Permutation-Invariant Cascaded Attentional Set Operator for Computational Nephropathology

Key PointsPermutation-invariant cascaded attentional set operator (PICASO) is a versatile set operator that uses Transformers to dynamically aggregate histopathologic features from a set of glomerular crops.For detecting active crescent in patients with IgA nephropathy on internal and external validation sets, PICASO achieved an area under the receiver-operating characteristic curve of 0.99 and 0.96, respectively.In the case-level classification of antibody-mediated rejection in kidney transplants, PICASO performed well, with an area under the receiver-operating characteristic curves of 0.97.BackgroundThe advent of digital nephropathology offers the potential to integrate deep learning algorithms into the diagnostic workflow. We introduce permutation-invariant cascaded attentional set operator (PICASO), a novel permutation-invariant set operator to dynamically aggregate histopathologic features from instances. We applied PICASO to two nephropathology scenarios: detecting active crescent lesions in sets of glomerular crops with IgA nephropathy (IgAN) and case-level classification for antibody-mediated rejection (AMR) in kidney transplant.MethodsPICASO is a Transformer-based set operator that aggregates features from sets of instances to make predictions. It uses initial histopathologic vectors as a static memory component and continuously updates them on the basis of input embeddings. For active crescent detection in patients with IgAN, we obtained 6206 periodic acid-Schiff-stained glomerular crops (5792 no active crescent, 414 active crescent) from three different health institutes. For the AMR classification, we have 1655 periodic acid-Schiff-stained glomerular crops (769 AMR and 886 non-AMR images) from 89 biopsies. The performance of PICASO as a set operator was compared with other set operators, such as DeepSet, Set Transformer, DeepSet++, and Set Transformer++, using metrics including area under the receiver-operating characteristic curve (AUROC), area under the precision-recall curves, recall, and accuracy.ResultsPICASO achieved superior performance in detecting active crescent in patients with IgAN, with an AUROC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) on internal validation and 0.96 (95% CI, 0.95 to 0.98) on external validation, significantly outperforming other set operators (P < 0.001). It also attained the highest AUROC of 0.97 (95% CI, 0.90 to 1.0, P = 0.02) for case-level AMR classification. The area under the precision-recall curve, recall, and accuracy scores were also higher when using PICASO, and it significantly outperformed baselines (P < 0.001).ConclusionsPICASO can potentially advance nephropathology by improving performance through dynamic feature aggregation. © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.