Department of Biomedical Engineering , Eindhoven University of Technology , Den Dolech 2, Eindhoven, 5612 AZ , The Netherlands ; Institute for Complex Molecular Systems , Eindhoven University of Technology , Den Dolech 2, Eindhoven, 5612 AZ , The Netherlands ; Netherlands Consortium for Systems Biology , University of Amsterdam , Science Park 904, Amsterdam, 1098 XH , The Netherlands.
Interface Focus. 2013 Apr 6;3(2):20120084. doi: 10.1098/rsfs.2012.0084.
Metabolic profiling in combination with pathway-based analyses and computational modelling are becoming increasingly important in clinical and preclinical research. Modelling multi-factorial, progressive diseases requires the integration of molecular data at the metabolome, proteome and transcriptome levels. Also the dynamic interaction of organs and tissues needs to be considered. The processes involved cover time scales that are several orders of magnitude different. We report applications of a computational approach to bridge the scales and different levels of biological detail. Analysis of dynamic adaptations in parameter trajectories (ADAPTs) aims to investigate phenotype transitions during disease development and after a therapeutic intervention. ADAPT is based on a time-dependent evolution of model parameters to describe the dynamics of metabolic adaptations. The progression of metabolic adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages. To get a better understanding of the concept, the ADAPT approach is illustrated in a theoretical study. Its application in research on progressive changes in lipoprotein metabolism is also discussed.
代谢组学分析与基于途径的分析和计算模型相结合，在临床和临床前研究中变得越来越重要。对多因素、进行性疾病的建模需要整合代谢组学、蛋白质组学和转录组学水平的分子数据。还需要考虑器官和组织之间的动态相互作用。所涉及的过程涵盖了几个数量级不同的时间尺度。我们报告了一种计算方法的应用，以弥合这些尺度和不同层次的生物学细节之间的差距。参数轨迹动态适应性分析（ADAPTs）旨在研究疾病发展过程中和治疗干预后的表型转变。ADAPT 基于模型参数的时变演化，以描述代谢适应的动力学。通过识别模型参数中必要的动态变化来预测代谢适应的进展，以描述在不同阶段获得的实验数据之间的转变。为了更好地理解这一概念，本文在理论研究中说明了 ADAPT 方法。还讨论了其在脂蛋白代谢进行性变化研究中的应用。
