SBMLsqueezer:: A CellDesigner plug-in to generate kinetic rate equations for biochemical networks
SBMLsqueezer:: A CellDesigner plug-in to generate kinetic rate equations for biochemical networks
复制标题
DOI：
10.1186/1752-0509-2-39
复制
发表时间：
2008-04-30
影响因子：
--
通讯作者：
Zell, Andreas
中科院分区：
文献类型：
--
作者：
Draeger, Andreas;Hassis, Nadine;Zell, Andreas
背景资料：复杂生物化学模型的开发已经通过机器可读表示的标准化（如SBML（系统生物学标记语言））得到促进。这一努力伴随着人类可读的图形表示SBGN（系统生物学图形表示法）的持续发展。图形化的SBML编辑器CellDesigner允许直接将SBGN转换为SBML，反之亦然。然而，对于分配的动力学速率定律，这个过程并不简单，因为它往往需要手动组装和特定知识的kinetic equations.Results：SBMLsqueezer促进正是通过自动方程生成这一建模步骤，克服了高度容易出错和手动分配动力学方程的繁琐过程。对于每个反应，动力学方程是从化学计量、参与物质（例如，蛋白质、mRNA或简单分子）以及SBGN图的调节关系（激活、抑制或其他调节）。这样的信息允许例如翻译、磷酸化或状态转换之间的区别。考虑的动力学类型很多，例如广义质量作用、Hill、便利性和几种基于Michaelis-Menten的动力学，每种动力学都包括激活和抑制。这些动力学允许SBMLsqueezer覆盖代谢，基因调控，信号转导和混合网络。当多个动力学适用于一个反应时，参数设置允许用户定义规格。调用SBMLsqueezer后，生成动力学公式并将其分配给模型，然后可以在CellDesigner或外部ODE求解器中进行模拟。此外，方程可以导出到SBML，LaTeX或纯文本格式。结论：SBMLsqueezer考虑所有参与的反应物，产物和监管机构的注释时，生成反应速率定律。因此，对于每个反应，只考虑适用的动力学公式。该建模方案根据图形表示创建动力学。相比之下，大多数先前公布的工具依赖于化学计量和反应的通用调节剂，从而忽略了通过过程图表达的信息，并可能与之相冲突。其他材料和源代码可以在项目主页上找到（URL可以在可用性和要求部分找到）。
Background: The development of complex biochemical models has been facilitated through the standardization of machine-readable representations like SBML (Systems Biology Markup Language). This effort is accompanied by the ongoing development of the human-readable diagrammatic representation SBGN (Systems Biology Graphical Notation). The graphical SBML editor CellDesigner allows direct translation of SBGN into SBML, and vice versa. For the assignment of kinetic rate laws, however, this process is not straightforward, as it often requires manual assembly and specific knowledge of kinetic equations.Results: SBMLsqueezer facilitates exactly this modeling step via automated equation generation, overcoming the highly error-prone and cumbersome process of manually assigning kinetic equations. For each reaction the kinetic equation is derived from the stoichiometry, the participating species (e.g., proteins, mRNA or simple molecules) as well as the regulatory relations (activation, inhibition or other modulations) of the SBGN diagram. Such information allows distinctions between, for example, translation, phosphorylation or state transitions. The types of kinetics considered are numerous, for instance generalized mass-action, Hill, convenience and several Michaelis-Menten-based kinetics, each including activation and inhibition. These kinetics allow SBMLsqueezer to cover metabolic, gene regulatory, signal transduction and mixed networks. Whenever multiple kinetics are applicable to one reaction, parameter settings allow for user-defined specifications. After invoking SBMLsqueezer, the kinetic formulas are generated and assigned to the model, which can then be simulated in CellDesigner or with external ODE solvers. Furthermore, the equations can be exported to SBML, LaTeX or plain text format.Conclusion: SBMLsqueezer considers the annotation of all participating reactants, products and regulators when generating rate laws for reactions. Thus, for each reaction, only applicable kinetic formulas are considered. This modeling scheme creates kinetics in accordance with the diagrammatic representation. In contrast most previously published tools have relied on the stoichiometry and generic modulators of a reaction, thus ignoring and potentially conflicting with the information expressed through the process diagram. Additional material and the source code can be found at the project homepage (URL found in the Availability and requirements section).