Department of Modeling of Biological Processes, COS Heidelberg/Bioquant, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany.
BMC Bioinformatics. 2021 Jan 11;22(1):21. doi: 10.1186/s12859-020-03913-8.
Computational modelling of cell biological processes is a frequently used technique to analyse the underlying mechanisms and to generally understand the behaviour of these processes in the context of a pathway, network or even the whole cell. The most common technique in this context is the usage of ordinary differential equations that describe the kinetics of the relevant processes in mechanistic detail. Here, it is usually assumed that the content of the cell is well-stirred and thus homogeneous - which is of course an over-simplification, but often worked in the past. However, many processes happen at membranes and thus not in 3D, but in 2D. The scaling of the rates of these processes poses a special problem, if volumes of compartments are changed. They will typically scale with an area, but not with the volume of the involved compartment. However, commonly, this is neglected when setting up models and/or volume scaling also sometimes automatically happens when using modelling software in the field.
Here, we investigate generic as well as specific, realistic cases to find out, how strong the impact of the wrong scaling is for the outcome of simulations. We show that the importance of correct area scaling depends on the architecture of the reaction site and its changes upon volume alterations and it is hard to foresee, if it has a significant impact or not just by looking at the original model set-up. Moreover, scaled rates might exhibit more or less control over the behaviour of the system and therefore, accordingly, incorrect scaling will have more or less influence.
Working with multi-compartment reactions requires a careful consideration of the correct scaling of the rates when changing the volumes of the involved compartments. The error following incorrect scaling - often done by scaling with the volume of the respective compartments can lead to significant aberrations of model behaviour.
细胞生物过程的计算建模是一种常用的技术，可用于分析潜在机制，并通常理解这些过程在途径、网络甚至整个细胞中的行为。在这种情况下，最常用的技术是使用常微分方程来详细描述相关过程的动力学。在这里，通常假设细胞的内容物是充分混合的，因此是均匀的 - 这当然是一种简化，但过去经常这样做。然而，许多过程发生在膜上，因此不是在 3D 中，而是在 2D 中。如果改变隔室的体积，这些过程的速率缩放会带来一个特殊的问题。它们通常会与面积成比例缩放，但不会与涉及的隔室的体积成比例缩放。然而，在建立模型时，通常会忽略这一点，并且在使用该领域的建模软件时，体积缩放有时也会自动发生。
在这里，我们研究了通用和特定的现实情况，以找出错误缩放对模拟结果的影响有多大。我们表明，正确的面积缩放的重要性取决于反应部位的结构及其在体积变化时的变化，并且仅通过查看原始模型设置，很难预测它是否会产生重大影响。此外，缩放后的速率可能会对系统的行为有或多或少的控制作用，因此，不正确的缩放会有或多或少的影响。
处理多隔室反应时，需要在改变涉及隔室的体积时仔细考虑速率的正确缩放。不正确缩放（通常通过与相应隔室的体积缩放）所导致的错误可能会导致模型行为出现显著偏差。
