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In this paper, we aim to address a significant challenge in the field of missing data imputation: identifying and leveraging the interdependencies among features to enhance missing data imputation for tabular data. We introduce a novel framework named the Bipartite and Complete Directed Graph Neural Network (BCGNN). Within BCGNN, observations and features are differentiated as two distinct node types, and the values of observed features are converted into attributed edges linking them. The bipartite segment of our framework inductively learns embedding representations for nodes, efficiently utilizing the comprehensive information encapsulated in the attributed edges. In parallel, the complete directed graph segment adeptly outlines and communicates the complex interdependencies among features. When compared to contemporary leading imputation methodologies, BCGNN consistently outperforms them, achieving a noteworthy average reduction of 15% in mean absolute error for feature imputation tasks under different missing mechanisms. Our extensive experimental investigation confirms that an in-depth grasp of the interdependence structure substantially enhances the model's feature embedding ability. We also highlight the model's superior performance in label prediction tasks involving missing data, and its formidable ability to generalize to unseen data points.

In this paper, we propose a novel framework, the Sampling-guided Heterogeneous Graph Neural Network (SHT-GNN), to effectively tackle the challenge of missing data imputation in longitudinal studies. Unlike traditional methods, which often require extensive preprocessing to handle irregular or inconsistent missing data, our approach accommodates arbitrary missing data patterns while maintaining computational efficiency. SHT-GNN models both observations and covariates as distinct node types, connecting observation nodes at successive time points through subject-specific longitudinal subnetworks, while covariate-observation interactions are represented by attributed edges within bipartite graphs. By leveraging subject-wise mini-batch sampling and a multi-layer temporal smoothing mechanism, SHT-GNN efficiently scales to large datasets, while effectively learning node representations and imputing missing data. Extensive experiments on both synthetic and real-world datasets, including the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, demonstrate that SHT-GNN significantly outperforms existing imputation methods, even with high missing data rates. The empirical results highlight SHT-GNN's robust imputation capabilities and superior performance, particularly in the context of complex, large-scale longitudinal data.

Radiology report generation is crucial in medical imaging,but the manual annotation process by physicians is time-consuming and labor-intensive, necessitating the develop-ment of automatic report generation methods. Existingresearch predominantly utilizes Transformers to generateradiology reports, which can be computationally intensive,limiting their use in real applications. In this work, we presentR2Gen-Mamba, a novel automatic radiology report genera-tion method that leverages the efficient sequence processingof the Mamba with the contextual benefits of Transformerarchitectures. Due to lower computational complexity ofMamba, R2Gen-Mamba not only enhances training and in-ference efficiency but also produces high-quality reports.Experimental results on two benchmark datasets with morethan 210,000 X-ray image-report pairs demonstrate the ef-fectiveness of R2Gen-Mamba regarding report quality andcomputational efficiency compared with several state-of-the-art methods. The source code can be accessed online., Comment: 4 pages pages for ISBI2025

Building on the success of deep learning models in cardiovascular structure segmentation, increasing attention has been focused on improving generalization and robustness, particularly in small, annotated datasets. Despite recent advancements, current approaches often face challenges such as overfitting and accuracy limitations, largely due to their reliance on large datasets and narrow optimization techniques. This paper introduces the UU-Mamba model, an extension of the U-Mamba architecture, designed to address these challenges in both cardiac and vascular segmentation. By incorporating Sharpness-Aware Minimization (SAM), the model enhances generalization by targeting flatter minima in the loss landscape. Additionally, we propose an uncertainty-aware loss function that combines region-based, distribution-based, and pixel-based components to improve segmentation accuracy by capturing both local and global features. While the UU-Mamba model has already demonstrated great performance, further testing is required to fully assess its generalization and robustness. We expand our evaluation by conducting new trials on the ImageCAS (coronary artery) and Aorta (aortic branches and zones) datasets, which present more complex segmentation challenges than the ACDC dataset (left and right ventricles) used in our previous work, showcasing the model's adaptability and resilience. We confirm UU-Mamba's superior performance over leading models such as TransUNet, Swin-Unet, nnUNet, and nnFormer. Moreover, we provide a more comprehensive evaluation of the model's robustness and segmentation accuracy, as demonstrated by extensive experiments.

