Knowledge-guided Contextual Gene Set Analysis Using Large Language Models

Gene set analysis (GSA) is a foundational approach for interpreting genomic data of diseases by linking genes to biological processes. However, conventional GSA methods overlook clinical context of the analyses, often generating long lists of enriched pathways with redundant, nonspecific, or irrelevant results. Interpreting these requires extensive, ad-hoc manual effort, reducing both reliability and reproducibility. To address this limitation, we introduce cGSA, a novel AI-driven framework that enhances GSA by incorporating context-aware pathway prioritization. cGSA integrates gene cluster detection, enrichment analysis, and large language models to identify pathways that are not only statistically significant but also biologically meaningful. Benchmarking on 102 manually curated gene sets across 19 diseases and ten disease-related biological mechanisms shows that cGSA outperforms baseline methods by over 30%, with expert validation confirming its increased precision and interpretability. Two independent case studies in melanoma and breast cancer further demonstrate its potential to uncover context-specific insights and support targeted hypothesis generation.

Transfer Learning and Explainable AI for Brain Tumor Classification: A Study Using MRI Data from Bangladesh

Brain tumors, regardless of being benign or malignant, pose considerable health risks, with malignant tumors being more perilous due to their swift and uncontrolled proliferation, resulting in malignancy. Timely identification is crucial for enhancing patient outcomes, particularly in nations such as Bangladesh, where healthcare infrastructure is constrained. Manual MRI analysis is arduous and susceptible to inaccuracies, rendering it inefficient for prompt diagnosis. This research sought to tackle these problems by creating an automated brain tumor classification system utilizing MRI data obtained from many hospitals in Bangladesh. Advanced deep learning models, including VGG16, VGG19, and ResNet50, were utilized to classify glioma, meningioma, and various brain cancers. Explainable AI (XAI) methodologies, such as Grad-CAM and Grad-CAM++, were employed to improve model interpretability by emphasizing the critical areas in MRI scans that influenced the categorization. VGG16 achieved the most accuracy, attaining 99.17%. The integration of XAI enhanced the system's transparency and stability, rendering it more appropriate for clinical application in resource-limited environments such as Bangladesh. This study highlights the capability of deep learning models, in conjunction with explainable artificial intelligence (XAI), to enhance brain tumor detection and identification in areas with restricted access to advanced medical technologies.

Anomaly-Driven Approach for Enhanced Prostate Cancer Segmentation

Magnetic Resonance Imaging (MRI) plays an important role in identifying clinically significant prostate cancer (csPCa), yet automated methods face challenges such as data imbalance, variable tumor sizes, and a lack of annotated data. This study introduces Anomaly-Driven U-Net (adU-Net), which incorporates anomaly maps derived from biparametric MRI sequences into a deep learning-based segmentation framework to improve csPCa identification. We conduct a comparative analysis of anomaly detection methods and evaluate the integration of anomaly maps into the segmentation pipeline. Anomaly maps, generated using Fixed-Point GAN reconstruction, highlight deviations from normal prostate tissue, guiding the segmentation model to potential cancerous regions. We compare the performance by using the average score, computed as the mean of the AUROC and Average Precision (AP). On the external test set, adU-Net achieves the best average score of 0.618, outperforming the baseline nnU-Net model (0.605). The results demonstrate that incorporating anomaly detection into segmentation improves generalization and performance, particularly with ADC-based anomaly maps, offering a promising direction for automated csPCa identification.

Class Imbalance Correction for Improved Universal Lesion Detection and Tagging in CT

Radiologists routinely detect and size lesions in CT to stage cancer and assess tumor burden. To potentially aid their efforts, multiple lesion detection algorithms have been developed with a large public dataset called DeepLesion (32,735 lesions, 32,120 CT slices, 10,594 studies, 4,427 patients, 8 body part labels). However, this dataset contains missing measurements and lesion tags, and exhibits a severe imbalance in the number of lesions per label category. In this work, we utilize a limited subset of DeepLesion (6\%, 1331 lesions, 1309 slices) containing lesion annotations and body part label tags to train a VFNet model to detect lesions and tag them. We address the class imbalance by conducting three experiments: 1) Balancing data by the body part labels, 2) Balancing data by the number of lesions per patient, and 3) Balancing data by the lesion size. In contrast to a randomly sampled (unbalanced) data subset, our results indicated that balancing the body part labels always increased sensitivity for lesions >= 1cm for classes with low data quantities (Bone: 80\% vs. 46\%, Kidney: 77\% vs. 61\%, Soft Tissue: 70\% vs. 60\%, Pelvis: 83\% vs. 76\%). Similar trends were seen for three other models tested (FasterRCNN, RetinaNet, FoveaBox). Balancing data by lesion size also helped the VFNet model improve recalls for all classes in contrast to an unbalanced dataset. We also provide a structured reporting guideline for a ``Lesions'' subsection to be entered into the ``Findings'' section of a radiology report. To our knowledge, we are the first to report the class imbalance in DeepLesion, and have taken data-driven steps to address it in the context of joint lesion detection and tagging.

