Generative models have shown strong potential for positron emission tomography (PET) image reconstruction. Although diffusion model-based reconstruction methods have demonstrated promising performance, they often require many reverse sampling steps with data-consistency updates incorporated into the sampling process. Flow matching offers an attractive alternative because it can directly estimate clean images from intermediate states, allowing data-consistency refinement to be separated from flow propagation. In this work, we proposed flow matching-based PET image reconstruction methods. We first established PET-FlowDPS by incorporating Poisson likelihood guidance with an expectation-maximization (EM)-based preconditioner into the FlowDPS framework. We then proposed a model-based PET reconstruction method that used a pretrained flow matching model as a prior, in which the flow-based prior, PET data refinement, and stochastic propagation were interpreted within an approximate Bayesian framework. Experimental results using [$^{\text{18}}\text{F}$]FDG brain PET datasets showed that the proposed method achieved better bias-variance trade-offs across different dose levels compared with other reference methods. These results demonstrated the potential of flow matching as a generative prior for quantitative PET image reconstruction.
Jesper Løve Hinrich, Pia Susan Mayer, Bekzod Khakimov +2q-bio.QM cs.LG
Overlapping peaks and sample-dependent chemical shift variability prevent reliable metabolite recovery from complex biological spectra. This problem is critical in one-dimensional proton (1D 1H) NMR which has become the standard method providing fast acquisition and information-rich spectra in metabolomics and foodomics. This study demonstrates how chemical shifts can be utilised as a strength in 1D 1H NMR, when suitably modeled through the proposed Bayesian Shift-Invariant Non-negative Matrix Factorization (BSI-NMF) procedure. We find that BSI-NMF accurately recovers the underlying chemical signals in 1D 1H NMR spectra missed by existing analyses approaches across simulations, laboratory created datasets, and a large urine dataset obtained from 2439 people across Europe. Our study highlights how shifts in the chemical signatures - until now perceived as a nuisance - can in fact when suitably modelled be instrumental for unique recovery of metabolites. This creates an opportunity to experimentally induce chemical shifts changes to facilitate unique recovery of spectra.
Predictive coding offers a powerful framework for cortical computation, yet scalable implementations that respect both Bayesian exactness and neurobiological constraints remain scarce. We bridge this gap by formally connecting predictive coding to Recursive Gaussian Processes (RGPs). RGPs employ a single Gaussian process \( g(t, \cdot) \) indexed by layer index and input value, preventing the representational collapse of standard deep Gaussian processes while allowing learnable cross-layer dependence via \( r_{1g} \). We demonstrate that RGPs intrinsically implement hierarchical Bayesian inference, uncertainty propagation, and precision-weighted prediction error. Critically, we map RGP components---the shared GP, spike-and-slab variable selection, and MCMC dynamics---onto the canonical cortical microcircuit, providing a neurobiological substrate for these computations. Drawing on the free energy principle, we show that RGP inference minimizes variational free energy, formally linking Bayesian mechanics to neuronal dynamics. Our synthesis positions RGPs as both a principled computational tool and a candidate model for the brain's predictive machinery, generating testable predictions for laminar-specific dynamics and spectral asymmetries between feedforward and feedback processing.
The emergence of orientation selectivity in the primary visual cortex (V1) remains a central question in computational neuroscience. Shirazi's Bayes-Markov model proposed a probabilistic explanation for how orientation-selective inhibition can arise from non-oriented lateral geniculate nucleus (LGN) inputs through local inference. In that formulation, the activity pattern of striate cortical inhibitory (SCI) cells is estimated from the LGN activity pattern by a maximum a posteriori (MAP) criterion over a two-layer hierarchical Markov random field, and the resulting inference is implemented through a local parallel relaxation algorithm. We provide a computationally explicit re-implementation and quantitative simulation study of this framework. We reconstruct the mathematical model, describe its fully LGN-driven update rule, and implement a vectorized simulation framework that preserves the original local clique operations while making systematic parameter sweeps feasible. We evaluate the model using orientation tuning curves, an orientation selectivity index (OSI), controlled LGN noise perturbations, contrast tests, and model-variant comparisons. We further add a spiking SCI-layer realization using leaky integrate-and-fire and Hodgkin-Huxley neurons to examine whether the rate-coded SCI field can be expressed through temporally explicit neural activity. The simulations support the central qualitative behavior of the Bayes-Markov framework: sharp orientation selectivity, robustness to moderate LGN noise, and a biologically interpretable proof-of-concept spiking realization of the inferred inhibitory field.
