arXiv subjects

Shuangge Ma

Publications and source records attributed to Shuangge Ma.

At least 19 recordsLinked to original sources

arXiv2026

Deep Multitask Learning for Mixed-Type Outcomes with Shared Sparsity

Most existing multitask learning approaches are limited by their reliance on task-specific loss functions tailored to the scale and type of each outcome. When outcomes differ across tasks, these losses are generally not directly comparable, which makes it difficult to formulate a unified objective and may limit information sharing across tasks. We propose a multitask transformation framework in which task-specific responses may differ through unknown monotone transformations. Motivated by high-dimensional biological applications in which the predictor dimension may diverge with the sample size while only a common subset of predictors is informative, we consider shared sparsity across tasks. Under this framework, we estimate the target functions and identify important predictors by optimizing a smoothed rank-based criterion with a group-Lasso penalty, implemented through a multitask deep neural network with a shared first layer. We establish the nonasymptotic excess-risk bounds, and variable-selection consistency for the proposed estimator. Simulation studies show that the proposed method achieves competitive prediction and variable-selection performance compared with competing approaches. Analyses of gene-expression studies with continuous, binary, and mixed outcomes further illustrate that the proposed method improves prediction and identifies biologically meaningful shared predictors.

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arXiv2026

AI-Assisted Causal Inference and Mediation Analyses of Environmental and Psychosocial Determinants of Subjective Cognitive Difficulties in the All of Us Research Program

Short-term environmental exposures have been linked to cognitive and behavioral outcomes, although many reported associations may reflect broader geographic and contextual differences. Using longitudinal data from the All of Us Research Program (2018--2024), we linked daily weather and air-pollution exposures to repeated attention-related and subjective cognitive outcomes. Associations were evaluated using pooled, fixed-effects, lagged, and event-study analyses. Additional machine-learning analyses were conducted to explore potential heterogeneity and latent psychosocial structure. Replication analyses were performed using the 2024 Behavioral Risk Factor Surveillance System (BRFSS). Several environmental exposure measures showed small associations with cognitive outcomes in pooled analyses, but most attenuated substantially after accounting for within-location temporal variation. Mediation, sensitivity, and machine-learning analyses yielded similar conclusions. In contrast, mental-health burden, loneliness, and social functioning were consistently associated with subjective cognitive difficulty and exhibited substantially larger effect sizes than environmental exposures. Similar patterns were observed in BRFSS. Exploratory AI-assisted analyses yielded findings broadly consistent with the primary longitudinal analyses. These findings suggest that short-term environmental perturbations may have limited associations with cognitive outcomes after accounting for within-location variation, whereas psychosocial factors appear to be more consistently associated with subjective cognitive burden.

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arXiv2026

AI-driven Multimodal Representation Learning for Latent Mediation Structure Discovery of Socioeconomic Disadvantage, Psychosocial Factors, and Cardiometabolic Multimorbidity: Insights from the All of Us Research Program

Social disadvantage is associated with multimorbidity, but the pathways linking social conditions to disease burden remain poorly understood. We developed an AI-driven multimodal mediation framework that integrates socioeconomic, psychosocial, clinical, laboratory, behavioral, and genomic data from the All of Us Research Program. Modality-specific variational autoencoders were used to derive latent representations of each data domain, and mediation analyses were subsequently performed in latent space to evaluate indirect associations between socioeconomic disadvantage, psychosocial factors, and multimorbidity. The final analytic cohort included 20,804 participants with complete multimodal data. Across 800 exposure--mediator--outcome combinations, mediation signals were concentrated within a small number of latent dimensions. The strongest indirect association linked a socioeconomic disadvantage dimension, a psychosocial vulnerability dimension, and a cardiometabolic multimorbidity dimension (NIE = 0.002517). The psychosocial dimension was characterized by poorer mental health, greater loneliness, lower social well-being, and lower health literacy, whereas the outcome dimension was associated with hypertension, diabetes, hyperlipidemia, obesity, chronic kidney disease, and heart disease. Bootstrap analyses supported the stability of the leading pathway. These findings suggest that psychosocial vulnerability was strongly represented in the dominant latent pathway linking socioeconomic disadvantage and cardiometabolic multimorbidity. More broadly, the proposed framework illustrates how AI-based representation learning can be used to investigate complex relationships across high-dimensional multimodal health data.

