Survival Meets Classification: A Novel Framework for Early Risk Prediction Models of Chronic Diseases

Chronic diseases are long-lasting conditions that require lifelong medical attention. Using big EMR data, we have developed early disease risk prediction models for five common chronic diseases: diabetes, hypertension, CKD, COPD, and chronic ischemic heart disease. In this study, we present a novel approach for disease risk models by integrating survival analysis with classification techniques. Traditional models for predicting the risk of chronic diseases predominantly focus on either survival analysis or classification independently. In this paper, we show survival analysis methods can be re-engineered to enable them to do classification efficiently and effectively, thereby making them a comprehensive tool for developing disease risk surveillance models. The results of our experiments on real-world big EMR data show that the performance of survival models in terms of accuracy, F1 score, and AUROC is comparable to or better than that of prior state-of-the-art models like LightGBM and XGBoost. Lastly, the proposed survival models use a novel methodology to generate explanations, which have been clinically validated by a panel of three expert physicians.

ELISA: An Interpretable Hybrid Generative AI Agent for Expression-Grounded Discovery in Single-Cell Genomics

Translating single-cell RNA sequencing (scRNA-seq) data into mechanistic biological hypotheses remains a critical bottleneck, as agentic AI systems lack direct access to transcriptomic representations while expression foundation models remain opaque to natural language. Here we introduce ELISA (Embedding-Linked Interactive Single-cell Agent), an interpretable framework that unifies scGPT expression embeddings with BioBERT-based semantic retrieval and LLM-mediated interpretation for interactive single-cell discovery. An automatic query classifier routes inputs to gene marker scoring, semantic matching, or reciprocal rank fusion pipelines depending on whether the query is a gene signature, natural language concept, or mixture of both. Integrated analytical modules perform pathway activity scoringacross 60+ gene sets, ligand--receptor interaction prediction using 280+ curated pairs, condition-aware comparative analysis, and cell-type proportion estimation all operating directly on embedded data without access to the original count matrix. Benchmarked across six diverse scRNA-seq datasets spanning inflammatory lung disease, pediatric and adult cancers, organoid models, healthy tissue, and neurodevelopment, ELISA significantly outperforms CellWhisperer in cell type retrieval (combined permutation test, $p < 0.001$), with particularly large gains on gene-signature queries (Cohen's $d = 5.98$ for MRR). ELISA replicates published biological findings (mean composite score 0.90) with near-perfect pathway alignment and theme coverage (0.98 each), and generates candidate hypotheses through grounded LLM reasoning, bridging the gap between transcriptomic data exploration and biological discovery. Code available at: https://github.com/omaruno/ELISA-An-AI-Agent-for-Expression-Grounded-Discovery-in-Single-Cell-Genomics.git (If you use ELISA in your research, please cite this work).

SNPgen: Phenotype-Supervised Genotype Representation and Synthetic Data Generation via Latent Diffusion

Polygenic risk scores and other genomic analyses require large individual-level genotype datasets, yet strict data access restrictions impede sharing. Synthetic genotype generation offers a privacy-preserving alternative, but most existing methods operate unconditionally, producing samples without phenotype alignment, or rely on unsupervised compression, creating a gap between statistical fidelity and downstream task utility. We present SNPgen, a two-stage conditional latent diffusion framework for generating phenotype-supervised synthetic genotypes. SNPgen combines GWAS-guided variant selection (1,024-2,048 trait-associated SNPs) with a variational autoencoder for genotype compression and a latent diffusion model conditioned on binary disease labels via classifier-free guidance. Evaluated on 458,724 UK Biobank individuals across four complex diseases (coronary artery disease, breast cancer, type 1 and type 2 diabetes), models trained on synthetic data matched real-data predictive performance in a train-on-synthetic, test-on-real protocol, approaching genome-wide PRS methods that use $2$-$6\times$ more variants. Privacy analysis confirmed zero identical matches, near-random membership inference (AUC $\approx 0.50$), preserved linkage disequilibrium structure, and high allele frequency correlation ($r \geq 0.95$) with source data. A controlled simulation with known causal effects verified faithful recovery of the imposed genetic association structure.

