arXiv Machine Learning September 30, 2026 By Eli N. Weinstein, Elizabeth B. Wood, David M. Blei

Estimating the Causal Effects of T Cell Receptors

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The paper introduces a method for estimating the causal effects of T cell receptor (TCR) sequences on patient outcomes using observational TCR sequencing and clinical data. It corrects for unobserved confounders by leveraging the pre-selection TCR repertoire generated through V(D)J recombination as a natural experiment, and employs permutation‑invariant neural networks to scale to millions of sequences. The approach is validated on semisynthetic data and applied to COVID‑19 severity, identifying TCRs that are observed in patients, bind SARS‑CoV‑2 antigens in vitro, and positively influence clinical outcomes.

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