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MCAnalysis: An Open-Source Package for Preprocessing, Modelling, and Visualisation of Menstrual Cycle Effects in Digital Health Data

Delray, Kyra, Lewis, Glyn, Grace, Bola, Hayes, Joseph, Evans, Robin

arXiv.org Machine Learning

Digital Health Technologies (DHTs) including consumer wearable devices and digital health applications offer an opportunity for continuous, large-scale data collection. Wearables give insight into physiological biomarkers that help us understand the human body, through passive data collection. Such data can be collected at a regularity that would be impossible otherwise. Digital health applications provide the chance to collect diverse types of data from clinically validated surveys, GPS, and contextual inputs. This combination has the ability to make profound advances in our understanding of the factors that affect individuals on a personal and population level [Grace et al., 2025]. One of these factors is the menstrual cycle. Particularly because of its inter-individual variability, studying it requires large sample sizes, and to truly grasp its effects on the human body, it needs to be observed on a near-daily scale [Bull et al., 2019].


Iterative Identification Closure: Amplifying Causal Identifiability in Linear SEMs

Ding, Ziyi, Zhang, Xiao-Ping

arXiv.org Machine Learning

The Half-Trek Criterion (HTC) is the primary graphical tool for determining generic identifiability of causal effect coefficients in linear structural equation models (SEMs) with latent confounders. However, HTC is inherently node-wise: it simultaneously resolves all incoming edges of a node, leaving a gap of "inconclusive" causal effects (15-23% in moderate graphs). We introduce Iterative Identification Closure (IIC), a general framework that decouples causal identification into two phases: (1) a seed function S_0 that identifies an initial set of edges from any external source of information (instrumental variables, interventions, non-Gaussianity, prior knowledge, etc.); and (2) Reduced HTC propagation that iteratively substitutes known coefficients to reduce system dimension, enabling identification of edges that standard HTC cannot resolve. The core novelty is iterative identification propagation: newly identified edges feed back to unlock further identification -- a mechanism absent from all existing graphical criteria, which treat each edge (or node) in isolation. This propagation is non-trivial: coefficient substitution alters the covariance structure, and soundness requires proving that the modified Jacobian retains generic full rank -- a new theoretical result (Reduced HTC Theorem). We prove that IIC is sound, monotone, converges in O(|E|) iterations (empirically <=2), and strictly subsumes both HTC and ancestor decomposition. Exhaustive verification on all graphs with n<=5 (134,144 edges) confirms 100% precision (zero false positives); with combined seeds, IIC reduces the HTC gap by over 80%. The propagation gain is gamma~4x (2 seeds identifying ~3% of edges to 97.5% total identification), far exceeding gamma<=1.2x of prior methods that incorporate side information without iterative feedback.


Debiased Machine Learning for Conformal Prediction of Counterfactual Outcomes Under Runtime Confounding

Barnatchez, Keith, Josey, Kevin P., Nethery, Rachel C., Parmigiani, Giovanni

arXiv.org Machine Learning

Data-driven decision making frequently relies on predicting counterfactual outcomes. In practice, researchers commonly train counterfactual prediction models on a source dataset to inform decisions on a possibly separate target population. Conformal prediction has arisen as a popular method for producing assumption-lean prediction intervals for counterfactual outcomes that would arise under different treatment decisions in the target population of interest. However, existing methods require that every confounding factor of the treatment-outcome relationship used for training on the source data is additionally measured in the target population, risking miscoverage if important confounders are unmeasured in the target population. In this paper, we introduce a computationally efficient debiased machine learning framework that allows for valid prediction intervals when only a subset of confounders is measured in the target population, a common challenge referred to as runtime confounding. Grounded in semiparametric efficiency theory, we show the resulting prediction intervals achieve desired coverage rates with faster convergence compared to standard methods. Through numerous synthetic and semi-synthetic experiments, we demonstrate the utility of our proposed method.


Identifying and Estimating Causal Direct Effects Under Unmeasured Confounding

Boileau, Philippe, Hejazi, Nima S., Malenica, Ivana, Gilbert, Peter B., Dudoit, Sandrine, van der Laan, Mark J.

arXiv.org Machine Learning

Causal mediation analysis provides techniques for defining and estimating effects that may be endowed with mechanistic interpretations. With many scientific investigations seeking to address mechanistic questions, causal direct and indirect effects have garnered much attention. The natural direct and indirect effects, the most widely used among such causal mediation estimands, are limited in their practical utility due to stringent identification requirements. Accordingly, considerable effort has been invested in developing alternative direct and indirect effect decompositions with relaxed identification requirements. Such efforts often yield effect definitions with nuanced and challenging interpretations. By contrast, relatively limited attention has been paid to relaxing the identification assumptions of the natural direct and indirect effects. Motivated by a secondary aim of a recent non-randomized vaccine prospective cohort study (NCT05168813), we present a set of relaxed conditions under which the natural direct effect is identifiable in spite of unobserved baseline confounding of the exposure-mediator pathway; we use this result to investigate the effect mediated by putative immune correlates of protection. Relaxing the commonly used but restrictive cross-world counterfactual independence assumption, we discuss strategies for evaluating the natural direct effect in non-randomized settings that arise in the analysis of vaccine studies. We revisit prior studies of semi-parametric efficiency theory to demonstrate the construction of flexible, multiply robust estimators of the natural direct effect and discuss efficient estimation strategies that do not place restrictive modeling assumptions on nuisance functions.


Causal Effect Inference with Deep Latent-Variable Models

Neural Information Processing Systems

Learning individual-level causal effects from observational data, such as inferring the most effective medication for a specific patient, is a problem of growing importance for policy makers. The most important aspect of inferring causal effects from observational data is the handling of confounders, factors that affect both an intervention and its outcome. A carefully designed observational study attempts to measure all important confounders. However, even if one does not have direct access to all confounders, there may exist noisy and uncertain measurement of proxies for confounders. We build on recent advances in latent variable modeling to simultaneously estimate the unknown latent space summarizing the confounders and the causal effect. Our method is based on Variational Autoencoders (VAE) which follow the causal structure of inference with proxies. We show our method is significantly more robust than existing methods, and matches the state-of-the-art on previous benchmarks focused on individual treatment effects.


Nonparametric Identification and Inference for Counterfactual Distributions with Confounding

Sun, Jianle, Zhang, Kun

arXiv.org Machine Learning

We propose nonparametric identification and semiparametric estimation of joint potential outcome distributions in the presence of confounding. First, in settings with observed confounding, we derive tighter, covariate-informed bounds on the joint distribution by leveraging conditional copulas. To overcome the non-differentiability of bounding min/max operators, we establish the asymptotic properties for both a direct estimator with polynomial margin condition and a smooth approximation with log-sum-exp operator, facilitating valid inference for individual-level effects under the canonical rank-preserving assumption. Second, we tackle the challenge of unmeasured confounding by introducing a causal representation learning framework. By utilizing instrumental variables, we prove the nonparametric identifiability of the latent confounding subspace under injectivity and completeness conditions. We develop a ``triple machine learning" estimator that employs cross-fitting scheme to sequentially handle the learned representation, nuisance parameters, and target functional. We characterize the asymptotic distribution with variance inflation induced by representation learning error, and provide conditions for semiparametric efficiency. We also propose a practical VAE-based algorithm for confounding representation learning. Simulations and real-world analysis validate the effectiveness of proposed methods. By bridging classical semiparametric theory with modern representation learning, this work provides a robust statistical foundation for distributional and counterfactual inference in complex causal systems.