Longitudinal Assessment of Lung Lesion Burden in CT

In the U.S., lung cancer is the second major cause of death. Early detection of suspicious lung nodules is crucial for patient treatment planning, management, and improving outcomes. Many approaches for lung nodule segmentation and volumetric analysis have been proposed, but few have looked at longitudinal changes in total lung tumor burden. In this work, we trained two 3D models (nnUNet) with and without anatomical priors to automatically segment lung lesions and quantified total lesion burden for each patient. The 3D model without priors significantly outperformed ($p < .001$) the model trained with anatomy priors. For detecting clinically significant lesions $>$ 1cm, a precision of 71.3\%, sensitivity of 68.4\%, and F1-score of 69.8\% was achieved. For segmentation, a Dice score of 77.1 $\pm$ 20.3 and Hausdorff distance error of 11.7 $\pm$ 24.1 mm was obtained. The median lesion burden was 6.4 cc (IQR: 2.1, 18.1) and the median volume difference between manual and automated measurements was 0.02 cc (IQR: -2.8, 1.2). Agreements were also evaluated with linear regression and Bland-Altman plots. The proposed approach can produce a personalized evaluation of the total tumor burden for a patient and facilitate interval change tracking over time.

Subspecialty-Specific Foundation Model for Intelligent Gastrointestinal Pathology

Gastrointestinal (GI) diseases represent a clinically significant burden, necessitating precise diagnostic approaches to optimize patient outcomes. Conventional histopathological diagnosis, heavily reliant on the subjective interpretation of pathologists, suffers from limited reproducibility and diagnostic variability. To overcome these limitations and address the lack of pathology-specific foundation models for GI diseases, we develop Digepath, a specialized foundation model for GI pathology. Our framework introduces a dual-phase iterative optimization strategy combining pretraining with fine-screening, specifically designed to address the detection of sparsely distributed lesion areas in whole-slide images. Digepath is pretrained on more than 353 million image patches from over 200,000 hematoxylin and eosin-stained slides of GI diseases. It attains state-of-the-art performance on 33 out of 34 tasks related to GI pathology, including pathological diagnosis, molecular prediction, gene mutation prediction, and prognosis evaluation, particularly in diagnostically ambiguous cases and resolution-agnostic tissue classification.We further translate the intelligent screening module for early GI cancer and achieve near-perfect 99.6% sensitivity across 9 independent medical institutions nationwide. The outstanding performance of Digepath highlights its potential to bridge critical gaps in histopathological practice. This work not only advances AI-driven precision pathology for GI diseases but also establishes a transferable paradigm for other pathology subspecialties.

An ensemble deep learning approach to detect tumors on Mohs micrographic surgery slides

Mohs micrographic surgery (MMS) is the gold standard technique for removing high risk nonmelanoma skin cancer however, intraoperative histopathological examination demands significant time, effort, and professionality. The objective of this study is to develop a deep learning model to detect basal cell carcinoma (BCC) and artifacts on Mohs slides. A total of 731 Mohs slides from 51 patients with BCCs were used in this study, with 91 containing tumor and 640 without tumor which was defined as non-tumor. The dataset was employed to train U-Net based models that segment tumor and non-tumor regions on the slides. The segmented patches were classified as tumor, or non-tumor to produce predictions for whole slide images (WSIs). For the segmentation phase, the deep learning model success was measured using a Dice score with 0.70 and 0.67 value, area under the curve (AUC) score with 0.98 and 0.96 for tumor and non-tumor, respectively. For the tumor classification, an AUC of 0.98 for patch-based detection, and AUC of 0.91 for slide-based detection was obtained on the test dataset. We present an AI system that can detect tumors and non-tumors in Mohs slides with high success. Deep learning can aid Mohs surgeons and dermatopathologists in making more accurate decisions.

