BRIDGE通过动态门控与生物证据优化,提升单细胞数据中基因调控网络预测的准确性。
BRIDGE: Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks

- 融合基因与细胞双空间对比学习,增强表达关系建模。
- 在7种细胞类型上平均AUPRC提升5%,跨细胞类型少样本迁移更优。
- 适合研究细胞状态特异性调控机制的生物信息学工作者。
从单细胞RNA测序(scRNA-seq)数据推断基因调控网络(GRN)对揭示细胞状态特异的转录程序至关重要。然而,scRNA-seq数据稀疏且噪声大,实验验证的转录因子-靶基因互作有限,导致可靠推断困难。尽管图神经网络已推动GRN预测发展,现有方法常依赖无生物学约束的图增强(如随机边扰动),且未能有效控制基因与细胞间的信息传递。这可能导致调控结构失真,并在噪声和弱监督条件下降低鲁棒性。为此,我们提出创新框架BRIDGE:从表达矩阵及其对偶矩阵中提取基因与细胞表征,在共表达优化的调控视图与原始图之间进行基因空间与细胞空间的对比学习;随后采用异构门控编码,自适应调节基因与细胞间信息流,实现稳健的转录因子到靶基因预测。在涵盖三种网络类型和七种细胞类型的基准数据集上,BRIDGE在多数设置下达到最优的AUROC与AUPRC。尤其在特定网络上,其平均AUPRC比第二佳基线GCLink提升5%。在跨细胞类型少样本迁移任务中,BRIDGE在全部六种目标细胞类型上均优于GCLink与GENELink。对人胚胎干细胞(hESC)的案例研究进一步验证预测的生物学相关性:前10个新发现互作中有9个、前100个中有46个被ChIPBase验证。
原文摘要 · Abstract (English)
Motivation: Gene regulatory network inference from single-cell RNA sequencing (scRNA-seq) data is important for uncovering cell-state-specific transcriptional programs. However, scRNA-seq measurements are sparse and noisy, and experimentally validated TF-target interactions remain limited, making reliable inference challenging. Although graph neural networks have advanced GRN prediction, existing methods often rely on biologically unconstrained graph augmentation, such as random edge perturbation, and insufficiently control information transfer between genes and cells. These limitations may distort regulatory structures and weaken robustness under noisy and weakly supervised settings. Results: To address these issues, we propose an innovative framework named Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks (BRIDGE). BRIDGE extracts gene and cell representations from the expression matrix and its matrix dual, and performs contrastive learning in the gene space and cell space between self and neighbors across the co-expression-refined regulatory view and the original graph. It then applies heterogeneous gated encoding to adaptively regulate information transfer between genes and cells, enabling robust transcription factor-to-target gene prediction. Experiments on benchmark datasets spanning three network types and seven cell types show that BRIDGE achieves state-of-the-art AUROC and AUPRC in most settings. In particular, on Specific networks, BRIDGE improves average AUPRC by 5% over the second-best baseline, GCLink. In cross-cell-type few-shot transfer, BRIDGE consistently outperforms GCLink and GENELink across all six target cell types. A case study on hESC further supports the biological relevance of the predictions, with 9 of the top 10 and 46 of the top 100 novel TF-target interactions validated by ChIPBase.
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