arXiv:2510.09594cs.LGq-bio.MN2025-10

用动态专家混合模型解析细胞行为的复杂转变,实现精准预测。

MODE: Learning compositional representations of complex systems with Mixtures Of Dynamical Experts

  • 通过神经门控机制拆解复杂动态为稀疏可解释成分。
  • 在真实单细胞数据中准确预测细胞命运抉择时间点。
  • 适合研究细胞周期与分化过程的生物学家和计算建模者。

生命科学中的动力系统常由重叠的行为模式混合而成。细胞亚群可能在周期性与稳态之间转换,或分支走向不同发育路径。这些转变常表现为噪声大、不规则,对传统基于流的方法(假设局部平滑)构成严峻挑战。为此,我们提出MODE(动态专家混合),一种图模型框架,其神经门控机制将复杂动态分解为稀疏、可解释的组件,既能无监督发现行为模式,又能准确预测跨状态转变的长期演化。关键在于,框架中的代理可跳转至不同控制规律,特别适用于此类噪声过渡。我们在合成与真实生物数据集上进行评估:首先在合成快照数据上系统测试无监督分类性能,涵盖噪声和小样本场景;其次展示其在模拟细胞周期与分支过程的挑战性预测任务中的成功;最后应用于人类单细胞RNA测序数据,不仅能区分增殖与分化动态,还可预测细胞何时做出最终命运决定,解决计算生物学中的核心难题。

原文摘要 · Abstract (English)

Dynamical systems in the life sciences are often composed of complex mixtures of overlapping behavioral regimes. Cellular subpopulations may shift from cycling to equilibrium dynamics or branch towards different developmental fates. The transitions between these regimes can appear noisy and irregular, posing a serious challenge to traditional, flow-based modeling techniques which assume locally smooth dynamics. To address this challenge, we propose MODE (Mixture Of Dynamical Experts), a graphical modeling framework whose neural gating mechanism decomposes complex dynamics into sparse, interpretable components, enabling both the unsupervised discovery of behavioral regimes and accurate long-term forecasting across regime transitions. Crucially, because agents in our framework can jump to different governing laws, MODE is especially tailored to the aforementioned noisy transitions. We evaluate our method on a battery of synthetic and real datasets from computational biology. First, we systematically benchmark MODE on an unsupervised classification task using synthetic dynamical snapshot data, including in noisy, few-sample settings. Next, we show how MODE succeeds on challenging forecasting tasks which simulate key cycling and branching processes in cell biology. Finally, we deploy our method on human, single-cell RNA sequencing data and show that it can not only distinguish proliferation from differentiation dynamics but also predict when cells will commit to their ultimate fate, a key outstanding challenge in computational biology.

动态系统单细胞预测模型生物建模

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