Fairness audits in clinical Artificial Intelligence convert continuous fairness metrics into binary pass-or-fail verdicts against operational thresholds, where hospital governance boards, payers, and regulators act on the resulting verdicts. Such audits are repeated over time and across hospital sites, thus the same verdict can flip between pass and fail across audits. Existing uncertainty methods such as Bayesian posteriors, bootstrap confidence intervals, and permutation tests address verdict instability only at the continuous-metric level. Converting metric-level uncertainty into a verdict-stability claim remains a manual step that scales poorly across the (model, metric, attribute) cells an audit covers. Existing uncertainty methods also leave open whether bias-mitigation steps, such as reweighing or per-group threshold shifts, yield a stable passing verdict at the cost of model discrimination measured as AUROC or AUPRC.To address this verdict-stability gap, we propose VFR-Audit, a framework built around the Verdict Flip Rate (VFR), a scalar bounded between 0 and 0.5 that measures the probability of verdict reversal under stratified bootstrap resampling. VFR-Audit reports VFR alongside three reliability axes, namely within-cohort resampling stability, audit-size sensitivity, and cross-hospital verdict agreement via Fleiss' kappa.
Real-time musculoskeletal (MSK) surrogates could support personalized rehabilitation for children with cerebral palsy (CP), but their credibility depends on subject-wise evaluation, low inference latency, and calibrated uncertainty. We develop a subject-conditioned causal neural surrogate using OpenSim-derived static parameters, temporal joint kinematics, true muscle capacities, and training-only perturbations. On a real pediatric CP gait dataset comprising nine children, we use leave-one-subject-out validation on six development subjects and evaluate a frozen configuration once on three locked test subjects. The surrogate accurately reproduces musculotendon lengths (R-square = 0.92 in development validation and approximately 0.95 on locked subjects; nRMSE < 8%) while requiring only sub-millisecond to few-millisecond neural inference, well below a 100 ms interactive-rehabilitation target. In contrast, direct muscle-force estimation remains unstable at this small, heterogeneous scale: pooled metrics can overstate within-subject, per-muscle accuracy. A Monte Carlo credibility pilot further shows that propagating only +/-5% anthropometry and muscle-capacity variation produces severely overconfident nominal 90% intervals (approximately 4% force coverage and below 1% MT-length coverage). These results establish a leakage-free evaluation and credibility framework for pediatric MSK surrogates, while identifying force modeling and epistemic uncertainty as the central next challenges for clinically credible digital twins.
Multi-organ ultrasound classifiers increasingly combine attention, mixture-of-experts routing, uncertainty gating, and evidential deep learning (EDL) objectives to address heterogeneous anatomy and acquisition. Yet a plausible design rationale does not by itself establish that an added component improves the trained system. We contribute a controlled complexity-audit framework, applied to the deployment decision between the maximal evidential candidate Full-EDL and simpler alternatives. Six candidates were evaluated on the primary dataset and three in an internal replication, using ten matched seeds, frozen image-level partitions, capacity- and optimisation-aware comparisons, symmetric temperature scaling, paired decision rules, and a separate out-of-distribution (OOD) veto. Retaining Full-EDL did not establish a reliable macro-F1 gain on either dataset, while the simplified alternatives remained inconclusive under the non-inferiority margin. Simple cross-entropy with temperature scaling (Simple-CE+TS) met the calibrated negative log-likelihood criterion on both datasets and showed favourable selective-risk ordering. The raw calibration advantage of evidential training disappeared after temperature scaling and did not recur on the second dataset. The gate had negligible observable influence at the audited checkpoints, and deleting the Full-only chain revealed no stable task or calibrated-loss benefit. Simple-CE nevertheless triggered the OOD veto against the fetal probe but not the lung probe, precluding an unconditional OOD-safety claim. We therefore selected Simple-CE+TS for the evaluated in-distribution objective while retaining Full-EDL as the maximal reference. Components should earn retention through functional and retraining-based evidence, and calibration and distribution-shift reliability should be evaluated separately.
