Distribution shift is the defining challenge of real-world machine learning. The dominant paradigm--Unsupervised Domain Adaptation (UDA)--enforces feature invariance, aligning source and target representations via symmetric divergence minimization [Ganin et al., 2016]. We demonstrate that this approach is fundamentally flawed: when domains are unequally informative (e.g., high-quality vs degraded sensors), strict invariance necessitates information destruction, causing "negative transfer" that can be catastrophic in safety-critical applications [Wang et al., 2019]. We propose a decision-theoretic framework grounded in Le Cam's theory of statistical experiments [Le Cam, 1986], using constructive approximations to replace symmetric invariance with directional simulability. We introduce Le Cam Distortion, quantified by the Deficiency Distance $δ(E_1, E_2)$, as a rigorous upper bound for transfer risk conditional on simulability. Our framework enables transfer without source degradation by learning a kernel that simulates the target from the source. Across five experiments (genomics, vision, reinforcement learning), Le Cam Distortion achieves: (1) near-perfect frequency estimation in HLA genomics (correlation $r=0.999$, matching classical methods), (2) zero source utility loss in CIFAR-10 image classification (81.2% accuracy preserved vs 34.7% drop for CycleGAN), and (3) safe policy transfer in RL control where invariance-based methods suffer catastrophic collapse. Le Cam Distortion provides the first principled framework for risk-controlled transfer learning in domains where negative transfer is unacceptable: medical imaging, autonomous systems, and precision medicine.

Machine Learning (ML) has been a foundational topic in artificial intelligence (AI), providing both theoretical groundwork and practical tools for its exciting advancements. From ResNet for visual recognition to Transformer for vision-language alignment, the AI models have achieved superior capability to humans. Furthermore, the scaling law has enabled AI to initially develop general intelligence, as demonstrated by Large Language Models (LLMs). To this stage, AI has had an enormous influence on society and yet still keeps shaping the future for humanity. However, distribution shift remains a persistent ``Achilles' heel'', fundamentally limiting the reliability and general usefulness of ML systems. Moreover, generalization under distribution shift would also cause trust issues for AIs. Motivated by these challenges, my research focuses on \textit{Trustworthy Machine Learning under Distribution Shifts}, with the goal of expanding AI's robustness, versatility, as well as its responsibility and reliability. We carefully study the three common distribution shifts into: (1) Perturbation Shift, (2) Domain Shift, and (3) Modality Shift. For all scenarios, we also rigorously investigate trustworthiness via three aspects: (1) Robustness, (2) Explainability, and (3) Adaptability. Based on these dimensions, we propose effective solutions and fundamental insights, meanwhile aiming to enhance the critical ML problems, such as efficiency, adaptability, and safety.

Accurate spatial interpolation of the air quality index (AQI), computed from concentrations of multiple air pollutants, is essential for regulatory decision-making, yet AQI fields are inherently non-Gaussian and often exhibit complex nonlinear spatial structure. Classical spatial prediction methods such as kriging are linear and rely on Gaussian assumptions, which limits their ability to capture these features and to provide reliable predictive distributions. In this study, we propose \textit{deep classifier kriging} (DCK), a flexible, distribution-free deep learning framework for estimating full predictive distribution functions for univariate and bivariate spatial processes, together with a \textit{data fusion} mechanism that enables modeling of non-collocated bivariate processes and integration of heterogeneous air pollution data sources. Through extensive simulation experiments, we show that DCK consistently outperforms conventional approaches in predictive accuracy and uncertainty quantification. We further apply DCK to probabilistic spatial prediction of AQI by fusing sparse but high-quality station observations with spatially continuous yet biased auxiliary model outputs, yielding spatially resolved predictive distributions that support downstream tasks such as exceedance and extreme-event probability estimation for regulatory risk assessment and policy formulation.

