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Decoding Causal Structure: End-to-End Mediation Pathways Inference

Neural Information Processing Systems

Causal mediation analysis is crucial for deconstructing complex mechanisms of action. However, in current mediation analysis, complex structures derived from causal discovery lack direct interpretation of mediation pathways, while traditional mediation analysis and effect estimation are limited by the reliance on pre-specified pathways, leading to a disconnection between structure discovery and causal mechanism understanding. Therefore, a unified framework integrating structure discovery, pathway identification, and effect estimation systematically quantifies mediation pathways under structural uncertainty, enabling automated identification and inference of mediation pathways. To this end, we propose Structure-Informed Guided Mediation Analysis (SIGMA), which guides automated mediation pathway identification through probabilistic causal structure discovery and uncertainty quantification, enabling end-to-end propagation of structural uncertainty from structure learning to effect estimation. Specifically, SIGMA employs differentiable Flow-Structural Equation Models to learn structural posteriors, generating diverse Directed Acyclic Graphs (DAGs) to quantify structural uncertainty. Based on these DAGs, we introduce the Path Stability Score to evaluate the marginal probability of pathways, identifying high-confidence mediation paths. For identified mediation pathways, we integrate Efficient Influence Functions with Bayesian model averaging to fuse within-structure estimation uncertainty and between-structure effect variation, propagating uncertainty to the final effect estimates. In synthetic data experiments, SIGMA achieves state-of-the-art performance in pathway identification accuracy and effect quantification precision under structural uncertainty, concurrent multiple pathways, and nonlinear scenarios. In real-world applications using Human Phenotype Project data, SIGMA identifies mediation effects of sleep quality on cardiovascular health through inflammatory and metabolic pathways, uncovering previously unspecified multiple mediation paths.


Optimal Adjustment Sets for Nonparametric Estimation of Weighted Controlled Direct Effect

Neural Information Processing Systems

The weighted controlled direct effect (WCDE) generalizes the standard controlled direct effect (CDE) by averaging over the mediator distribution, providing a robust estimate when treatment effects vary across mediator levels. This makes the WCDE especially relevant in fairness analysis, where it isolates the direct effect of an exposure on an outcome, independent of mediating pathways. This work establishes three fundamental advances for WCDE in observational studies: First, we establish necessary and sufficient conditions for the identifiability of the WCDE, clarifying when it diverges from the CDE. Next, we consider nonparametric estimation of the WCDE and derive its influence function, focusing on the class of regular and asymptotically linear estimators. Lastly, we characterize the optimal covariate adjustment set that minimizes the asymptotic variance, demonstrating how mediator-confounder interactions introduce distinct requirements compared to average treatment effect (ATE) estimation. Using synthetic and real-world data, we validate our theory numerically, showing that the proposed optimal valid adjustment set yields the lowest variance at practical sample sizes. Our results offer a principled framework for efficient estimation of direct effects in complex causal systems, with practical applications in fairness and mediation analysis.


Path-specific effects for pulse-oximetry guided decisions in critical care

Neural Information Processing Systems

Identifying and measuring biases associated with sensitive attributes is a crucial consideration in healthcare to prevent treatment disparities. One prominent issue is inaccurate pulse oximeter readings, which tend to overestimate oxygen saturation for dark-skinned patients and misrepresent supplemental oxygen needs. Most existing research has revealed statistical disparities linking device measurement errors to patient outcomes in intensive care units (ICUs) without causal formalization. This study causally investigates how racial discrepancies in oximetry measurements affect invasive ventilation in ICU settings. We employ a causal inference-based approach using path-specific effects to isolate the impact of bias by race on clinical decision-making.


When Additive Noise Meets Unobserved Mediators: Bivariate Denoising Diffusion for Causal Discovery

Neural Information Processing Systems

Distinguishing cause and effect from bivariate observational data is a foundational problem in many disciplines, but challenging without additional assumptions. Additive noise models (ANMs) are widely used to enable sample-efficient bivariate causal discovery. However, conventional ANM-based methods fail when unobserved mediators corrupt the causal relationship between variables. This paper makes three key contributions: first, we rigorously characterize why standard ANM approaches break down in the presence of unmeasured mediators. Second, we demonstrate that prior solutions for hidden mediation are brittle in finite sample settings, limiting their practical utility. To address these gaps, we propose Bivariate Denoising Diffusion (BiDD) for causal discovery, a method designed to handle latent noise introduced by unmeasured mediators. Unlike prior methods that infer directionality through mean squared error loss comparisons, our approach introduces a novel independence test statistic: during the noising and denoising processes for each variable, we condition on the other variable as input and evaluate the independence of the predicted noise relative to this input. We prove asymptotic consistency of BiDD under the ANM, and conjecture that it performs well under hidden mediation. Experiments on synthetic and real-world data demonstrate consistent performance, outperforming existing methods in mediator-corrupted settings while maintaining strong performance in mediator-free settings.


Cooperative Bargaining Games Without Utilities: Mediated Solutions from Direction Oracles

Neural Information Processing Systems

Cooperative bargaining games are widely used to model resource allocation and conflict resolution. Traditional solutions assume the mediator can access agents' utility function values and gradients. However, there is an increasing number of settings, such as human-AI interactions, where utility values may be inaccessible or incomparable due to unknown, nonaffine transformations. To model such settings, we consider that the mediator has access only to agents' most preferred directions--normalized utility gradients in the decision space. To this end, we propose a cooperative bargaining algorithm where a mediator has access to only the direction oracle of each agent. We prove that unlike popular approaches such as the Nash and Kalai-Smorodinsky bargaining solutions, our approach is invariant to monotonic nonaffine transformations, and that under strong convexity and smoothness assumptions, this approach enjoys global asymptotic convergence to Pareto stationary solutions. Moreover, we show that the bargaining solutions found by our algorithm also satisfy the axioms of symmetry and (under slightly stronger conditions) independence of irrelevant alternatives, which are popular in the literature. Finally, we conduct experiments in two domains, multi-agent formation assignment and mediated stock portfolio allocation, which validate these theoretical results.


