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HiSTOR: Structured Treatment-outcome Representation Learning for High-Dimensional Longitudinal Data

Chuanqi Lao Junzhou Huang Qiao Liu
Oct 2026
Artificial Intelligence Machine Learning

Abstract

Estimating potential outcomes under alternative treatment sequences is essential for personalized decision-making, but remains challenging with high-dimensional covariates and time-varying confounding. In this study, we propose HiSTOR (High-dimensional Structured Treatment-Outcome Representation), an end-to-end framework that integrates nonlinear dimension reduction with longitudinal counterfactual prediction. The central idea is to learn structured low-dimensional representations of both current patient states and evolving histories, according to their shared and distinct relationships with treatment assignment and outcomes. This extends latent-space covariate adjustment to longitudinal settings, jointly addressing covariate dimensionality and historical complexity. The resulting framework supports one-step and multi-step outcome prediction under specified treatment sequences. Experiments on CVSim and CancerSim demonstrate the superiority of HiSTOR across varying covariate dimensions, confounding strengths, and prediction horizons compared to state-of-the-art methods. To sum up, HiSTOR offers a unified approach to connecting high-dimensional covariate adjustment with longitudinal potential-outcome prediction.

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