Sedwards Sean, Mazza Tommaso
Microsoft Research-University of Trento Centre for Computational & Systems Biology, Italy.
Bioinformatics. 2007 Oct 15;23(20):2800-2. doi: 10.1093/bioinformatics/btm416. Epub 2007 Sep 13.
Compartments and membranes are the basis of cell topology and more than 30% of the human genome codes for membrane proteins. While it is possible to represent compartments and membrane proteins in a nominal way with many mathematical formalisms used in systems biology, few, if any, explicitly model the topology of the membranes themselves. Discrete stochastic simulation potentially offers the most accurate representation of cell dynamics. Since the details of every molecular interaction in a pathway are often not known, the relationship between chemical species in not necessarily best described at the lowest level, i.e. by mass action. Simulation is a form of computer-aided analysis, relying on human interpretation to derive meaning. To improve efficiency and gain meaning in an automatic way, it is necessary to have a formalism based on a model which has decidable properties.
We present Cyto-Sim, a stochastic simulator of membrane-enclosed hierarchies of biochemical processes, where the membranes comprise an inner, outer and integral layer. The underlying model is based on formal language theory and has been shown to have decidable properties (Cavaliere and Sedwards, 2006), allowing formal analysis in addition to simulation. The simulator provides variable levels of abstraction via arbitrary chemical kinetics which link to ordinary differential equations. In addition to its compact native syntax, Cyto-Sim currently supports models described as Petri nets, can import all versions of SBML and can export SBML and MATLAB m-files.
Cyto-Sim is available free, either as an applet or a stand-alone Java program via the web page (http://www.cosbi.eu/Rpty_Soft_CytoSim.php). Other versions can be made available upon request.
区室和膜是细胞拓扑结构的基础，超过30%的人类基因组编码膜蛋白。虽然可以用系统生物学中使用的许多数学形式主义以名义方式表示区室和膜蛋白，但很少有（如果有的话）能明确地对膜本身的拓扑结构进行建模。离散随机模拟可能提供细胞动态最准确的表示。由于通路中每个分子相互作用的细节通常未知，化学物质之间的关系不一定在最低层次（即通过质量作用）得到最佳描述。模拟是一种计算机辅助分析形式，依赖于人类解释来得出意义。为了提高效率并以自动方式获得意义，有必要拥有一种基于具有可判定属性的模型的形式主义。
我们展示了Cyto - Sim，一种用于生化过程的膜封闭层次结构的随机模拟器，其中膜包括内层、外层和整合层。基础模型基于形式语言理论，并且已被证明具有可判定属性（Cavaliere和Sedwards，2006），除了模拟之外还允许形式分析。该模拟器通过与常微分方程相关联的任意化学动力学提供不同层次的抽象。除了其紧凑的原生语法外，Cyto - Sim目前支持将模型描述为Petri网，可导入所有版本的SBML，并可导出SBML和MATLAB m文件。
Cyto - Sim可免费获取，既可以作为小程序，也可以通过网页（http://www.cosbi.eu/Rpty_Soft_CytoSim.php）作为独立的Java程序获取。其他版本可根据要求提供。
