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Brent A. Orr

Publications and source records attributed to Brent A. Orr.

3 recordsLinked to original sources

Evaluating Single and Multi-Omics Based Explainable Artificial Intelligence (MOXAI) for Molecular Subclass Classification of Adult-Type Diffuse Gliomas

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.

cs.CV↗

UNIStainNet: Foundation-Model-Guided Virtual Staining of H&E to IHC

Virtual immunohistochemistry (IHC) staining from hematoxylin and eosin (H&E) images can accelerate diagnostics by providing preliminary molecular insight directly from routine sections, reducing the need for repeat sectioning when tissue is limited. Existing methods improve realism through contrastive objectives, prototype matching, or domain alignment, yet the generator itself receives no direct guidance from pathology foundation models. We present UNIStainNet, a SPADE-UNet conditioned on dense spatial tokens from a frozen pathology foundation model (UNI), providing tissue-level semantic guidance for stain translation. A misalignment-aware loss suite preserves stain quantification accuracy, and learned stain embeddings enable a single model to serve multiple IHC markers simultaneously. On MIST, UNIStainNet achieves state-of-the-art distributional metrics on all four stains (HER2, Ki67, ER, PR) from a single unified model, where prior methods typically train separate per-stain models. On BCI, it also achieves the best distributional metrics. A tissue-type stratified failure analysis reveals that remaining errors are systematic, concentrating in non-tumor tissue. Code is available at https://github.com/facevoid/UNIStainNet.

cs.CV↗

Learned Image resizing with efficient training (LRET) facilitates improved performance of large-scale digital histopathology image classification models

Histologic examination plays a crucial role in oncology research and diagnostics. The adoption of digital scanning of whole slide images (WSI) has created an opportunity to leverage deep learning-based image classification methods to enhance diagnosis and risk stratification. Technical limitations of current approaches to training deep convolutional neural networks (DCNN) result in suboptimal model performance and make training and deployment of comprehensive classification models unobtainable. In this study, we introduce a novel approach that addresses the main limitations of traditional histopathology classification model training. Our method, termed Learned Resizing with Efficient Training (LRET), couples efficient training techniques with image resizing to facilitate seamless integration of larger histology image patches into state-of-the-art classification models while preserving important structural information. We used the LRET method coupled with two distinct resizing techniques to train three diverse histology image datasets using multiple diverse DCNN architectures. Our findings demonstrate a significant enhancement in classification performance and training efficiency. Across the spectrum of experiments, LRET consistently outperforms existing methods, yielding a substantial improvement of 15-28% in accuracy for a large-scale, multiclass tumor classification task consisting of 74 distinct brain tumor types. LRET not only elevates classification accuracy but also substantially reduces training times, unlocking the potential for faster model development and iteration. The implications of this work extend to broader applications within medical imaging and beyond, where efficient integration of high-resolution images into deep learning pipelines is paramount for driving advancements in research and clinical practice.

cs.CV↗