Time series experiments, in which experimental units receive a sequence of treatments over time, are frequently employed in many technological companies to evaluate the performance of a newly developed policy, product, or treatment relative to a baseline control. Many existing A/B testing solutions assume a fully observable experimental environment that satisfies the Markov condition, which often does not hold in practice. This paper studies the optimal design for A/B testing in partially observable environments. We introduce a controlled (vector) autoregressive moving average model to capture partial observability. We introduce a small signal asymptotic framework to simplify the analysis of asymptotic mean squared errors of average treatment effect estimators under various designs. We develop two algorithms to estimate the optimal design: one utilizing constrained optimization and the other employing reinforcement learning. We demonstrate the superior performance of our designs using a dispatch simulator and two real datasets from a ride-sharing company. A Python implementation of our proposal is available at https://github.com/datake/ARMADesign.

Medical Image Foundation Models have proven to be powerful tools for mask prediction across various datasets. However, accurately assessing the uncertainty of their predictions remains a significant challenge. To address this, we propose a new model, U-MedSAM, which integrates the MedSAM model with an uncertainty-aware loss function and the Sharpness-Aware Minimization (SharpMin) optimizer. The uncertainty-aware loss function automatically combines region-based, distribution-based, and pixel-based loss designs to enhance segmentation accuracy and robustness. SharpMin improves generalization by finding flat minima in the loss landscape, thereby reducing overfitting. Our method was evaluated in the CVPR24 MedSAM on Laptop challenge, where U-MedSAM demonstrated promising performance., Comment: arXiv admin note: text overlap with arXiv:2405.17496

Off-policy evaluation (OPE) is widely applied in sectors such as pharmaceuticals and e-commerce to evaluate the efficacy of novel products or policies from offline datasets. This paper introduces a causal deepset framework that relaxes several key structural assumptions, primarily the mean-field assumption, prevalent in existing OPE methodologies that handle spatio-temporal interference. These traditional assumptions frequently prove inadequate in real-world settings, thereby restricting the capability of current OPE methods to effectively address complex interference effects. In response, we advocate for the implementation of the permutation invariance (PI) assumption. This innovative approach enables the data-driven, adaptive learning of the mean-field function, offering a more flexible estimation method beyond conventional averaging. Furthermore, we present novel algorithms that incorporate the PI assumption into OPE and thoroughly examine their theoretical foundations. Our numerical analyses demonstrate that this novel approach yields significantly more precise estimations than existing baseline algorithms, thereby substantially improving the practical applicability and effectiveness of OPE methodologies. A Python implementation of our proposed method is available at https://github.com/BIG-S2/Causal-Deepsets.

The recent emergence of Medical Large Vision Language Models (Med-LVLMs) has enhanced medical diagnosis. However, current Med-LVLMs frequently encounter factual issues, often generating responses that do not align with established medical facts. Retrieval-Augmented Generation (RAG), which utilizes external knowledge, can improve the factual accuracy of these models but introduces two major challenges. First, limited retrieved contexts might not cover all necessary information, while excessive retrieval can introduce irrelevant and inaccurate references, interfering with the model's generation. Second, in cases where the model originally responds correctly, applying RAG can lead to an over-reliance on retrieved contexts, resulting in incorrect answers. To address these issues, we propose RULE, which consists of two components. First, we introduce a provably effective strategy for controlling factuality risk through the calibrated selection of the number of retrieved contexts. Second, based on samples where over-reliance on retrieved contexts led to errors, we curate a preference dataset to fine-tune the model, balancing its dependence on inherent knowledge and retrieved contexts for generation. We demonstrate the effectiveness of RULE on medical VQA and report generation tasks across three datasets, achieving an average improvement of 47.4% in factual accuracy. We publicly release our benchmark and code in https://github.com/richard-peng-xia/RULE., Comment: EMNLP 2024 main

