arXiv:2505.04891cs.LGcs.AI2025-05

将细胞通讯信息融入深度学习,提升单细胞数据聚类精度

Clustering with Communication: A Variational Framework for Single Cell Representation Learning

  • 用配体-受体互作构建通信感知的核函数,指导潜在空间学习
  • 在4个数据集上聚类评分显著优于传统VAE基线
  • 适合关注细胞间互作与功能解析的研究者

单细胞RNA测序揭示了复杂的细胞异质性,但近期研究强调理解生物功能还需建模细胞间通讯(CCC),即通过配体-受体对介导的信号交互来协调细胞行为。如CellChat等工具已证明CCC在细胞分化、组织再生和免疫应答中起关键作用,且转录组数据天然蕴含丰富的细胞间信号信息。本文提出CCCVAE,一种将CCC信号整合进单细胞表征学习的变分自编码框架。通过利用基于配体-受体互作的通信感知核函数及稀疏高斯过程,将生物学先验嵌入潜在空间。与传统独立处理每细胞的VAE不同,CCCVAE促使潜在嵌入同时反映转录相似性和细胞间信号背景。在四个scRNA-seq数据集上的实证结果表明,该方法提升了聚类性能,评估得分高于标准VAE基线。本工作验证了在深度生成模型中嵌入生物学先验对无监督单细胞分析的价值。

原文摘要 · Abstract (English)

Single-cell RNA sequencing (scRNA-seq) has revealed complex cellular heterogeneity, but recent studies emphasize that understanding biological function also requires modeling cell-cell communication (CCC), the signaling interactions mediated by ligand-receptor pairs that coordinate cellular behavior. Tools like CellChat have demonstrated that CCC plays a critical role in processes such as cell differentiation, tissue regeneration, and immune response, and that transcriptomic data inherently encodes rich information about intercellular signaling. We propose CCCVAE, a novel variational autoencoder framework that incorporates CCC signals into single-cell representation learning. By leveraging a communication-aware kernel derived from ligand-receptor interactions and a sparse Gaussian process, CCCVAE encodes biologically informed priors into the latent space. Unlike conventional VAEs that treat each cell independently, CCCVAE encourages latent embeddings to reflect both transcriptional similarity and intercellular signaling context. Empirical results across four scRNA-seq datasets show that CCCVAE improves clustering performance, achieving higher evaluation scores than standard VAE baselines. This work demonstrates the value of embedding biological priors into deep generative models for unsupervised single-cell analysis.

单细胞生成模型细胞通讯聚类

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