arXiv:2602.04901q-bio.GNcs.LG2026-02被引 3

建模基因协同调控程序,提升单细胞扰动预测精度

Beyond Independent Genes: Learning Module-Inductive Representations for Single-Cell Gene Perturbation Prediction

  • 从数据中自动发现基因功能模块,显式建模其协同变化
  • 在未见和组合扰动上平均比顶尖方法高6.7%
  • 适合研究基因调控网络与复杂遗传干预的学者

预测基因扰动引起的转录响应是功能基因组学的核心问题。实际中,扰动反应很少独立于单个基因,而是表现为功能相关基因间的协调性、程序级转录变化。然而,现有方法大多未显式建模此类协调性,受限于基因粒度的建模范式及无法捕捉动态程序重组的静态生物先验。为此,我们提出scBIG,一种模块归纳式的扰动预测框架,能显式建模协同基因程序。scBIG通过基因关系聚类从数据中诱导出一致的基因程序,利用基因簇感知编码器捕捉程序间交互,并通过结构感知对齐目标保持模块化协调性。这些结构化表征随后通过条件流匹配建模,实现灵活且可泛化的扰动预测。在多个单细胞扰动基准测试中,scBIG持续优于当前最先进方法,尤其在未见和组合扰动设置下表现突出,平均较最强基线提升6.7%。代码已开源:https://github.com/ttruan2426-dot/scBIG。

原文摘要 · Abstract (English)

Predicting transcriptional responses to genetic perturbations is a central problem in functional genomics. In practice, perturbation responses are rarely gene-independent but instead manifest as coordinated, program-level transcriptional changes among functionally related genes. However, most existing methods do not explicitly model such coordination, due to gene-wise modeling paradigms and reliance on static biological priors that cannot capture dynamic program reorganization. To address these limitations, we propose scBIG, a module-inductive perturbation prediction framework that explicitly models coordinated gene programs. scBIG induces coherent gene programs from data via Gene-Relation Clustering, captures inter-program interactions through a Gene-Cluster-Aware Encoder, and preserves modular coordination using structure-aware alignment objectives. These structured representations are then modeled using conditional flow matching to enable flexible and generalizable perturbation prediction. Extensive experiments on multiple single-cell perturbation benchmarks show that scBIG consistently outperforms state-of-the-art methods, particularly on unseen and combinatorial perturbation settings, achieving an average improvement of 6.7% over the strongest baselines. The code is available at https://github.com/ttruan2426-dot/scBIG.

单细胞基因扰动模块化表型预测

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