Alfieri Roberta, Merelli Ivan, Mosca Ettore, Milanesi Luciano
Istituto di Tecnologie Biomediche - Consiglio Nazionale delle Ricerche, via F,lli Cervi 93, Segrate (Milano), Italy.
BMC Syst Biol. 2007 Aug 1;1:35. doi: 10.1186/1752-0509-1-35.
The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies.
In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process.
This integrated system is freely available in order to support systems biology research on the cell cycle and it aims to become a useful resource for collecting all the information related to actual and future models of this network. The flexibility of the database allows the addition of mathematical data which are used for simulating the behavior of the cell cycle components in the different models. The resource deals with two relevant problems in systems biology: data integration and mathematical simulation of a crucial biological process related to cancer, such as the cell cycle. In this way the resource is useful both to retrieve information about cell cycle model components and to analyze their dynamical properties. The Cell Cycle Database can be used to find system-level properties, such as stable steady states and oscillations, by coupling structure and dynamical information about models.
细胞周期是系统生物学研究中最常被研究的生物过程之一，它涉及大量基因和蛋白质相互作用网络的知识。对这一生物过程分子层面的深入了解有助于使癌症研究更加准确和创新。在这种背景下，细胞周期的数学建模对于量化系统各组成部分的行为具有重要作用。诸如细胞周期这样的生物过程的数学建模允许进行系统描述，有助于突出一些特征，如涌现特性，而这些特性在仅从还原论角度进行分析时可能会被隐藏。此外，在对复杂系统进行建模时，对所有组件进行完整注释对于理解网络内部的相互作用机制同样重要：因此，模型组件的数据整合在系统生物学研究中具有高度相关性。
在这项工作中，我们展示了一个资源，即细胞周期数据库，旨在支持基于酵母和哺乳动物这两种生物体对细胞周期过程进行系统生物学分析。该数据库整合了与细胞周期过程相关的基因和蛋白质信息，存储了相互作用网络的完整模型，并允许对每个组件的定量行为随时间进行数学模拟。为完成此任务，我们开发了一个网络界面，用于浏览与细胞周期基因、蛋白质和数学模型相关的信息。在此框架下，我们实现了一个管道，允许用户处理模型的数学部分，以便使用不同变量求解描述生物过程的常微分方程组。
这个集成系统可免费获取，以支持关于细胞周期的系统生物学研究，并且旨在成为收集与该网络当前和未来模型相关的所有信息的有用资源。数据库的灵活性允许添加用于模拟不同模型中细胞周期组件行为的数学数据。该资源解决了系统生物学中的两个相关问题：数据整合以及与癌症相关的关键生物过程（如细胞周期）的数学模拟。通过这种方式，该资源既有助于检索有关细胞周期模型组件的信息，又有助于分析其动态特性。细胞周期数据库可用于通过结合模型的结构和动态信息来找到系统级特性，如稳定稳态和振荡。