Qasim Siddiqui, Adrian Friebel, Maiju Myllys +4cs.CV
Liver fibrosis, the principal predictor of long-term outcome in chronic liver disease, is staged from histological estimates of collagen content. Sirius Red (SR) provides the standard quantitative readout (collagen proportionate area, CPA) but is not acquired at every clinical centre and consumes tissue, time, and reagent cost beyond the routine Hematoxylin and eosin (H&E) stain. AI-based virtual staining can generate SR directly from H&E, yet systematic benchmarks of unsupervised models are scarce and their predictive uncertainty has not been quantified, even though visually plausible outputs may not faithfully reproduce the underlying tissue structure. We therefore benchmark six unsupervised image-to-image architectures (GAN-based and diffusion-based) across 54 scaling configurations on a newly released paired H&E to SR mouse liver dataset, the first open resource for this translation task. Each configuration is evaluated jointly on perceptual, distributional, and task-specific axes plus a blinded expert reader study; the best per family is then retrained as a deep ensemble, the first systematic comparison of epistemic uncertainty across unsupervised stain-to-stain architectures. Across families, perceptual quality, task-specific error, and ensemble agreement measure largely independent axes of model fitness: GAN-based methods cluster tightly on perceptual metrics yet differ substantially on task error and ensemble agreement, while the diffusion-based method (CycleDiffusion) is qualitatively different on all three. No single metric captures these differences, so reliable virtual staining requires reporting and selecting on all three jointly. The dataset, tiling pipeline, models, and evaluation code are released publicly.
Manos Giannopoulos, Yi Shen, Michael M. Zavlanoscs.LG
In high-stakes healthcare applications, machine learning models are frequently trained on data from one patient population and deployed on another, creating a distribution shift that degrades both accuracy and reliability. Semi-Supervised Domain Adaptation (SSDA) addresses this by leveraging labeled data from some source domain to improve model performance on a target domain where labels are scarce. However, existing SSDA methods optimize primarily for point-prediction accuracy and offer no principled uncertainty quantification --- a prerequisite for clinical trust. Conformal Prediction (CP) can address this limitation by providing prediction sets with rigorous, distribution-free coverage guarantees. However, applying CP post-hoc to a pre-trained model can yield prohibitively large prediction sets, as SSDA pre-training methods do not account for the nonconformity score geometry that determines conformal set size. Conformal Risk Minimization (CRM) has been used to resolve this issue in the fully supervised setting by integrating the CP objective directly into model training, but it requires a large labeled dataset to compute nonconformity thresholds during training, precisely the data that is scarce in the SSDA regime. We propose an end-to-end framework that integrates CRM into the SSDA training objective, enabling effective CRM in the limited-labeled-target-data regime. The key idea is to utilize Optimal Transport (OT) to generate pseudolabels for unlabeled target instances, providing the additional training signal needed by CRM to operate using only a small labeled target set. This results in a model jointly optimized for domain invariance and conformal efficiency, producing prediction sets that are compact, coverage-valid, and support domain-specific constraints such as excluding mutually contradictory diagnoses in skin lesion classification.
Jacob Idoko, Siddhartha Paudel, Mariana Bento +2cs.AI
Artificial intelligence is increasingly being introduced into healthcare workflows, yet most evaluations emphasize model accuracy rather than whether adoption is economically worthwhile in real clinical settings. This study proposes FLARE, a systematic and uncertainty-aware framework for evaluating the financial and operational implications of adopting AI in healthcare. FLARE combines fuzzy logic, time-driven activity-based costing, and return on investment analysis to estimate the cost of clinical service delivery, the cost of AI development and operation, and the economic consequences of workflow integration under uncertainty. The framework was demonstrated through an early health technology assessment case study of AI-assisted large vessel occlusion detection in the CT stroke pathway for acute ischemic stroke. The case study shows how FLARE can quantify conventional pathway cost, AI-related development and recurring costs, and AI-enabled service savings within a unified activity-based model. Under expected assumptions, the analysis identified a break-even threshold of approximately 3,992 patients per year, with positive first-year return on investment at typical annual stroke volumes of about 5,000 patients. The results further show that economic benefit depends not only on algorithmic performance, but also on patient volume, verification time, infrastructure choices, and workflow design. FLARE provides a transparent and practical decision-support framework for early-stage evaluation of AI adoption in healthcare. By making uncertainty, resource use, and implementation trade-offs explicit, it helps clinicians, administrators, and policymakers determine when AI deployment is economically viable and where operational changes may improve value.
Hyeonsu Lee, Juyeon Kim, Erkhembayar Jadamba +2cs.LG
Drug discovery and development underpins healthcare but remains costly and failure-prone. A critical bottleneck lies in predicting molecular properties such as solubility, potency, and toxicity, which directly determine whether a candidate can advance from preclinical to clinical trials. Artificial Intelligence (AI) has accelerated this process, yet its reliability is often undermined by distribution shift, as experimental conditions frequently diverge from training data. In addition, conventional point predictions provide only single-value estimates, offering limited guidance for high-stakes experimental design. We address these challenges with a conformal prediction framework tailored to label shift. By weighting conformal scores using marginal label probability ratios, our method produces statistically rigorous prediction intervals without retraining. This enables robust uncertainty quantification even when property distributions drift, directly tackling one of the most pervasive obstacles to applying AI in real-world drug development. By moving beyond accuracy alone to provide actionable confidence measures, our approach enhances the trustworthiness of AI-driven predictions. This further aligns predictive modeling with regulatory demands for transparency and uncertainty reporting and ultimately supports more reliable decision-making in billion-dollar development pipelines.
