← 研踪 PaperTrailarXiv:2606.08493 · v4
Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement
首次提交 2026-06-07 15:41
版本更新 2026-11-05 17:36
雷达观测 2026-11-06 12:09
摘要
Tissue graph counterfactuals ask what a cell would express if its spatial neighborhood were altered, a question central to predicting cell behavior in tissues. Existing methods, however, present only specific instances of such queries. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina, a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for in-silico perturbation predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in observational and interventional screens, Cellina outperforms both spatially-informed and non-spatial competitors in in-silico perturbations, while training as fast as non-spatial methods. Moreover, we show that Cellina reveals cancer subdomains with distinct signaling programs in an unsupervised manner and enables targeted neighbor perturbation simulations.
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v4 · 2026-11-05 17:36 · 最新观测版本
Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement
Tissue graph counterfactuals ask what a cell would express if its spatial neighborhood were altered, a question central to predicting cell behavior in tissues. Existing methods, however, present only specific instances of such queries. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina, a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for in-silico perturbation predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in observational and interventional screens, Cellina outperforms both spatially-informed and non-spatial competitors in in-silico perturbations, while training as fast as non-spatial methods. Moreover, we show that Cellina reveals cancer subdomains with distinct signaling programs in an unsupervised manner and enables targeted neighbor perturbation simulations.
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