Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, 7522NH Enschede, The Netherlands.
Gene. 2014 Jan 1;533(1):379-84. doi: 10.1016/j.gene.2013.10.010. Epub 2013 Oct 12.
Computational modeling of biological networks permits the comprehensive analysis of cells and tissues to define molecular phenotypes and novel hypotheses. Although a large number of software tools have been developed, the versatility of these tools is limited by mathematical complexities that prevent their broad adoption and effective use by molecular biologists. This study clarifies the basic aspects of molecular modeling, how to convert data into useful input, as well as the number of time points and molecular parameters that should be considered for molecular regulatory models with both explanatory and predictive potential. We illustrate the necessary experimental preconditions for converting data into a computational model of network dynamics. This model requires neither a thorough background in mathematics nor precise data on intracellular concentrations, binding affinities or reaction kinetics. Finally, we show how an interactive model of crosstalk between signal transduction pathways in primary human articular chondrocytes allows insight into processes that regulate gene expression.
生物网络的计算模型允许对细胞和组织进行全面分析，以定义分子表型和新的假说。尽管已经开发了大量的软件工具，但这些工具的多功能性受到数学复杂性的限制，这阻碍了它们被分子生物学家广泛采用和有效使用。本研究阐明了分子建模的基本方面，如何将数据转换为有用的输入，以及具有解释和预测潜力的分子调控模型应考虑的时间点和分子参数的数量。我们说明了将数据转换为网络动态计算模型所需的必要实验前提条件。该模型既不需要深入的数学背景，也不需要关于细胞内浓度、结合亲和力或反应动力学的精确数据。最后，我们展示了如何通过交互式模型来研究人原代关节软骨细胞中信号转导通路之间的串扰，从而深入了解调节基因表达的过程。
