Wu Nuosi, Huang Jiang, Zhang Xiao-Fei, Ou-Yang Le, He Shan, Zhu Zexuan, Xie Weixin
College of Electronics and Information Engineering, Shenzhen University, Shenzhen, China.
College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China.
Front Genet. 2019 Jul 22;10:623. doi: 10.3389/fgene.2019.00623. eCollection 2019.
Gene regulatory networks (GRNs) are often inferred based on Gaussian graphical models that could identify the conditional dependence among genes by estimating the corresponding precision matrix. Classical Gaussian graphical models are usually designed for single network estimation and ignore existing knowledge such as pathway information. Therefore, they can neither make use of the common information shared by multiple networks, nor can they utilize useful prior information to guide the estimation. In this paper, we propose a new weighted fused pathway graphical lasso (WFPGL) to jointly estimate multiple networks by incorporating prior knowledge derived from known pathways and gene interactions. Based on the assumption that two genes are less likely to be connected if they do not participate together in any pathways, a pathway-based constraint is considered in our model. Moreover, we introduce a weighted fused lasso penalty in our model to take into account prior gene interaction data and common information shared by multiple networks. Our model is optimized based on the alternating direction method of multipliers (ADMM). Experiments on synthetic data demonstrate that our method outperforms other five state-of-the-art graphical models. We then apply our model to two real datasets. Hub genes in our identified state-specific networks show some shared and specific patterns, which indicates the efficiency of our model in revealing the underlying mechanisms of complex diseases.
基因调控网络(GRNs)通常基于高斯图形模型进行推断,该模型可以通过估计相应的精度矩阵来识别基因之间的条件依赖性。经典的高斯图形模型通常设计用于单网络估计,并且忽略了诸如通路信息等现有知识。因此,它们既无法利用多个网络共享的共同信息,也无法利用有用的先验信息来指导估计。在本文中,我们提出了一种新的加权融合通路图形套索(WFPGL)方法,通过纳入从已知通路和基因相互作用中获得的先验知识来联合估计多个网络。基于这样的假设:如果两个基因没有共同参与任何通路,那么它们之间连接的可能性较小,我们的模型考虑了基于通路的约束。此外,我们在模型中引入了加权融合套索惩罚项,以考虑先验基因相互作用数据和多个网络共享的共同信息。我们的模型基于交替方向乘子法(ADMM)进行优化。对合成数据的实验表明,我们的方法优于其他五种最先进的图形模型。然后,我们将模型应用于两个真实数据集。我们在识别出的状态特异性网络中的枢纽基因显示出一些共同和特定的模式,这表明我们的模型在揭示复杂疾病潜在机制方面的有效性。