arXiv:2607.13120cs.LGcs.AI2026-07

用新基准和扩散模型,提升单细胞数据中基因调控网络的精准预测。

CoDiffGRN: Rethinking Gene Regulatory Network Inference via the BEELINE-KGC Benchmark and Co-evolutionary Discrete Diffusion

论文配图:CoDiffGRN: Rethinking Gene Regulatory Network Inference via the BEELINE-KGC Benchmark and Co-evolutionary Discrete Diffusion
图 1 · 摘自论文原文
  • 将基因网络推断转为归纳式排序任务,聚焦高置信度互作发现。
  • 在新基准上显著超越现有方法,在未见基因上仍保持高精度。
  • 适合需要实验验证的生物学家,尤其关注新型调控关系挖掘。

从单细胞转录组数据推断基因调控网络(GRNs)对生物发现至关重要,但现有方法与真实需求存在根本性脱节。研究人员通常希望获得少量高置信度调控互作用于实验验证,且常涉及此前未见基因。然而,当前基准多采用归纳式划分并依赖全局分类指标,而主流模型在归纳设置下泛化能力差。为此,我们重新定义GRN推断为归纳式、以排序为中心的图补全问题,并提出 extbf{enchmark},一个包含归纳式基因留出划分及知识图谱补全指标的新基准,更优评估前 ranked 预测。基于此,我们提出 extbf{/method},首个共进化离散扩散框架,联合建模生物一致的离散基因表达状态与调控互作,实现鲁棒的归纳泛化与优异的前 ranked 调控发现。我们进一步引入 TF-ALL 子图采样(TASS)以支持可扩展训练。在 {enchmark} 上的大量实验表明,{/method} 建立了新的最先进性能,显著优于现有方法,尤其在新调控关系发现上表现突出,消融实验也验证了设计的有效性。

原文摘要 · Abstract (English)

Inferring gene regulatory networks (GRNs) from single-cell transcriptomic data is crucial for biological discovery, yet existing approaches suffer from a fundamental misalignment with real-world needs. Researchers typically seek a small set of high-confidence regulatory interactions for experimental validation, often involving previously unseen genes. However, current benchmarks rely on transductive splits with global classification metrics, while prevailing models struggle to generalize under inductive settings. To bridge this gap, we reformulate GRN inference as an inductive, ranking-centric graph completion problem and introduce \textbf{\benchmark}, a new benchmark that incorporates an inductive gene-holdout split together with knowledge graph completion metrics to better evaluate top-ranked predictions. Building on this, we propose \textbf{\method}, the first co-evolutionary discrete diffusion framework that jointly models biologically coherent discretized gene expression states and regulatory interactions for robust inductive generalization and improved top-ranked regulatory discovery. We further introduce TF-ALL Subgraph Sampling (TASS) for scalable training. Extensive experiments on {\benchmark} show that {\method} establishes new state-of-the-art performance, significantly outperforming existing methods in novel regulatory discovery, and ablation studies further verify the effectiveness of our design.

基因网络扩散模型单细胞归纳学习

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