arXiv:2605.28659cs.LG2026-05

用动态图模型捕捉细胞发育中的基因调控变化,比静态模型更准。

Applications of temporal graph learning for predicting the dynamics of biological systems

论文配图:Applications of temporal graph learning for predicting the dynamics of biological systems
图 1 · 摘自论文原文
  • 将细胞按伪时间分段,构建随时间演化的基因调控图
  • 在小鼠发育数据上,预测基因表达和关键基因节点效果优于scGPT等模型
  • 适合研究发育或疾病中细胞状态演变的生物学家

生物基础模型通过将Transformer直接应用于基因表达矩阵,在单细胞表征学习中表现优异。然而,这些方法多为静态设置,未显式建模细胞发育程序的时间演化。建模此类动态对理解细胞状态如何逐步形成、分化和重组至关重要。本文提出一种基于时序图的新视角:将细胞状态表示为伪时间分辨的基因调控网络,并将其建模为随持久基因身份演化的图结构。从单细胞转录组数据出发,推断伪时间轨迹,将细胞离散化为发育快照,每个快照重建一个基因调控网络,并应用时序图神经网络预测生物状态。我们在两个公开的小鼠发育数据集(红系原肠胚形成和胰腺内分泌发生)上评估该框架,涵盖基因表达预测、边预测和出度中心性预测三项任务。结果表明,图模型优于scGPT和scFoundation等知名基础模型,说明显式建模演化调控结构可提供超越静态预训练表征的有用信息。在边预测和中心性预测中,时序图学习捕捉到非平凡的调控动态,有助于识别关键时序基因枢纽。总体而言,时序图学习为建模动态生物系统提供了有前景的方向,可作为当前基础模型方法的互补范式。

原文摘要 · Abstract (English)

Biological foundation models have shown strong performance in single-cell representation learning by applying transformer architectures directly to gene-expression matrices. However, these approaches predominantly operate in static settings and do not explicitly model the temporal evolution of developmental programs in the cell. Modeling such dynamics is important for understanding how cellular states progressively emerge, differentiate, and reorganize during development or disease progression. In this work-in-progress paper, we investigate an alternative temporal graph-based perspective in which cellular states are represented through pseudotime-resolved gene regulatory networks and modeled as evolving graph structures over persistent gene identities. Starting from single-cell transcriptomic data, we infer pseudotime trajectories, discretize cells into developmental snapshots, reconstruct one gene regulatory network per snapshot, and apply temporal graph neural networks to forecast biological states. We evaluate this framework on two publicly available mouse developmental datasets, erythroid gastrulation and pancreatic endocrinogenesis, considering three complementary tasks: gene-expression forecasting, link prediction, and out-degree centrality prediction. Our results show that graph-based models outperform well-known foundation-model such as scGPT and scFoundation, suggesting that explicitly modeling evolving regulatory structure provides useful information beyond static pretrained representations. For link prediction and centrality forecasting, temporal graph learning captures non-trivial regulatory dynamics and enables the identification of temporally important gene hubs. Overall, our findings support temporal graph learning as a promising direction for modeling dynamic biological systems and as a complementary paradigm to current foundation model approaches in single-cell biology.

时序图单细胞发育生物学

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