arXiv:2607.28090cs.AI2026-07被引 1

用跨细胞环境迁移方法,精准预测缺失的基因扰动效应。

PerturbMap: Cross-Context Transfer of Single-Cell Perturbation Responses

论文配图:PerturbMap: Cross-Context Transfer of Single-Cell Perturbation Responses
图 1 · 摘自论文原文
  • 构建低秩基底+源到受体的岭回归专家,融合已测扰动数据。
  • 在黑色素瘤数据集上,误差比局部基底降低4.1%,接近中心化参考。
  • 适合缺乏完整扰动实验但需跨条件推断的研究者使用。

单细胞扰动图谱通常无法在所有细胞环境中测量每种干预效果:一个查询扰动常在某些源环境中有观测,但在目标环境(需预测效应)中缺失。忽略这些已测响应会丢失特异性实验证据,而直接复制或弱校准则可能传递错误信号。我们提出PerturbMap,通过结合目标环境本地的低秩基底与源环境测得响应的迁移路径,利用配对训练扰动拟合的源-受体岭回归专家进行信号传输,并根据验证锚点估计路径可靠性动态调整权重。在Perturb-CITE-seq黑色素瘤队列上,PerturbMap相比仅依赖目标环境的低秩基底,全效应均方误差降低4.1%,优于联邦平均、零响应、原始复制、校准复制及身份随机仿射等对照组。其误差仅比集中式词匹配池化参考高出2.82×10⁻⁶,表现出色。条件均值特异性诊断显示,同一目标环境下前10名相似扰动的余弦检索准确率从低秩基底的74.5%提升至PerturbMap的80.5%。

原文摘要 · Abstract (English)

Single-cell perturbation atlases rarely measure every intervention in every cellular context: a query perturbation is often observed in one or more source contexts but missing in the recipient context where its effect is needed. Ignoring those measured responses discards query-specific experimental evidence, whereas copying or weakly calibrating them across contexts risks transferring the wrong signal. We propose PerturbMap, which predicts a missing recipient-context effect by combining a recipient-local low-rank base with accepted proposals that transport the same perturbation's measured source responses through source-to-recipient ridge experts fit on paired training perturbations, with proposal weights determined by route reliability estimated on validation anchors. On the Perturb-CITE-seq melanoma cohort, PerturbMap improves full-effect MSE by 4.1\% over a recipient-local low-rank base and achieves lower MSE than FedAvg, zero-response, raw-copy, calibrated-copy, and identity-shuffled affine controls. It remains within $2.82\times10^{-6}$ MSE of our centralized token-matched pooled reference, which uses a stronger training interface. A condition-mean specificity diagnostic shows the same direction: same-recipient top-10 counterpart retrieval by cosine increases from 74.5\% for the low-rank base to 80.5\% for PerturbMap.

单细胞扰动预测跨环境迁移低秩建模

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