Cooperative Bargaining Games Without Utilities: Mediated Solutions from Direction Oracles

Neural Information Processing Systems

Cooperative bargaining games are widely used to model resource allocation and conflict resolution. Traditional solutions assume the mediator can access agents' utility function values and gradients. However, there is an increasing number of settings, such as human-AI interactions, where utility values may be inaccessible or incomparable due to unknown, nonaffine transformations. To model such settings, we consider that the mediator has access only to agents' $\textit{most preferred directions}-$normalized utility gradients in the decision space. To this end, we propose a cooperative bargaining algorithm where a mediator has access to only the direction oracle of each agent. We prove that unlike popular approaches such as the Nash and Kalai-Smorodinsky bargaining solutions, our approach is invariant to monotonic nonaffine transformations, and that under strong convexity and smoothness assumptions, this approach enjoys global asymptotic convergence to Pareto stationary solutions. Moreover, we show that the bargaining solutions found by our algorithm also satisfy the axioms of symmetry and (under slightly stronger conditions) independence of irrelevant alternatives, which are popular in the literature. Finally, we conduct experiments in two domains, multi-agent formation assignment and mediated stock portfolio allocation, which validate these theoretical results.


Proximal Path-Specific Inference

arXiv.org Machine Learning

Mediation analysis (Robins & Greenland 1992, Pearl 2001, Imai, Keele & Tingley 2010, Tchetgen Tchetgen & Shpitser 2012) provides a principled framework for investigating causal mechanisms by decomposing the effect of a treatment A on an outcome Y into pathways operating through a mediator of interest M. Classical mediation analysis focuses on the natural indirect effect, corresponding to the pathway from Ato Y through M, and the natural direct effect, corresponding to pathways not through M. These estimands are well understood when a single mediator is present and strong identification assumptions hold. However, in many applications, there exist multiple intermediate variables between treatment and outcome. In such settings, conventional mediation analysis typically requires the absence of treatment-induced mediator-outcome confounders--often referred to as recanting witnesses--as well as the absence of unmeasured confounding. Under these circumstances, commonly used identification assumptions such as sequential ignorability (Imai, Keele & Yamamoto 2010) or nonparametric structural equation models with independent errors (NPSEM-IE) (Pearl 2009) no longer suffice to identify natural indirect effects (Avin et al. 2005, Tchetgen Tchetgen & VanderWeele 2014). Figure 1 illustrates this issue: the recanting witness D is directly affected by A and simultaneously confounds the relationship between M and Y. Such treatment-induced confounding is common in epidemiologic studies, particularly when the mediator of interest occurs long after the treatment initiation (Robins 1999). A motivating example arises in studies of preterm birth. Mediation analysis has been widely used to explore whether adequate prenatal care (A) reduces the risk of preterm birth (Y) through preeclampsia (M) (Vansteelandt & VanderWeele 2012, VanderWeele et al. 2014, Xia & Chan 2023).


Distributional Causal Mediation via Conditional Generative Modeling

arXiv.org Machine Learning

Mediation analysis has traditionally focused on outcome-level summary contrasts, such as mean effects, which may obscure substantial distributional changes induced by complex and nonlinear causal mechanisms. We propose Distributional Causal Mediation Analysis (DCMA), a generative learning framework for identifying and estimating treatment effects on entire outcome distributions transmitted through multiple mediators. DCMA learns conditional generative models for the mediators and the outcome, recovering the relevant conditional distributions from observational data. Leveraging the identification formulas, it reconstructs interventional outcome distributions via Monte Carlo forward simulation by noise resampling, enabling the capture of both classical summary effects and rich distributional contrasts such as energy distance and the Wasserstein distance. Analytical error bounds are derived to decompose how estimation errors in the learned conditional models propagate to the reconstructed interventional outcome distributions. The empirical effectiveness of DCMA is demonstrated through numerical experiments and real-world data applications.


AMDP: An Adaptive Detection Procedure for False Discovery Rate Control in High-Dimensional Mediation Analysis

Neural Information Processing Systems

High-dimensional mediation analysis is often associated with a multiple testing problem for detecting significant mediators. Assessing the uncertainty of this detecting process via false discovery rate (FDR) has garnered great interest. To control the FDR in multiple testing, two essential steps are involved: ranking and selection. Existing approaches either construct p-values without calibration or disregard the joint information across tests, leading to conservation in FDR control or non-optimal ranking rules for multiple hypotheses. In this paper, we develop an adaptive mediation detection procedure (referred to as "AMDP") to identify relevant mediators while asymptotically controlling the FDR in high-dimensional mediation analysis. AMDP produces the optimal rule for ranking hypotheses and proposes a data-driven strategy to determine the threshold for mediator selection. This novel method captures information from the proportions of composite null hypotheses and the distribution of p-values, which turns the high dimensionality into an advantage instead of a limitation. The numerical studies on synthetic and real data sets illustrate the performances of AMDP compared with existing approaches.