Emmanuel M. Rockwell, Patrick J. Smith, Michael R. Kosorok +1stat.ME stat.ML
The value of an individualized treatment rule (ITR), defined as the expected outcome under treatment assignment according to the rule, is useful for assessing average clinical benefit but does not explain how the benefit of a rule is generated. We propose a causal mediation framework for decomposing the value contrast between a prespecified candidate ITR and a clinically meaningful reference rule into direct and indirect components. Using rule-specific nested potential outcomes, we define natural direct and indirect rule effects that quantify the extent to which the improvement in value arises through pathways operating directly on the outcome versus through a specified mediator. We give identification conditions under which these components are identified by a rule-level mediation g-formula. For estimation, we adapt Bayesian causal mediation forests to obtain posterior inference for the value contrast and its path-specific components. Our simulations demonstrate that the proposed estimator achieved near-nominal credible interval coverage with decreasing bias and root mean squared error as sample size increased in settings with varying direct and mediated contributions. We further illustrate the method using data from the TRIUMPH trial, decomposing the cognitive benefit of a lifestyle intervention rule through candidate neurovascular, cardiorespiratory, and behavioral mediators. The proposed framework complements optimal ITR learning with explanation using mediation, providing a natural approach for mechanistic evaluation of ITRs.
L. Raczynski, W. Krzemien, A. Coussat +5physics.med-ph cs.CV physics.comp-ph
PET provides functional images relying on two-photon coincidences from positron-electron annihilation. In human tissue, about 40\% of annihilations are preceded by Ps formation, of which o-Ps component partially decays into three photons, with the remainder annihilating via pick-off or spin-exchange into two photons. This three-photon channel carries additional information about the surrounding micro-environment, including the three-to-two-photon yield ratio as a potential diagnostic marker. We propose the TRIO algorithm, a novel three-photon event-by-event image reconstruction algorithm formulated as a Bayesian maximum a posteriori inference problem. TRIO unifies time-based trilateration, energy-based reconstruction and, for the first time, a physics-informed prior derived from the QED description of Ps decay within a single probabilistic framework. In contrast to positronium lifetime imaging, which requires a prompt photon and is therefore restricted to specific radionuclides, TRIO relies solely on the three photons and is fully compatible with standard radionuclides such as 18F. Monte Carlo simulation modelled after the Siemens Biograph Quadra scanner demonstrates a mean position error of 1.62~cm, improving by approximately a factor of two over the time-based trilateration (3.05 cm) and by about an order of magnitude over energy-based reconstruction alone (18 cm). More importantly, the proposed Bayesian approach is compatible with existing TOF-PET scanners that can register three-photon annihilation coincidences.
