Deep learning-based molecular morphometrics for kidney biopsies

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 anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN), an immune-mediated disease with aggressive glomerular damage and irreversible loss of kidney function. Previously unknown morphometric signatures of podocyte depletion were identified in patients with ANCA-GN, which allowed patient classification and showed potential for risk stratification in combination with routine clinical tools. Together, our approach enables robust and scalable molecular morphometric analysis of human tissues, yielding deeper biological insights into the human kidney pathophysiology.SummaryDeep learning enables robust and scalable molecular morphometric analysis of human tissues, yielding deeper biological insights into the human kidney pathophysiology.

Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension

“…Then, the slides were blocked with 1% BSA for 1 hour. To identify podocyte nuclei, three primary antibodies were initially assessed: dachshund 1 (DACH1, 1:1000 dilution, 10914-1-AP; Proteintech), 41 (preprint) Wilms tumor 1 (WT1, 1:150 dilution, sc-7385; Santa Cruz Biotechnology, Santa Cruz, CA), and transducing-like enhancer of split 4 (TLE4, 1:250 dilution, SC-365406; Santa Cruz Biotechnology). Double labeling with WT1 and TLE4 confirmed that all DACH1-positive nuclei belonged to podocytes (Figure 1).…”