Leon Koole, Jiapan Guo, Matias Valdenegro-Torocs.CV cs.LG
Skin lesion classifiers can be confidently wrong on the cases that matter most, so knowing when a prediction should not be trusted is clinically as useful as the prediction. We study uncertainty quantification on a dataset pooled from many ISIC sources, with a shared backbone and two jointly learned heads: a binary malignant versus non-malignant head and a five-class diagnostic head. Five UQ methods (MC Dropout, DropConnect, Flipout, Deep Ensembles, DUQ) are compared on accuracy, calibration, uncertainty decomposition, and risk-coverage. Difficulty is largely method-agnostic: even methods with narrow entropy distributions rank the same samples as hard (per-sample entropy correlations of $0.54$ to $0.91$). The choice of method matters more for calibration and uncertainty decomposition, where Deep Ensembles is the clear winner, than for finding difficult cases. The ranking is also good enough that deferring the most uncertain cases removes a disproportionate share of errors, supporting uncertainty-based selective referral, evaluated here in-distribution only.
Deep learning models have emerged as the standard computational tool for a wide range of applications in genomics. Yet, uncertainty quantification (UQ) -- and more specifically, the reliability of different uncertainty estimates in this domain -- has received little systematic attention. This work presents an empirical analysis of UQ in deep learning models, focusing on genomics applications. In a series of experiments, we contrast Deep Ensembles, Bayesian Neural Networks, and Monte Carlo-dropout methods. We assess their ability to quantify uncertainty in different scenarios, accounting for common dataset characteristics in two genomic application areas and modalities: sequence-to-activity models, and single-cell expression analysis. Our systematic comparison framework provides guidelines for the applicability and reliability of UQ methods in genomics, highlighting their strengths and limitations in different scenarios. We show that Bayesian Neural Networks are better at capturing uncertainty caused by strong class imbalance and out-of-distribution data in genomics, despite their computational disadvantages. Moreover, we show how uncertainty scores can be used to select high-quality predictions in protein-RNA interactions.
Reliable clinical deployment of machine learning requires models that know when they are likely to fail, particularly for subgroups underrepresented in training data. A common case is pediatric care, where models trained on adult cohorts can silently under-perform on children with no indication that something has gone wrong. As retraining with labeled pediatric data is often infeasible, detecting such failures at inference time is a critical clinical need. Building on the VIDS (Variational Inference under Distribution Shifts) framework, we introduce VIDS-Seg, which applies amortized variational inference over a lightweight prediction head to make this adaptive, OOD-aware prior tractable for dense image segmentation. We evaluate VIDS-Seg on left ventricular segmentation in echocardiography, a setting where pediatric anatomy differs systematically from the adult population most segmentation models are trained on, training on an adult cohort (EchoNet-Dynamic) and evaluating zero-shot on a pediatric cohort (EchoNet-Pediatric). Across all age strata, VIDS-Seg matches competitive baselines in segmentation accuracy while producing substantially higher spatial correspondence between predicted uncertainty and segmentation error, an advantage that persists even after applying temperature scaling to all baselines. Downstream, it yields more accurate and stable ejection fraction estimates and more reliable detection of cardiac malfunction in the infant subgroup. Our results indicate that OOD-aware uncertainty quantification can serve as a practical safety layer for deployed segmentation models, enabling detection of silent failures in underrepresented subgroups without retraining or additional labeled data.
Aneta Neumann, Ty Stanford, Dorothea Dumuid +1stat.ML cs.AI cs.LG cs.NE
The daily allocation of the finite 24-hour time budget is strongly associated with physical, mental, and cognitive health. While predictive models can estimate the relationship between time-use compositions and health outcomes such as body mass index, life satisfaction, and cognition, most optimization approaches focus only on maximizing expected benefit and do not consider the uncertainty inherent in data-driven prediction. Ignoring uncertainty in health-related decisions can lead to unrealistic time-use recommendations. To address this gap, we introduce an uncertainty quantification Quality Diversity (QD) framework for a more reliable time-use recommendation. Objective functions are derived using compositional data analysis using a large child cohort dataset n > 1000, to capture the relationship between daily activity compositions and multiple health indicators. We develop a new approach that incorporates predictive uncertainty into QD processes and produces more reliable recommendations that balance the expected health benefits with the confidence of the model. We explore the solution space through variable-based and objective-based behavioral representations, revealing diverse high-quality time-use composition and explicit relationships between health outcomes under uncertainty. By embedding uncertainty directly into optimization, our framework shifts the time-use recommendations toward regions of lower uncertainty while preserving high-quality structures for more reliable decision-making in behavioral health.
