Supercharging Bayesian Inference with Reliable AI-Informed Priors

Modern predictive systems encode beliefs that can act as useful prior information for statistical inference in data-limited settings. Using them for prior construction introduces a tradeoff: an informative prior built from a predictive model can sharpen inference from limited data, but also risks propagating error from the model into the posterior. We propose a framework for AI-informed prior elicitation that mitigates this tension by rectifying the AI-induced law that generates synthetic data before using it to inform a prior. The rectified law can be embedded into synthetic data-driven prior elicitation techniques, including as a base measure in a Dirichlet process (DP) prior on the data-generating process. We refer to the resulting prior and corresponding posterior as the rectified AI prior and rectified AI posterior. We establish Gaussian asymptotics for the rectified AI posterior under non-vanishing prior strength and derive a first-order expression for its centering bias. Our rectified AI priors substantially reduce bias compared to standard approaches, improve the coverage of credible intervals, and make AI-powered prior information more reliable. We additionally apply the rectified AI prior to a real skin disease classification task and show that it can meaningfully boost predictive performance.

Bridging Sequence and Graph Structure for Epigenetic Age Prediction

Epigenetic clocks based on DNA methylation have emerged as powerful tools for estimating biological age, with broad applications in aging research, age-related disease studies, and longevity science. Despite advances across machine learning approaches to epigenetic age prediction, spanning penalised linear regression, deep feedforward networks, residual architectures, and graph neural networks, no existing method jointly models co-methylation graph structure and site-specific DNA sequence context within a unified framework. We propose a unified sequence--graph integration framework for epigenetic age prediction that addresses this gap, integrating eight-dimensional DNA sequence statistical features through a lightweight gated modulation mechanism that adaptively scales each site's methylation signal according to its sequence-determined biological relevance prior to graph convolution. Evaluated on 3,707 blood methylation samples against a comprehensive set of baselines, our method achieves a test MAE of 3.149 years, a 12.8\% improvement over the strongest graph-based baseline. Biologically informed statistical features outperform CNN-based sequence encoding, demonstrating that handcrafted sequence features are more effective than end-to-end learned representations in this data regime. Post-hoc interpretability analysis identifies CpG density and local adenine frequency as features with age-dependent importance shifts, consistent with known mechanisms of age-related hypermethylation at CpG-dense promoter regions. Our code is at https://github.com/yaoli2022/graphage-seq.

Learning the Interaction Prior for Protein-Protein Interaction Prediction: A Model-Agnostic Approach

Protein-protein interactions (PPIs) are fundamental to cellular function and disease mechanisms. Current learning-based PPI predictors focus on learning powerful protein representations but neglect designing specialized classification heads. They mainly rely on generic aggregating methods like concatenation or dot products, which lack biological insight. Motivated by the biological "L3 rule", where multiple length-3 paths between a pair of proteins indicate their interaction likelihood, our study addresses this gap by designing a biologically informed PPI classifier. In this paper, we provide empirical evidence that popular PPI datasets strongly support the L3 rule. We propose an L3-path-regularized graph prompt learning method called L3-PPI, which can generate a prompt graph with virtual L3 paths based on protein representations and controls the number of paths. L3-PPI reformulates the classification of protein embedding pairs into a graph-level classification task over the generated prompt graph. This lightweight module seamlessly integrates with PPI predictors as a plug-and-play component, injecting the interaction prior of complementarity to enhance performance. Extensive experiments show that L3-PPI achieves superior performance enhancements over advanced competitors.

Marrying Generative Model of Healthcare Events with Digital Twin of Social Determinants of Health for Disease Reasoning

Despite the central role of sensor-derived measurements such as imaging traits and plasma biomarkers in biomedical research and clinical practice, existing generative models for disease prediction largely depend on event-level representations from hospital and registry data. Given the multi-factorial nature of human disease, the absence of explicit modeling of social determinants of health (SDoH), even in the limited form of ICD-coded proxies (chapters Z and V--Y in ICD-10), limits the capacity for personalized disease modeling and clinical decision support. To address this limitation, we propose a generative model with ICD-coded proxies of SDoH for \textit{in silico} modeling of disease reasoning, a conditioned latent diffusion framework that establishes the connection between multi-organ sensor data with tokenized healthcare events. Specifically, we introduce a novel geometric diffusion model to characterize the temporal evolution of complex data representation such as brain networks (region-to-region connectivity encoded in a graph), in parallel with diffusion models for tabular data from other organ systems. Together, we integrate the generative model with digitalized SDoH proxies (coined \modelname{}) for simulated intervention and reasoning of future disease trajectories. We conduct extensive experiments on the UK Biobank (UKB) dataset, which contains organ-specific imaging traits, including brain (44,834), heart (23,987), liver (28,722), and kidney (32,155), along with nearly 500k medical history sequences (age range: 25$\sim$89 years). Our \modelname{} achieves significant improvements over state-of-the-art human disease autoregressive models and imaging trait generative baselines.

