EMT/BSSE: A Computational Framework for Inferring Self-Regulatory Properties from High-Dimensional Dynamic Models of Biological Systems

EMT/BSSE：从生物系统高维动态模型推断自我调节特性的计算框架

• 批准号: 0829742
• 负责人: Robert Clewley
• 金额: $ 10万
• 依托单位: Georgia State University Research Foundation, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0829742&HistoricalAwards=false
• 关键词: EMT; BSSE; Computational; Framework; Inferring

Biological forms of computation present some of the most promising?yet challenging?examples of adaptive mechanisms that we would like to understand well enough to engineer ourselves. However, models for biological processes are becoming increasingly detailed and unwieldy in an effort to reproduce ever-more detailed experimental observations. This research involves the development of mathematical theory, algorithms, and software for efficiently constraining models to data and to analyze their properties mathematically. A sufficiently detailed understanding through mathematical analysis permits the generalization of operating principles that provide biological insights and a basis for engineering similar mechanisms. In particular, the investigators apply these methods to infer adaptive and self-governing properties from detailed dynamical models of excitable neural and cardiac tissue. Although detailed models of physical systems may involve many variables and parameters, mathematical analysis often demonstrates effective lower dimensionality in their operating principles. A decomposition of a complex model to approximate lower-dimensional sub-regimes facilitates analysis by standard techniques from dynamical systems and optimization theory. In contrast to a priori reductions to ?toy? models, software tools monitor and control the sources of error in the approximations, in particular the assumptions underlying the decomposition are validated against global constraints to ensure consistency with the behavior of the full physical system. To study abstract properties of the system such as adaptiveness, decompositions can be made in terms of measurements of qualitative features in the dynamics. These features may be simple or complex according to the needs of the problem. Their formalized definition in software structures enables existing techniques for model optimization and inference to be applied more intelligently, particularly in the context of model behavior that may resemble experimental data only in qualitative terms.

生物形式的计算呈现出一些最有前途的？然而挑战吗?适应性机制的例子，我们想了解得足够好，以设计我们自己。然而，为了重现更详细的实验观察，生物过程的模型正变得越来越详细和笨拙。这项研究涉及数学理论、算法和软件的发展，以有效地将模型约束到数据中，并从数学上分析它们的属性。通过数学分析获得足够详细的理解，可以概括出操作原理，从而提供生物学见解和工程类似机制的基础。特别是，研究人员应用这些方法从可兴奋的神经和心脏组织的详细动力学模型中推断出自适应和自管理特性。虽然物理系统的详细模型可能涉及许多变量和参数，但数学分析经常在其操作原理中证明有效的低维度。将复杂模型分解为近似低维子状态，便于采用动力系统和优化理论的标准技术进行分析。与先验还原为？toy？模型、软件工具监控和控制近似中的误差来源，特别是分解背后的假设是针对全局约束进行验证的，以确保与整个物理系统的行为一致。为了研究系统的抽象特性，如自适应，可以根据动力学中定性特征的测量进行分解。根据问题的需要，这些特性可能简单也可能复杂。它们在软件结构中的形式化定义使模型优化和推理的现有技术能够更智能地应用，特别是在模型行为的上下文中，模型行为可能仅在定性方面类似于实验数据。