arXiv:2606.00568cs.LGq-bio.GN2026-06

批量基因表达数据中因果关系是否可恢复?研究给出理论边界。

On the Recoverability of Causal Relations from Bulk Gene Expression Data

论文配图:On the Recoverability of Causal Relations from Bulk Gene Expression Data
图 1 · 摘自论文原文
  • 从聚合机制出发,定义因果可恢复的两种一致性条件
  • 仅在线性聚合与仿射结构方程下可保证因果可恢复
  • 实测数据表明基因调控多呈非线性,支持度有限

批量基因表达分析通过汇总生物样本内多个细胞的RNA,仍具重要价值,因其通常比单细胞检测更少噪声、更灵敏且成本更低。因此,越来越多计算方法尝试从批量数据中推断基因间的因果关系。然而,聚合是一种有损且不可逆的系统粗化过程,目前尚不明确因果关系在何种条件下可从聚合数据中恢复。为此,本文通过功能形式一致性和条件独立性一致性两个概念形式化了可恢复性,并推导出必要充分条件:只有在线性聚合(如求和/均值)结合仿射结构方程时,因果关系才可恢复。通过对四组批量与四组单细胞基因表达数据的分析发现,两类数据中基因间估计的成对调控函数均偏离线性,对可恢复所需的线性假设提供有限实证支持。综合结果警示:在缺乏强额外假设的情况下,不应盲目从聚合批量数据中推断因果关系。

原文摘要 · Abstract (English)

Bulk gene expression profiling, which aggregates pooled RNA across cells within a biological sample, remains important in the single-cell era because it is typically less noisy, more sensitive, and more cost-effective than single-cell assays. Accordingly, a growing body of computational methods seeks to recover causal relations among genes from bulk expression data. However, aggregation is a lossy, non-invertible coarsening of the underlying cellular system, and it remains unclear whether and under what conditions causal relations are recoverable from aggregated bulk gene expression data. To answer this, we formalize recoverability under aggregation through two notions of consistency: functional-form consistency and conditional-independence consistency. We then derive necessary and sufficient conditions for recoverability, showing that these properties are preserved only under linear aggregations (e.g., sum/mean) coupled with affine structural equations. To assess the practical plausibility of these conditions, analyses of four bulk and four single-cell gene expression datasets further reveal that the estimated pairwise regulatory functions among genes deviate from linearity in both data types, providing limited empirical support for the linearity assumptions required for recoverability. Together, these results caution against recovering causal relations from aggregated bulk expression data without strong additional assumptions.

因果推断基因网络批量数据

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。