Clinical Graph-Mediated Distillation for Unpaired MRI-to-CFI Hypertension Prediction

Retinal fundus imaging enables low-cost and scalable hypertension (HTN) screening, but HTN-related retinal cues are subtle, yielding high-variance predictions. Brain MRI provides stronger vascular and small-vessel-disease markers of HTN, yet it is expensive and rarely acquired alongside fundus images, resulting in modality-siloed datasets with disjoint MRI and fundus cohorts. We study this unpaired MRI-fundus regime and introduce Clinical Graph-Mediated Distillation (CGMD), a framework that transfers MRI-derived HTN knowledge to a fundus model without paired multimodal data. CGMD leverages shared structured biomarkers as a bridge by constructing a clinical similarity kNN graph spanning both cohorts. We train an MRI teacher, propagate its representations over the graph, and impute brain-informed representation targets for fundus patients. A fundus student is then trained with a joint objective combining HTN supervision, target distillation, and relational distillation. Experiments on our newly collected unpaired MRI-fundus-biomarker dataset show that CGMD consistently improves fundus-based HTN prediction over standard distillation and non-graph imputation baselines, with ablations confirming the importance of clinically grounded graph connectivity. Code is available at https://github.com/DillanImans/CGMD-unpaired-distillation.

Chronological Contrastive Learning: Few-Shot Progression Assessment in Irreversible Diseases

Quantitative disease severity scoring in medical imaging is costly, time-consuming, and subject to inter-reader variability. At the same time, clinical archives contain far more longitudinal imaging data than expert-annotated severity scores. Existing self-supervised methods typically ignore this chronological structure. We introduce ChronoCon, a contrastive learning approach that replaces label-based ranking losses with rankings derived solely from the visitation order of a patient's longitudinal scans. Under the clinically plausible assumption of monotonic progression in irreversible diseases, the method learns disease-relevant representations without using any expert labels. This generalizes the idea of Rank-N-Contrast from label distances to temporal ordering. Evaluated on rheumatoid arthritis radiographs for severity assessment, the learned representations substantially improve label efficiency. In low-label settings, ChronoCon significantly outperforms a fully supervised baseline initialized from ImageNet weights. In a few-shot learning experiment, fine-tuning ChronoCon on expert scores from only five patients yields an intraclass correlation coefficient of 86% for severity score prediction. These results demonstrate the potential of chronological contrastive learning to exploit routinely available imaging metadata to reduce annotation requirements in the irreversible disease domain. Code is available at https://github.com/cirmuw/ChronoCon.

Hierarchical Multiscale Structure-Function Coupling for Brain Connectome Integration

Integrating structural and functional connectomes remains challenging because their relationship is non-linear and organized over nested modular hierarchies. We propose a hierarchical multiscale structure-function coupling framework for connectome integration that jointly learns individualized modular organization and hierarchical coupling across structural connectivity (SC) and functional connectivity (FC). The framework includes: (i) Prototype-based Modular Pooling (PMPool), which learns modality-specific multiscale communities by selecting prototypical ROIs and optimizing a differentiable modularity-inspired objective; (ii) an Attention-based Hierarchical Coupling Module (AHCM) that models both within-hierarchy and cross-hierarchy SC-FC interactions to produce enriched hierarchical coupling representations; and (iii) a Coupling-guided Clustering loss (CgC-Loss) that regularizes SC and FC community assignments with coupling signals, allowing cross-modal interactions to shape community alignment across hierarchies. We evaluate the model's performance across four cohorts for predicting brain age, cognitive score, and disease classification. Our model consistently outperforms baselines and other state-of-the-art approaches across three tasks. Ablation and sensitivity analyses verify the contributions of key components. Finally, the visualizations of learned coupling reveal interpretable differences, suggesting that the framework captures biologically meaningful structure-function relationships.

BVSIMC: Bayesian Variable Selection-Guided Inductive Matrix Completion for Improved and Interpretable Drug Discovery

Recent advances in drug discovery have demonstrated that incorporating side information (e.g., chemical properties about drugs and genomic information about diseases) often greatly improves prediction performance. However, these side features can vary widely in relevance and are often noisy and high-dimensional. We propose Bayesian Variable Selection-Guided Inductive Matrix Completion (BVSIMC), a new Bayesian model that enables variable selection from side features in drug discovery. By learning sparse latent embeddings, BVSIMC improves both predictive accuracy and interpretability. We validate our method through simulation studies and two drug discovery applications: 1) prediction of drug resistance in Mycobacterium tuberculosis, and 2) prediction of new drug-disease associations in computational drug repositioning. On both synthetic and real data, BVSIMC outperforms several other state-of-the-art methods in terms of prediction. In our two real examples, BVSIMC further reveals the most clinically meaningful side features.

