用动态最优传输联合学习细胞嵌入与轨迹,提升单细胞数据的时序重建精度。
CellStream: Dynamical Optimal Transport Informed Embeddings for Reconstructing Cellular Trajectories from Snapshots Data
- 融合自编码器与非平衡动态最优传输,联合优化嵌入与轨迹。
- 在模拟与真实数据上显著提升时序一致性,噪声敏感性降低。
- 适合研究细胞发育、分化等连续过程的生物学家使用。
单细胞RNA测序(scRNA-seq)尤其是时间解析数据,可在离散时间点实现单细胞分辨率下的全基因组表达动态分析。然而,现有技术仅提供稀疏、静态的细胞状态快照,且受技术噪声影响,难以推断和表征连续转录动态。尽管嵌入方法可降维并缓解噪声,但多数现有方法将轨迹推断与嵌入构建分离,常忽略时间结构。为此,我们提出CellStream,一种新型深度学习框架,通过将自编码器与非平衡动态最优传输结合,从单细胞快照数据中联合学习嵌入与细胞动态。相比现有方法,CellStream生成的嵌入能稳健捕捉时间发育过程,同时保持与底层数据流形的高度一致性。我们在模拟数据及真实scRNA-seq数据(包括空间转录组)上验证了其有效性,实验显示在表征细胞轨迹方面显著优于当前最佳方法,具备更强时序连贯性与更低噪声敏感性。总体而言,CellStream为从嘈杂、静态的单细胞表达快照中学习和表征连续流提供了新工具。
原文摘要 · Abstract (English)
Single-cell RNA sequencing (scRNA-seq), especially temporally resolved datasets, enables genome-wide profiling of gene expression dynamics at single-cell resolution across discrete time points. However, current technologies provide only sparse, static snapshots of cell states and are inherently influenced by technical noise, complicating the inference and representation of continuous transcriptional dynamics. Although embedding methods can reduce dimensionality and mitigate technical noise, the majority of existing approaches typically treat trajectory inference separately from embedding construction, often neglecting temporal structure. To address this challenge, here we introduce CellStream, a novel deep learning framework that jointly learns embedding and cellular dynamics from single-cell snapshot data by integrating an autoencoder with unbalanced dynamical optimal transport. Compared to existing methods, CellStream generates dynamics-informed embeddings that robustly capture temporal developmental processes while maintaining high consistency with the underlying data manifold. We demonstrate CellStream's effectiveness on both simulated datasets and real scRNA-seq data, including spatial transcriptomics. Our experiments indicate significant quantitative improvements over state-of-the-art methods in representing cellular trajectories with enhanced temporal coherence and reduced noise sensitivity. Overall, CellStream provides a new tool for learning and representing continuous streams from the noisy, static snapshots of single-cell gene expression.
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