We propose Nodewise Loreg, a nodewise $L_0$-penalized regression method for estimating high-dimensional sparse precision matrices. We establish its asymptotic properties, including convergence rates, support recovery, and asymptotic normality under high-dimensional sub-Gaussian settings. Notably, the Nodewise Loreg estimator is asymptotically unbiased and normally distributed, eliminating the need for debiasing required by Nodewise Lasso. We also develop a desparsified version of Nodewise Loreg, similar to the desparsified Nodewise Lasso estimator. The asymptotic variances of the undesparsified Nodewise Loreg estimator are upper bounded by those of both desparsified Nodewise Loreg and Lasso estimators for Gaussian data, potentially offering more powerful statistical inference. Extensive simulations show that the undesparsified Nodewise Loreg estimator generally outperforms the two desparsified estimators in asymptotic normal behavior. Moreover, Nodewise Loreg surpasses Nodewise Lasso, CLIME, and GLasso in most simulations in terms of matrix norm losses, support recovery, and timing performance. Application to a breast cancer gene expression dataset further demonstrates Nodewise Loreg's superiority over the three $L_1$-norm based methods.

Artificial intelligence has significantly impacted medical applications, particularly with the advent of Medical Large Vision Language Models (Med-LVLMs), sparking optimism for the future of automated and personalized healthcare. However, the trustworthiness of Med-LVLMs remains unverified, posing significant risks for future model deployment. In this paper, we introduce CARES and aim to comprehensively evaluate the Trustworthiness of Med-LVLMs across the medical domain. We assess the trustworthiness of Med-LVLMs across five dimensions, including trustfulness, fairness, safety, privacy, and robustness. CARES comprises about 41K question-answer pairs in both closed and open-ended formats, covering 16 medical image modalities and 27 anatomical regions. Our analysis reveals that the models consistently exhibit concerns regarding trustworthiness, often displaying factual inaccuracies and failing to maintain fairness across different demographic groups. Furthermore, they are vulnerable to attacks and demonstrate a lack of privacy awareness. We publicly release our benchmark and code in https://cares-ai.github.io/., Comment: NeurIPS 2024 Datasets and Benchmarks Track

This paper studies policy evaluation with multiple data sources, especially in scenarios that involve one experimental dataset with two arms, complemented by a historical dataset generated under a single control arm. We propose novel data integration methods that linearly integrate base policy value estimators constructed based on the experimental and historical data, with weights optimized to minimize the mean square error (MSE) of the resulting combined estimator. We further apply the pessimistic principle to obtain more robust estimators, and extend these developments to sequential decision making. Theoretically, we establish non-asymptotic error bounds for the MSEs of our proposed estimators, and derive their oracle, efficiency and robustness properties across a broad spectrum of reward shift scenarios. Numerical experiments and real-data-based analyses from a ridesharing company demonstrate the superior performance of the proposed estimators.

Biomedical image segmentation is critical for accurate identification and analysis of anatomical structures in medical imaging, particularly in cardiac MRI. Manual segmentation is labor-intensive, time-consuming, and prone to errors, highlighting the need for automated methods. However, current machine learning approaches face challenges like overfitting and data demands. To tackle these issues, we propose a new UU-Mamba model, integrating the U-Mamba model with the Sharpness-Aware Minimization (SAM) optimizer and an uncertainty-aware loss function. SAM enhances generalization by locating flat minima in the loss landscape, thus reducing overfitting. The uncertainty-aware loss combines region-based, distribution-based, and pixel-based loss designs to improve segmentation accuracy and robustness. Evaluation of our method is performed on the ACDC cardiac dataset, outperforming state-of-the-art models including TransUNet, Swin-Unet, nnUNet, and nnFormer. Our approach achieves Dice Similarity Coefficient (DSC) and Mean Squared Error (MSE) scores, demonstrating its effectiveness in cardiac MRI segmentation.

This paper offers a detailed investigation of switchback designs in A/B testing, which alternate between baseline and new policies over time. Our aim is to thoroughly evaluate the effects of these designs on the accuracy of their resulting average treatment effect (ATE) estimators. We propose a novel "weak signal analysis" framework, which substantially simplifies the calculations of the mean squared errors (MSEs) of these ATEs in Markov decision process environments. Our findings suggest that (i) when the majority of reward errors are positively correlated, the switchback design is more efficient than the alternating-day design which switches policies in a daily basis. Additionally, increasing the frequency of policy switches tends to reduce the MSE of the ATE estimator. (ii) When the errors are uncorrelated, however, all these designs become asymptotically equivalent. (iii) In cases where the majority of errors are negative correlated, the alternating-day design becomes the optimal choice. These insights are crucial, offering guidelines for practitioners on designing experiments in A/B testing. Our analysis accommodates a variety of policy value estimators, including model-based estimators, least squares temporal difference learning estimators, and double reinforcement learning estimators, thereby offering a comprehensive understanding of optimal design strategies for policy evaluation in reinforcement learning., Comment: We recently spotted some errors in our proof

