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Muxuan Liang

Publications and source records attributed to Muxuan Liang.

At least 19 recordsLinked to original sources
arXiv2026

ATHENA: Knowledge-guided agentic neural architecture search for AutoFormer-based electronic health record modeling

Transformer-based models are widely used for clinical prediction from electronic health records (EHRs), yet their architectures require manual tuning, and the optimal configuration may vary across tasks and hospitals. Neural architecture search (NAS) automates architecture design, but conventional methods are computationally costly for Transformer-based EHR models. Recent large language model (LLM)-guided NAS methods reduce manual search design but conduct each search independently, without reusing architecture knowledge across hospitals. In this study, we propose ATHENA (Agentic Transfer across Hospitals for EHR Neural Architecture Search), a knowledge-guided agentic NAS framework for Transformer-based EHR modeling. ATHENA uses a weight-sharing supernet that is pretrained once per hospital, allowing candidate architectures to be instantiated as inherited subnetworks and evaluated through fine-tuning rather than independent pretraining. It incorporates a two-layer cross-hospital architecture prior. The first layer retrieves high-performing architecture examples from source sites based on task descriptors, while the second estimates the effects of architectural components using SHapley Additive exPlanations (SHAP)-based meta-regression. These priors guide a multi-agent LLM search using validation feedback from the target hospital. Across six clinical prediction tasks evaluated at one held-out OneFlorida+ site and one external MIMIC-IV site, ATHENA significantly outperforms all four baselines in 9 of 12 site-task evaluations under a strict equal-compute comparison. Using a common pretrained AutoFormer supernet for candidate evaluation, ATHENA ranks first in 9 of 12 evaluations at a search budget of 30. It also shows more consistent architecture selection across repeated searches. ATHENA provides a practical approach for reducing manual architecture tuning in Transformer-based EHR modeling.

cs.AI↗
arXiv2026

An Interpretable Deep Learning Framework for Discovery and Clinical Validation of Deep Radiomic Signatures in Tumor Classification

Imaging signatures are quantitative features extracted from medical images that provide clinically meaningful information for tumor diagnosis, characterization, prognosis, and treatment planning. Although deep learning has shown great potential for imaging signature discovery, its limited interpretability remains a major barrier to clinical adoption. Existing approaches often achieve high predictive performance but provide little biological insight into the identified signatures. We propose a unified framework for interpretable imaging signature discovery by integrating deep learning based segmentation, explainable classification, and radiomic analysis. A robust segmentation model is first used to accurately delineate tumors, followed by a Grad-CAM guided pipeline that identifies diagnostically important regions as candidate imaging signatures. A mutual information based adaptive thresholding strategy enables patient-specific signature extraction. The resulting signatures are validated using a downstream deep learning classification model, while radiomic features extracted from the signature regions are evaluated with traditional machine learning models and interpreted using SHAP to identify the most discriminative biomarkers. The proposed framework is evaluated on the public BUSI breast ultrasound, KiTS renal CT, and BraTS brain tumor datasets, as well as a private UF Health renal CT cohort. Compared with conventional whole-tumor radiomics, the proposed signature-based approach achieves improved discriminative performance while providing greater biological interpretability. By converting deep learning attention into reproducible quantitative imaging biomarkers, this framework offers an interpretable and reproducible solution for non-invasive tumor characterization and imaging biomarker discovery.

eess.IV↗
arXiv2026

CASCADE Conformal Prediction: Uncertainty-Adaptive Prediction Intervals for Two-Stage Clinical Decision Support