Here we introduce ELECTRIC (Evidential Learning-Enhanced CT Reconstruction via Iterative Correction), a physics-guided Bayesian formulation. An evidential neural network provides an image proposal and an error-predictive epistemic-uncertainty surrogate. The latter is converted into an adaptive precision field and inserted into a Poisson-weighted MAP update. The resulting image-evidence-precision-reconstruction loop treats prior confidence as a learned state variable of iterative reconstruction. In addition to the formulation and theoretical analysis, we report two simulation studies on image slices from the AAPM Mayo Clinic Low-Dose CT dataset: a mechanism-validation pilot using transparent surrogate estimators, and a feasibility study in which a trained Normal-Inverse-Gamma evidential network drives the full closed loop. On held-out patients, the learned prior mean reduces reconstruction error by roughly 70 percent relative to filtered back-projection, the learned epistemic uncertainty is error-predictive and supports selective trust, and the physics-guided update restores measurement consistency while the adaptive-precision reconstruction matches or exceeds a validation-tuned fixed prior and remains markedly more robust to prior-strength misspecification. Together these results demonstrate the complete ELECTRIC closed-loop pipeline, while identifying formal uncertainty calibration and joint training as the principal directions for future work.
Brain-computer interfaces (BCIs) have long sought calibration-free operation, but classifiers are typically benchmarked by discrimination alone, blind to whether predicted probabilities are well calibrated - a meaningful gap given nonstationary electroencephalogram (EEG) signals and the risk of overconfident point-estimate classifiers under distribution shift. We conducted a large-scale study contrasting Bayesian complete-pooling models against frequentist baselines for cross-subject, left-hand versus right-hand motor imagery EEG classification across 20 datasets. Six frequentist pipelines were each paired with an analogous Bayesian pipeline sharing identical feature engineering, fit via Markov chain Monte Carlo posterior sampling. Our primary metric was the Brier score, decomposed into reliability and resolution, alongside AUROC for discrimination and Shannon entropy for sharpness. Each metric was analyzed via random-effects meta-analysis (REML, Knapp-Hartung adjustment), verified by leave-one-out influence analysis. Bayesian complete-pooling produced statistically but not practically significant improvements in reliability and increases in predictive uncertainty (lower sharpness); Brier score, resolution, and discrimination showed no significant differences. Between-study heterogeneity was low across all metrics, though the reliability result was sensitive to leave-one-out removal. We additionally profiled computational cost, finding that Bayesian pipelines consumed roughly thirteen times more energy than their frequentist counterparts, a cost that remains modest relative to common household appliances. These results suggest that Bayesian complete-pooling alone offers limited practical benefit for cross-subject motor imagery classification, and that partial-pooling across subjects and sessions is a more promising direction for future work.
Learning causal graphs from interventional data is a challenging problem with broad applications. In molecular biology, for example, a central goal is to uncover gene regulatory networks from large-scale perturbation data. An ideal algorithm for this task should scale to thousands of nodes, incorporate interventions even when their targets are unknown, quantify uncertainty, and provide identifiability guarantees. However, existing approaches---e.g. approaches using score-based optimization or approximate Bayesian inference---often fail to meet all of these criteria. To address these limitations, we develop Amortized Bayesian Causal Discovery of Extended Factor Graphs (ABCDEFG). Our method guarantees exact acyclicity, scales to graphs with thousands of nodes, and naturally handles interventions even when their targets are unknown. Additionally, ABCDEFG estimates a posterior distribution whose maximum a posteriori estimate provably identifies the true causal graph up to an equivalence class. On simulated datasets, ABCDEFG achieves state-of-the-art accuracy, producing a well-calibrated posterior distribution while outperforming previous score-based and approximate Bayesian methods. Applied to large-scale single-cell perturbation data, ABCDEFG identifies both established and novel gene targets of growth factors.
Yuankang Zhao, Youngsoo Baek, Felipe A. Medeiros +2stat.ML cs.LG stat.CO
Scalable Bayesian inference for generalized linear mixed models (GLMMs) provides uncertainty-aware analysis of correlated longitudinal data, but existing scalable approaches largely assume low-dimensional tabular predictors and do not directly accommodate high-dimensional modalities such as images and text. We address this limitation by learning one or more modality-specific neural encoders jointly with a GLMM objective, then performing variance-corrected stochasticgradient MCMC for the GLMM parameters conditional on the learned representation. This conditional-Bayes design combines supervised representation learning with posterior uncertainty quantification for population-level effects, subjectspecific heterogeneity, and modality-level random slopes. The resulting model preserves interpretable fixed and random effects for structured covariates and learned modalities while scaling gracefully to large longitudinal datasets. In simulation studies, our method recovers posterior means and variance estimates from full-data MCMC benchmarks after covariance correction. We further evaluate uncertainty through parameter-level interval coverage in simulations and predictive calibration on held-out data. Applications to glaucoma progression and adolescent mental health demonstrate that the framework allows nuanced assessment of the relative importance of each modality on both individual and population levels without sacrificing predictive performance.
