arXiv:2506.13344cs.LGcs.AI2025-06

用图扩散模型生成高质量单细胞数据,还能抵抗网络结构噪声。

LapDDPM: A Conditional Graph Diffusion Model for scRNA-seq Generation with Spectral Adversarial Perturbations

  • 结合图结构与扩散模型,用谱对抗扰动提升鲁棒性。
  • 在多个数据集上生成的细胞类型特异性样本生物合理性高。
  • 适合需要可控、真实单细胞数据的生物研究者使用。

生成高保真且生物学合理的条件化单细胞RNA测序(scRNA-seq)数据极具挑战,因其维度高、稀疏性强且生物变异复杂。现有生成模型难以捕捉这些特性,也缺乏对细胞网络结构噪声的鲁棒性。本文提出LapDDPM,一种新型条件图扩散概率模型,通过在图边权重上引入谱对抗扰动机制,增强对结构变异的鲁棒性。其贡献包括:利用拉普拉斯位置编码(LPEs)丰富潜在空间中的细胞关系信息;构建条件得分驱动扩散模型以有效学习复杂scRNA-seq分布;采用独特的谱对抗训练方案提升模型稳定性。在多种scRNA-seq数据集上的实验表明,LapDDPM性能优异,生成数据保真度高,且具备高度生物学合理性,尤其能生成细胞类型特异性的样本,为条件化scRNA-seq数据生成设立了新基准,适用于各类下游生物应用。

原文摘要 · Abstract (English)

Generating high-fidelity and biologically plausible synthetic single-cell RNA sequencing (scRNA-seq) data, especially with conditional control, is challenging due to its high dimensionality, sparsity, and complex biological variations. Existing generative models often struggle to capture these unique characteristics and ensure robustness to structural noise in cellular networks. We introduce LapDDPM, a novel conditional Graph Diffusion Probabilistic Model for robust and high-fidelity scRNA-seq generation. LapDDPM uniquely integrates graph-based representations with a score-based diffusion model, enhanced by a novel spectral adversarial perturbation mechanism on graph edge weights. Our contributions are threefold: we leverage Laplacian Positional Encodings (LPEs) to enrich the latent space with crucial cellular relationship information; we develop a conditional score-based diffusion model for effective learning and generation from complex scRNA-seq distributions; and we employ a unique spectral adversarial training scheme on graph edge weights, boosting robustness against structural variations. Extensive experiments on diverse scRNA-seq datasets demonstrate LapDDPM's superior performance, achieving high fidelity and generating biologically-plausible, cell-type-specific samples. LapDDPM sets a new benchmark for conditional scRNA-seq data generation, offering a robust tool for various downstream biological applications.

单细胞生成图神经网络扩散模型生物数据合成

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