Emmanuel M. Rockwell, Michael R. Kosorok, Nikki L. B. Freemanstat.ME stat.ML
A central objective of precision medicine is learning optimal dynamic treatment regimes (DTRs) from data. Classification-based methods, like outcome weighted learning (OWL) for single-stage and backward OWL (BOWL) for multi-stage problems, leverage machine learning to directly learn optimal DTRs. However, these methods lack a natural way to quantify uncertainty in treatment decisions at the individual level. In this paper, we extend Bayesian OWL, a Bayesian reformulation of OWL, to the multi-stage setting. We call this method backward Bayesian outcome weighted learning (BBOWL). Like BOWL, our method directly learns an optimal DTR via backward induction, and unlike existing methods, our approach propagates uncertainty backward through the DTR learning process and provides uncertainty quantification of individualized treatment recommendations. We present a theoretical justification of BBOWL and verify its performance via a simulation study.
Medical vision-language models (VLMs) can retain high observed marginal coverage after clinical shift while substantially under-covering an individual disease class. The affected class varies with acquisition protocol and backbone geometry, so source prevalence does not reliably reveal the failure. Existing localized and tail-aware conformal methods respectively adapt to test neighborhoods and source-frequency tails, leaving held-out class-wise coverage failure unmodeled. We introduce Class-Tail Adaptive Localized Conformal Deferral (CALCoDe), a post-hoc reliability layer for frozen medical VLMs. Cross-fitted validation predictions identify classes at risk of undercoverage, and a disjoint calibration split estimates their class-conditional tail thresholds. CALCoDe combines each protected threshold with a localized conformal threshold using a one-sided maximum. The resulting set contains every label admitted by the localized rule, with additional protection confined to validation-identified classes. An independently calibrated support audit defers cases with insufficient inlier support. Under exchangeability among accepted examples within each protected class, CALCoDe provides finite-sample coverage at the prespecified guard level and contains the corresponding localized conformal sets; coverage on shifted external cohorts is evaluated empirically. Among standard conformal baselines and recent VLM-specific conformal methods evaluated across two dermatology shifts (HAM10000 to ISIC 2019 and HAM10000 to PAD-UFES-20) and four frozen VLM backbones (BiomedCLIP, OpenAI CLIP ViT-B/32, PubMedCLIP ViT-B/32, and MedSigLIP-448), CALCoDe is the only approach whose observed marginal and worst-class accepted coverage both reach 0.95 in all eight settings. On HAM10000 to ISIC 2019, its average worst-class accepted coverage is 0.970, compared with 0.926 for sTACP and 0.864 for LCP-VLM.
This Good Practice Guide presents work done in the QUMPHY project (Uncertainty quantification for machine learning models applied to photoplethysmography signals) that considered both machine learning and uncertainty quantification for problems which used photoplethysmography (PPG) signals from wearable devices as input. It provides high-level guidance on what types of machine learning model might be used and how different models compare when applied to both regression and classification tasks. It provides guidance on the implementation of different methods for uncertainty quantification, covering both model-dependent and model-independent techniques, and on the validation of the results provided by those methods. It also describes six benchmark problems together with pointers to different benchmark datasets for each problem. Software is described that can assist practitioners in implementing the methods described herein and there is a brief consideration of ethical issues. It concludes with a summary and recommendations.
Tom Hendriks, William Consagra, Anna Vilanova +2cs.CV
Diffusion Magnetic Resonance Imaging (dMRI) is a powerful tool for probing brain microstructure, but clinical acquisitions are often limited by low out-of-plane resolution, resulting in degraded structural information and reduced utility for advanced analysis. We introduce SIINR (Structurally Informed Implicit Neural Representations), a general framework for super-resoltion of clinical dMRI datasets while quantifying uncertainty in the reconstructed outputs. SIINR utilizes a supervised 3D U-net as a prior and combines it with a self-supervised implicit neural representation (INR) that fuses the high-resolution prior and the original low-resolution data. The INR enables joint modeling across spatial and angular domains, enforces data consistency, and provides analytic approximate posterior distributions for downstream uncertainty quantification. We validate the framework on a diverse set of open-access dMRI datasets, demonstrating that SIINR outperforms standard interpolation methods in both quantitative error metrics and qualitative anatomical fidelity. Experiments on clinical cases, including subjects with multiple sclerosis and brain lesions, illustrate the framework its ability to propagate intensity changes and flag uncertain regions in challenging scenarios. SIINR is flexible, modular, and can be adapted to different upsampling ratios and downstream tasks, providing a principled approach for enhancing clinical dMRI and supporting robust interpretation of derived neuroimaging metrics.