Autonomous FAIR Digital Objects: From Passive Assertions to Active Knowledge

Scientific knowledge on the Web is published as passive assertions and cannot decide when to validate evidence, reconcile contradictions, or update confidence as findings accumulate. Curation depends on centralised middleware and institutional continuity, but when registries close, active stewardship stops even when data remain online. We advance the concept of Autonomous FAIR Digital Objects (aFDOs) from an abstract idea to an operational model, to offer a route from passive scientific publication toward accountable, standards-aligned automation that can outlive its publishing institutions. aFDO augments FDOs with three capabilities anchored in Semantic Web standards, namely 1) a policy layer over RDF-star aligned with PROV-O, SHACL, and ODRL for portable condition-action rules, 2) an announcement layer over ActivityStreams 2.0 that bounds per-announcement evaluation cost, and 3) an agreement layer that resolves multi-source contradictions through reputation and confidence weighted agreement under a bounded adversarial model. We provide a formal definition that distinguishes policy specifications, event handlers, and communication interfaces. We evaluate an open reference implementation on 4,305 FDOs grounded in rare-disease ontologies, namely ClinVar, HPO, and Orphanet, combined with controlled synthetic observations. The consensus mechanism resolves 56.3% of 3,914 naturally occurring ClinVar conflicts where multiple submitters disagree and an expert panel has subsequently adjudicated. Under Sybil, collusion, and poisoning attacks, the mechanism degrades gracefully within its design Byzantine-tolerance bound (f < n/5), and fails as predicted beyond that bound.

Biosignal Fingerprinting: A Cross-Modal PPG-ECG Foundation Model

Cardiovascular disease remains the leading cause of global mortality, yet scalable cardiac monitoring is hindered by the gap between diagnostic-rich ECG and ubiquitous wearable PPG. Bridging this gap requires representations that are compact, transferable across modalities and devices, and deployable without task-specific retraining. Here we introduce biosignal fingerprints: compact latent representations of cardiovascular state derived from a cross-modal foundation model, the Multi-modal Masked Autoencoder (M2AE), trained on over 3.4 million paired ECG and PPG signals. M2AE integrates modality-specific encoders with a shared bottleneck and dual decoders, jointly optimized using reconstruction and cross-modal contrastive objectives, yielding generalizable fingerprints that retain intra- and inter-modality features. Like a biometric fingerprint, these representations uniquely encode an individual's cardiovascular state in a modality-agnostic, privacy-preserving form reusable across clinical tasks without exposing raw waveform data or requiring model retraining. Across 7 downstream tasks, spanning cross-modal reconstruction, cardiovascular disease classification, hypertension detection, mortality prediction, and demographic inference, biosignal fingerprints achieve competitive or superior performance compared to leading domain-specialist foundation models in frozen settings, including an AUROC of 0.974 for five-class CVD classification and 0.877 for hypertension detection, with a maximum improvement of 27.7% in AUROC across 5 classification tasks. Critically, strong performance is maintained with only a single modality, enabling deployment in resource-constrained, single-sensor environments typical of real-world wearable monitoring, with direct implications for continuous cardiovascular monitoring across clinical and consumer health settings.

Image-Based Whole-Heart Cardiac Flow Simulations in Health and Congenital Heart Disease

Intracardiac flow patterns are shaped by the coupled motion of the cardiac chambers and heart valves and provide important information about cardiac function. However, clinical flow imaging remains limited by exam times, noise, resolution, and incomplete details of the three-dimensional flow. Computational fluid dynamics (CFD) can potentially provide detailed flow quantification and predictive insight into treatment outcomes, but clinical translation requires frameworks that reproduce patient-specific measurements while balancing physiological realism, computational cost, and modeling effort. Herein, we present an image-based, patient-specific computational framework for simulating whole-heart intracardiac hemodynamics that balances physiological fidelity with computational efficiency. The framework first employs machine learning-based segmentation and mesh propagation to reconstruct moving cardiac anatomies from time-resolved images. CFD simulations are then performed to resolve blood flow in deforming domains, while resistive immersed surfaces (RIS) are used to model all four cardiac valves with physiologically realistic opening and closing dynamics. The framework was applied to model hemodynamics in a healthy adult and a pediatric patient with complex congenital heart disease (CHD). In the healthy case, the simulations reproduced physiologic pressure-volume behavior, valve timing, and ventricular vortex formation. In the CHD case, simulated chamber and vessel pressures showed agreement with cardiac catheterization measurements. Simulated flow fields were qualitatively consistent with 4D-Flow MRI, while providing higher-resolution visualization of flow structures that were partially obscured by imaging artifacts. Comparison between the healthy and CHD cases further revealed altered diastolic flow organization and elevated normalized viscous dissipation in the CHD heart.

