Conformal Diffusion Models for Individual Treatment Effect Estimation and Inference

Estimating treatment effects from observational data is of central interest across numerous application domains. Individual treatment effect offers the most granular measure of treatment effect on an individual level, and is the most useful to facilitate personalized care. However, its estimation and inference remain underdeveloped due to several challenges. In this article, we propose a novel conformal diffusion model-based approach that addresses those intricate challenges. We integrate the highly flexible diffusion modeling, the model-free statistical inference paradigm of conformal inference, along with propensity score and covariate local approximation that tackle distributional shifts. We unbiasedly estimate the distributions of potential outcomes for individual treatment effect, construct an informative confidence interval, and establish rigorous theoretical guarantees. We demonstrate the competitive performance of the proposed method over existing solutions through extensive numerical studies.

Synthetic Oversampling: Theory and A Practical Approach Using LLMs to Address Data Imbalance

Imbalanced data and spurious correlations are common challenges in machine learning and data science. Oversampling, which artificially increases the number of instances in the underrepresented classes, has been widely adopted to tackle these challenges. In this article, we introduce OPAL (\textbf{O}versam\textbf{P}ling with \textbf{A}rtificial \textbf{L}LM-generated data), a systematic oversampling approach that leverages the capabilities of large language models (LLMs) to generate high-quality synthetic data for minority groups. Recent studies on synthetic data generation using deep generative models mostly target prediction tasks. Our proposal differs in that we focus on handling imbalanced data and spurious correlations. More importantly, we develop a novel theory that rigorously characterizes the benefits of using the synthetic data, and shows the capacity of transformers in generating high-quality synthetic data for both labels and covariates. We further conduct intensive numerical experiments to demonstrate the efficacy of our proposed approach compared to some representative alternative solutions.

Testing for the Markov Property in Time Series via Deep Conditional Generative Learning

The Markov property is widely imposed in analysis of time series data. Correspondingly, testing the Markov property, and relatedly, inferring the order of a Markov model, are of paramount importance. In this article, we propose a nonparametric test for the Markov property in high-dimensional time series via deep conditional generative learning. We also apply the test sequentially to determine the order of the Markov model. We show that the test controls the type-I error asymptotically, and has the power approaching one. Our proposal makes novel contributions in several ways. We utilize and extend state-of-the-art deep generative learning to estimate the conditional density functions, and establish a sharp upper bound on the approximation error of the estimators. We derive a doubly robust test statistic, which employs a nonparametric estimation but achieves a parametric convergence rate. We further adopt sample splitting and cross-fitting to minimize the conditions required to ensure the consistency of the test. We demonstrate the efficacy of the test through both simulations and the three data applications.

Sequential Best-Arm Identification with Application to Brain-Computer Interface

A brain-computer interface (BCI) is a technology that enables direct communication between the brain and an external device or computer system. It allows individuals to interact with the device using only their thoughts, and holds immense potential for a wide range of applications in medicine, rehabilitation, and human augmentation. An electroencephalogram (EEG) and event-related potential (ERP)-based speller system is a type of BCI that allows users to spell words without using a physical keyboard, but instead by recording and interpreting brain signals under different stimulus presentation paradigms. Conventional non-adaptive paradigms treat each word selection independently, leading to a lengthy learning process. To improve the sampling efficiency, we cast the problem as a sequence of best-arm identification tasks in multi-armed bandits. Leveraging pre-trained large language models (LLMs), we utilize the prior knowledge learned from previous tasks to inform and facilitate subsequent tasks. To do so in a coherent way, we propose a sequential top-two Thompson sampling (STTS) algorithm under the fixed-confidence setting and the fixed-budget setting. We study the theoretical property of the proposed algorithm, and demonstrate its substantial empirical improvement through both synthetic data analysis as well as a P300 BCI speller simulator example.

Optimizing Pessimism in Dynamic Treatment Regimes: A Bayesian Learning Approach

In this article, we propose a novel pessimism-based Bayesian learning method for optimal dynamic treatment regimes in the offline setting. When the coverage condition does not hold, which is common for offline data, the existing solutions would produce sub-optimal policies. The pessimism principle addresses this issue by discouraging recommendation of actions that are less explored conditioning on the state. However, nearly all pessimism-based methods rely on a key hyper-parameter that quantifies the degree of pessimism, and the performance of the methods can be highly sensitive to the choice of this parameter. We propose to integrate the pessimism principle with Thompson sampling and Bayesian machine learning for optimizing the degree of pessimism. We derive a credible set whose boundary uniformly lower bounds the optimal Q-function, and thus does not require additional tuning of the degree of pessimism. We develop a general Bayesian learning method that works with a range of models, from Bayesian linear basis model to Bayesian neural network model. We develop the computational algorithm based on variational inference, which is highly efficient and scalable. We establish the theoretical guarantees of the proposed method, and show empirically that it outperforms the existing state-of-the-art solutions through both simulations and a real data example.

