用组学数据驱动酵母生物过程建模,同时估计预测不确定性。
Omics-driven hybrid dynamic modeling of bioprocesses with uncertainty estimation
- 通过随机森林筛选关键蛋白,降低组学数据维度
- 用高斯过程将蛋白表达与模型参数关联,构建可微分混合模型
- 适用于多尺度生物系统建模,适合系统生物学研究者
本文提出一种组学驱动的建模流程,整合机器学习工具以支持多尺度生物系统的动态建模。采用随机森林与置换特征重要性分析挖掘组学数据,指导特征选择与降维。训练连续可微的机器学习函数,将简化后的组学特征集与动态模型关键成分关联,形成混合模型。以酿酒酵母的高维蛋白质组数据为案例,识别与细胞生长相关的关键胞内蛋白,设计靶向动态实验,利用高斯过程将关键模型参数表示为选定蛋白的函数。该方法在不同蛋白组背景下捕捉酵母菌株的动态行为,并对混合模型预测结果进行不确定性估计。该建模框架可扩展至其他场景,如融合多层组学数据构建更复杂的多尺度生物系统模型,或使用其他机器学习方法处理更大规模数据。本研究为系统生物学与生物过程工程中利用组学数据指导多尺度动态建模提供了可行策略。
原文摘要 · Abstract (English)
This work presents an omics-driven modeling pipeline that integrates machine-learning tools to facilitate the dynamic modeling of multiscale biological systems. Random forests and permutation feature importance are proposed to mine omics datasets, guiding feature selection and dimensionality reduction for dynamic modeling. Continuous and differentiable machine-learning functions can be trained to link the reduced omics feature set to key components of the dynamic model, resulting in a hybrid model. As proof of concept, we apply this framework to a high-dimensional proteomics dataset of $\textit{Saccharomyces cerevisiae}$. After identifying key intracellular proteins that correlate with cell growth, targeted dynamic experiments are designed, and key model parameters are captured as functions of the selected proteins using Gaussian processes. This approach captures the dynamic behavior of yeast strains under varying proteome profiles while estimating the uncertainty in the hybrid model's predictions. The outlined modeling framework is adaptable to other scenarios, such as integrating additional layers of omics data for more advanced multiscale biological systems, or employing alternative machine-learning methods to handle larger datasets. Overall, this study outlines a strategy for leveraging omics data to inform multiscale dynamic modeling in systems biology and bioprocess engineering.
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