arXiv:2509.02639q-bio.GNcs.AI2025-09被引 2

融合基因表达与基因互作关系,提升单细胞测序数据的嵌入质量。

Enhanced Single-Cell RNA-seq Embedding through Gene Expression and Data-Driven Gene-Gene Interaction Integration

  • 构建细胞叶图与近邻图,联合学习基因调控与表达相似性。
  • 在多个数据集上显著提升稀有细胞类型识别与轨迹推断性能。
  • 适合从事单细胞分析、生物机制研究的科研人员使用。

单细胞RNA测序(scRNA-seq)为解析细胞异质性提供了前所未有的视角,可在单细胞分辨率下深入分析复杂生物系统。然而,高维数据与技术噪声带来了重大分析挑战。现有嵌入方法主要关注基因表达水平,常忽略调控细胞身份与功能的关键基因-基因互作。为此,我们提出一种新嵌入方法,整合基因表达谱与数据驱动的基因-基因互作。首先利用随机森林模型构建细胞叶图(CLG)以捕捉基因间的调控关系,同时构建K近邻图(KNNG)表示细胞间表达相似性。两图融合形成增强型细胞叶图(ECLG),作为图神经网络输入以计算细胞嵌入。通过结合表达水平与基因互作,该方法提供更全面的细胞状态表征。在多个数据集上的广泛评估表明,该方法显著提升稀有细胞群检测能力,并改善可视化、聚类与轨迹推断等下游分析。这一整合策略代表了单细胞数据分析的重要进展,为理解细胞多样性和动态提供了更完整的框架。

原文摘要 · Abstract (English)

Single-cell RNA sequencing (scRNA-seq) provides unprecedented insights into cellular heterogeneity, enabling detailed analysis of complex biological systems at single-cell resolution. However, the high dimensionality and technical noise inherent in scRNA-seq data pose significant analytical challenges. While current embedding methods focus primarily on gene expression levels, they often overlook crucial gene-gene interactions that govern cellular identity and function. To address this limitation, we present a novel embedding approach that integrates both gene expression profiles and data-driven gene-gene interactions. Our method first constructs a Cell-Leaf Graph (CLG) using random forest models to capture regulatory relationships between genes, while simultaneously building a K-Nearest Neighbor Graph (KNNG) to represent expression similarities between cells. These graphs are then combined into an Enriched Cell-Leaf Graph (ECLG), which serves as input for a graph neural network to compute cell embeddings. By incorporating both expression levels and gene-gene interactions, our approach provides a more comprehensive representation of cellular states. Extensive evaluation across multiple datasets demonstrates that our method enhances the detection of rare cell populations and improves downstream analyses such as visualization, clustering, and trajectory inference. This integrated approach represents a significant advance in single-cell data analysis, offering a more complete framework for understanding cellular diversity and dynamics.

单细胞测序基因互作图神经网络

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