsies, which combines indirect immunofluorescence imaging with U-Net-based architectures for image-to-image translation and dual segmentation tasks, achieving human-level accuracy. In the kidney, podocyte loss represents a hallmark of glomerular injury and can be estimated in diagnostic biopsies. Thus, we profiled over 27,000 podocytes from 110 human samples, including patients with antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN), an immune-mediated disease with aggressive glomerular damage and irreversible loss of kidney function. We identified previously unknown morphometric signatures of podocyte depletion in patients with ANCA-GN, which allowed patient classification and, in combination with routine clinical tools, showed potential for risk stratification. Our approach enables robust and scalable molecular morphometric analysis of human tissues, yielding deeper biological insights into the human kidney pathophysiology.
Authors 19
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Universität Hamburg · University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Institute of Medical Systems Biology, Center for Biomedical AI (bAIome), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Universität Hamburg · University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Institute of Medical Systems Biology, Center for Biomedical AI (bAIome), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Universität Hamburg · University Medical Center Hamburg-Eppendorf
Affiliation as printed
Institute of Medical Systems Biology, Center for Biomedical AI (bAIome), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Affiliation as printed
Department of Nephrology and Clinical Immunology and
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Affiliation as printed
Department of Nephrology and Clinical Immunology and
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Sankt-Antonius-Hospital Eschweiler · Martin Luther University Halle-Wittenberg
Affiliation as printed
Department of Urology and Kidney Transplantation, Martin-Luther-University, Halle, Germany
St.-Antonius Hospital Eschweiler, Department of Urology, Eschweiler, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
III. Department of Medicine, Division of Translational Immunology, and
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
III. Department of Medicine, Division of Translational Immunology, and
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Erasmus MC · RWTH Aachen University
Affiliation as printed
Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Nephrology and Clinical Immunology and
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Tobias Bruno Huber corresponding
University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Stefan Bonn corresponding
Universität Hamburg · University Medical Center Hamburg-Eppendorf
Affiliation as printed
Institute of Medical Systems Biology, Center for Biomedical AI (bAIome), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Victor G. Puelles corresponding
University Medical Center Hamburg-Eppendorf
Affiliation as printed
III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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