用神经微分方程建模代谢通路动态,提升预测精度与推理速度。
Neural Ordinary Differential Equations for Simulating Metabolic Pathway Dynamics from Time-Series Multiomics Data
- 基于神经微分方程学习蛋白组与代谢组的连续动态关系。
- 在柠檬烯和异戊醇通路数据上误差降低超90%,最高达97.65%。
- 推理速度提升1000倍,适合精准医疗与合成生物学应用。
人类健康寿命与生物工程的进步依赖于对复杂生物系统行为的预测。尽管高通量多组学数据日益丰富,但将其转化为可操作的预测模型仍是瓶颈。高容量的数据驱动仿真系统在此领域至关重要;与依赖先验知识的经典机制模型不同,这些架构能直接从观测数据中推断潜在交互,实现时间轨迹模拟及下游干预效果预测,适用于个性化医疗与合成生物学。为此,我们引入神经常微分方程(NODEs)作为动态框架,用于学习蛋白质组与代谢组之间的复杂相互作用。该框架应用于工程化大肠杆菌的时间序列数据,建模代谢通路的连续动态。所提出的NODE架构在捕捉系统动态方面优于传统机器学习流程。结果显示,在柠檬烯(最高94.38%改进)和异戊醇(最高97.65%改进)路径数据集上,均实现超过90%的均方根误差降低。此外,NODE模型推理速度提升1000倍,证明其是下一代代谢工程与生物发现中可扩展、高保真度的工具。
原文摘要 · Abstract (English)
The advancement of human healthspan and bioengineering relies heavily on predicting the behavior of complex biological systems. While high-throughput multiomics data is becoming increasingly abundant, converting this data into actionable predictive models remains a bottleneck. High-capacity, datadriven simulation systems are critical in this landscape; unlike classical mechanistic models restricted by prior knowledge, these architectures can infer latent interactions directly from observational data, allowing for the simulation of temporal trajectories and the anticipation of downstream intervention effects in personalized medicine and synthetic biology. To address this challenge, we introduce Neural Ordinary Differential Equations (NODEs) as a dynamic framework for learning the complex interplay between the proteome and metabolome. We applied this framework to time-series data derived from engineered Escherichia coli strains, modeling the continuous dynamics of metabolic pathways. The proposed NODE architecture demonstrates superior performance in capturing system dynamics compared to traditional machine learning pipelines. Our results show a greater than 90% improvement in root mean squared error over baselines across both Limonene (up to 94.38% improvement) and Isopentenol (up to 97.65% improvement) pathway datasets. Furthermore, the NODE models demonstrated a 1000x acceleration in inference time, establishing them as a scalable, high-fidelity tool for the next generation of metabolic engineering and biological discovery.
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