Post-Regularization Confidence Bands for Ordinary Differential Equations

Ordinary differential equation (ODE) is an important tool to study the dynamics of a system of biological and physical processes. A central question in ODE modeling is to infer the significance of individual regulatory effect of one signal variable on another. However, building confidence band for ODE with unknown regulatory relations is challenging, and it remains largely an open question. In this article, we construct post-regularization confidence band for individual regulatory function in ODE with unknown functionals and noisy data observations. Our proposal is the first of its kind, and is built on two novel ingredients. The first is a new localized kernel learning approach that combines reproducing kernel learning with local Taylor approximation, and the second is a new de-biasing method that tackles infinite-dimensional functionals and additional measurement errors. We show that the constructed confidence band has the desired asymptotic coverage probability, and the recovered regulatory network approaches the truth with probability tending to one. We establish the theoretical properties when the number of variables in the system can be either smaller or larger than the number of sampling time points, and we study the regime-switching phenomenon. We demonstrate the efficacy of the proposed method through both simulations and illustrations with two data applications.

Testing Directed Acyclic Graph via Structural, Supervised and Generative Adversarial Learning

In this article, we propose a new hypothesis testing method for directed acyclic graph (DAG). While there is a rich class of DAG estimation methods, there is a relative paucity of DAG inference solutions. Moreover, the existing methods often impose some specific model structures such as linear models or additive models, and assume independent data observations. Our proposed test instead allows the associations among the random variables to be nonlinear and the data to be time-dependent. We build the test based on some highly flexible neural networks learners. We establish the asymptotic guarantees of the test, while allowing either the number of subjects or the number of time points for each subject to diverge to infinity. We demonstrate the efficacy of the test through simulations and a brain connectivity network analysis.

Nonparametric Trace Regression in High Dimensions via Sign Series Representation

Learning of matrix-valued data has recently surged in a range of scientific and business applications. Trace regression is a widely used method to model effects of matrix predictors and has shown great success in matrix learning. However, nearly all existing trace regression solutions rely on two assumptions: (i) a known functional form of the conditional mean, and (ii) a global low-rank structure in the entire range of the regression function, both of which may be violated in practice. In this article, we relax these assumptions by developing a general framework for nonparametric trace regression models via structured sign series representations of high dimensional functions. The new model embraces both linear and nonlinear trace effects, and enjoys rank invariance to order-preserving transformations of the response. In the context of matrix completion, our framework leads to a substantially richer model based on what we coin as the "sign rank" of a matrix. We show that the sign series can be statistically characterized by weighted classification tasks. Based on this connection, we propose a learning reduction approach to learn the regression model via a series of classifiers, and develop a parallelable computation algorithm to implement sign series aggregations. We establish the excess risk bounds, estimation error rates, and sample complexities. Our proposal provides a broad nonparametric paradigm to many important matrix learning problems, including matrix regression, matrix completion, multi-task learning, and compressed sensing. We demonstrate the advantages of our method through simulations and two applications, one on brain connectivity study and the other on high-rank image completion.

Orthogonal Statistical Inference for Multimodal Data Analysis

Multimodal imaging has transformed neuroscience research. While it presents unprecedented opportunities, it also imposes serious challenges. Particularly, it is difficult to combine the merits of interpretability attributed to a simple association model and flexibility achieved by a highly adaptive nonlinear model. In this article, we propose an orthogonal statistical inferential framework, built upon the Neyman orthogonality and a form of decomposition orthogonality, for multimodal data analysis. We target the setting that naturally arises in almost all multimodal studies, where there is a primary modality of interest, plus additional auxiliary modalities. We successfully establish the root-$N$-consistency and asymptotic normality of the estimated primary parameter, the semi-parametric estimation efficiency, and the asymptotic honesty of the confidence interval of the predicted primary modality effect. Our proposal enjoys, to a good extent, both model interpretability and model flexibility. It is also considerably different from the existing statistical methods for multimodal data integration, as well as the orthogonality-based methods for high-dimensional inferences. We demonstrate the efficacy of our method through both simulations and an application to a multimodal neuroimaging study of Alzheimer's disease.

Image-on-Scalar Regression via Deep Neural Networks

A research topic of central interest in neuroimaging analysis is to study the associations between the massive imaging data and a set of covariates. This problem is challenging, due to the ultrahigh dimensionality, the high and heterogeneous level of noise, and the limited sample size of the imaging data. To address those challenges, we develop a novel image-on-scalar regression model, where the spatially-varying coefficients and the individual spatial effects are all constructed through deep neural networks (DNN). Compared with the existing solutions, our method is much more flexible in capturing the complex patterns among the brain signals, of which the noise level and the spatial smoothness appear to be heterogeneous across different brain regions. We develop a hybrid stochastic gradient descent estimation algorithm, and derive the asymptotic properties when the number of voxels grows much faster than the sample size. We show that the new method outperforms the existing ones through both extensive simulations and two neuroimaging data examples.