arXiv:2510.22835cs.LGstat.CO2025-10

用去噪扩散模型提升单细胞数据聚类精度,保留原始结构同时增强生物一致性。

Clustering by Denoising: Latent plug-and-play diffusion for single-cell data

  • 在低维潜在空间中通过扩散模型去噪,高维空间重新引入噪声引导过程。
  • 合成与真实数据上聚类准确率显著提升,尤其在噪声和数据偏移下表现稳健。
  • 适合单细胞组学研究者,特别适用于噪声大或缺乏标注的样本分析。

单细胞RNA测序(scRNA-seq)可解析细胞异质性,但因测量噪声和生物学变异,聚类准确性仍受限。标准潜在空间(如PCA)中不同细胞类型的数据常被投影至相近区域,导致聚类困难。本文提出一种潜空间即插即用扩散框架,分离观测空间与去噪空间。通过新型吉布斯采样流程:在低维潜在空间使用学习到的扩散先验进行去噪,同时在原始高维观测空间重新引入噪声以引导去噪过程。这种独特“输入空间引导”确保去噪轨迹忠实于原始数据结构。本方法具三大优势:(1) 通过可调先验与观测数据权衡实现自适应噪声处理;(2) 通过严谨不确定性估计支持下游分析;(3) 利用干净参考数据去噪更嘈杂数据集,并通过平均提升质量,超越训练集水平。在合成与真实单细胞基因组数据上评估,方法在不同噪声水平与数据偏移下均提升聚类准确性。真实数据中,所得细胞簇生物一致性更强,边界更契合已知细胞类型标记物及发育轨迹。

原文摘要 · Abstract (English)

Single-cell RNA sequencing (scRNA-seq) enables the study of cellular heterogeneity. Yet, clustering accuracy, and with it downstream analyses based on cell labels, remain challenging due to measurement noise and biological variability. In standard latent spaces (e.g., obtained through PCA), data from different cell types can be projected close together, making accurate clustering difficult. We introduce a latent plug-and-play diffusion framework that separates the observation and denoising space. This separation is operationalized through a novel Gibbs sampling procedure: the learned diffusion prior is applied in a low-dimensional latent space to perform denoising, while to steer this process, noise is reintroduced into the original high-dimensional observation space. This unique "input-space steering" ensures the denoising trajectory remains faithful to the original data structure. Our approach offers three key advantages: (1) adaptive noise handling via a tunable balance between prior and observed data; (2) uncertainty quantification through principled uncertainty estimates for downstream analysis; and (3) generalizable denoising by leveraging clean reference data to denoise noisier datasets, and via averaging, improve quality beyond the training set. We evaluate robustness on both synthetic and real single-cell genomics data. Our method improves clustering accuracy on synthetic data across varied noise levels and dataset shifts. On real-world single-cell data, our method demonstrates improved biological coherence in the resulting cell clusters, with cluster boundaries that better align with known cell type markers and developmental trajectories.

单细胞去噪扩散模型聚类

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。