Digitally enriching a screening population for pancreatic cancer using routine blood-based measures and clinical histories

Earlier detection of pancreatic cancer is key to enabling wider access to curative treatment and reducing cancer deaths; however, screening is presently not viable. Latent indicators of pathology are evident in an individual's disease and blood test trajectories and may predict the development of pancreatic cancer. Longitudinal sequences of coded diagnoses and blood test values accrued by patients throughout their clinical interactions were used to train a custom Transformer-based neural network with a multi-head attention mechanism to predict risk of pancreatic cancer with a multi-year lead time and risk-stratify populations for targeted screening. The cohort comprised 6,017 adults with pancreatic cancer and 177,081 controls (overall median age 75, 45% female) with median 12 years (interquartile range 6.9-16.2) of medical history prior to pancreatic cancer diagnosis. External validation via leave-one-site-out, out-of-sample testing predicting pancreatic cancer 1-, 2-, and 3-years prior to diagnosis demonstrated mean area under the receiver operating characteristic of 0.837 (95% confidence interval 0.827-0.848), 0.797 (95% confidence interval 0.782-0.813), and 0.760 (95% confidence interval 0.745-0.776), respectively. Estimated pancreatic cancer risks were well-calibrated (calibration plot slope 1.08, intercept of -0.077; Brier score 0.025), and a Bayesian population pancreatic cancer prevalence update allows estimated cancer risk outputs to be transportable across settings. At testing, a screening threshold of >3.3% risk of pancreatic cancer in 1-year offered a diagnostic odds ratio of 18.2. Our work therefore lays the foundation for a first population-level digital enrichment tool to widen access to curative-intent management of pancreatic cancer.

iLoRA: Bayesian Low-Rank Adaptation with Latent Interaction Graphs for Microbiome Diagnosis

Parameter-efficient adaptation has made LLMs practical for domain prediction, but standard LoRA still relies on a static low-rank update and does not expose the latent interactions that often drive scientific labels. We introduce iLoRA. To our knowledge, it is the first Bayesian graph-conditioned LoRA framework. It infers a latent interaction graph from the input and uses it to generate input-conditioned LoRA updates. As a result, iLoRA learns prediction and latent interaction structure jointly, rather than training a predictor and applying interaction analysis only post hoc. We instantiate this idea for microbiome diagnosis, where disease state can depend on both species-level abundance and microbe-microbe cross-talk, and evaluate it in two complementary settings: interactive QA with human-annotated graphs, which tests latent structure recovery, and multi-cohort IBD diagnosis, which tests biomedical utility. Across both settings, iLoRA improves over strong LoRA and Bayesian adaptation baselines, recovers graphs aligned with human annotations and cohort-level microbiome associations, and provides calibrated uncertainty with moderate graph-branch overhead.

Treatment-Conditioned Diffusion for Forecasting Neurodegenerative Disease Progression

Forecasting the progression of neurodegenerative diseases, such as Parkinson's disease, is essential for effective long-term planning and personalized therapeutic intervention. Existing systems typically produce scalar clinical scores that ignore the rich structure of longitudinal neuroimaging, while traditional generative approaches suffer from a loss of anatomical details and blurring subtle progression patterns. To address this, we introduce a novel treatment-conditioned diffusion framework that predicts high-fidelity future brain states by conditioning the generative process on patients' screening DaTscan images and levodopa equivalent daily dose over one year. The pipeline uses a Transformer-based encoder to represent non-linear, time-dependent pharmacological dynamics and optimizes generation through a multi-weight region-of-interest mask that focuses on biologically critical areas. Experimental evaluation shows that our framework maintains sharp anatomical boundaries and significantly improves clinical fidelity relative to the baseline, achieving 14.0% lower MSE, 7.2% lower MAE, and 4.9% higher SSIM.