Effective medication management in Parkinson's Disease (PD) is challenging due to heterogeneous disease progression, variable patient response, and medication side effects. While AI models can forecast levodopa equivalent daily dose (LEDD) as a measure of medication needs, standard uncertainty quantification often fails to communicate the reliability of these predictions, treating high and low confidence clinical decisions identically. We introduce CASCADE (Calibrated Adaptive Scaling via Conformal And Distributional Estimation), a novel conformal prediction framework that propagates epistemic uncertainty from a screening classifier to adapt downstream predictions. Unlike standard conformal methods that rely on auxiliary residual regression, we leverage epistemic uncertainty from a primary classification task (identifying whether a medication change is needed) to dynamically scale the prediction intervals of a secondary regression task (predicting how much change). By mapping Venn-Abers multi-probabilistic uncertainty directly to non-conformity scores, our framework achieves continuous risk adaptation. We demonstrate that this ``cascade effect'' produces highly efficient intervals for confident patients (38.9% narrower than standard conformal baselines) while automatically expanding intervals to ensure robust coverage for uncertain cases, bridging the gap between discrete clinical decision-making and continuous dose forecasting in PD.

cs.LG↗
arXiv2026

A Unified Framework for Structure-Aware Clustering and Heterogeneous Causal Graph Learning

In complex multivariate systems, interactions among variables are defined by dependency structures, often encoded as directed acyclic graphs ($\text{DAGs}$). However, dependency structures can vary across subjects, and ignoring this structural heterogeneity introduces bias and obscures subpopulation-specific dependencies. To address this, we propose Directed Acyclic Graph-based Dependency Clustering via Alternating Direction Method of Multipliers (DAG-DC-ADMM), a unified framework built upon Structural Equation Modeling (SEM) that jointly learns cluster assignments and cluster-specific dependency structures. We encode acyclicity via a smooth constraint and integrate a groupwise truncated Lasso fusion penalty (gTLP) to cluster subjects based on their structural similarity. This yields a nonconvex optimization problem that incorporates sparsity, acyclicity, and structural consensus constraints. We address the nonconvexity by using the augmented Lagrangian method and solve it with an adapted version of the Alternating Direction Method of Multipliers (ADMM) for difference-of-convex programs. For certain graph structures, such as upper triangular adjacency matrices, our algorithm is guaranteed to converge to a Karush-Kuhn-Tucker (KKT) point. Experiments demonstrate that our method recovers cluster-specific causal dependency structures with a high true positive rate and a low false discovery rate. This capability enables the robust discovery of heterogeneous dependencies across subjects where the subpopulation label is unknown.

stat.ML↗
arXiv2026

Inference with non-differentiable surrogate loss in a general high-dimensional classification framework

Penalized empirical risk minimization with a surrogate loss function is often used to learn a high-dimensional linear decision rule in classification problems. Although much of the literature focus on the generalization error, there is a lack of inference procedures for identifying the driving factors of the estimated decision rule, especially when the surrogate loss is non-differentiable. We propose a kernel-smoothed decorrelated score to construct hypothesis tests and interval estimators for a linear decision rule estimated using a piece-wise linear surrogate loss, which has a discontinuous gradient and non-regular Hessian. Specifically, we adopt kernel approximations to smooth the discontinuous gradient near discontinuity points and approximate the non-regular Hessian of the surrogate loss. In applications where additional nuisance parameters are involved, we propose a novel cross-fitted version to accommodate flexible nuisance estimates and kernel approximations. We establish the limiting distribution of the kernel-smoothed decorrelated score and its cross-fitted version in a high-dimensional setup. Simulation and real data analysis are conducted to demonstrate the validity and the superiority of the proposed method.

stat.ME↗
arXiv2026

Classification-Powered Conformal Inference for Zero-inflated Outcomes

Zero-inflated outcomes, where responses are zero with positive probability and otherwise continuous, are common in biomedical, environmental, and social science studies. We propose a conformal prediction based framework that provides distribution-free uncertainty quantification tailored to such outcomes. Standard conformal methods often ignore strong predictors distinguishing zero from non-zero outcomes, leading to overly conservative and unnecessarily long prediction sets. Our method integrates a classification step to identify zero outcomes and applies conformal inference to the non-zero part, producing prediction sets that are either ${0}$ or an interval. Under exchangeability, we establish that the proposed procedure attains the target marginal coverage and achieves asymptotically minimal interval length within this framework, regardless of the choice of classification or regression models. Extensive simulations and real-data application demonstrate the superior performance of our approach.

