系统建模和不确定性量化AMP激活蛋白激酶信号的系统建模和不确定性量化
Nathaniel Linden-Santangeli1, Jin Zhang2, Boris Kramer3
1Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, USA.
NPJ systems biology and applications
|October 14, 2025
概括
AMP激活蛋白激酶 (AMPK) 集成细胞信号以保持代谢平衡. 使用不确定性定量化的新建模拟方法揭示了AMPKK.
科学领域:
- 系统生物学 系统生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- AMP激活蛋白激酶 (AMPK) 对于细胞能量平衡至关重要,作为一个中央信号枢纽.
- 由于途径的复杂性和激活机制的不确定性,AMPK信号传递的现有机制模型是有限的.
- 与AMPK相比,MAPK/ERK和NF-κB等已建立的途径具有更发达的模型.
研究的目的:
- 开发一种新的,基于数据的AMPK信号传输机械模型.
- 用不确定性量化 (UQ) 来解决AMPK路径建模中的认识体系不确定性.
- 预测AMPK活性,以应对生理刺激,如运动.
主要方法:
- 杆不确定性量化 (UQ) 方法和新型AMPK生物传感器.
- 应用贝叶斯参数估计和模型选择,用于稳健的模型开发.
- 有限制的模型预测与AMPK活动的实验测量.
主要成果:
- 开发了一种新的,基于数据的AMPK信号传输模型.
- 预测AMPK活动响应运动类刺激,揭示时间和运动依赖的整合.
- 证明了UQ在减少不确定性和促进复杂路径的模型开发方面的实用性.
结论:
- 在系统生物学中,UQ是构建机械模型的强大工具,特别是对于像AMPK这样的复杂信号通路.
- 开发的模型提供了关于AMPK作为细胞输入的动态集成器的作用的见解.
- 这种方法可以结合尖端的实验数据,通过建模推动生物发现.
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