AIBuildAI-2: A Knowledge-Enhanced Agent for Automatically Building AI Models

AI models underpin data-centric applications from image and text processing to scientific discovery in biology, physics, and chemistry. Yet developing them remains heavily manual, requiring practitioners to design architectures, build training pipelines, and iteratively refine solutions, making it challenging for natural scientists without specialized AI engineering expertise to build the high-performing models their research demands. To reduce this burden and broaden access to AI for scientific discovery, agents that automatically build AI models have been proposed. However, the performance of these agents is largely limited by the parametric knowledge of their underlying large language models, which is static, often outdated, and sparse on practical AI model engineering know-how. To address this limitation, we introduce AIBuildAI-2, a knowledge-enhanced agent with an external, evolving knowledge system for automatically building AI models. The knowledge system of AIBuildAI-2 is hierarchical, organizing curated AI development knowledge into high-level knowledge instructions over topical categories and low-level knowledge documents under each category, from which the agent dynamically loads only the context relevant to its current state and the AI task being solved, grounding each design and implementation decision in concrete, externally verifiable expertise. The system is initialized by collecting and cleaning AI-development-related documents from the web and organizing them into the corresponding categories, and continually evolves from the agent's own experience by distilling each completed run on an AI task into structured takeaways that are written back into the knowledge system. AIBuildAI-2 achieves state-of-the-art results, ranking first on MLE-Bench with a 70.7% medal rate and placing in the top 6.6% among 4,370 human-expert teams in a heart disease prediction competition.

GraD-IBD: Graph Representation Learning from Diagnosis Trajectories for Early Detection of Inflammatory Bowel Disease

International Classification of Diseases (ICD) is a globally recognized coding system that records diagnostic events during each patient encounter, providing a standardized data foundation for various clinical tasks. However, the irregular and hierarchical nature of ICD code sequences poses challenges for N-D lattice-based sequential modeling methods, leading to overly complex model designs. In this paper, we propose GraD-IBD, a graph diagnosis model that reformulates longitudinal ICD trajectories as visit-bucketized, temporally directed graphs to detect the risk of inflammatory bowel disease (IBD). A novel context-aware, time-decay message passing mechanism was developed to capture temporal dependencies while reducing model complexity. The experimental results using a real-world clinical dataset demonstrated consistent and robust improvements in IBD detection over state-of-the-art methods, with significant reductions in computational complexity compared to sequential models. These findings highlight the potential of graph representation learning to enable efficient, scalable, and accurate disease risk prediction from longitudinal ICD diagnosis codes.

Adaptive Temporal Gating of Longitudinal Magnetic Resonance Imaging for Alzheimer's Prediction

Predicting conversion from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) is critical for early intervention. Current deep learning paradigms predominantly rely on cross-sectional structural MRI, neglecting prognostic value in patient-specific anatomical trajectories. We introduce the Temporal Adaptive Fusion Network (TAF-Net), a hybrid CNN-Transformer architecture that models paired longitudinal 3D MRI scans. Central to TAF-Net is a Temporal Fusion Module governed by an Adaptive Temporal Gate, which learns patient-specific weightings to synthesize three spatiotemporal representations: explicit structural change, region-to-region temporal cross-attention, and bilateral feature concatenation. Evaluated on the Alzheimer's Disease Neuroimaging Initiative cohort for three-year MCI-to-AD conversion prediction, TAF-Net achieved the highest discriminative performance among all evaluated methods using only structural MRI, significantly outperforming the strongest baseline and approaching multimodal methods requiring PET, CSF, or genetic data. The architecture exhibited exceptional data efficiency, matching baseline performance with a fraction of training data. Ablation studies demonstrate that longitudinal fusion improves discrimination while reducing predictive variance by 48% compared to single-timepoint evaluation. Interpretability analyses reveal spatial attention aligned with established AD pathology in the medial temporal lobe and ventricles, while the gating mechanism prioritizes explicit volumetric change with strong positive correlation to conversion risk.

Applications of temporal graph learning for predicting the dynamics of biological systems

Biological foundation models have shown strong performance in single-cell representation learning by applying transformer architectures directly to gene-expression matrices. However, these approaches predominantly operate in static settings and do not explicitly model the temporal evolution of developmental programs in the cell. Modeling such dynamics is important for understanding how cellular states progressively emerge, differentiate, and reorganize during development or disease progression. In this work-in-progress paper, we investigate an alternative temporal graph-based perspective in which cellular states are represented through pseudotime-resolved gene regulatory networks and modeled as evolving graph structures over persistent gene identities. Starting from single-cell transcriptomic data, we infer pseudotime trajectories, discretize cells into developmental snapshots, reconstruct one gene regulatory network per snapshot, and apply temporal graph neural networks to forecast biological states. We evaluate this framework on two publicly available mouse developmental datasets, erythroid gastrulation and pancreatic endocrinogenesis, considering three complementary tasks: gene-expression forecasting, link prediction, and out-degree centrality prediction. Our results show that graph-based models outperform well-known foundation-model such as scGPT and scFoundation, suggesting that explicitly modeling evolving regulatory structure provides useful information beyond static pretrained representations. For link prediction and centrality forecasting, temporal graph learning captures non-trivial regulatory dynamics and enables the identification of temporally important gene hubs. Overall, our findings support temporal graph learning as a promising direction for modeling dynamic biological systems and as a complementary paradigm to current foundation model approaches in single-cell biology.