G2DR: A Genotype-First Framework for Genetics-Informed Target Prioritization and Drug Repurposing

Human genetics offers a promising route to therapeutic discovery, yet practical frameworks translating genotype-derived signal into ranked target and drug hypotheses remain limited, particularly when matched disease transcriptomics are unavailable. Here we present G2DR, a genotype-first prioritization framework propagating inherited variation through genetically predicted expression, multi-method gene-level testing, pathway enrichment, network context, druggability, and multi-source drug--target evidence integration. In a migraine case study with 733 UK Biobank participants under stratified five-fold cross-validation, we imputed expression across seven transcriptome-weight resources and ranked genes using a reproducibility-aware discovery score from training and validation data, followed by a balanced integrated score for target selection. Discovery-based prioritization generalized to held-out data, achieving gene-level ROC-AUC of 0.775 and PR-AUC of 0.475, while retaining enrichment for curated migraine biology. Mapping prioritized genes to compounds via Open Targets, DGIdb, and ChEMBL yielded drug sets enriched for migraine-linked compounds relative to a global background, though recovery favoured broader mechanism-linked and off-label space over migraine-specific approved therapies. Directionality filtering separated broadly recovered compounds from mechanistically compatible candidates. G2DR is a modular framework for genetics-informed hypothesis generation, not a clinically actionable recommendation system. All outputs require independent experimental, pharmacological, and clinical validation.

SDE-Driven Spatio-Temporal Hypergraph Neural Networks for Irregular Longitudinal fMRI Connectome Modeling in Alzheimer's Disease

Longitudinal neuroimaging is essential for modeling disease progression in Alzheimer's disease (AD), yet irregular sampling and missing visits pose substantial challenges for learning reliable temporal representations. To address this challenge, we propose SDE-HGNN, a stochastic differential equation (SDE)-driven spatio-temporal hypergraph neural network for irregular longitudinal fMRI connectome modeling. The framework first employs an SDE-based reconstruction module to recover continuous latent trajectories from irregular observations. Based on these reconstructed representations, dynamic hypergraphs are constructed to capture higher-order interactions among brain regions over time. To further model temporal evolution, hypergraph convolution parameters evolve through SDE-controlled recurrent dynamics conditioned on inter-scan intervals, enabling disease-stage-adaptive connectivity modeling. We also incorporate a sparsity-based importance learning mechanism to identify salient brain regions and discriminative connectivity patterns. Extensive experiments on the OASIS-3 and ADNI cohorts demonstrate consistent improvements over state-of-the-art graph and hypergraph baselines in AD progression prediction. The source code is available at https://anonymous.4open.science/r/SDE-HGNN-017F.

ODySSeI: An Open-Source End-to-End Framework for Automated Detection, Segmentation, and Severity Estimation of Lesions in Invasive Coronary Angiography Images

Invasive Coronary Angiography (ICA) is the clinical gold standard for the assessment of coronary artery disease. However, its interpretation remains subjective and prone to intra- and inter-operator variability. In this work, we introduce ODySSeI: an Open-source end-to-end framework for automated Detection, Segmentation, and Severity estimation of lesions in ICA images. ODySSeI integrates deep learning-based lesion detection and lesion segmentation models trained using a novel Pyramidal Augmentation Scheme (PAS) to enhance robustness and real-time performance across diverse patient cohorts (2149 patients from Europe, North America, and Asia). Furthermore, we propose a quantitative coronary angiography-free Lesion Severity Estimation (LSE) technique that directly computes the Minimum Lumen Diameter (MLD) and diameter stenosis from the predicted lesion geometry. Extensive evaluation on both in-distribution and out-of-distribution clinical datasets demonstrates ODySSeI's strong generalizability. Our PAS yields large performance gains in highly complex tasks as compared to relatively simpler ones, notably, a 2.5-fold increase in lesion detection performance versus a 1-3\% increase in lesion segmentation performance over their respective baselines. Our LSE technique achieves high accuracy, with predicted MLD values differing by only $\pm$ 2-3 pixels from the corresponding ground truths. On average, ODySSeI processes a raw ICA image within only a few seconds on a CPU and in a fraction of a second on a GPU and is available as a plug-and-play web interface at swisscardia.epfl.ch. Overall, this work establishes ODySSeI as a comprehensive and open-source framework which supports automated, reproducible, and scalable ICA analysis for real-time clinical decision-making.

