Rubinstein Amir, Hazan Ofir, Chor Benny, Pinter Ron Y, Kassir Yona
School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel.
BMC Res Notes. 2013 Aug 6;6:311. doi: 10.1186/1756-0500-6-311.
Bench biologists often do not take part in the development of computational models for their systems, and therefore, they frequently employ them as "black-boxes". Our aim was to construct and test a model that does not depend on the availability of quantitative data, and can be directly used without a need for intensive computational background.
We present a discrete transition model. We used cell-cycle in budding yeast as a paradigm for a complex network, demonstrating phenomena such as sequential protein expression and activity, and cell-cycle oscillation. The structure of the network was validated by its response to computational perturbations such as mutations, and its response to mating-pheromone or nitrogen depletion. The model has a strong predicative capability, demonstrating how the activity of a specific transcription factor, Hcm1, is regulated, and what determines commitment of cells to enter and complete the cell-cycle.
The model presented herein is intuitive, yet is expressive enough to elucidate the intrinsic structure and qualitative behavior of large and complex regulatory networks. Moreover our model allowed us to examine multiple hypotheses in a simple and intuitive manner, giving rise to testable predictions. This methodology can be easily integrated as a useful approach for the study of networks, enriching experimental biology with computational insights.
实验台生物学家通常不参与其研究系统的计算模型开发，因此，他们常常将这些模型当作“黑匣子”来使用。我们的目标是构建并测试一个不依赖于定量数据可用性的模型，并且无需深厚的计算背景知识即可直接使用。
我们提出了一个离散转换模型。我们以芽殖酵母中的细胞周期作为复杂网络的范例，展示了诸如蛋白质的顺序表达和活性以及细胞周期振荡等现象。该网络的结构通过其对诸如突变等计算扰动的响应以及对交配信息素或氮耗竭的响应得到了验证。该模型具有很强的预测能力，展示了特定转录因子Hcm1的活性是如何被调控的，以及是什么决定了细胞进入并完成细胞周期的进程。
本文提出的模型直观易懂，但又足以清晰地阐释大型复杂调控网络的内在结构和定性行为。此外，我们的模型使我们能够以简单直观的方式检验多种假设，从而得出可验证的预测。这种方法可以很容易地作为一种有用的网络研究方法加以整合，用计算见解丰富实验生物学。