Identifying regions of interest in whole slide images of renal cell carcinoma

The histopathological images contain a huge amount of information, which can make diagnosis an extremely timeconsuming and tedious task. In this study, we developed a completely automated system to detect regions of interest (ROIs) in whole slide images (WSI) of renal cell carcinoma (RCC), to reduce time analysis and assist pathologists in making more accurate decisions. The proposed approach is based on an efficient texture descriptor named dominant rotated local binary pattern (DRLBP) and color transformation to reveal and exploit the immense texture variability at the microscopic high magnifications level. Thereby, the DRLBPs retain the structural information and utilize the magnitude values in a local neighborhood for more discriminative power. For the classification of the relevant ROIs, feature extraction of WSIs patches was performed on the color channels separately to form the histograms. Next, we used the most frequently occurring patterns as a feature selection step to discard non-informative features. The performances of different classifiers on a set of 1800 kidney cancer patches originating from 12 whole slide images were compared and evaluated. Furthermore, the small size of the image dataset allows to investigate deep learning approach based on transfer learning for image patches classification by using deep features and fine-tuning methods. High recognition accuracy was obtained and the classifiers are efficient, the best precision result was 99.17% achieved with SVM. Moreover, transfer learning models perform well with comparable performance, and the highest precision using ResNet-50 reached 98.50%. The proposed approach results revealed a very efficient image classification and demonstrated efficacy in identifying ROIs. This study presents an automatic system to detect regions of interest relevant to the diagnosis of kidney cancer in whole slide histopathology images.

Automating tumor-infiltrating lymphocyte assessment in breast cancer histopathology images using QuPath: a transparent and accessible machine learning pipeline

In this study, we built an end-to-end tumor-infiltrating lymphocytes (TILs) assessment pipeline within QuPath, demonstrating the potential of easily accessible tools to perform complex tasks in a fully automatic fashion. First, we trained a pixel classifier to segment tumor, tumor-associated stroma, and other tissue compartments in breast cancer H&E-stained whole-slide images (WSI) to isolate tumor-associated stroma for subsequent analysis. Next, we applied a pre-trained StarDist deep learning model in QuPath for cell detection and used the extracted cell features to train a binary classifier distinguishing TILs from other cells. To evaluate our TILs assessment pipeline, we calculated the TIL density in each WSI and categorized them as low, medium, or high TIL levels. Our pipeline was evaluated against pathologist-assigned TIL scores, achieving a Cohen's kappa of 0.71 on the external test set, corroborating previous research findings. These results confirm that existing software can offer a practical solution for the assessment of TILs in H&E-stained WSIs of breast cancer.

A Foundation Model Framework for Multi-View MRI Classification of Extramural Vascular Invasion and Mesorectal Fascia Invasion in Rectal Cancer

Background: Accurate MRI-based identification of extramural vascular invasion (EVI) and mesorectal fascia invasion (MFI) is pivotal for risk-stratified management of rectal cancer, yet visual assessment is subjective and vulnerable to inter-institutional variability. Purpose: To develop and externally evaluate a multicenter, foundation-model-driven framework that automatically classifies EVI and MFI on axial and sagittal T2-weighted MRI. Methods: This retrospective study used 331 pre-treatment rectal cancer MRI examinations from three European hospitals. After TotalSegmentator-guided rectal patch extraction, a self-supervised frequency-domain harmonization pipeline was trained to minimize scanner-related contrast shifts. Four classifiers were compared: ResNet50, SeResNet, the universal biomedical pretrained transformer (UMedPT) with a lightweight MLP head, and a logistic-regression variant using frozen UMedPT features (UMedPT_LR). Results: UMedPT_LR achieved the best EVI detection when axial and sagittal features were fused (AUC = 0.82; sensitivity = 0.75; F1 score = 0.73), surpassing the Chaimeleon Grand-Challenge winner (AUC = 0.74). The highest MFI performance was attained by UMedPT on axial harmonized images (AUC = 0.77), surpassing the Chaimeleon Grand-Challenge winner (AUC = 0.75). Frequency-domain harmonization improved MFI classification but variably affected EVI performance. Conventional CNNs (ResNet50, SeResNet) underperformed, especially in F1 score and balanced accuracy. Conclusion: These findings demonstrate that combining foundation model features, harmonization, and multi-view fusion significantly enhances diagnostic performance in rectal MRI.