This article studies the benefits of using spatially randomized experimental designs which partition the experimental area into distinct, non-overlapping units with treatments assigned randomly. Such designs offer improved policy evaluation in online experiments by providing more precise policy value estimators and more effective A/B testing algorithms than traditional global designs, which apply the same treatment across all units simultaneously. We examine both parametric and nonparametric methods for estimating and inferring policy values based on this randomized approach. Our analysis includes evaluating the mean squared error of the treatment effect estimator and the statistical power of the associated tests. Additionally, we extend our findings to experiments with spatio-temporal dependencies, where treatments are allocated sequentially over time, and account for potential temporal carryover effects. Our theoretical insights are supported by comprehensive numerical experiments.

Neural Radiance Fields (NeRF), as a pioneering technique in computer vision, offer great potential to revolutionize medical imaging by synthesizing three-dimensional representations from the projected two-dimensional image data. However, they face unique challenges when applied to medical applications. This paper presents a comprehensive examination of applications of NeRFs in medical imaging, highlighting four imminent challenges, including fundamental imaging principles, inner structure requirement, object boundary definition, and color density significance. We discuss current methods on different organs and discuss related limitations. We also review several datasets and evaluation metrics and propose several promising directions for future research.

Brain magnetic resonance imaging (MRI) has been extensively employed across clinical and research fields, but often exhibits sensitivity to site effects arising from non-biological variations such as differences in field strength and scanner vendors. Numerous retrospective MRI harmonization techniques have demonstrated encouraging outcomes in reducing the site effects at the image level. However, existing methods generally suffer from high computational requirements and limited generalizability, restricting their applicability to unseen MRIs. In this paper, we design a novel disentangled latent energy-based style translation (DLEST) framework for unpaired image-level MRI harmonization, consisting of (a) site-invariant image generation (SIG), (b) site-specific style translation (SST), and (c) site-specific MRI synthesis (SMS). Specifically, the SIG employs a latent autoencoder to encode MRIs into a low-dimensional latent space and reconstruct MRIs from latent codes. The SST utilizes an energy-based model to comprehend the global latent distribution of a target domain and translate source latent codes toward the target domain, while SMS enables MRI synthesis with a target-specific style. By disentangling image generation and style translation in latent space, the DLEST can achieve efficient style translation. Our model was trained on T1-weighted MRIs from a public dataset (with 3,984 subjects across 58 acquisition sites/settings) and validated on an independent dataset (with 9 traveling subjects scanned in 11 sites/settings) in four tasks: histogram and feature visualization, site classification, brain tissue segmentation, and site-specific structural MRI synthesis. Qualitative and quantitative results demonstrate the superiority of our method over several state-of-the-arts.

The clinical trial is a pivotal and costly process, often spanning multiple years and requiring substantial financial resources. Therefore, the development of clinical trial outcome prediction models aims to exclude drugs likely to fail and holds the potential for significant cost savings. Recent data-driven attempts leverage deep learning methods to integrate multimodal data for predicting clinical trial outcomes. However, these approaches rely on manually designed modal-specific encoders, which limits both the extensibility to adapt new modalities and the ability to discern similar information patterns across different modalities. To address these issues, we propose a multimodal mixture-of-experts (LIFTED) approach for clinical trial outcome prediction. Specifically, LIFTED unifies different modality data by transforming them into natural language descriptions. Then, LIFTED constructs unified noise-resilient encoders to extract information from modal-specific language descriptions. Subsequently, a sparse Mixture-of-Experts framework is employed to further refine the representations, enabling LIFTED to identify similar information patterns across different modalities and extract more consistent representations from those patterns using the same expert model. Finally, a mixture-of-experts module is further employed to dynamically integrate different modality representations for prediction, which gives LIFTED the ability to automatically weigh different modalities and pay more attention to critical information. The experiments demonstrate that LIFTED significantly enhances performance in predicting clinical trial outcomes across all three phases compared to the best baseline, showcasing the effectiveness of our proposed key components.

