arXiv:2606.13713q-bio.GNcs.AI2026-06被引 1

基于基因功能与调控机制,预测单细胞中基因扰动的转录响应。

CisTransCell: Single-Cell Perturbation Prediction via Gene Function, Regulatory Control, and Cellular Context

论文配图:CisTransCell: Single-Cell Perturbation Prediction via Gene Function, Regulatory Control, and Cellular Context
图 1 · 摘自论文原文
  • 融合基因序列功能与调控信息,建模扰动传导路径。
  • 在零样本场景下,对未见基因组合的扰动预测准确率显著提升。
  • 适合研究基因调控网络与药物靶点发现的科研人员。

预测基因扰动引起的细胞转录响应是单细胞生物学的核心问题,尤其在零样本设置下——即扰动基因或基因组合在训练时未出现。主要难点在于:扰动效应不仅取决于表达状态,还受被扰动基因产物如何影响其他基因蛋白、下游因子如何作用于顺式调控元件,以及当前细胞状态下活跃的调控程序共同决定。为此,我们提出CisTransCell,一种细胞条件化的多模态框架,为每个基因添加两个互补先验:调控序列先验(捕捉基因如何被控制),编码序列先验(捕捉基因产物的功能)。通过整合这些先验与细胞表达状态,CisTransCell将扰动响应建模为从基因功能到调控控制再到下游转录变化的级联过程。在基准单细胞扰动数据集上的实验表明,该方法在零样本扰动预测中表现优异。

原文摘要 · Abstract (English)

Predicting cellular transcriptional responses to genetic perturbations is a central problem in single-cell biology, especially in the zero-shot setting where the perturbed gene or gene combination is unseen during training. A major difficulty is that perturbation effects are not determined by expression state alone: they depend on how the perturbed gene product influences other genes and proteins, how those downstream factors act on cis-regulatory elements, and which regulatory programs are active in the current cell state. To better capture this biological complexity, we propose CisTransCell, a cell-conditioned multi-modal framework for single-cell perturbation prediction that augments each gene with two complementary priors: a regulatory-sequence prior that captures how the gene is controlled, and a coding-sequence prior that captures what the gene product does. By integrating these priors with cellular expression state, CisTransCell models perturbation response as a cascade from gene function to regulatory control to downstream transcriptional change. Experiments on benchmark single-cell perturbation datasets show that CisTransCell achieves strong performance in zero-shot perturbation prediction.

单细胞基因扰动预测模型转录调控

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