Wu Zujian, Pang Wei, Coghill George M
College of Information Science and Technology, Jinan University, Guangzhou, 510632 Guangdong People's Republic of China.
School of Natural and Computing Sciences, University of Aberdeen, Aberdeen, AB24 3UE Scotland, UK.
Cognit Comput. 2015;7(6):637-651. doi: 10.1007/s12559-015-9328-x. Epub 2015 May 3.
Both qualitative and quantitative model learning frameworks for biochemical systems have been studied in computational systems biology. In this research, after introducing two forms of pre-defined component patterns to represent biochemical models, we propose an integrative qualitative and quantitative modelling framework for inferring biochemical systems. In the proposed framework, interactions between reactants in the candidate models for a target biochemical system are evolved and eventually identified by the application of a qualitative model learning approach with an evolution strategy. Kinetic rates of the models generated from qualitative model learning are then further optimised by employing a quantitative approach with simulated annealing. Experimental results indicate that our proposed integrative framework is feasible to learn the relationships between biochemical reactants qualitatively and to make the model replicate the behaviours of the target system by optimising the kinetic rates quantitatively. Moreover, potential reactants of a target biochemical system can be discovered by hypothesising complex reactants in the synthetic models. Based on the biochemical models learned from the proposed framework, biologists can further perform experimental study in wet laboratory. In this way, natural biochemical systems can be better understood.
在计算系统生物学中,已经对生化系统的定性和定量模型学习框架进行了研究。在本研究中,在引入两种预定义的组件模式来表示生化模型之后,我们提出了一种用于推断生化系统的综合定性和定量建模框架。在所提出的框架中,目标生化系统候选模型中反应物之间的相互作用通过应用带有进化策略的定性模型学习方法进行演化并最终确定。然后,通过采用带有模拟退火的定量方法,对从定性模型学习生成的模型的动力学速率进行进一步优化。实验结果表明,我们提出的综合框架在定性学习生化反应物之间的关系以及通过定量优化动力学速率使模型复制目标系统行为方面是可行的。此外,通过在合成模型中假设复杂反应物,可以发现目标生化系统的潜在反应物。基于从所提出的框架中学到的生化模型,生物学家可以在湿实验室中进一步进行实验研究。通过这种方式,可以更好地理解自然生化系统。