arXiv:2607.04527stat.MLcs.LG2026-07

基于层级结构的高效因果发现,加速基因调控网络推断。

Causal ASCEND: Scalable Two-tier Causal Discovery on High Dimensional Multi-omics Data

论文配图:Causal ASCEND: Scalable Two-tier Causal Discovery on High Dimensional Multi-omics Data
图 1 · 摘自论文原文
  • 利用已知上下层级结构,动态维护条件集减少计算量。
  • 在高维多组学数据上实现多项式时间复杂度,速度远超传统方法。
  • 适合整合上游遗传因子与下游表达数据的因果分析任务。

生物系统具有从上游调控因子到下游效应的层级结构。尽管这一结构为因果推断提供了天然框架,但多数因果发现与基因调控网络(GRN)方法或忽略层级关系,或需对所有上游变量进行条件依赖测试,难以处理高维多组学数据。本文提出ASCEND(Ancestral Scalable Causal discovEry via iNherited Descent),一种基于约束的框架,利用已知的两层结构实现基因组尺度的因果发现。ASCEND采用分治策略,为每个下游变量动态维护祖先条件集,显著降低所需的条件独立性检验次数,实现多项式时间复杂度,而传统方法面临指数级增长。通过大量模拟和真实生物数据验证,ASCEND能准确恢复祖先关系,具备良好可扩展性与极快运行速度,在因果精度与计算效率上均优于现有方法。该算法解析方向性的能力使其特别适用于联合测量上游调控因子(如SNPs、甲基化位点)与下游响应(如基因表达)的多组学数据整合。

原文摘要 · Abstract (English)

Biological systems exhibit a hierarchical structure, characterised by directed flow from upstream regulators to downstream effects. Although this ordering provides a natural scaffold for causal inference, most causal discovery and GRN methods either ignore the tiered organisation or condition on all upstream variables, which becomes infeasible for high-dimensional omics data. We present ASCEND (Ancestral Scalable Causal discovEry via iNherited Descent), a constraint-based framework that leverages known two-tiered structure to enable genome-scale causal discovery. ASCEND introduces a divide-and-conquer strategy that maintains dynamically updated ancestral conditioning sets for each downstream variable, dramatically reducing the number of conditional independence tests required, and achieves polynomial-time complexity where traditional approaches face exponential blow-up. Through extensive simulations and real biological data, we demonstrate that ASCEND accurately recovers ancestral relationships, scales properly and much faster, and outperforms existing gene regulatory network inference methods in both causal precision and computational efficiency. The algorithm's ability to resolve directionality makes it particularly suited for integrating multi-omic data where upstream regulators (e.g., SNPs, methylation sites) and downstream responses (e.g., gene expression) are measured jointly.

因果发现多组学基因调控

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