Accurate protein-ligand binding affinity prediction is central to computational drug discovery, yet modern docking engines frequently disagree without indicating which prediction to trust. Consensus scoring and ensemble methods improve mean accuracy but treat all predictions identically without interpretable confidence measures or uncertainty decomposition, ignoring the chemical context of each protein-ligand pair. To address this limitation, we introduce RELIABLE-BA (RELIABiLity-aware Evidential fusion for Binding Affinity), an evidential framework for multi-engine binding affinity prediction. Our model comprises three steps: (1) modeling each engine as an evidential expert via Normal-Inverse-Gamma distributions, (2) scaling epistemic uncertainty through learned reliability from molecular context while preserving each expert's predictive mean, and (3) fusing experts through closed-form aggregation that captures both individual uncertainty and inter-engine disagreement. Experiments on the PDBBind and BDB2020+ benchmarks demonstrate competitive point prediction with substantially improved uncertainty calibration, and additional validation on the SARS-CoV-2 Mpro dataset and 5HT2A receptor demonstrates applicability to clinically relevant drug targets. Crucially, these uncertainty estimates enable reliable filtering of protein-ligand pairs, reducing prediction error by up to 25% when retaining only high-confidence pairs. To our knowledge, RELIABLE-BA is the first multi-engine binding affinity prediction framework to combine evidential fusion with context-dependent reliability, offering a principled path toward trustworthy AI-guided drug discovery. Our code is publicly available at https://github.com/yongchand/RELIABLE-BA.
Christelle Schneuwly Diaz, Narmina Baghirova, Duy-Thanh Vu +4q-bio.NC cs.LG
Accurate diagnostic classification and disease-severity prediction for Alzheimer's disease are hampered by the incompleteness and heterogeneity of real-world clinical data. Left unaddressed, these barriers prevent reliable disease modelling and hinder effective clinical evaluation. Conventional imputation strategies introduce systematic bias, distort inter-feature relationships, and yield overconfident predictions, limitations especially consequential in diagnostic settings. Here, we propose NITROGEN, an imputation-free transformer that jointly models within-patient feature dependencies and between-patient relational structure through masked and intersample attention, enabling robust multimodal learning directly from partially observed records. We trained NITROGEN on ADNI (N=7858 scans), and evaluated it on two independent cohorts: OASIS-3 (N=2675 scans) and AIBL (N=1286 scans). Across cohorts and diagnostic and cognitive score prediction tasks, NITROGEN showed robust calibration and uncertainty quantification advantages over tree-based ensemble methods, while maintaining competitive discriminative performance. Cross-cohort and cross-method analyses identified cortical thickness in the temporal pole, age, and APOE genotype as important, though not individually sufficient, features for AD classification. We further introduced a modality-aware uncertainty adjustment that augments predictive uncertainty proportionally to the importance of absent modalities, enabling calibrated confidence when diagnostic information is unavailable. Together, our results show that imputation-free attention learning preserved meaningful discrimination under cohort shift, revealing expected degradation on more distributionally different cohorts, and demonstrate that evaluating models along calibration, interpretability, and cross-cohort reliability, not accuracy alone, is essential for clinical deployment.
Accurate dengue forecasting is crucial for public health planning, but remains challenging because incidence series are often short, noisy, non-stationary, nonlinear, and often affected by long-range temporal dependence. Fractional differencing in Autoregressive Fractionally Integrated Moving Average (ARFIMA) helps balance non-stationarity and persistence, but its linear structure limits its ability to capture nonlinear dynamics. Deep neural networks can model nonlinear patterns, but usually require large training samples and do not explicitly encode statistical long memory. Echo State Networks (ESNs), a widely used reservoir computing framework, are attractive in this setting because they retain nonlinear recurrent dynamics while training only a simple readout, making them suitable for data-scarce scenarios. However, standard ESNs lack long-term memory from a time-series perspective. This study proposes a long-memory reservoir computing framework that integrates dedicated long-memory and short-memory ESN reservoirs with a ridge-regression readout. We introduce two variants: Fractional ESN (fESN), which incorporates fractional-differencing dynamics into the reservoir to encode long-range dependence directly, and Wavelet ESN (wESN), which extracts stable low-frequency components through wavelet smoothing before modeling them with a memory-aware reservoir. We establish theoretical guarantees for closed-loop reservoir dynamics, showing that standard ESNs induce short-memory processes under mild conditions, whereas the proposed long-memory reservoirs generate polynomially decaying dependence consistent with statistical long memory. Across multiple dengue datasets and forecasting horizons, fESN and wESN outperform statistical and deep learning baselines. Combining conformal prediction with fESN and wESN provides distribution-free calibrated uncertainty intervals.