Recent advancements in Artificial Intelligence (AI) have significantly influenced the field of Cardiovascular Disease (CVD) analysis, particularly in image-based diagnostics. Our paper presents an extensive review of AI applications in image-based CVD analysis, offering insights into its current state and future potential. We systematically categorize the literature based on the primary anatomical structures related to CVD, dividing them into non-vessel structures (such as ventricles and atria) and vessel structures (including the aorta and coronary arteries). This categorization provides a structured approach to explore various imaging modalities like Magnetic Resonance Imaging (MRI), which are commonly used in CVD research. Our review encompasses these modalities, giving a broad perspective on the diverse imaging techniques integrated with AI for CVD analysis. Additionally, we compile a list of publicly accessible cardiac image datasets and code repositories, intending to support research reproducibility and facilitate data and algorithm sharing within the community. We conclude with an examination of the challenges and limitations inherent in current AI-based CVD analysis methods and suggest directions for future research to overcome these hurdles.

Traditional functional linear regression usually takes a one-dimensional functional predictor as input and estimates the continuous coefficient function. Modern applications often generate two-dimensional covariates, which become matrices when observed at grid points. To avoid the inefficiency of the classical method involving estimation of a two-dimensional coefficient function, we propose a functional bilinear regression model, and introduce an innovative three-term penalty to impose roughness penalty in the estimation. The proposed estimator exhibits minimax optimal property for prediction under the framework of reproducing kernel Hilbert space. An iterative generalized cross-validation approach is developed to choose tuning parameters, which significantly improves the computational efficiency over the traditional cross-validation approach. The statistical and computational advantages of the proposed method over existing methods are further demonstrated via simulated experiments, the Canadian weather data, and a biochemical long-range infrared light detection and ranging data., Comment: 48 pages, 19 figures

Recent advances in Large Language Models (LLMs) have presented new opportunities for integrating Artificial General Intelligence (AGI) into biological research and education. This study evaluated the capabilities of leading LLMs, including GPT-4, GPT-3.5, PaLM2, Claude2, and SenseNova, in answering conceptual biology questions. The models were tested on a 108-question multiple-choice exam covering biology topics in molecular biology, biological techniques, metabolic engineering, and synthetic biology. Among the models, GPT-4 achieved the highest average score of 90 and demonstrated the greatest consistency across trials with different prompts. The results indicated GPT-4's proficiency in logical reasoning and its potential to aid biology research through capabilities like data analysis, hypothesis generation, and knowledge integration. However, further development and validation are still required before the promise of LLMs in accelerating biological discovery can be realized.

A/B testing is critical for modern technological companies to evaluate the effectiveness of newly developed products against standard baselines. This paper studies optimal designs that aim to maximize the amount of information obtained from online experiments to estimate treatment effects accurately. We propose three optimal allocation strategies in a dynamic setting where treatments are sequentially assigned over time. These strategies are designed to minimize the variance of the treatment effect estimator when data follow a non-Markov decision process or a (time-varying) Markov decision process. We further develop estimation procedures based on existing off-policy evaluation (OPE) methods and conduct extensive experiments in various environments to demonstrate the effectiveness of the proposed methodologies. In theory, we prove the optimality of the proposed treatment allocation design and establish upper bounds for the mean squared errors of the resulting treatment effect estimators.

Controlling the degree of stylization in the Neural Style Transfer (NST) is a little tricky since it usually needs hand-engineering on hyper-parameters. In this paper, we propose the first deep Reinforcement Learning (RL) based architecture that splits one-step style transfer into a step-wise process for the NST task. Our RL-based method tends to preserve more details and structures of the content image in early steps, and synthesize more style patterns in later steps. It is a user-easily-controlled style-transfer method. Additionally, as our RL-based model performs the stylization progressively, it is lightweight and has lower computational complexity than existing one-step Deep Learning (DL) based models. Experimental results demonstrate the effectiveness and robustness of our method., Comment: Accepted by IJCAI 2023. The contributions of Chengming Feng and Jing Hu to this paper were equal. arXiv admin note: substantial text overlap with arXiv:2309.13672