stat.ME↗
arXiv2026

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

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

cs.LG↗
arXiv2026

Two-sample Testing with Block-wise Missingness in Multi-source Data

Multi-source and multi-modal datasets are increasingly common in scientific research, yet they often exhibit block-wise missingness, where entire modalities are systematically absent in some sources or no single source contains all modalities. This structured missingness poses major challenges for two-sample hypothesis testing. Standard approaches, such as imputation or complete-case analysis, may introduce bias or suffer efficiency loss, especially under missingness-not-at-random mechanisms. To address this challenge, we propose the Block-Pattern Enhanced Test, a general framework for constructing two-sample testing statistics that explicitly accounts for block-wise missingness. We show that the framework yields valid tests under a new condition allowing for missing-not-at-random mechanism. Building on this general framework, we further propose the Block-wise Rank In Similarity graph Edge-count (BRISE) test, which accommodate heterogeneous modalities using rank-based similarity graphs. Theoretically, we establish that the null distribution of BRISE converges to a $χ^2$ distribution, and that the test is consistent both in the standard asymptotic regime and in the high-dimensional low-sample-size setting under mild conditions. Simulation studies demonstrate that BRISE controls the type-I error rate and achieves strong power across a wide range of alternatives. Applications to two real-world datasets with block-wise missingness further illustrate the practical utility of the proposed method.

stat.ME↗
arXiv2025

Fast-DDPM: Fast Denoising Diffusion Probabilistic Models for Medical Image-to-Image Generation

Denoising diffusion probabilistic models (DDPMs) have achieved unprecedented success in computer vision. However, they remain underutilized in medical imaging, a field crucial for disease diagnosis and treatment planning. This is primarily due to the high computational cost associated with (1) the use of large number of time steps (e.g., 1,000) in diffusion processes and (2) the increased dimensionality of medical images, which are often 3D or 4D. Training a diffusion model on medical images typically takes days to weeks, while sampling each image volume takes minutes to hours. To address this challenge, we introduce Fast-DDPM, a simple yet effective approach capable of improving training speed, sampling speed, and generation quality simultaneously. Unlike DDPM, which trains the image denoiser across 1,000 time steps, Fast-DDPM trains and samples using only 10 time steps. The key to our method lies in aligning the training and sampling procedures to optimize time-step utilization. Specifically, we introduced two efficient noise schedulers with 10 time steps: one with uniform time step sampling and another with non-uniform sampling. We evaluated Fast-DDPM across three medical image-to-image generation tasks: multi-image super-resolution, image denoising, and image-to-image translation. Fast-DDPM outperformed DDPM and current state-of-the-art methods based on convolutional networks and generative adversarial networks in all tasks. Additionally, Fast-DDPM reduced the training time to 0.2x and the sampling time to 0.01x compared to DDPM. Our code is publicly available at: https://github.com/mirthAI/Fast-DDPM.

eess.IV↗
arXiv2025

Uncertainty-Aware Prediction of Parkinson's Disease Medication Needs: A Two-Stage Conformal Prediction Approach