Computational Modeling of Antibody-Antigen Complexes: PLM-Based and MSA-Based Approaches

Antibodies play a central role in the immune response by specifically recognizing and neutralizing antigens, and therapeutic antibodies have become major drugs for cancer and autoimmune diseases. However, their discovery still relies on extensive in vitro screening, and accurate computational modeling of antibody structures and antibody-antigen interactions can prioritize candidates, reduce experimental burden, and accelerate rational design. Despite recent advances in high-accuracy protein and complex prediction, a persistent performance gap remains for antibody-related tasks compared with general protein-protein interactions, limiting downstream design. This thesis investigates why antibody-related tasks are harder and proposes improvements along two complementary directions. First, we investigate protein language model (PLM)-based methods for antibody and antibody-antigen structure prediction. Using embeddings from multiple PLMs, our approach achieves the best CDR-H3 accuracy among compared PLM-based methods on antibody monomer prediction. Extending it to complex prediction does not generalize: without co-evolutionary signals between antibody and antigen, single-sequence PLM representations do not reliably identify binding interfaces. Second, we develop two MSA-based interventions for antibody-antigen complex prediction: MSA refinement, which combines CDR-focused filtering with depth recovery from a larger sequence database, and convergence-aware recycling, which selects a stable intermediate recycle state for final diffusion sampling. Together, these interventions provide consistent gains over the AlphaFold3 baseline on a held-out antibody-antigen test set. Because the methods modify MSA construction and recycling behavior rather than model parameters, they apply without retraining or weight access.

Implementation of Big Data Analytics for Diabetes Management: Needs Assessment in the Rwanda Healthcare System

Diabetes is a chronic metabolic disease that can lead to serious health problems if not diagnosed and managed early. Big Data Analytics (BDA) and machine learning offer practical tools for analyzing large health datasets and supporting early detection and better treatment decisions. However, their use in routine clinical practice is still limited. This study examines the readiness of Rwanda's healthcare system to adopt big data analytics for diabetes management. As the country continues to expand its use of electronic medical records and health information systems, new opportunities arise for improving prediction, monitoring, and clinical decision-making. A five-day workshop involving 25 key stakeholders, including clinicians, data managers, policymakers, medical researchers, nutritionists, and technology providers, was conducted to assess preparedness and identify existing gaps. The findings highlight both the potential and the main challenges of BDA implementation. Based on these results, the paper proposes a practical BDA framework to support diabetes management strategies using explainable machine learning models.

SL-BiLEM: Structured Learnable Behavior-in-the-Loop Epidemic Modeling for Forecasting and Policy Evaluation

Epidemic forecasting faces a fundamental challenge: human behavior dynamically responds to disease spread, creating feedback loops that induce distribution shifts at policy intervention points. This renders data-driven models unreliable under distribution shift. We propose \textbf{SL-BiLEM} (Structured Learnable Behavior-in-the-Loop Epidemic Model), leveraging physical constraints as regularization for robust extrapolation. The framework decomposes effective transmission as $β_{\text{eff}}(t,g) = β_0(g) \times m_{\text{policy}}(t) \times m_{\text{media}}(t) \times m_{\text{comp}}(t,g)$, where monotonicity, smoothness, and bounded-jump constraints on the learned compliance function maintain predictive validity under novel policy regimes. Beyond forecasting, SL-BiLEM enables counterfactual analysis for intervention decision support. We validate forecasting on three real-world datasets (cruise ship, school influenza, and school-district COVID-19 surveillance) and evaluate counterfactual recovery on synthetic benchmarks with known ground truth. SL-BiLEM demonstrates: (1) 76\% improvement over neural-mechanistic baselines, with only 53\% OOD degradation versus 1142\% for neural baselines under policy-induced shift; (2) 100\% bootstrap CI coverage across 27 synthetic counterfactual experiments; and (3) Treatment Effect Accuracy exceeding 0.85. These results establish SL-BiLEM as an interpretable tool for public health decision-makers seeking accurate prediction and principled intervention planning.