Most existing Image-to-Image Translation (I2IT) methods generate images in a single run of a deep learning (DL) model. However, designing such a single-step model is always challenging, requiring a huge number of parameters and easily falling into bad global minimums and overfitting. In this work, we reformulate I2IT as a step-wise decision-making problem via deep reinforcement learning (DRL) and propose a novel framework that performs RL-based I2IT (RL-I2IT). The key feature in the RL-I2IT framework is to decompose a monolithic learning process into small steps with a lightweight model to progressively transform a source image successively to a target image. Considering that it is challenging to handle high dimensional continuous state and action spaces in the conventional RL framework, we introduce meta policy with a new concept Plan to the standard Actor-Critic model, which is of a lower dimension than the original image and can facilitate the actor to generate a tractable high dimensional action. In the RL-I2IT framework, we also employ a task-specific auxiliary learning strategy to stabilize the training process and improve the performance of the corresponding task. Experiments on several I2IT tasks demonstrate the effectiveness and robustness of the proposed method when facing high-dimensional continuous action space problems. Our implementation of the RL-I2IT framework is available at https://github.com/Algolzw/SPAC-Deformable-Registration.

The rise of large language models (LLMs) has marked a pivotal shift in the field of natural language processing (NLP). LLMs have revolutionized a multitude of domains, and they have made a significant impact in the medical field. Large language models are now more abundant than ever, and many of these models exhibit bilingual capabilities, proficient in both English and Chinese. However, a comprehensive evaluation of these models remains to be conducted. This lack of assessment is especially apparent within the context of radiology NLP. This study seeks to bridge this gap by critically evaluating thirty two LLMs in interpreting radiology reports, a crucial component of radiology NLP. Specifically, the ability to derive impressions from radiologic findings is assessed. The outcomes of this evaluation provide key insights into the performance, strengths, and weaknesses of these LLMs, informing their practical applications within the medical domain.

Resting-state functional magnetic resonance imaging (rs-fMRI) can reflect spontaneous neural activities in brain and is widely used for brain disorder analysis.Previous studies propose to extract fMRI representations through diverse machine/deep learning methods for subsequent analysis. But the learned features typically lack biological interpretability, which limits their clinical utility. From the view of graph theory, the brain exhibits a remarkable modular structure in spontaneous brain functional networks, with each module comprised of functionally interconnected brain regions-of-interest (ROIs). However, most existing learning-based methods for fMRI analysis fail to adequately utilize such brain modularity prior. In this paper, we propose a Brain Modularity-constrained dynamic Representation learning (BMR) framework for interpretable fMRI analysis, consisting of three major components: (1) dynamic graph construction, (2) dynamic graph learning via a novel modularity-constrained graph neural network(MGNN), (3) prediction and biomarker detection for interpretable fMRI analysis. Especially, three core neurocognitive modules (i.e., salience network, central executive network, and default mode network) are explicitly incorporated into the MGNN, encouraging the nodes/ROIs within the same module to share similar representations. To further enhance discriminative ability of learned features, we also encourage the MGNN to preserve the network topology of input graphs via a graph topology reconstruction constraint. Experimental results on 534 subjects with rs-fMRI scans from two datasets validate the effectiveness of the proposed method. The identified discriminative brain ROIs and functional connectivities can be regarded as potential fMRI biomarkers to aid in clinical diagnosis.

Many modern tech companies, such as Google, Uber, and Didi, utilize online experiments (also known as A/B testing) to evaluate new policies against existing ones. While most studies concentrate on average treatment effects, situations with skewed and heavy-tailed outcome distributions may benefit from alternative criteria, such as quantiles. However, assessing dynamic quantile treatment effects (QTE) remains a challenge, particularly when dealing with data from ride-sourcing platforms that involve sequential decision-making across time and space. In this paper, we establish a formal framework to calculate QTE conditional on characteristics independent of the treatment. Under specific model assumptions, we demonstrate that the dynamic conditional QTE (CQTE) equals the sum of individual CQTEs across time, even though the conditional quantile of cumulative rewards may not necessarily equate to the sum of conditional quantiles of individual rewards. This crucial insight significantly streamlines the estimation and inference processes for our target causal estimand. We then introduce two varying coefficient decision process (VCDP) models and devise an innovative method to test the dynamic CQTE. Moreover, we expand our approach to accommodate data from spatiotemporal dependent experiments and examine both conditional quantile direct and indirect effects. To showcase the practical utility of our method, we apply it to three real-world datasets from a ride-sourcing platform. Theoretical findings and comprehensive simulation studies further substantiate our proposal.