Matt Y. Cheung, Ashok Veeraraghavan, Guha Balakrishnaneess.IV cs.CV cs.LG physics.med-ph stat.AP
Radiomic features derived from medical images and segmentation masks are used to support decision making in clinical imaging pipelines. In practice, these features are often computed from predicted masks, but segmentation models can be overconfident or poorly calibrated, making derived measurements appear more reliable than they are. Conformal prediction (CP) provides distribution-free prediction intervals with finite-sample marginal coverage guarantees, but black-box intervals for segmentation-derived radiomics can be inefficient because they ignore test-time information about image appearance, mask geometry, and segmentation uncertainty. We propose ConRad, a conformal framework for scalar radiomic targets that uses covariates derived from the predicted mask, input image, predicted radiomics, and boundary uncertainty to construct adaptive intervals while maintaining coverage. Across five 2D medical imaging datasets and 171 retained radiomic targets, we show that ConRad improves feature-level efficiency compared to baselines while maintaining near-nominal empirical coverage. Ablation results further indicate that segmentation boundary uncertainty features are the largest contributors to interval efficiency.
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.
Yue Zhang, Nandini Amit Gadhia, Georgios Karagiannis +1q-bio.QM cs.LG
Classifying heterogeneous omics data remains a fundamental challenge in computational biology, particularly in high-dimensional, small-sample settings where nonlinear interactions dominate and class imbalance further complicates reliable prediction of minority phenotypes. While traditional kernel methods rely on feature abundance, they fail to leverage the known interaction landscapes of biological systems. In this work, we propose a structured Gaussian process classification framework that integrates graph-encoded biological pathways directly into the kernel construction. By propagating information along known interaction networks and combining this with abundance-derived features, the resulting classifier captures both quantitative measurements and topological context. We benchmark our proposed methodology on three publicly available gut and fecal microbiome datasets. To address severe class imbalance, we evaluate complementary strategies, including data-level resampling, threshold calibration, and confusion-matrix-based adjustments, and report minority-class performance alongside accuracy. The hybrid approach yields a performance gain over unstructured baselines and matches the performance of established benchmarks for similar datasets. Furthermore, the probabilistic nature of the framework naturally provides calibrated predictive uncertainty, enabling robust differentiation between confident predictions and ambiguous samples.
Outbreak transmission reconstruction treats epidemiological timing and transmission labels as deterministic ground truth; neither has been systematically evaluated. We trained a logistic regression temporal prior on eleven disease families, locked all parameters before accessing any target outbreak data, and applied it without refitting to a strict Andes virus (ANDV) parent-ranking benchmark of 29 tasks. The locked prior achieved mean reciprocal rank (MRR) 0.571 versus 0.274 and Top-1 accuracy 37.9% versus 13.8% against the best source-trained parametric baseline (permutation p <= 0.0002; 7-8 reversals to lose MRR significance). A phylogenetic concordance audit of 75 NYC mpox inter-host pairs - independent label-reliability evidence rather than a prior validation - found that 54.67% (exact 95% CI: 42.75-66.21%) were genomically unresolved or unsupported. Retaining uncertain edges in ANDV and Guangdong Delta graphs shifted top-5 source-priority sets (Jaccard 0.429-0.667). Transmission-label uncertainty was measurable in the outbreak evidence modules examined, and retaining uncertain links changed which source cases were prioritized for intervention.
Marta Colmenar Herrera, Pablo Márquez Neila, Şerife Seda Kucur Ergünay +2cs.CV cs.AI
Forecasting visual fields (VFs) is critical for personalized monitoring and treatment planning in glaucoma. This is inherently uncertain due to heterogeneous disease progression and measurement variability, yet most existing methods produce single deterministic predictions that fail to represent this uncertainty. We formulate VF forecasting as a probabilistic prediction problem and the use of conditioned denoising diffusion models to generate distributions of plausible future VFs from longitudinal observations with irregular follow-up intervals. Experiments on two independent VF cohorts show that diffusion-based predictions produce well-calibrated distributions for clinically relevant VF measures. When reduced to a standard point-estimate, the proposed approach achieves state-of-the-art accuracy compared to clinical baselines and prior learning-based methods. Our results highlight the advantages of distributional modeling for VF forecasting and support a shift from point-estimate prediction toward uncertainty-aware, clinically interpretable risk assessment in glaucoma.