Tabular LLMs for Interpretable Few-Shot Alzheimer's Disease Prediction with Multimodal Biomedical Data

Accurate diagnosis of Alzheimer's disease (AD) requires handling tabular biomarker data, yet such data are often small and incomplete, where deep learning models frequently fail to outperform classical methods. Pretrained large language models (LLMs) offer few-shot generalization, structured reasoning, and interpretable outputs, providing a powerful paradigm shift for clinical prediction. We propose TAP-GPT Tabular Alzheimer's Prediction GPT, a domain-adapted tabular LLM framework built on TableGPT2 and fine-tuned for few-shot AD classification using tabular prompts rather than plain texts. We evaluate TAP-GPT across four ADNI-derived datasets, including QT-PAD biomarkers and region-level structural MRI, amyloid PET, and tau PET for binary AD classification. Across multimodal and unimodal settings, TAP-GPT improves upon its backbone models and outperforms traditional machine learning baselines in the few-shot setting while remaining competitive with state-of-the-art general-purpose LLMs. We show that feature selection mitigates degradation in high-dimensional inputs and that TAP-GPT maintains stable performance under simulated and real-world missingness without imputation. Additionally, TAP-GPT produces structured, modality-aware reasoning aligned with established AD biology and shows greater stability under self-reflection, supporting its use in iterative multi-agent systems. To our knowledge, this is the first systematic application of a tabular-specialized LLM to multimodal biomarker-based AD prediction, demonstrating that such pretrained models can effectively address structured clinical prediction tasks and laying the foundation for tabular LLM-driven multi-agent clinical decision-support systems. The source code is publicly available on GitHub: https://github.com/sophie-kearney/TAP-GPT.

Clinical Priors Guided Lung Disease Detection in 3D CT Scans

Accurate classification of lung diseases from chest CT scans plays an important role in computer-aided diagnosis systems. However, medical imaging datasets often suffer from severe class imbalance, which may significantly degrade the performance of deep learning models, especially for minority disease categories. To address this issue, we propose a gender-aware two-stage lung disease classification framework. The proposed approach explicitly incorporates gender information into the disease recognition pipeline. In the first stage, a gender classifier is trained to predict the patient's gender from CT scans. In the second stage, the input CT image is routed to a corresponding gender-specific disease classifier to perform final disease prediction. This design enables the model to better capture gender-related imaging characteristics and alleviate the influence of imbalanced data distribution. Experimental results demonstrate that the proposed method improves the recognition performance for minority disease categories, particularly squamous cell carcinoma, while maintaining competitive performance on other classes.

GIP-RAG: An Evidence-Grounded Retrieval-Augmented Framework for Interpretable Gene Interaction and Pathway Impact Analysis

Understanding mechanistic relationships among genes and their impacts on biological pathways is essential for elucidating disease mechanisms and advancing precision medicine. Despite the availability of extensive molecular interaction and pathway data in public databases, integrating heterogeneous knowledge sources and enabling interpretable multi-step reasoning across biological networks remain challenging. We present GIP-RAG (Gene Interaction Prediction through Retrieval-Augmented Generation), a computational framework that combines biomedical knowledge graphs with large language models (LLMs) to infer and interpret gene interactions. The framework constructs a unified gene interaction knowledge graph by integrating curated data from KEGG, WikiPathways, SIGNOR, Pathway Commons, and PubChem. Given user-specified genes, a query-driven module retrieves relevant subgraphs, which are incorporated into structured prompts to guide LLM-based stepwise reasoning. This enables identification of direct and indirect regulatory relationships and generation of mechanistic explanations supported by biological evidence. Beyond pairwise interactions, GIP-RAG includes a pathway-level functional impact module that simulates propagation of gene perturbations through signaling networks and evaluates potential pathway state changes. Evaluation across diverse biological scenarios demonstrates that the framework generates consistent, interpretable, and evidence-supported insights into gene regulatory mechanisms. Overall, GIP-RAG provides a general and interpretable approach for integrating knowledge graphs with retrieval-augmented LLMs to support mechanistic reasoning in complex molecular systems.