DT-BEHRT: Disease Trajectory-aware Transformer for Interpretable Patient Representation Learning

The growing adoption of electronic health record (EHR) systems has provided unprecedented opportunities for predictive modeling to guide clinical decision making. Structured EHRs contain longitudinal observations of patients across hospital visits, where each visit is represented by a set of medical codes. While sequence-based, graph-based, and graph-enhanced sequence approaches have been developed to capture rich code interactions over time or within the same visits, they often overlook the inherent heterogeneous roles of medical codes arising from distinct clinical characteristics and contexts. To this end, in this study we propose the Disease Trajectory-aware Transformer for EHR (DT-BEHRT), a graph-enhanced sequential architecture that disentangles disease trajectories by explicitly modeling diagnosis-centric interactions within organ systems and capturing asynchronous progression patterns. To further enhance the representation robustness, we design a tailored pre-training methodology that combines trajectory-level code masking with ontology-informed ancestor prediction, promoting semantic alignment across multiple modeling modules. Extensive experiments on multiple benchmark datasets demonstrate that DT-BEHRT achieves strong predictive performance and provides interpretable patient representations that align with clinicians' disease-centered reasoning. The source code is publicly accessible at https://github.com/GatorAIM/DT-BEHRT.git.

TA-RNN-Medical-Hybrid: A Time-Aware and Interpretable Framework for Mortality Risk Prediction

Accurate and interpretable mortality risk prediction in intensive care units (ICUs) remains a critical challenge due to the irregular temporal structure of electronic health records (EHRs), the complexity of longitudinal disease trajectories, and the lack of clinically grounded explanations in many data-driven models. To address these challenges, we propose \textit{TA-RNN-Medical-Hybrid}, a time-aware and knowledge-enriched deep learning framework that jointly models longitudinal clinical sequences and irregular temporal dynamics through explicit continuous-time encoding, along with standardized medical concept representations. The proposed framework extends time-aware recurrent modeling by integrating explicit continuous-time embeddings that operate independently of visit indexing, SNOMED-based disease representations, and a hierarchical dual-level attention mechanism that captures both visit-level temporal importance and feature/concept-level clinical relevance. This design enables accurate mortality risk estimation while providing transparent and clinically meaningful explanations aligned with established medical knowledge. We evaluate the proposed approach on the MIMIC-III critical care dataset and compare it against strong time-aware and sequential baselines. Experimental results demonstrate that TA-RNN-Medical-Hybrid consistently improves predictive performance in terms of AUC, accuracy, and recall-oriented F$_2$-score. Moreover, qualitative analysis shows that the model effectively decomposes mortality risk across time and clinical concepts, yielding interpretable insights into disease severity, chronicity, and temporal progression. Overall, the proposed framework bridges the gap between predictive accuracy and clinical interpretability, offering a scalable and transparent solution for high-stakes ICU decision support systems.

Tau-BNO: Brain Neural Operator for Tau Transport Model

Mechanistic modeling provides a biophysically grounded framework for studying the spread of pathological tau protein in tauopathies like Alzheimer's disease. Existing approaches typically model tau propagation as a diffusive process on the brain's structural connectome, reproducing macroscopic patterns but neglecting microscale cellular transport and reaction mechanisms. The Network Transport Model (NTM) was introduced to fill this gap, explaining how region-level progression of tau emerges from microscale biophysical processes. However, the NTM faces a common challenge for complex models defined by large systems of partial differential equations: the inability to perform parameter inference and mechanistic discovery due to high computational burden and slow model simulations. To overcome this barrier, we propose Tau-BNO, a Brain Neural Operator surrogate framework for rapidly approximating NTM dynamics that captures both intra-regional reaction kinetics and inter-regional network transport. Tau-BNO combines a function operator that encodes kinetic parameters with a query operator that preserves initial state information, while approximating anisotropic transport through a spectral kernel that retains directionality. Empirical evaluations demonstrate high predictive accuracy ($R^2\approx$ 0.98) across diverse biophysical regimes and an 89\% performance improvement over state-of-the-art sequence models like Transformers and Mamba, which lack inherent structural priors. By reducing simulation time from hours to seconds, we show that the surrogate model is capable of producing new insights and generating new hypotheses. This framework is readily extensible to a broader class of connectome-based biophysical models, showcasing the transformative value of deep learning surrogates to accelerate analysis of large-scale, computationally intensive dynamical systems.