Structured tabular data dominates clinical medicine, yet existing benchmarks fail to reflect real-world properties like complex survey sampling, demographic oversampling, and subgroup fairness. We introduce the NHANES Accelerometry Cardiometabolic Benchmark, derived from NHANES 2003-2006, comprising 1,381 adults with hip-worn accelerometry, fasting laboratory biomarkers, dietary intake, and anthropometrics. We evaluate three tabular learning methods -- ridge regression, XGBoost, and the foundation model TabPFN v2 -- to predict glycated haemoglobin (HbA1c), fasting triglycerides, and C-reactive protein (CRP) from activity phenotypes and lifestyle covariates. TabPFN v2 achieves the best overall performance (HbA1c R^2=0.156, CRP R^2=0.383), while triglycerides remain largely unpredictable (R^2 < 0.05), consistent with known genetic dominance. We apply split conformal prediction to generate distribution-free 90% prediction intervals and evaluate demographic coverage equity across sex and race/ethnicity subgroups. Marginal coverage aligns with the 90% target for CRP and HbA1c but falls below for triglycerides. At the subgroup level, we observe localized undercoverage (e.g., HbA1c for Mexican American participants), illustrating the gap between marginal guarantees and the conditional coverage required for clinical fairness. Code and data are at https://github.com/felizzi/nhanes-accel-cardiometabolic-benchmark.
Diffusion posterior samplers for accelerated MRI can reconstruct accurately yet still disagree on the acquired k-space across samples, placing posterior variability on coefficients the scanner has already measured. We identify this measured-subspace leakage as a physical-admissibility failure. Under a hard-constraint model it violates the measurement constraint and inflates the reported uncertainty with disagreement about coefficients the scanner has already determined. To quantify this leakage, we introduce complementary measured- and unmeasured-subspace k-space dispersion metrics (MSD/USD). We then present Measured-Subspace Consistency (MSC), a training-free terminal correction that wraps any compatible image-space posterior sampler with a standard multi-coil consistency lock. The ideal lock follows classical range/null-space data consistency. Our contribution is to repurpose it as a black-box posterior audit and correction rather than a new reconstructor or learned sampler. Theoretically, we prove that the ideal transform confines pairwise sample differences to the MRI null space and bound the residual cross-subspace coupling left by practical sensitivity-weighted implementations. Across six base samplers and two MRI anatomies, including out-of-distribution transfer where a knee prior reconstructs brain, MSC substantially reduces measured-subspace dispersion for Soft samplers (a median 16.5x reduction for DPS across five brain contrasts, up to ~29x), while preserving unmeasured-subspace diversity and acting as a near-identity map for Consistent ones. Furthermore, MSC maintains or modestly improves PSNR/SSIM, with no retraining, retuning, or significant computational overhead.
Eileanor LaRocco, Sarah Tan, Adarsh Subbaswamy +4cs.AI cs.HC
Autonomous AI systems are transitioning from advisory roles to autonomous ones for medication prescriptions. Recent U.S. bill H.R. 238 and Utah's prescription-renewal pilot program both authorize AI to prescribe medications in an agentic capacity. While many regulatory guidelines suggest aggregate model performance metrics at the point of clearance, they do not require i) calibrated per-prediction confidence for action-gated thresholds, ii) differentiated communication between uncertainty arising from model ignorance (epistemic) from genuine clinical ambiguity (aleatoric), and iii) inferential transparency at the moment of decision enabling liability allocation. Here, we argue these three architectural features are minimum conditions for safe autonomous prescribing, and validate them with a survey of 136 U.S. prescribing clinicians. Our results suggest prescribing clinicians i) would not permit autonomous prescribing without a confidence-based escalation mechanism, ii) preferred a competing-options summary for aleatoric uncertainty but preferred abstention for epistemic uncertainty, and iii) were only willing to accept liability when inferential transparency enabled them to make a decision under acknowledged uncertainty. These findings indicate that our recommended architectural features would encourage higher rates of clinician adoption of autonomous AI prescribing, largely through collapsing much of what "autonomy" conventionally means.
