arXiv:2606.00685cs.LG2026-06KDD

用少量生物先验和跨模态注意力,从单细胞数据推断基因调控网络。

Prior-Guided Multi-Omic Transformers for Single-Cell Gene Regulatory Network Inference

论文配图:Prior-Guided Multi-Omic Transformers for Single-Cell Gene Regulatory Network Inference
图 1 · 摘自论文原文
  • 通过基因-峰交叉注意力学习联合表征,动态聚合开放染色质信号。
  • 在仅有少量标签时,利用批量数据先验提升调控关系预测准确率。
  • 适合研究细胞状态调控的生物学家,尤其关注单细胞多组学整合。

基因调控网络(GRNs)刻画转录因子与靶基因间的相互作用,是理解细胞状态调控与疾病机制的核心。从配对的单细胞转录组与染色质可及性数据重构GRN具有潜力但面临挑战:scATAC数据极度稀疏,且多数方法依赖固定的峰值到基因关联及弱监督。我们提出EpiAwareNet,一种基于先验引导的多组学Transformer框架,仅使用轻量级生物先验即可从配对单细胞数据中重构GRN。第一阶段,通过基因-峰交叉注意力模块学习联合基因-峰表征,实现数据驱动、基因特异性的可及性信号聚合,而非硬编码的峰值-基因分配。第二阶段,引入来自批量数据的GRN先验作为噪声正例,提供弱监督以在标签稀缺下优化调控评分,同时保持对先验噪声的鲁棒性。实验表明,EpiAwareNet在代表性单/多组学基线之上显著提升GRN重构性能,生成的网络更具生物学合理性,例如更优地恢复已知调控关系,表明结合自适应跨模态表征学习,轻量级批量数据先验可有效指导单细胞GRN推断。代码与数据将发布于https://github.com/tianyang-x/EpiAwareNet_pub。

原文摘要 · Abstract (English)

Gene regulatory networks (GRNs) capture transcription factor-target interactions and are central to understanding cell-state regulation and disease. Reconstructing GRNs from paired single-cell transcriptomic and chromatin accessibility data is promising but challenging: scATAC is extremely sparse, and most methods rely on fixed peak-to-gene links and weak supervision. We present EpiAwareNet, a prior-guided multi-omic Transformer framework that reconstructs GRNs from paired single-cell data using only lightweight biological priors. In Stage 1, EpiAwareNet learns joint gene-peak representations with a gene-peak cross-attention module, enabling data-driven, gene-specific aggregation of accessibility signals rather than hard-coded peak-to-gene assignments. In Stage 2, EpiAwareNet incorporates a bulk-derived GRN prior as noisy positive edges to provide weak supervision under label scarcity, refining regulatory scores while remaining robust to prior noise. In our experiments, EpiAwareNet improves GRN reconstruction over representative single- and multi-omic baselines and yields GRNs with greater biological plausibility, such as improved recovery of known regulatory interactions, suggesting that lightweight biological priors from bulk data can effectively guide single-cell GRN inference when combined with adaptive cross-modal representation learning. Code and data will be available at https://github.com/tianyang-x/EpiAwareNet_pub.

基因调控单细胞多组学Transformer

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