用神经网络学习细胞间动态互动,揭示基因调控变化机制。
STAGED: A Multi-Agent Neural Network for Learning Cellular Interaction Dynamics
- 结合智能体模型与图神经网络,动态建模细胞间通信
- 通过注意力机制学习基因调控网络的交互强度变化
- 适合研究空间转录组中细胞状态演变的科研人员
单细胞技术推动了对正常及疾病状态下组织内细胞状态与亚群的理解,传统方法将细胞视为独立数据点。随着空间转录组的发展,可捕捉细胞的空间组织及其动态相互作用。然而,仍需关键计算突破来实现对复杂细胞互动动态的数据驱动学习。尽管基于智能体的建模(ABM)具有潜力,但传统方法依赖人工设定规则而非数据驱动。为此,我们提出时空智能体图演化动力学(STAGED),融合ABM与深度学习,建模细胞间通讯及其对细胞内基因调控网络的影响。采用共享权重的图微分方程网络(GDEs),将基因表示为顶点,相互作用为有向边,通过设计的注意力机制动态学习其强度。模型在模拟和空间转录组推断的连续轨迹上训练,捕捉了细胞间与细胞内的动态交互,实现更自适应、准确的细胞动态表征。
原文摘要 · Abstract (English)
The advent of single-cell technology has significantly improved our understanding of cellular states and subpopulations in various tissues under normal and diseased conditions by employing data-driven approaches such as clustering and trajectory inference. However, these methods consider cells as independent data points of population distributions. With spatial transcriptomics, we can represent cellular organization, along with dynamic cell-cell interactions that lead to changes in cell state. Still, key computational advances are necessary to enable the data-driven learning of such complex interactive cellular dynamics. While agent-based modeling (ABM) provides a powerful framework, traditional approaches rely on handcrafted rules derived from domain knowledge rather than data-driven approaches. To address this, we introduce Spatio Temporal Agent-Based Graph Evolution Dynamics(STAGED) integrating ABM with deep learning to model intercellular communication, and its effect on the intracellular gene regulatory network. Using graph ODE networks (GDEs) with shared weights per cell type, our approach represents genes as vertices and interactions as directed edges, dynamically learning their strengths through a designed attention mechanism. Trained to match continuous trajectories of simulated as well as inferred trajectories from spatial transcriptomics data, the model captures both intercellular and intracellular interactions, enabling a more adaptive and accurate representation of cellular dynamics.
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