Tailoring stroke rehabilitation requires assessing how movements are organized, not merely if they succeed. Currently, this assessment is a rate-limiting bottleneck. Instruments like the Action Research Arm Test (ARAT) compress rich behavioral observations into single ordinal endpoints, discarding the movement-quality details that distinguish recovery from compensation. Automated alternatives typically chase accuracy on noisy, single-observer labels to output opaque scores - a technology-centric approach that rarely reaches clinical practice. To address this, we present xAARA: an engine designed to augment rather than replace clinical judgment. From multi-view video, xAARA returns ARAT assessments with calibrated uncertainty and explanations across task, movement-phase, and movement-quality levels. Treating clinical scoring as an ill-posed inference problem, xAARA composes 692 calibrated multimodal models via a Dynamic Bayesian Network with entropy-based gating. It qualifies results against clinical validity rules and defers low-confidence cases. In 105 stroke survivors (788 exercises), xAARA achieved 94.2% task accuracy (Cohen's kappa=0.934) and 81.3% movement-phase accuracy (kappa=0.727), reducing predictive uncertainty by 96.1% compared to single-clinician scoring. For subjective cases, it matched at least one rater 100% of the time and never returned out-of-range scores. Four independent clinicians validated the assessments and indicated willingness to adopt the system. We argue that principled uncertainty quantification and clinician-aligned explainability are the critical bridges moving automated assessment from technical demonstration to a deployable clinical tool.
Hana Jebril, Thomas Pinetz, Günter Klambauer +1cs.CV cs.LG
Reliable pixel-level uncertainty quantification holds the potential to transform clinical workflows by enabling high-fidelity longitudinal monitoring and distinguishing true pathological changes from artifacts. Ideally, these models provide the stability required for critical treatment planning and surgical intervention. However, standard deep learning models often suffer from miscalibration, yielding overconfident predictions that mask underlying vulnerabilities at subtle pathological boundaries. To address this, we propose QUAM-SM, a post-hoc framework using targeted adversarial search to identify "adversarially fragile" pixels. By actively seeking perturbations that expose predictive instability, our method highlights regions where decisions are most vulnerable to being flipped. Importantly, the framework disentangles epistemic uncertainty from aleatoric uncertainty. Experiments on two public datasets with multiple expert annotations demonstrate that QUAM-SM outperforms both standard and recent uncertainty estimation approaches in terms of reliability and boundary sensitivity. Code is available at https://github.com/HanaJebril/quam_sm
Recent advances in Large Language Models (LLMs) and multi-agent systems have driven the rise of Agentic AI, showing promise for medical reasoning. However, open-ended conversational agents remain prone to two critical failure modes: premature diagnostic handoff and silent clinical hallucinations that may go undetected before reaching the patient. In this work, we propose a multi-agent framework that addresses both issues by replacing ``LLM-as-a-judge'' routing with deterministic orchestration constraints. The framework incorporates two safety mechanisms. First, a neuro-symbolic state-tracking gate enforces completeness of the OLDCARTS clinical protocol (Onset, Location, Duration, Character, Aggravating/Alleviating factors, Radiation, Timing, and Severity) by blocking diagnostic transitions until all required dimensions are collected. Second, an epistemic uncertainty quantification (UQ) gate computes semantic entropy (H) across K=5 independent diagnostic samples to identify and intercept divergent outputs before delivery. We evaluate the system using simulated patient agents powered by the llama-3.1-70b-instruct model on 150 test cases. The full architecture achieves 49.3% diagnostic precision, representing an absolute improvement of 11.3 percentage points over an unconstrained baseline. Additionally, we observe a statistically significant negative correlation (r = -0.181, p < 0.05) between OLDCARTS completeness (σ) and semantic entropy (H), suggesting that structured information gathering is associated with reduced diagnostic uncertainty.
Ahmed Karam Eldaly, Matteo Figini, Daniel C. Alexandercs.CV stat.AP
We propose a novel Bayesian framework for joint image reconstruction and uncertainty quantification from compressed sensing magnetic resonance imaging data. The problem is formulated as a linear inverse problem, where prior distributions are assigned to the unknown image parameters. Specifically, the image is assumed to be sparse in a given transform domain. We develop a general framework applicable to any sparsifying transform and demonstrate its performance using (1) a total variation transform based on image spatial gradients and (2) a wavelet-domain transform. Bayesian inference is performed using a split-and-augmented Gibbs sampler, while the resulting non-differentiable conditional distributions are efficiently sampled using a proximal Markov chain Monte Carlo method. The proposed algorithms are validated on both single-coil and multi-coil datasets using various k-space sampling patterns and acceleration factors. The results demonstrate that the proposed Bayesian methods consistently outperform their optimisation-based counterparts in image reconstruction while providing uncertainty estimates for the reconstructed images. Furthermore, the estimated uncertainty maps show a strong correlation with the true reconstruction errors and substantially outperformed deep learning-based uncertainty estimation methods.