Adolphus Wagala, Mehmet Samur, Giovanni Parmigianistat.ML cs.LG stat.ME
Binary data factorization is common, but real-valued methods ignore discreteness and yield hard-to-interpret factors. Boolean Matrix Factorization (BooMF) instead decomposes a binary matrix into two lower-rank binary matrices via logical AND and OR, expressing the data as a Boolean disjunction of interpretable patterns. In cancer genomics, BooMF can reveal coordinated feature changes that may drive tumor evolution, unlike rotational or additive decompositions. Most existing BooMF methods are heuristic, greedy, sensitive to initialization, prone to local optima, and do not support principled model selection or uncertainty quantification. We introduce Bayesian Boolean Matrix Factorization (BBMF), a fully conjugate generative model with sparsity-inducing priors. It enforces Boolean constraints, yields interpretable latent factors with coherent uncertainty quantification, and admits Gibbs sampling with closed-form full conditionals. Because cancer evolution often involves widespread, near-simultaneous chromosome-number changes (e.g., whole-genome duplication followed by instability and selection), Boolean factorizations capture these patterns more naturally than additive models. Applied to arm-level copy-number alteration data in multiple myeloma, where entries indicate presence/absence of chromosomal-arm amplifications, BBMF finds a small set of interpretable bicliques linking patient subsets to recurrently co-altered chromosomal arms, providing a compact, biologically meaningful summary of tumor heterogeneity and demonstrating BBMF's utility for uncovering discrete latent structure in complex binary data.
Circulating-tumour DNA (ctDNA) carries evidence of drug resistance months before imaging shows it, but the earliest evidence lives below the assay's limit of detection (LoD): a nascent subclone is detected only intermittently, producing a flickering sequence of faint detects and non-detects. Commercial liquid biopsies treat each draw as an independent snapshot and a non-detect as nothing. We argue a non-detect is a left-censored observation, and the pattern of non-detects and faint detects over time carries actionable evidence of growth before any single value is trustworthy. We introduce Span, a censored-Poisson Bayesian latent-growth change-point detector that models the binary detection process, accumulates a sequential generalised-likelihood-ratio statistic for an upward change-point in the per-variant detection rate, and raises a competing-risks alarm with calibrated false-alarm control. Span has no learned weights, so there is nothing to overfit. On a synthetic cohort of HR+/HER2- metastatic breast cancer on first-line CDK4/6-inhibitor plus endocrine therapy, at a matched 10% false-alarm rate, Span roughly doubles the fraction of impending progressions caught three months ahead (indolent regime: 25% vs 11% for the snapshot), with a falsifiable dose-response: large for indolent emergence, vanishing for fast emergence. A value-trajectory baseline performs identically to the snapshot, isolating the gain to the censored detection model. The survival backbone matches a Cox baseline on real breast-cancer data (GBSG-2, n=686; C-index 0.67 vs 0.68), and on a real longitudinal cohort with clean biomarkers (PBC2, n=312) the same pipeline correctly declines to win, a falsifiable boundary test confirming the mechanism is regime-specific. All ctDNA trajectories are synthetic.