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arXiv2026

Adaptive Multi-Prior Lasso for High-Dimensional Generalized Linear Models

Incorporation of external information into high-dimensional modeling for gene expression data has been shown, both theoretically and empirically, to substantially enhance performance. Such external information, sometimes referred to as prior information or priors, has become increasingly accessible from multiple sources, yet its reliability may vary considerably. Existing approaches often integrate these priors without sufficiently accounting for their quality, which may result in unsatisfactory or even misleading results. To effectively and selectively exploit such priors, we propose adaptive Multi-Prior Lasso, a novel regularization approach that simultaneously identifies reliable prior sources and integrates them to improve model performance. For high-dimensional generalized linear models (GLMs), an adaptive data-driven weight is assigned to each prior, so that more reliable sources are emphasized while less credible ones are downweighted. Theoretical guarantees are established, and the proposed method is shown through extensive simulations to improve estimation, prediction, and variable selection. An application to TCGA breast cancer gene expression data further illustrates the practical value of the proposed method, showing that incorporating prior information from PubMed published studies improves model performance.

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arXiv2026

Sparse Bayesian Deep Functional Learning with Structured Region Selection

In modern applications such as ECG monitoring, neuroimaging, wearable sensing, and industrial equipment diagnostics, complex and continuously structured data are ubiquitous, presenting both challenges and opportunities for functional data analysis. However, existing methods face a critical trade-off: conventional functional models are limited by linearity, whereas deep learning approaches lack interpretable region selection for sparse effects. To bridge these gaps, we propose a sparse Bayesian functional deep neural network (sBayFDNN). It learns adaptive functional embeddings through a deep Bayesian architecture to capture complex nonlinear relationships, while a structured prior enables interpretable, region-wise selection of influential domains with quantified uncertainty. Theoretically, we establish rigorous approximation error bounds, posterior consistency, and region selection consistency. These results provide the first theoretical guarantees for a Bayesian deep functional model, ensuring its reliability and statistical rigor. Empirically, comprehensive simulations and real-world studies confirm the effectiveness and superiority of sBayFDNN. Crucially, sBayFDNN excels in recognizing intricate dependencies for accurate predictions and more precisely identifies functionally meaningful regions, capabilities fundamentally beyond existing approaches.

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arXiv2026

Doubly robust estimators of the restricted mean time in favor estimands in individual- and cluster-randomized trials

Progressive multi-state survival outcomes are common in trials with recurrent or sequential events and require treatment effect estimands that remain interpretable without proportional intensity or Markov assumptions. The restricted mean time in favor of treatment (RMT-IF) extends the restricted mean survival time to ordered multi-state processes and provides such an interpretable estimand. However, existing RMT-IF methods are nonparametric, assume covariate-independent censoring for independent observations, and do not accommodate cluster-randomized trials (CRTs), limiting both efficiency and applicability. We develop a class of doubly robust estimators for RMT-IF under right censoring using an augmented inverse-probability weighting framework that combines stage-specific outcome regression with arm-specific censoring models, yielding consistency when either nuisance model is correctly specified. We further extend the framework to CRTs by formalizing both cluster-level and individual-level average RMT-IF estimands to address informative cluster size and by constructing corresponding doubly robust estimators that account for within-cluster correlation. For inference, we employ model-agnostic jackknife variance estimators in both individually randomized and cluster-randomized settings. Extensive simulation studies demonstrate finite-sample performance, and the methods are illustrated using two randomized trial examples.

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arXiv2025

Joint identification of spatially variable genes via a network-assisted Bayesian regularization approach

Identifying genes that display spatial patterns is critical to investigating expression interactions within a spatial context and further dissecting biological understanding of complex mechanistic functionality. Despite the increase in statistical methods designed to identify spatially variable genes, they are mostly based on marginal analysis and share the limitation that the dependence (network) structures among genes are not well accommodated, where a biological process usually involves changes in multiple genes that interact in a complex network. Moreover, the latent cellular composition within spots may introduce confounding variations, negatively affecting identification accuracy. In this study, we develop a novel Bayesian regularization approach for spatial transcriptomic data, with the confounding variations induced by varying cellular distributions effectively corrected. Significantly advancing from the existing studies, a thresholded graph Laplacian regularization is proposed to simultaneously identify spatially variable genes and accommodate the network structure among genes. The proposed method is based on a zero-inflated negative binomial distribution, effectively accommodating the count nature, zero inflation, and overdispersion of spatial transcriptomic data. Extensive simulations and the application to real data demonstrate the competitive performance of the proposed method.