The conditional randomization test (CRT) was recently proposed to test whether two random variables X and Y are conditionally independent given random variables Z. The CRT assumes that the conditional distribution of X given Z is known under the null hypothesis and then it is compared to the distribution of the observed samples of the original data. The aim of this paper is to develop a novel alternative of CRT by using nearest-neighbor sampling without assuming the exact form of the distribution of X given Z. Specifically, we utilize the computationally efficient 1-nearest-neighbor to approximate the conditional distribution that encodes the null hypothesis. Then, theoretically, we show that the distribution of the generated samples is very close to the true conditional distribution in terms of total variation distance. Furthermore, we take the classifier-based conditional mutual information estimator as our test statistic. The test statistic as an empirical fundamental information theoretic quantity is able to well capture the conditional-dependence feature. We show that our proposed test is computationally very fast, while controlling type I and II errors quite well. Finally, we demonstrate the efficiency of our proposed test in both synthetic and real data analyses., Comment: Accepted at AAAI 2023; 9 Pages, 3 Figures, 2 Tables

Unsupervised domain adaptation (UDA) via deep learning has attracted appealing attention for tackling domain-shift problems caused by distribution discrepancy across different domains. Existing UDA approaches highly depend on the accessibility of source domain data, which is usually limited in practical scenarios due to privacy protection, data storage and transmission cost, and computation burden. To tackle this issue, many source-free unsupervised domain adaptation (SFUDA) methods have been proposed recently, which perform knowledge transfer from a pre-trained source model to unlabeled target domain with source data inaccessible. A comprehensive review of these works on SFUDA is of great significance. In this paper, we provide a timely and systematic literature review of existing SFUDA approaches from a technical perspective. Specifically, we categorize current SFUDA studies into two groups, i.e., white-box SFUDA and black-box SFUDA, and further divide them into finer subcategories based on different learning strategies they use. We also investigate the challenges of methods in each subcategory, discuss the advantages/disadvantages of white-box and black-box SFUDA methods, conclude the commonly used benchmark datasets, and summarize the popular techniques for improved generalizability of models learned without using source data. We finally discuss several promising future directions in this field., Comment: 19 pages, 10 figures

The aim of this paper is to provide a comprehensive review of statistical challenges in neuroimaging data analysis from neuroimaging techniques to large-scale neuroimaging studies to statistical learning methods. We briefly review eight popular neuroimaging techniques and their potential applications in neuroscience research and clinical translation. We delineate the four common themes of neuroimaging data and review major image processing analysis methods for processing neuroimaging data at the individual level. We briefly review four large-scale neuroimaging-related studies and a consortium on imaging genomics and discuss four common themes of neuroimaging data analysis at the population level. We review nine major population-based statistical analysis methods and their associated statistical challenges and present recent progress in statistical methodology to address these challenges., Comment: 73 pages, 4 Figures

This paper is motivated by the joint analysis of genetic, imaging, and clinical (GIC) data collected in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We propose a regression framework based on partially functional linear regression models to map high-dimensional GIC-related pathways for Alzheimer's Disease (AD). We develop a joint model selection and estimation procedure by embedding imaging data in the reproducing kernel Hilbert space and imposing the L0 penalty for the coefficients of genetic variables. We apply the proposed method to the ADNI dataset to identify important features from tens of thousands of genetic polymorphisms (reduced from millions using a preprocessing step) and study the effects of a certain set of informative genetic variants and the baseline hippocampus surface on thirteen future cognitive scores measuring different aspects of cognitive function. We explore the shared and different heritability patterns of these cognitive scores. Analysis results suggest that both the hippocampal and genetic data have heterogeneous effects on different scores, with the trend that the value of both hippocampi is negatively associated with the severity of cognition deficits. Polygenic effects are observed for all thirteen cognitive scores. The well-known APOE4 genotype only explains a small part of cognitive function. Shared genetic etiology exists, however, greater genetic heterogeneity exists within disease classifications after accounting for the baseline diagnosis status. These analyses are useful in further investigation of functional mechanisms for AD evolution.

