Theoretical Biology Laboratory, RIKEN, Wako 351-0198, Japan.
J Theor Biol. 2013 Oct 21;335:130-46. doi: 10.1016/j.jtbi.2013.06.009. Epub 2013 Jun 15.
Modern biology provides many networks describing regulations between many species of molecules. It is widely believed that the dynamics of molecular activities based on such regulatory networks are the origin of biological functions. However, we currently have a limited understanding of the relationship between the structure of a regulatory network and its dynamics. In this study we develop a new theory to provide an important aspect of dynamics from information of regulatory linkages alone. We show that the "feedback vertex set" (FVS) of a regulatory network is a set of "determining nodes" of the dynamics. The theory is powerful to study real biological systems in practice. It assures that (i) any long-term dynamical behavior of the whole system, such as steady states, periodic oscillations or quasi-periodic oscillations, can be identified by measurements of a subset of molecules in the network, and that (ii) the subset is determined from the regulatory linkage alone. For example, dynamical attractors possibly generated by a signal transduction network with 113 molecules can be identified by measurement of the activity of only 5 molecules, if the information on the network structure is correct. Our theory therefore provides a rational criterion to select key molecules to control a system. We also demonstrate that controlling the dynamics of the FVS is sufficient to switch the dynamics of the whole system from one attractor to others, distinct from the original.
现代生物学提供了许多描述分子间调控关系的网络。人们普遍认为,基于这些调控网络的分子活性的动力学是生物功能的起源。然而,我们目前对调控网络的结构与其动力学之间的关系的理解是有限的。在本研究中,我们发展了一种新的理论,仅从调控关联的信息中提供动力学的一个重要方面。我们表明,调控网络的“反馈顶点集”(FVS)是动力学的一组“决定节点”。该理论在实际研究真实生物系统时非常有效。它保证了(i)整个系统的任何长期动力学行为,如稳定状态、周期性振荡或准周期性振荡,都可以通过测量网络中分子的子集来识别,并且(ii)子集仅由调控关联单独确定。例如,如果网络结构的信息是正确的,那么由具有 113 个分子的信号转导网络生成的可能的动力学吸引子可以通过仅测量 5 个分子的活性来识别。因此,我们的理论为选择关键分子来控制系统提供了一个合理的标准。我们还证明,控制 FVS 的动力学足以将整个系统的动力学从一个吸引子切换到其他与原始不同的吸引子。