什么使得表征对单细胞扰动预测有效? / What Makes a Representation Good for Single-Cell Perturbation Prediction?
1️⃣ 一句话总结
本文提出了一种名为PerturbedVAE的通用框架,通过将稀疏的扰动特异性信号与占主导地位的扰动不变信号明确分离,有效解决了单细胞基因表达预测中信号不平衡的问题,从而在分布外组合预测等任务上达到了最先进性能,并能揭示可解释的扰动响应机制。
Single-cell perturbation modeling is fundamental for understanding and predicting cellular responses to genetic perturbations. However, existing approaches, from causal representation learning to foundation models, often struggle with an overlooked challenge: gene expression is dominated by perturbation-invariant information, while perturbation-specific signals are intrinsically sparse. As a result, learned representations either entangle invariant and perturbation-specific information, leading to spurious and non-generalizable predictors, or suppress perturbation-specific signals altogether, rendering them ineffective for prediction. To address this, we propose PerturbedVAE, a general framework designed to resolve this signal imbalance. The framework explicitly separates perturbation-specific information from dominant invariant structure and recovers causal representations to effectively utilize such information for prediction. We further provide an identifiability analysis that characterizes the conditions under which sparse perturbation effects can be reliably recovered, thereby clarifying how the framework can be concretely specified under such conditions. Empirically, PerturbedVAE achieves state-of-the-art performance on a widely used benchmark across multiple evaluation settings, yielding significant gains on out-of-distribution combinatorial predictions and uncovering interpretable perturbation-response programs.
什么使得表征对单细胞扰动预测有效? / What Makes a Representation Good for Single-Cell Perturbation Prediction?
本文提出了一种名为PerturbedVAE的通用框架,通过将稀疏的扰动特异性信号与占主导地位的扰动不变信号明确分离,有效解决了单细胞基因表达预测中信号不平衡的问题,从而在分布外组合预测等任务上达到了最先进性能,并能揭示可解释的扰动响应机制。
源自 arXiv: 2605.19343