Fixed-Confidence Best-Arm Identification for Causal Mediation Analysis

This paper studies the problem of identifying the treatment that maximizes the expected natural direct potential outcome (NDPO), which captures the potential outcome of an intervention while excluding the pathway transmitted through a mediator that researchers may wish to remove from evaluation. We first establish population-level identification of the expected NDPO in a causal bandit setting using observable interventional distributions. We then develop a fixed-confidence best-arm identification (BAI) algorithm based on the Track-and-Stop (TaS) framework, employing a cutting-set method to solve the resulting semi-infinite optimization problem. The proposed algorithm achieves sample-efficient identification with a high-probability correctness guarantee. We prove that it satisfies $δ$-correctness and asymptotic optimality. Finally, we validate the approach through empirical evaluations on a large-scale real-world advertising dataset (IPinYou).

RetiSEM: Generalising Causal Models for Fragmented Biomedical Data

Learning causal models from fragmented biomedical data is challenging because clinical, molecular, and imaging variables are often incomplete or not jointly observed. We propose RetiSEM, a domain-constrained structural equation modelling (SEM) framework for causal graph recovery and mediation analysis under limited multimodal resources. This proposed work organises variables into biologically informed blocks, applies forbidden-edge constraints, and decomposes pathway-level effects into TE, NDE, and NIE components. We evaluate RetiSEM across ten synthetic benchmark scenarios that vary in dimensionality, nonlinearity, causal depth, and pathway structure, together with a fragmented real-world setting that combines NHANES clinical variables with externally derived retinal representations. This approach achieves lower structural error and higher causal accuracy than unconstrained baselines across the synthetic benchmarks. In the real-data analysis, retinal variables behave mainly as downstream biomarker-like indicators, with smaller but detectable indirect effects. These findings support our strategy as an interpretable framework for testing structured causal hypotheses in limited-resource biomedical AI. The code and resources for this work are publicly available at: https://github.com/Inamullah-Colab/ReitSEM.

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.

Proximal Mediation Analysis with Hidden Recanting Witnesses

Mediation analysis is essential for decomposing the causal effect of a treatment into direct and indirect pathways. However, many practical settings rely on the stringent assumption that recanting witnesses, defined as treatment-induced mediator-outcome confounders, are either absent or fully known a priori. Such a requirement is often untenable, especially when these variables remain unobservable due to measurement difficulties or privacy constraints. In this paper, we leverage proximal causal inference to develop three novel identification strategies to address the challenge of identifying path-specific effects in the presence of unknown recanting witnesses. Building on this, we develop a semiparametric inference framework that derives the efficient influence function and proposes a proximal multiply robust estimator, which remains consistent if at least one set of nuisance models is correctly specified. When all nuisance models are correctly specified and converge at appropriate rates, the estimator is asymptotically normal and achieves the semiparametric efficiency bound. We provide a minimax optimization-based debiased machine learning procedure for point estimation and constructing valid confidence intervals. The performance of the proposed methods is demonstrated by simulation studies and a real data application.