arXiv:2506.23287cs.LGq-bio.QM2025-06中稿 · ICML

用生成模型建模细胞分化层级,提升谱系推断的准确性和稳定性。

HDTree: Generative Modeling of Cellular Hierarchies for Robust Lineage Inference

  • 基于统一层级码本与量化扩散过程建模细胞状态演化。
  • 在多个数据集上谱系推断准确率超越现有方法,且保持结构一致性。
  • 适合研究细胞分化、发育生物学的科研人员使用。

单细胞研究中,追踪和分析高通量单细胞分化轨迹对理解生物过程至关重要。关键在于鲁棒地建模调控细胞发育的层级结构。传统方法存在计算成本高、性能差和稳定性不足的问题。基于变分自编码器(VAE)的方法虽有进展,但仍需分支专属模块,限制可扩展性与稳定性,常出现后验崩溃。为此,我们提出HDTree,一种用于鲁棒谱系推断的生成建模框架。该方法通过统一的层级码本捕捉潜空间中的树状关系,并采用量化扩散过程建模连续细胞状态转变。通过与Waddington景观对齐,该方法不仅提升稳定性与可扩展性,还增强推断谱系的生物学合理性。在通用及单细胞数据集上的对比验证表明,HDTree在谱系推断准确率、重建质量与层级一致性方面均优于现有方法。该成果实现对细胞分化路径的精准高效建模,为生物发现提供可靠依据。

原文摘要 · Abstract (English)

In single-cell research, tracing and analyzing high-throughput single-cell differentiation trajectories is crucial for understanding biological processes. Key to this is the robust modeling of hierarchical structures that govern cellular development. Traditional methods face limitations in computational cost, performance, and stability. VAE-based approaches have made strides but still require branch-specific network modules, limiting their scalability and stability, while often suffering from posterior collapse. To overcome these challenges, we introduce HDTree, a generative modeling framework designed for robust lineage inference. HDTree captures tree relationships within a hierarchical latent space using a unified hierarchical codebook and employs a quantized diffusion process to model continuous cell state transitions. By aligning the generative process with the Waddington landscape, this method not only improves stability and scalability but also enhances the biological plausibility of inferred lineages. HDTree's effectiveness is demonstrated through comparisons on both general-purpose and single-cell datasets, where it outperforms existing methods in lineage inference accuracy, reconstruction quality, and hierarchical consistency. These contributions enable accurate and efficient modeling of cellular differentiation paths, offering reliable insights for biological discovery.\footnote{Code is available at https://github.com/zangzelin/code\_HDTree\_icml.

细胞分化生成模型谱系推断

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