Parkinson's Disease (PD) medication management presents unique challenges due to heterogeneous disease progression and treatment response. Neurologists must balance symptom control with optimal dopaminergic dosing based on functional disability while minimizing side effects. This balance is crucial as inadequate or abrupt changes can cause levodopa-induced dyskinesia, wearing off, and neuropsychiatric effects, significantly reducing quality of life. Current approaches rely on trial-and-error decisions without systematic predictive methods. Despite machine learning advances, clinical adoption remains limited due to reliance on point predictions that do not account for prediction uncertainty, undermining clinical trust and utility. Clinicians require not only predictions of future medication needs but also reliable confidence measures. Without quantified uncertainty, adjustments risk premature escalation to maximum doses or prolonged inadequate symptom control. We developed a conformal prediction framework anticipating medication needs up to two years in advance with reliable prediction intervals and statistical guarantees. Our approach addresses zero-inflation in PD inpatient data, where patients maintain stable medication regimens between visits. Using electronic health records from 631 inpatient admissions at University of Florida Health (2011-2021), our two-stage approach identifies patients likely to need medication changes, then predicts required levodopa equivalent daily dose adjustments. Our framework achieved marginal coverage while reducing prediction interval lengths compared to traditional approaches, providing precise predictions for short-term planning and wider ranges for long-term forecasting. By quantifying uncertainty, our approach enables evidence-based decisions about levodopa dosing, optimizing symptom control while minimizing side effects and improving life quality.

cs.LG↗
arXiv2025

Late Fusion Multi-task Learning for Semiparametric Inference with Nuisance Parameters

In the age of large and heterogeneous datasets, the integration of information from diverse sources is essential to improve parameter estimation. Multi-task learning offers a powerful approach by enabling simultaneous learning across related tasks. In this work, we introduce a late fusion framework for multi-task learning with semiparametric models that involve infinite-dimensional nuisance parameters, focusing on applications such as heterogeneous treatment effect estimation across multiple data sources, including electronic health records from different hospitals or clinical trial data. Our framework is two-step: first, initial double machine-learning estimators are obtained through individual task learning; second, these estimators are adaptively aggregated to exploit task similarities while remaining robust to task-specific differences. In particular, the framework avoids individual level data sharing, preserving privacy. Additionally, we propose a novel multi-task learning method for nuisance parameter estimation, which further enhances parameter estimation when nuisance parameters exhibit similarity across tasks. We establish theoretical guarantees for the method, demonstrating faster convergence rates compared to individual task learning when tasks share similar parametric components. Extensive simulations and real data applications complement the theoretical findings of our work while highlight the effectiveness of our framework even in moderate sample sizes.

stat.ME↗
arXiv2025

DeepJ: Graph Convolutional Transformers with Differentiable Pooling for Patient Trajectory Modeling

In recent years, graph learning has gained significant interest for modeling complex interactions among medical events in structured Electronic Health Record (EHR) data. However, existing graph-based approaches often work in a static manner, either restricting interactions within individual encounters or collapsing all historical encounters into a single snapshot. As a result, when it is necessary to identify meaningful groups of medical events spanning longitudinal encounters, existing methods are inadequate in modeling interactions cross encounters while accounting for temporal dependencies. To address this limitation, we introduce Deep Patient Journey (DeepJ), a novel graph convolutional transformer model with differentiable graph pooling to effectively capture intra-encounter and inter-encounter medical event interactions. DeepJ can identify groups of temporally and functionally related medical events, offering valuable insights into key event clusters pertinent to patient outcome prediction. DeepJ significantly outperformed five state-of-the-art baseline models while enhancing interpretability, demonstrating its potential for improved patient risk stratification.

cs.LG↗
arXiv2025

Towards the Efficient Inference by Incorporating Automated Computational Phenotypes under Covariate Shift

Collecting gold-standard phenotype data via manual extraction is typically labor-intensive and slow, whereas automated computational phenotypes (ACPs) offer a systematic and much faster alternative. However, simply replacing the gold-standard with ACPs, without acknowledging their differences, could lead to biased results and misleading conclusions. Motivated by the complexity of incorporating ACPs while maintaining the validity of downstream analyses, in this paper, we consider a semi-supervised learning setting that consists of both labeled data (with gold-standard) and unlabeled data (without gold-standard), under the covariate shift framework. We develop doubly robust and semiparametrically efficient estimators that leverage ACPs for general target parameters in the unlabeled and combined populations. In addition, we carefully analyze the efficiency gains achieved by incorporating ACPs, comparing scenarios with and without their inclusion. Notably, we identify that ACPs for the unlabeled data, instead of for the labeled data, drive the enhanced efficiency gains. To validate our theoretical findings, we conduct comprehensive synthetic experiments and apply our method to multiple real-world datasets, confirming the practical advantages of our approach. \hfill{\texttt{Code}: \href{https://github.com/brucejunjin/ICML2025-ACPCS}{\faGithub}}