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arXiv2025

Federated Online Learning for Heterogeneous Multisource Streaming Data

Federated learning has emerged as an essential paradigm for distributed multi-source data analysis under privacy concerns. Most existing federated learning methods focus on the ``static" datasets. However, in many real-world applications, data arrive continuously over time, forming streaming datasets. This introduces additional challenges for data storage and algorithm design, particularly under high-dimensional settings. In this paper, we propose a federated online learning (FOL) method for distributed multi-source streaming data analysis. To account for heterogeneity, a personalized model is constructed for each data source, and a novel ``subgroup" assumption is employed to capture potential similarities, thereby enhancing model performance. We adopt the penalized renewable estimation method and the efficient proximal gradient descent for model training. The proposed method aligns with both federated and online learning frameworks: raw data are not exchanged among sources, ensuring data privacy, and only summary statistics of previous data batches are required for model updates, significantly reducing storage demands. Theoretically, we establish the consistency properties for model estimation, variable selection, and subgroup structure recovery, demonstrating optimal statistical efficiency. Simulations illustrate the effectiveness of the proposed method. Furthermore, when applied to the financial lending data and the web log data, the proposed method also exhibits advantageous prediction performance. Results of the analysis also provide some practical insights.

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arXiv2025

ContinualFlow: Learning and Unlearning with Neural Flow Matching

We introduce ContinualFlow, a principled framework for targeted unlearning in generative models via Flow Matching. Our method leverages an energy-based reweighting loss to softly subtract undesired regions of the data distribution without retraining from scratch or requiring direct access to the samples to be unlearned. Instead, it relies on energy-based proxies to guide the unlearning process. We prove that this induces gradients equivalent to Flow Matching toward a soft mass-subtracted target, and validate the framework through experiments on 2D and image domains, supported by interpretable visualizations and quantitative evaluations.

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arXiv2025

A flexible Bayesian framework for detecting cross-sample spatial expression variability in heterogeneous tissues

Spatial transcriptomics measures gene expression alongside the spatial coordinates of each capture spot or cell across tissue samples. The detection of spatially variable (SV) genes, whose expression exhibits systematic spatial variation, enables the delineation of functional tissue domains and the identification of region-specific transcriptional changes that underlie disease heterogeneity. However, empirical evidence from spatial transcriptomics data indicates that existing methods are hindered by two practical issues: reliance on predefined spatial patterns that often miss tissue complexity, and a lack of standardized approaches for multi-sample integration, which undermines reproducibility and biological interpretability. To address these issues, we propose a novel integrated Bayesian hierarchical model that combines flexible nonparametric spatial modeling with information sharing across samples. The model uses an adaptive spatial process that can capture a wide range of spatial patterns while remaining interpretable. We also introduce a new prior that borrows strength across samples, enabling robust detection of SV genes from multiple tissue sections. An efficient variational approximation is developed for scalable posterior computation. Analyzing spatial transcriptomics data from human brain and skin cancer tissues, our framework identifies spatially structured SV genes, enabling the delineation of tissue domains and the discovery of functionally coherent gene clusters through pathway enrichment analysis.