Correcting heterogeneous diagnostic bias when developing clinical prediction models using causal hidden Markov models

In routine care, individuals identified a priori as high-risk are usually tested for conditions more frequently. Protected attributes, such as sex or ethnicity may also determine testing frequency. Such heterogeneous detection rates across a population induce label error. This causes systematic model error for specific groups and biases performance metrics during validation. This paper proposes a method to correct for such bias in prediction models due to differential diagnostic delay. We use a causal inference framework to define our target estimand: an individual's diagnosis probability in a counterfactual scenario where their diagnosis rate matches that of a reference group. We model the longitudinal process as a hidden Markov model, in which confirmatory test results are emissions from a latent progressive disease stage. We validate our approach in simulated data and apply it to a case study of chronic kidney disease prediction using electronic health records. In simulations, our method reduces prediction bias and improves calibration-in-the-large, correcting the Observed:Expected ratio in the underdiagnosed group from 1.34 (standard deviation: 0.09) in a model developed without any correction for underdiagnosis bias to 1.02 (0.09). Violations of assumptions in the simulation affected the estimation of model parameters, but the proposed approach nonetheless remained better calibrated than the standard model. In the clinical case study, we identify diabetes as the main driver of observability, with an odds ratio of 10.36 (95% confidence interval, 9.80 - 11.02) in 6-month urine albumin-creatinine ratio testing rate. Using our approach to predict the counterfactual diagnostic rate in patients without diabetes, we improved the Observed:Expected ratio of a developed clinical prediction model from 1.55 (1.51 - 1.59) to 1.01 (0.98 - 1.04).

Event-Based Early Warning of Vineyard Disease Risk from Environmental Time Series

Accurate early warning of vineyard disease risk from environmental observations is essential for timely intervention and more sustainable crop protection. However, many existing studies formulate disease prediction as daily presence classification, which can favor persistence-driven predictions and provide only limited support for actionable short-horizon warning. In this paper, we present an event-based approach for early warning of vineyard disease risk from environmental time series and evaluate it through a vineyard case study. Rather than predicting daily disease status, the task is reformulated to predict transitions into annotated disease-risk periods within a future window of 3-7 days. To reduce fragmentation caused by short interruptions in the binary labels, new events are defined only after a minimum disease-free gap. This formulation encourages models to capture environmental precursors associated with upcoming risk periods instead of merely reproducing temporal persistence. Using multi-year agro-meteorological data, we construct input representations that capture humidity dynamics, rainfall accumulation, temperature variability, and seasonal structure through cyclic temporal encoding. We evaluate representative methods from classical machine learning and deep learning, including XGBoost, Long Short-Term Memory (LSTM) networks, and Temporal Convolutional Networks (TCNs), using both standard classification metrics and an event-oriented early warning protocol. The results show that the event-based formulation supports practical short-horizon warning, while the compared models exhibit distinct trade-offs between event recall, lead time, and false-alert behavior. Overall, the study underscores the importance of problem formulation in environmental time-series learning and demonstrates the value of event-based prediction for vineyard disease warning systems.

Eliciting associations between clinical variables from LLMs via comparison questions across populations

The training data of large language models (LLMs) comprises a wide range of biomedical literature, reflecting data from many different patient populations. We investigate how it might be possible to recover information on correlation and causal links between patient characteristics, as a key building block for medical decision making. To avoid the pitfalls of direct elicitation, we propose an approach based on structured comparison questions, specifically patient comparison triplet questions. This is combined with a statistical model for the LLM representation that provides estimates of correlations without access to activations or model internals. Intuitively, we consider how similarity decisions of LLMs based on a first variable are affected by providing information on a second variable for one of the patients being assessed. We then induce prompt-level environment shifts to obtain correlation estimates for different subpopulations, which enables an invariant causal prediction (ICP) approach to obtain conservative candidate parent links. We demonstrate the method in two clinical domains, chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS). Across prompted environments, the elicited correlations are smooth, stable, and clinically interpretable, yet vary in a statistically significant way that supports downstream invariance testing, such that ICP provides a small set of candidate invariant parent links. These results show that indirect elicitation via triplet comparisons can recover meaningful association structure from LLMs and offer a cautious route from implicit correlations to causal statements that are congruent with LLM answering patterns.