Haunschild Marc Daniel, Freisleben Bernd, Takors Ralf, Wiechert Wolfgang
Department of Simulation, University of Siegen, Paul-Bonatz-Strasse 9-11, D-57068 Siegen, Germany.
Bioinformatics. 2005 Apr 15;21(8):1617-25. doi: 10.1093/bioinformatics/bti225. Epub 2004 Dec 16.
Supporting the evolutionary modeling process of dynamic biochemical networks based on sampled in vivo data requires more than just simulation. In the course of the modeling process, the modeler is typically concerned not only with a single model but also with sequences, alternatives and structural variants of models. Powerful automatic methods are then required to assist the modeler in the organization and the evaluation of alternative models. Moreover, the structure and peculiarities of the data require dedicated tool support.
To support all stages of an evolutionary modeling process, a new general formalism for the combinatorial specification of large model families is introduced. It allows for automatic navigation in the space of models and excludes biologically meaningless models on the basis of elementary flux mode analysis. An incremental usage of the measured data is supported by using splined data instead of state variables. With MMT2, a versatile tool has been developed as a computational engine intended to be built into a tool chain. Using automatic code generation, automatic differentiation for sensitivity analysis and grid computing technology, a high performance computing environment is achieved. MMT2 supplies XML model specification and several software interfaces. The performance of MMT2 is illustrated by several examples from ongoing research projects.
http://www.simtec.mb.uni-siegen.de/
基于体内采样数据支持动态生化网络的进化建模过程，所需的不仅仅是模拟。在建模过程中，建模者通常不仅关注单个模型，还关注模型的序列、替代方案和结构变体。因此，需要强大的自动方法来协助建模者组织和评估替代模型。此外，数据的结构和特性需要专门的工具支持。
为了支持进化建模过程的所有阶段，引入了一种用于大型模型族组合规范的新通用形式主义。它允许在模型空间中自动导航，并基于基本通量模式分析排除生物学上无意义的模型。通过使用样条数据而非状态变量来支持对测量数据的增量使用。借助MMT2，开发了一种通用工具作为计算引擎，旨在构建到工具链中。利用自动代码生成、用于灵敏度分析的自动微分和网格计算技术，实现了高性能计算环境。MMT2提供XML模型规范和多个软件接口。通过正在进行的研究项目中的几个示例说明了MMT2的性能。
http://www.simtec.mb.uni-siegen.de/