How important are the genes to explain the outcome - the asymmetric Shapley value as an honest importance metric for high-dimensional features

In clinical prediction settings the importance of a high-dimensional feature like genomics is often assessed by evaluating the change in predictive performance when adding it to a set of traditional clinical variables. This approach is questionable, because it does not account for collinearity nor known directionality of dependencies between variables. We suggest to use asymmetric Shapley values as a more suitable alternative to quantify feature importance in the context of a mixed-dimensional prediction model. We focus on a setting that is particularly relevant in clinical prediction: disease state as a mediating variable for genomic effects, with additional confounders for which the direction of effects may be unknown. We derive efficient algorithms to compute local and global asymmetric Shapley values for this setting. The former are shown to be very useful for inference, whereas the latter provide interpretation by decomposing any predictive performance metric into contributions of the features. Throughout, we illustrate our framework by a leading example: the prediction of progression-free survival for colorectal cancer patients.

Comparative Evaluation of Traditional Methods and Deep Learning for Brain Glioma Imaging. Review Paper

Segmentation is crucial for brain gliomas as it delineates the glioma s extent and location, aiding in precise treatment planning and monitoring, thus improving patient outcomes. Accurate segmentation ensures proper identification of the glioma s size and position, transforming images into applicable data for analysis. Classification of brain gliomas is also essential because different types require different treatment approaches. Accurately classifying brain gliomas by size, location, and aggressiveness is essential for personalized prognosis prediction, follow-up care, and monitoring disease progression, ensuring effective diagnosis, treatment, and management. In glioma research, irregular tissues are often observable, but error free and reproducible segmentation is challenging. Many researchers have surveyed brain glioma segmentation, proposing both fully automatic and semi-automatic techniques. The adoption of these methods by radiologists depends on ease of use and supervision, with semi-automatic techniques preferred due to the need for accurate evaluations. This review evaluates effective segmentation and classification techniques post magnetic resonance imaging acquisition, highlighting that convolutional neural network architectures outperform traditional techniques in these tasks.

MIRAGE: Knowledge Graph-Guided Cross-Cohort MRI Synthesis for Alzheimer's Disease Prediction

Reliable Alzheimer's disease (AD) diagnosis increasingly relies on multimodal assessments combining structural Magnetic Resonance Imaging (MRI) and Electronic Health Records (EHR). However, deploying these models is bottlenecked by modality missingness, as MRI scans are expensive and frequently unavailable in many patient cohorts. Furthermore, synthesizing de novo 3D anatomical scans from sparse, high-dimensional tabular records is technically challenging and poses severe clinical risks. To address this, we introduce MIRAGE, a novel framework that reframes the missing-MRI problem as an anatomy-guided cross-modal latent distillation task. First, MIRAGE leverages a Biomedical Knowledge Graph (KG) and Graph Attention Networks to map heterogeneous EHR variables into a unified embedding space that can be propagated from cohorts with real MRIs to cohorts without them. To bridge the semantic gap and enforce physical spatial awareness, we employ a frozen pre-trained 3D U-Net decoder strictly as an auxiliary regularization engine. Supported by a novel cohort-aggregated skip feature compensation strategy, this decoder acts as a rigorous structural penalty, forcing 1D latent representations to encode biologically plausible, macro-level pathological semantics. By exclusively utilizing this distilled "diagnostic-surrogate" representation during inference, MIRAGE completely bypasses computationally expensive 3D voxel reconstruction. Experiments demonstrate that our framework successfully bridges the missing-modality gap, improving the AD classification rate by 13% compared to unimodal baselines in cohorts without real MRIs.

Freezing of Gait Prediction using Proactive Agent that Learns from Selected Experience and DDQN Algorithm

Freezing of Gait (FOG) is a debilitating motor symptom commonly experienced by individuals with Parkinson's Disease (PD) which often leads to falls and reduced mobility. Timely and accurate prediction of FOG episodes is essential for enabling proactive interventions through assistive technologies. This study presents a reinforcement learning-based framework designed to identify optimal pre-FOG onset points, thereby extending the prediction horizon for anticipatory cueing systems. The model implements a Double Deep Q-Network (DDQN) architecture enhanced with Prioritized Experience Replay (PER) allowing the agent to focus learning on high-impact experiences and refine its policy. Trained over 9000 episodes with a reward shaping strategy that promotes cautious decision-making, the agent demonstrated robust performance in both subject-dependent and subject-independent evaluations. The model achieved a prediction horizon of up to 8.72 seconds prior to FOG onset in subject-independent scenarios and 7.89 seconds in subject-dependent settings. These results highlight the model's potential for integration into wearable assistive devices, offering timely and personalized interventions to mitigate FOG in PD patients.