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arXiv2025

Heterogeneous gene network estimation for single-cell transcriptomic data via a joint regularized deep neural network

Estimation of intracellular gene networks has been a critical component of single-cell transcriptomic data analysis, which can provide crucial insights into the complex interplay between genes, facilitating the discovery of the biological basis of human life at single-cell resolution. Despite notable achievements, existing methodologies often falter in their practicality, primarily due to their narrow focus on simplistic linear relationships and inadequate handling of cellular heterogeneity. To bridge these gaps, we propose a joint regularized deep neural network method incorporating Mahalanobis distance-based K-means clustering (JRDNN-KM) to estimate multiple networks for various cell subgroups simultaneously, accounting for both unknown cellular heterogeneity and zero inflation, and, more importantly, complex nonlinear relationships among genes. We introduce an innovative selection layer for network construction, along with hidden layers that include both shared and subgroup-specific neurons, to capture common patterns and subgroup-specific variations across networks. Applied to real single-cell transcriptomic data from multiple tissues and species, JRDNN-KM demonstrates higher accuracy and biological interpretability in network estimation, and more accurately identifies cell subgroups compared to current state-of-the-art methods.Building on network construction, we further find hub genes with important biological implications and modules with statistical enrichment of biological processes.

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arXiv2024

Deep Transformation Model

There has been a significant recent surge in deep neural network (DNN) techniques. Most of the existing DNN techniques have restricted model formats/assumptions. To overcome their limitations, we propose the nonparametric transformation model, which encompasses many popular models as special cases and hence is less sensitive to model mis-specification. This model also has the potential of accommodating heavy-tailed errors, a robustness property not broadly shared. Accordingly, a new loss function, which fundamentally differs from the existing ones, is developed. For computational feasibility, we further develop a double rectified linear unit (DReLU)-based estimator. To accommodate the scenario with a diverging number of input variables and/or noises, we propose variable selection based on group penalization. We further expand the scope to coherently accommodate censored survival data. The estimation and variable selection properties are rigorously established. Extensive numerical studies, including simulations and data analyses, establish the satisfactory practical utility of the proposed methods.

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arXiv2024

The Spike-and-Slab Quantile LASSO for Robust Variable Selection in Cancer Genomics Studies

Data irregularity in cancer genomics studies has been widely observed in the form of outliers and heavy-tailed distributions in the complex traits. In the past decade, robust variable selection methods have emerged as powerful alternatives to the non-robust ones to identify important genes associated with heterogeneous disease traits and build superior predictive models. In this study, to keep the remarkable features of the quantile LASSO and fully Bayesian regularized quantile regression while overcoming their disadvantage in the analysis of high-dimensional genomics data, we propose the spike-and-slab quantile LASSO through a fully Bayesian spike-and-slab formulation under the robust likelihood by adopting the asymmetric Laplace distribution (ALD). The proposed robust method has inherited the prominent properties of selective shrinkage and self-adaptivity to the sparsity pattern from the spike-and-slab LASSO (Ročková and George, 2018). Furthermore, the spike-and-slab quantile LASSO has a computational advantage to locate the posterior modes via soft-thresholding rule guided Expectation-Maximization (EM) steps in the coordinate descent framework, a phenomenon rarely observed for robust regularization with non-differentiable loss functions. We have conducted comprehensive simulation studies with a variety of heavy-tailed errors in both homogeneous and heterogeneous model settings to demonstrate the superiority of the spike-and-slab quantile LASSO over its competing methods. The advantage of the proposed method has been further demonstrated in case studies of the lung adenocarcinomas (LUAD) and skin cutaneous melanoma (SKCM) data from The Cancer Genome Atlas (TCGA).

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arXiv2024

Supervised Bayesian joint graphical model for simultaneous network estimation and subgroup identification

Heterogeneity is a fundamental characteristic of cancer. To accommodate heterogeneity, subgroup identification has been extensively studied and broadly categorized into unsupervised and supervised analysis. Compared to unsupervised analysis, supervised approaches potentially hold greater clinical implications. Under the unsupervised analysis framework, several methods focusing on network-based subgroup identification have been developed, offering more comprehensive insights than those restricted to mean, variance, and other simplistic distributions by incorporating the interconnections among variables. However, research on supervised network-based subgroup identification remains limited. In this study, we develop a novel supervised Bayesian graphical model (SBJGM) for jointly identifying multiple heterogeneous networks and subgroups. In the proposed model, heterogeneity is not only reflected in molecular data but also associated with a clinical outcome, and a novel similarity prior is introduced to effectively accommodate similarities among the networks of different subgroups, significantly facilitating clinically meaningful biological network construction and subgroup identification. The consistency properties of the estimates are rigorously established, and an efficient algorithm is developed. Extensive simulation studies and a real-world application to The Cancer Genome Atlas (TCGA) data are conducted, which demonstrate the advantages of the proposed approach in terms of both subgroup and network identification.