Wastewater influenza surveillance can reveal community circulation before clinical reporting, but wastewater alone is not a fully identifiable proxy for human burden. Existing wastewater models assume a fixed evidence set, while generic evidence-acquisition methods treat official surveillance streams as interchangeable costly features. We cast wastewater-first influenza monitoring as a selective decision problem: starting from mandatory wastewater evidence, the system must decide whether wastewater is sufficient, which delayed official stream to query next, and when abstention is the only scientifically defensible action under source ambiguity. We propose Bayesian Selective Latent Inference (BSLI), a principled Bayesian method that maintains a posterior over latent burden and identifiability, certifies answerability through explicit scientific gates, and optimizes query-stop decisions with an exact cost-calibrated Bellman policy. We prove the key variational, answerability, Bellman-optimality, and one-dimensional cost-calibration properties. On a fixed public-data benchmark with 5,933 forecasting episodes and 3,102 source-ambiguity episodes, BSLI improves the matched-budget cost-performance frontier while preserving conservative abstention under source ambiguity.
Marco Morik, Xiao Ruiting, Shinichi Nakajima +2cs.LG
Classical sparse Type-II Bayesian methods for M/EEG brain imaging support joint estimation of source and noise hyperparameters, but rely on fixed iterative update rules. Although these updates are principled and interpretable, their dynamics cannot be adapted from data. We propose to learn the update mechanism itself while preserving the underlying Bayesian structure by unfolding a classical joint hyperparameter-learning solver into a trainable neural architecture whose layers mirror the original iterations. The resulting framework is initialized to recover the classical solver exactly before training and is enriched through progressively more expressive correction-learning mechanisms, ranging from learnable biases to adaptive MLP and attention-based contextual refinements. In this way, training does not replace Bayesian inference with a black-box predictor, but instead learns structured correction terms while retaining the interpretability and model-based character of the original update dynamics. Structured correction learning therefore aims to improve empirical reconstruction performance without replacing the original model-based inference mechanism. Experimental results show that the learned correction variants improve reconstruction performance and convergence behavior over the baseline unfolded solver while preserving its algorithmic transparency.
We propose an extended family of structured spatial priors that incorporates the total variation (TV) function with $\ell_p$ norms. The prior is proven to be proper and incorporated into a Bayesian regression framework to enable uncertainty quantification in $T_1$ mapping, with posterior inference performed using the No-U-Turn Sampler (NUTS). This TV--$\ell_p$ construction is proven to constitute a well-defined family of prior distributions, and it naturally enforces spatial consistency and smooth variations in the estimated parameter maps. The method was evaluated in comparison to maximum-likelihood estimation and several Bayesian alternative priors based on the uniform, Gamma, and bounded TV priors. The evaluation includes experiments on synthetic brain and cardiac $T_1$ mapping datasets, as well as a real in-vivo breast $T_1$ mapping dataset. The results show that the TV--$\ell_p$ prior yields more concentrated posterior densities, indicating reduced uncertainty. It also consistently achieves lower variance and smaller (negative) bias, leading to more reliable estimates. Overall, embedding a TV-based structured penalty along with $\ell_p$ norms in a prior in a Bayesian model improves spatial coherence in $T_1$ maps and enhances uncertainty quantification, offering a robust approach for $T_1$ mapping with uncertainties.
Reliable neural architecture selection is an open challenge in time-series forecasting under limited, noisy, and heterogeneous data, where standard heuristic architecture design and validation approaches fail to ensure accurate and reliable prediction and generalization. We propose EVIDENT (EVidence-based IDEntification of Neural archiTectures), a framework for architecture selection that integrates Bayesian training, evidence-based ranking, and task-specific validation under uncertainty. The framework explores the candidate architecture pool and identifies the lowest-capacity model that satisfies a prescribed validation criterion. We demonstrate this method using temporal convolutional networks (TCNs) for individualized blood glucose forecasting in type 1 diabetes patients. The results show that EVIDENT systematically rejects both under- and over-parameterized TCN architectures on population-level diabetes data, while identifying models that generalize reliably to unseen patients. When multiple architectures are competitive, the framework further supports plausibility-weighted ensemble predictions that enhance predictive performance. Compared with a random-search baseline, EVIDENT identified smaller architectures with more consistent forecasting performance on unseen patients. These findings establish EVIDENT as a strategy to neural architecture discovery, enabling reliable model selection for high-consequence forecasting in data-limited and heterogeneous settings.