The aim of this paper is to propose a novel estimation method of using genetic-predicted observations to estimate trans-ancestry genetic correlations, which describes how genetic architecture of complex traits varies among populations, in genome-wide association studies (GWAS). Our new estimator corrects for prediction errors caused by high-dimensional weak GWAS signals, while addressing the heterogeneity of GWAS data across ethnicities, such as linkage disequilibrium (LD) differences, which can lead to biased findings in homogeneity-agnostic analyses. Moreover, our estimator only requires one population to have a large GWAS sample size, and the second population can only have a much smaller number of participants (for example, hundreds). It is designed to specifically address the unbalanced data resources such that the GWAS sample size for European populations is usually larger than that of non-European ancestry groups. Extensive simulations and real data analyses of 30 complex traits in the UK Biobank study show that our method is capable of providing reliable estimates of a wide range of complex traits. Our results provide deep insights into the transferability of population-specific genetic findings., Comment: 25 pages, 4 figures

Genetic prediction of complex traits and diseases has attracted enormous attention in precision medicine, mainly because it has the potential to translate discoveries from genome-wide association studies (GWAS) into medical advances. As the high dimensional covariance matrix (or the linkage disequilibrium (LD) pattern) of genetic variants has a block-diagonal structure, many existing methods attempt to account for the dependence among variants in predetermined local LD blocks/regions. Moreover, due to privacy restrictions and data protection concerns, genetic variant dependence in each LD block is typically estimated from external reference panels rather than the original training dataset. This paper presents a unified analysis of block-wise and reference panel-based estimators in a high-dimensional prediction framework without sparsity restrictions. We find that, surprisingly, even when the covariance matrix has a block-diagonal structure with well-defined boundaries, block-wise estimation methods adjusting for local dependence can be substantially less accurate than methods controlling for the whole covariance matrix. Further, estimation methods built on the original training dataset and external reference panels are likely to have varying performance in high dimensions, which may reflect the cost of having only access to summary level data from the training dataset. This analysis is based on our novel results in random matrix theory for block-diagonal covariance matrix. We numerically evaluate our results using extensive simulations and the large-scale UK Biobank real data analysis of 36 complex traits., Comment: 27 pages, 5 figures

Uplift modeling is a rapidly growing approach that utilizes causal inference and machine learning methods to directly estimate the heterogeneous treatment effects, which has been widely applied to various online marketplaces to assist large-scale decision-making in recent years. The existing popular models, like causal forest (CF), are limited to either discrete treatments or posing parametric assumptions on the outcome-treatment relationship that may suffer model misspecification. However, continuous treatments (e.g., price, duration) often arise in marketplaces. To alleviate these restrictions, we use a kernel-based doubly robust estimator to recover the non-parametric dose-response functions that can flexibly model continuous treatment effects. Moreover, we propose a generic distance-based splitting criterion to capture the heterogeneity for the continuous treatments. We call the proposed algorithm generalized causal forest (GCF) as it generalizes the use case of CF to a much broader setting. We show the effectiveness of GCF by deriving the asymptotic property of the estimator and comparing it to popular uplift modeling methods on both synthetic and real-world datasets. We implement GCF on Spark and successfully deploy it into a large-scale online pricing system at a leading ride-sharing company. Online A/B testing results further validate the superiority of GCF.

We consider reinforcement learning (RL) methods in offline domains without additional online data collection, such as mobile health applications. Most of existing policy optimization algorithms in the computer science literature are developed in online settings where data are easy to collect or simulate. Their generalizations to mobile health applications with a pre-collected offline dataset remain unknown. The aim of this paper is to develop a novel advantage learning framework in order to efficiently use pre-collected data for policy optimization. The proposed method takes an optimal Q-estimator computed by any existing state-of-the-art RL algorithms as input, and outputs a new policy whose value is guaranteed to converge at a faster rate than the policy derived based on the initial Q-estimator. Extensive numerical experiments are conducted to back up our theoretical findings. A Python implementation of our proposed method is available at https://github.com/leyuanheart/SEAL.