pathology software developers

Abstract: Cross-resolution knowledge distillation aims to improve low-magnification whole- slide analysis by transferring high-magnification representations, yet the conditions for useful transfer remain unclear. We develop a decomposition-based analysis of teacher access, representation loss, and model excess, motivating three questions: whether (a) teacher targets help the task, (b) low-magnification students can predict them, and (c) slide models benefit from those predictions. We investigate them through controlled experiments across ten pathology cohorts spanning classifi- cation, grading, and survival prediction. In the main comparison, providing teacher regional means alongside native low-magnification features improves downstream performance in all ten cohorts. Direct prediction achieves lower reconstruction error than residual prediction, yet the predicted features underrepresent variation in the teacher targets. Moreover, better reconstruction does not consistently improve downstream scores, and retaining native features changes performance even when the predicted teacher features are held fixed. Together, these findings expose a gap between reconstructing teacher representations and realizing their downstream value. They challenge the sufficiency of reconstruction error as a measure of cross-resolution transfer and provide a diagnostic framework for examining where that transfer breaks down. Future distillation designs must account for both what students can predict and how slide models use those predictions.

Abstract: DNA methylation (DNAM) profiling has emerged as a powerful diagnostic tool for classifying brain and solid tumors. However, existing computational models typically analyze methylation and copy number variation (CNV) data separately, failing to capture the complementary information their integration could provide. Moreover, current classification models lack mechanisms for within-class risk assessment analogous to traditional tumor grading, and no established explainability method can attribute classification decisions to specific genomic loci. In this paper, we present MOXAI (Multi-Omics Based Explainable AI), a deep learning framework that integrates DNA methylation and copy number data from methylation arrays to classify molecular subtypes of adult-type diffuse gliomas, alongside single-modality variants for comparison. Using a cohort from The Cancer Genome Atlas (TCGA), we trained ResNet50, DINOv2, and Graph Attention Network (GAT) models on methylation data alone, copy number data alone, and combined multimodal data. We further developed explainable AI (XAI) methods based on class activation maps (CAMs) and gradient-weighted CAM (Grad-CAM) to identify the specific CpG sites, genes, and chromosomal regions most relevant to each classification decision. The multimodal model achieved up to 92.98% cross-validation accuracy, outperforming models trained on CNV data alone. DINOv2 showed the strongest generalization, reaching 94.25% accuracy (confidence >0.9) on independent validation sets. XAI results aligned with established molecular features of adult-type diffuse glioma subtypes, confirming the biological interpretability of the framework.