Neural posterior estimation (NPE) is a simulation-based approach to Bayesian inference that trains a neural network to approximate the posterior distribution from simulated parameter - data pairs, bypassing likelihood evaluation. We apply NPE -- to our knowledge for the first time -- to stochastic susceptible-infectious-removed (SIR) epidemic models observed through final outcome data, considering both homogeneously mixing and household-structured populations. Such data arise naturally in retrospective outbreak investigations and household transmission studies, yet inference is computationally challenging: data-augmentation Markov chain Monte Carlo (MCMC) can be slow to mix in large populations and difficult to implement, while Approximate Bayesian Computation (ABC) suffers from low acceptance rates, particularly for large populations or unlikely outcomes. The discrete, low-dimensional nature of such observations makes this setting particularly well suited to NPE. We show that a logNormal posterior approximation, parameterised by a feed-forward neural network, accurately recovers reference posteriors across a range of population sizes and transmission regimes, and extends naturally to joint inference on global and local transmission rates in the household model. Once trained, the network produces approximate posterior distributions in seconds and generalises reliably to population sizes and structures not seen during training. Performance on both synthetic and real outbreak datasets is consistently strong, with results in close agreement with published analyses.
Predicting whether an individual with Alzheimer's disease will experience mild or severe disease progression is essential for personalized treatment. Typically, practitioners seek to predict the distribution of a discrete disease score, conditional on an individual's current MRI volume and their historical disease trajectory. Classical statistical regression models and single-task neural networks are not well-suited for this purpose because fitting separate models is infeasible (since each individual typically has few observations), while ignoring individual-level correlation leads to poor generalization. Meta-learning, in contrast, provides a natural avenue to dynamically predict distributions without retraining and model nonlinear relationships between the outcome and covariates. Motivated by this, we propose a Bayesian meta-learner that is trained on multiple individuals but tailors the predictive disease score distribution to each individual's historical data. Our model predicts on unseen individuals without retraining, scales linearly with the number of historical observations, and is guaranteed to be less overconfident when predicting long-term disease scores compared to its deterministic counterpart. On real-world data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, our model achieves performance competitive with both single-task models and deterministic meta-learners, while substantially improving performance when predicting long-term disease progression.
Antonio Ortiz-Gonzalez, Erich Kobler, Lukas Schletter +1cs.CV
Magnetic resonance imaging (MRI) is highly susceptible to patient motion due to its relatively long acquisition times and the fact that data are acquired sequentially in k-space. Even small patient movements introduce phase inconsistencies across measurements, leading to severe artifacts such as blurring, ghosting, and geometric distortions that can compromise diagnostic quality. Retrospective motion compensation remains challenging, particularly in accelerated acquisitions, due to the ill-posed nature of the joint reconstruction and motion estimation problem. In this work, we propose a unified Bayesian framework for motion-compensated 3D MRI that jointly estimates the anatomical image, rigid-body motion parameters, and coil sensitivity maps directly from motion-corrupted k-space data. Our approach integrates pretrained 3D complex-valued score-based diffusion models as expressive anatomical image priors within a physics-based forward model. Inference is performed by alternating diffusion posterior image updates with efficient proximal optimization steps for motion and coil sensitivity estimation, enabling fully unsupervised reconstruction without the need for paired motion-free training data. Experiments on simulated and real-motion brain MRI datasets demonstrate that the proposed method achieves improved image quality and motion robustness compared to state-of-the-art classical and learning-based motion correction techniques, particularly in the presence of severe motion and high acceleration.