Causal inference is a key research area in machine learning, yet confusion reigns over the tools needed to tackle it. There are prevalent claims in the machine learning literature that you need a bespoke causal framework or notation to answer causal questions. In this paper, we want to make it clear that you \emph{can} answer any causal inference question within the realm of probabilistic modelling and inference, without causal-specific tools or notation. Through concrete examples, we demonstrate how causal questions can be tackled by writing down the probability of everything. Lastly, we reinterpret causal tools as emerging from standard probabilistic modelling and inference, elucidating their necessity and utility.

Optimization under heavy-tailed noise has become popular recently, since it better fits many modern machine learning tasks, as captured by empirical observations. Concretely, instead of a finite second moment on gradient noise, a bounded ${\frak p}$-th moment where ${\frak p}\in(1,2]$ has been recognized to be more realistic (say being upper bounded by $σ_{\frak l}^{\frak p}$ for some $σ_{\frak l}\ge0$). A simple yet effective operation, gradient clipping, is known to handle this new challenge successfully. Specifically, Clipped Stochastic Gradient Descent (Clipped SGD) guarantees a high-probability rate ${\cal O}(σ_{\frak l}\ln(1/δ)T^{1/{\frak p}-1})$ (resp. ${\cal O}(σ_{\frak l}^2\ln^2(1/δ)T^{2/{\frak p}-2})$) for nonsmooth convex (resp. strongly convex) problems, where $δ\in(0,1]$ is the failure probability and $T\in\mathbb{N}$ is the time horizon. In this work, we provide a refined analysis for Clipped SGD and offer two faster rates, ${\cal O}(σ_{\frak l}d_{\rm eff}^{-1/2{\frak p}}\ln^{1-1/{\frak p}}(1/δ)T^{1/{\frak p}-1})$ and ${\cal O}(σ_{\frak l}^2d_{\rm eff}^{-1/{\frak p}}\ln^{2-2/{\frak p}}(1/δ)T^{2/{\frak p}-2})$, than the aforementioned best results, where $d_{\rm eff}\ge1$ is a quantity we call the $\textit{generalized effective dimension}$. Our analysis improves upon the existing approach on two sides: better utilization of Freedman's inequality and finer bounds for clipping error under heavy-tailed noise. In addition, we extend the refined analysis to convergence in expectation and obtain new rates that break the known lower bounds. Lastly, to complement the study, we establish new lower bounds for both high-probability and in-expectation convergence. Notably, the in-expectation lower bounds match our new upper bounds, indicating the optimality of our refined analysis for convergence in expectation.

Attenuation bias -- the systematic underestimation of regression coefficients due to measurement errors in input variables -- affects astronomical data-driven models. For linear regression, this problem was solved by treating the true input values as latent variables to be estimated alongside model parameters. In this paper, we show that neural networks suffer from the same attenuation bias and that the latent variable solution generalizes directly to neural networks. We introduce LatentNN, a method that jointly optimizes network parameters and latent input values by maximizing the joint likelihood of observing both inputs and outputs. We demonstrate the correction on one-dimensional regression, multivariate inputs with correlated features, and stellar spectroscopy applications. LatentNN reduces attenuation bias across a range of signal-to-noise ratios where standard neural networks show large bias. This provides a framework for improved neural network inference in the low signal-to-noise regime characteristic of astronomical data. This bias correction is most effective when measurement errors are less than roughly half the intrinsic data range; in the regime of very low signal-to-noise and few informative features. Code is available at https://github.com/tingyuansen/LatentNN.

