Song Le, Kolar Mladen, Xing Eric P
School of Computer Science, Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Bioinformatics. 2009 Jun 15;25(12):i128-36. doi: 10.1093/bioinformatics/btp192.
Gene regulatory networks underlying temporal processes, such as the cell cycle or the life cycle of an organism, can exhibit significant topological changes to facilitate the underlying dynamic regulatory functions. Thus, it is essential to develop methods that capture the temporal evolution of the regulatory networks. These methods will be an enabling first step for studying the driving forces underlying the dynamic gene regulation circuitry and predicting the future network structures in response to internal and external stimuli.
We introduce a kernel-reweighted logistic regression method (KELLER) for reverse engineering the dynamic interactions between genes based on their time series of expression values. We apply the proposed method to estimate the latent sequence of temporal rewiring networks of 588 genes involved in the developmental process during the life cycle of Drosophila melanogaster. Our results offer the first glimpse into the temporal evolution of gene networks in a living organism during its full developmental course. Our results also show that many genes exhibit distinctive functions at different stages along the developmental cycle.
Source codes and relevant data will be made available at http://www.sailing.cs.cmu.edu/keller.
诸如细胞周期或生物体生命周期等时间进程背后的基因调控网络,可能会展现出显著的拓扑变化,以促进潜在的动态调控功能。因此,开发能够捕捉调控网络时间演变的方法至关重要。这些方法将是研究动态基因调控回路背后驱动力以及预测响应内部和外部刺激的未来网络结构的关键第一步。
我们引入了一种核加权逻辑回归方法(KELLER),用于根据基因表达值的时间序列对基因间的动态相互作用进行逆向工程。我们应用所提出的方法来估计黑腹果蝇生命周期中参与发育过程的588个基因的时间重连网络的潜在序列。我们的结果首次揭示了生物体在其整个发育过程中基因网络的时间演变。我们的结果还表明,许多基因在发育周期的不同阶段表现出独特的功能。
源代码和相关数据将在http://www.sailing.cs.cmu.edu/keller上提供。