stat.ME↗
arXiv2025

Penalized Linear Models for Highly Correlated High-Dimensional Immunophenotyping Data

Accurate prediction and identification of variables associated with outcomes or disease states are critical for advancing diagnosis, prognosis, and precision medicine in biomedical research. Regularized regression techniques, such as lasso, are widely employed to enhance interpretability by reducing model complexity and identifying significant variables. However, when applying to biomedical datasets, e.g., immunophenotyping dataset, there are two major challenges that may lead to unsatisfactory results using these methods: 1) high correlation between predictors, which leads to the exclusion of important variables with included predictors in variable selection, and 2) the presence of skewness, which violates key statistical assumptions of these methods. Current approaches that fail to address these issues simultaneously may lead to biased interpretations and unreliable coefficient estimates. To overcome these limitations, we propose a novel two-step approach, the Bootstrap-Enhanced Regularization Method (BERM). BERM outperforms existing two-step approaches and demonstrates consistent performance in terms of variable selection and estimation accuracy across simulated sparsity scenarios. We further demonstrate the effectiveness of BERM by applying it to a human immunophenotyping dataset identifying important immune parameters associated the autoimmune disease, type 1 diabetes.

stat.AP↗
arXiv2025

Multi-Class Segmentation of Aortic Branches and Zones in Computed Tomography Angiography: The AortaSeg24 Challenge

Multi-class segmentation of the aorta in computed tomography angiography (CTA) scans is essential for diagnosing and planning complex endovascular treatments for patients with aortic dissections. However, existing methods reduce aortic segmentation to a binary problem, limiting their ability to measure diameters across different branches and zones. Furthermore, no open-source dataset is currently available to support the development of multi-class aortic segmentation methods. To address this gap, we organized the AortaSeg24 MICCAI Challenge, introducing the first dataset of 100 CTA volumes annotated for 23 clinically relevant aortic branches and zones. This dataset was designed to facilitate both model development and validation. The challenge attracted 121 teams worldwide, with participants leveraging state-of-the-art frameworks such as nnU-Net and exploring novel techniques, including cascaded models, data augmentation strategies, and custom loss functions. We evaluated the submitted algorithms using the Dice Similarity Coefficient (DSC) and Normalized Surface Distance (NSD), highlighting the approaches adopted by the top five performing teams. This paper presents the challenge design, dataset details, evaluation metrics, and an in-depth analysis of the top-performing algorithms. The annotated dataset, evaluation code, and implementations of the leading methods are publicly available to support further research. All resources can be accessed at https://aortaseg24.grand-challenge.org.

eess.IV↗
arXiv2024

Estimating optimal tailored active surveillance strategy under interval censoring

Active surveillance (AS) using repeated biopsies to monitor disease progression has been a popular alternative to immediate surgical intervention in cancer care. However, a biopsy procedure is invasive and sometimes leads to severe side effects of infection and bleeding. To reduce the burden of repeated surveillance biopsies, biomarker-assistant decision rules are sought to replace the fix-for-all regimen with tailored biopsy intensity for individual patients. Constructing or evaluating such decision rules is challenging. The key AS outcome is often ascertained subject to interval censoring. Furthermore, patients will discontinue their participation in the AS study once they receive a positive surveillance biopsy. Thus, patient dropout is affected by the outcomes of these biopsies. In this work, we propose a nonparametric kernel-based method to estimate the true positive rates (TPRs) and true negative rates (TNRs) of a tailored AS strategy, accounting for interval censoring and immediate dropouts. Based on these estimates, we develop a weighted classification framework to estimate the optimal tailored AS strategy and further incorporate the cost-benefit ratio for cost-effectiveness in medical decision-making. Theoretically, we provide a uniform generalization error bound of the derived AS strategy accommodating all possible trade-offs between TPRs and TNRs. Simulation and application to a prostate cancer surveillance study show the superiority of the proposed method.