In applications with significant class imbalance or asymmetric costs, metrics such as the $F_β$-measure, AM measure, Jaccard similarity coefficient, and weighted accuracy offer more suitable evaluation criteria than standard binary classification loss. However, optimizing these metrics present significant computational and statistical challenges. Existing approaches often rely on the characterization of the Bayes-optimal classifier, and use threshold-based methods that first estimate class probabilities and then seek an optimal threshold. This leads to algorithms that are not tailored to restricted hypothesis sets and lack finite-sample performance guarantees. In this work, we introduce principled algorithms for optimizing generalized metrics, supported by $H$-consistency and finite-sample generalization bounds. Our approach reformulates metric optimization as a generalized cost-sensitive learning problem, enabling the design of novel surrogate loss functions with provable $H$-consistency guarantees. Leveraging this framework, we develop new algorithms, METRO (Metric Optimization), with strong theoretical performance guarantees. We report the results of experiments demonstrating the effectiveness of our methods compared to prior baselines.

Modern generative and vision-language models (VLMs) are increasingly used in scientific and medical decision support, where predicted probabilities must be both accurate and well calibrated. Despite strong empirical results with moderate data, it remains unclear when such predictions generalize uniformly across inputs, classes, or subpopulations, rather than only on average-a critical issue in biomedicine, where rare conditions and specific groups can exhibit large errors even when overall loss is low. We study this question from a finite-sample perspective and ask: under what structural assumptions can generative and VLM-based predictors achieve uniformly accurate and calibrated behavior with practical sample sizes? Rather than analyzing arbitrary parameterizations, we focus on induced families of classifiers obtained by varying prompts or semantic embeddings within a restricted representation space. When model outputs depend smoothly on a low-dimensional semantic representation-an assumption supported by spectral structure in text and joint image-text embeddings-classical uniform convergence tools yield meaningful non-asymptotic guarantees. Our main results give finite-sample uniform convergence bounds for accuracy and calibration functionals of VLM-induced classifiers under Lipschitz stability with respect to prompt embeddings. The implied sample complexity depends on intrinsic/effective dimension, not ambient embedding dimension, and we further derive spectrum-dependent bounds that make explicit how eigenvalue decay governs data requirements. We conclude with implications for data-limited biomedical modeling, including when current dataset sizes can support uniformly reliable predictions and why average calibration metrics may miss worst-case miscalibration.

We consider problems of parameter estimation where design variables can be actively optimized to maximize information gain. To this end, we introduce JADAI, a framework that jointly amortizes Bayesian adaptive design and inference by training a policy, a history network, and an inference network end-to-end. The networks minimize a generic loss that aggregates incremental reductions in posterior error along experimental sequences. Inference networks are instantiated with diffusion-based posterior estimators that can approximate high-dimensional and multimodal posteriors at every experimental step. Across standard adaptive design benchmarks, JADAI achieves superior or competitive performance.

Large language models (LLMs) have achieved remarkable performance but face critical challenges: hallucinations and high inference costs. Leveraging multiple experts offers a solution: deferring uncertain inputs to more capable experts improves reliability, while routing simpler queries to smaller, distilled models enhances efficiency. This motivates the problem of learning with multiple-expert deferral. This thesis presents a comprehensive study of this problem and the related problem of learning with abstention, supported by strong consistency guarantees. First, for learning with abstention (a special case of deferral), we analyze score-based and predictor-rejector formulations in multi-class classification. We introduce new families of surrogate losses and prove strong non-asymptotic, hypothesis set-specific consistency guarantees, resolving two existing open questions. We analyze both single-stage and practical two-stage settings, with experiments on CIFAR-10, CIFAR-100, and SVHN demonstrating the superior performance of our algorithms. Second, we address general multi-expert deferral in classification. We design new surrogate losses for both single-stage and two-stage scenarios and prove they benefit from strong $H$-consistency bounds. For the two-stage scenario, we show that our surrogate losses are realizable $H$-consistent for constant cost functions, leading to effective new algorithms. Finally, we introduce a novel framework for regression with deferral to address continuous label spaces. Our versatile framework accommodates multiple experts and various cost structures, supporting both single-stage and two-stage methods. It subsumes recent work on regression with abstention. We propose new surrogate losses with proven $H$-consistency and demonstrate the empirical effectiveness of the resulting algorithms.