生物系统多层模型中的模块化动态范式:软件设计和PBPK/PD验证
1Departamento de Ingeniería Gráfica and Multilevel Modeling and Emerging Technologies in Bioengineering Group, ETSi, Universidad de Sevilla, C. de los descubrimientos s/n, Seville, 41092, Spain.
Computers in biology and medicine
|February 22, 2025
概括
本研究介绍了Cyborgs模拟器 (CybSim),这是一个用于生物系统的新型建模和模拟工具. CybSim采用模块化动力学范式,用于灵活和不断演变的机械模型,并通过生理学基础药理动力学 (PBPK) 模型进行验证.
科学领域:
- 计算生物学 计算生物学
- 系统生物学 系统生物学
- 药理动力学 药理动力学
背景情况:
- 机械建模和模拟 (M&S) 对于理解复杂的生物系统至关重要.
- 现有的M&S工具往往在生物组件和它们的动态之间强加了严格的联系.
- 进步需要灵活的M&S工具,以适应不断变化的机械知识.
研究的目的:
- 为了介绍Cyborgs模拟器 (CybSim),一个新的M&S软件工具.
- 在非因果的面向对象建模语言 (OOML) 架构中引入一个模块化建模范式.
- 促进将新的机械学发现纳入生物系统模型.
主要方法:
- 开发了基于模块化动态范式和无因果OOML架构的CybSim.
- 实现的功能包括多模拟,生物和人工组件的分离,以及算法块.
- 通过构建和比较基于生理学上的药理动力学 (PBPK) 模型与其他M&S工具中公布的参考资料来验证CybSim.
主要成果:
- 在预测细菌数量 (对数绝对误差<2%) 和生理参数方面,CybSim表现出高准确度.
- CybSim中的预测错误与已建立的集成商的数值精度相当.
- 在CybSim中模块化建模范式被证明是可靠的,对于复杂的PBPK/PD模型需要最小的组件.
结论:
- 模块化动力学范式可以在现代的OOML M&S工具中有效地实现.
- CybSim成功地整合了这个范式,为生物系统建模提供了一个灵活的图形工具.
- 验证证实了CybSim对PBPK建模的可靠性及其在推进机理生物学理解方面的潜力.
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