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arXiv2024

Penalized Generative Variable Selection

Deep networks are increasingly applied to a wide variety of data, including data with high-dimensional predictors. In such analysis, variable selection can be needed along with estimation/model building. Many of the existing deep network studies that incorporate variable selection have been limited to methodological and numerical developments. In this study, we consider modeling/estimation using the conditional Wasserstein Generative Adversarial networks. Group Lasso penalization is applied for variable selection, which may improve model estimation/prediction, interpretability, stability, etc. Significantly advancing from the existing literature, the analysis of censored survival data is also considered. We establish the convergence rate for variable selection while considering the approximation error, and obtain a more efficient distribution estimation. Simulations and the analysis of real experimental data demonstrate satisfactory practical utility of the proposed analysis.

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arXiv2023

Hierarchical False Discovery Rate Control for High-dimensional Survival Analysis with Interactions

With the development of data collection techniques, analysis with a survival response and high-dimensional covariates has become routine. Here we consider an interaction model, which includes a set of low-dimensional covariates, a set of high-dimensional covariates, and their interactions. This model has been motivated by gene-environment (G-E) interaction analysis, where the E variables have a low dimension, and the G variables have a high dimension. For such a model, there has been extensive research on estimation and variable selection. Comparatively, inference studies with a valid false discovery rate (FDR) control have been very limited. The existing high-dimensional inference tools cannot be directly applied to interaction models, as interactions and main effects are not ``equal". In this article, for high-dimensional survival analysis with interactions, we model survival using the Accelerated Failure Time (AFT) model and adopt a ``weighted least squares + debiased Lasso'' approach for estimation and selection. A hierarchical FDR control approach is developed for inference and respect of the ``main effects, interactions'' hierarchy. { The asymptotic distribution properties of the debiased Lasso estimators} are rigorously established. Simulation demonstrates the satisfactory performance of the proposed approach, and the analysis of a breast cancer dataset further establishes its practical utility.

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arXiv2023

Identification of Influencing Factors on Self-reported Count Data with Multiple Potential Inflated Values

The Online Chauffeured Service Demand (OCSD) research is an exploratory market study of designated driver services in China. Researchers are interested in the influencing factors of chauffeured service adoption and usage and have collected relevant data using a self-reported questionnaire. As self-reported count measure data is typically inflated, there exist challenges to its validity, which may bias estimation and increase error in empirical research. Motivated by the analysis of self-reported data with multiple inflated values, we propose a novel approach to simultaneously achieve data-driven inflated value selection and identification of important influencing factors. In particular, the regularization technique is applied to the mixing proportions of inflated values and the regression parameters to obtain shrinkage estimates. We analyze the OCSD data with the proposed approach, deriving insights into the determinants impacting service demand. The proper interpretations and implications contribute to service promotion and related policy optimization. Extensive simulation studies and consistent asymptotic properties further establish the effectiveness of the proposed approach.

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arXiv2023

Regulation-incorporated Gene Expression Network-based Heterogeneity Analysis

Gene expression-based heterogeneity analysis has been extensively conducted. In recent studies, it has been shown that network-based analysis, which takes a system perspective and accommodates the interconnections among genes, can be more informative than that based on simpler statistics. Gene expressions are highly regulated. Incorporating regulations in analysis can better delineate the "sources" of gene expression effects. Although conditional network analysis can somewhat serve this purpose, it does render enough attention to the regulation relationships. In this article, significantly advancing from the existing heterogeneity analyses based only on gene expression networks, conditional gene expression network analyses, and regression-based heterogeneity analyses, we propose heterogeneity analysis based on gene expression networks (after accounting for or "removing" regulation effects) as well as regulations of gene expressions. A high-dimensional penalized fusion approach is proposed, which can determine the number of sample groups and parameter values in a single step. An effective computational algorithm is proposed. It is rigorously proved that the proposed approach enjoys the estimation, selection, and grouping consistency properties. Extensive simulations demonstrate its practical superiority over closely related alternatives. In the analysis of two breast cancer datasets, the proposed approach identifies heterogeneity and gene network structures different from the alternatives and with sound biological implications.

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