stat.ME↗
arXiv2024

MicroSegNet: A Deep Learning Approach for Prostate Segmentation on Micro-Ultrasound Images

Micro-ultrasound (micro-US) is a novel 29-MHz ultrasound technique that provides 3-4 times higher resolution than traditional ultrasound, potentially enabling low-cost, accurate diagnosis of prostate cancer. Accurate prostate segmentation is crucial for prostate volume measurement, cancer diagnosis, prostate biopsy, and treatment planning. However, prostate segmentation on micro-US is challenging due to artifacts and indistinct borders between the prostate, bladder, and urethra in the midline. This paper presents MicroSegNet, a multi-scale annotation-guided transformer UNet model designed specifically to tackle these challenges. During the training process, MicroSegNet focuses more on regions that are hard to segment (hard regions), characterized by discrepancies between expert and non-expert annotations. We achieve this by proposing an annotation-guided binary cross entropy (AG-BCE) loss that assigns a larger weight to prediction errors in hard regions and a lower weight to prediction errors in easy regions. The AG-BCE loss was seamlessly integrated into the training process through the utilization of multi-scale deep supervision, enabling MicroSegNet to capture global contextual dependencies and local information at various scales. We trained our model using micro-US images from 55 patients, followed by evaluation on 20 patients. Our MicroSegNet model achieved a Dice coefficient of 0.939 and a Hausdorff distance of 2.02 mm, outperforming several state-of-the-art segmentation methods, as well as three human annotators with different experience levels. Our code is publicly available at https://github.com/mirthAI/MicroSegNet and our dataset is publicly available at https://zenodo.org/records/10475293.

cs.CV↗
arXiv2023

Image Registration of In Vivo Micro-Ultrasound and Ex Vivo Pseudo-Whole Mount Histopathology Images of the Prostate: A Proof-of-Concept Study

Early diagnosis of prostate cancer significantly improves a patient's 5-year survival rate. Biopsy of small prostate cancers is improved with image-guided biopsy. MRI-ultrasound fusion-guided biopsy is sensitive to smaller tumors but is underutilized due to the high cost of MRI and fusion equipment. Micro-ultrasound (micro-US), a novel high-resolution ultrasound technology, provides a cost-effective alternative to MRI while delivering comparable diagnostic accuracy. However, the interpretation of micro-US is challenging due to subtle gray scale changes indicating cancer vs normal tissue. This challenge can be addressed by training urologists with a large dataset of micro-US images containing the ground truth cancer outlines. Such a dataset can be mapped from surgical specimens (histopathology) onto micro-US images via image registration. In this paper, we present a semi-automated pipeline for registering in vivo micro-US images with ex vivo whole-mount histopathology images. Our pipeline begins with the reconstruction of pseudo-whole-mount histopathology images and a 3-dimensional (3D) micro-US volume. Each pseudo-whole-mount histopathology image is then registered with the corresponding axial micro-US slice using a two-stage approach that estimates an affine transformation followed by a deformable transformation. We evaluated our registration pipeline using micro-US and histopathology images from 18 patients who underwent radical prostatectomy. The results showed a Dice coefficient of 0.94 and a landmark error of 2.7 mm, indicating the accuracy of our registration pipeline. This proof-of-concept study demonstrates the feasibility of accurately aligning micro-US and histopathology images. To promote transparency and collaboration in research, we will make our code and dataset publicly available.

cs.CV↗