University of Portsmouth, Portsmouth and National Institute of Medical Research, London.
IEEE/ACM Trans Comput Biol Bioinform. 2012;9(2):358-71. doi: 10.1109/TCBB.2011.87. Epub 2011 Apr 29.
In this paper, we investigate the problem of reverse engineering the topology of gene regulatory networks from temporal gene expression data. We adopt a computational intelligence approach comprising swarm intelligence techniques, namely particle swarm optimization (PSO) and ant colony optimization (ACO). In addition, the recurrent neural network (RNN) formalism is employed for modeling the dynamical behavior of gene regulatory systems. More specifically, ACO is used for searching the discrete space of network architectures and PSO for searching the corresponding continuous space of RNN model parameters. We propose a novel solution construction process in the context of ACO for generating biologically plausible candidate architectures. The objective is to concentrate the search effort into areas of the structure space that contain architectures which are feasible in terms of their topological resemblance to real-world networks. The proposed framework is initially applied to the reconstruction of a small artificial network that has previously been studied in the context of gene network reverse engineering. Subsequently, we consider an artificial data set with added noise for reconstructing a subnetwork of the genetic interaction network of S. cerevisiae (yeast). Finally, the framework is applied to a real-world data set for reverse engineering the SOS response system of the bacterium Escherichia coli. Results demonstrate the relative advantage of utilizing problem-specific knowledge regarding biologically plausible structural properties of gene networks over conducting a problem-agnostic search in the vast space of network architectures.
在本文中,我们研究了从时间基因表达数据中反向工程基因调控网络拓扑的问题。我们采用了一种包含群体智能技术的计算智能方法,即粒子群优化(PSO)和蚁群优化(ACO)。此外,递归神经网络(RNN)形式用于对基因调控系统的动态行为进行建模。更具体地说,ACO 用于搜索网络结构的离散空间,而 PSO 用于搜索 RNN 模型参数的相应连续空间。我们在 ACO 的上下文中提出了一种新的解决方案构造过程,用于生成具有生物学合理性的候选结构。目标是将搜索工作集中在结构空间的区域,这些区域包含在拓扑上与真实网络相似的可行结构。该框架最初应用于重建一个小型人工网络,该网络以前在基因网络反向工程的背景下进行了研究。随后,我们考虑了一个带有添加噪声的人工数据集,用于重建酿酒酵母(酵母)遗传相互作用网络的子网。最后,该框架应用于一个真实世界的数据集,用于反向工程细菌大肠杆菌的 SOS 反应系统。结果表明,利用关于基因网络生物学合理结构特性的特定于问题的知识相对于在网络结构的巨大空间中进行无问题的搜索具有相对优势。