Xenitidis P, Seimenis I, Kakolyris S, Adamopoulos A
Medical Physics Laboratory, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Medical Physics Laboratory, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
J Theor Biol. 2017 Aug 7;426:1-16. doi: 10.1016/j.jtbi.2017.05.010. Epub 2017 May 17.
High-throughput technology like microarrays is widely used in the inference of gene regulatory networks (GRNs). We focused on time series data since we are interested in the dynamics of GRNs and the identification of dynamic networks. We evaluated the amount of information that exists in artificial time series microarray data and the ability of an inference process to produce accurate models based on them. We used dynamic artificial gene regulatory networks in order to create artificial microarray data. Key features that characterize microarray data such as the time separation of directly triggered genes, the percentage of directly triggered genes and the triggering function type were altered in order to reveal the limits that are imposed by the nature of microarray data on the inference process. We examined the effect of various factors on the inference performance such as the network size, the presence of noise in microarray data, and the network sparseness. We used a system theory approach and examined the relationship between the pole placement of the inferred system and the inference performance. We examined the relationship between the inference performance in the time domain and the true system parameter identification. Simulation results indicated that time separation and the percentage of directly triggered genes are crucial factors. Also, network sparseness, the triggering function type and noise in input data affect the inference performance. When two factors were simultaneously varied, it was found that variation of one parameter significantly affects the dynamic response of the other. Crucial factors were also examined using a real GRN and acquired results confirmed simulation findings with artificial data. Different initial conditions were also used as an alternative triggering approach. Relevant results confirmed that the number of datasets constitutes the most significant parameter with regard to the inference performance.
像微阵列这样的高通量技术被广泛应用于基因调控网络(GRN)的推断。由于我们对基因调控网络的动态变化以及动态网络的识别感兴趣,所以我们专注于时间序列数据。我们评估了人工时间序列微阵列数据中存在的信息量以及基于这些数据的推断过程生成准确模型的能力。我们使用动态人工基因调控网络来创建人工微阵列数据。为了揭示微阵列数据的性质对推断过程所施加的限制,我们改变了表征微阵列数据的关键特征,如直接触发基因的时间间隔、直接触发基因的百分比以及触发函数类型。我们研究了各种因素对推断性能的影响,如网络规模、微阵列数据中的噪声以及网络稀疏性。我们采用系统理论方法,研究了推断系统的极点配置与推断性能之间的关系。我们研究了时域中的推断性能与真实系统参数识别之间的关系。仿真结果表明,时间间隔和直接触发基因的百分比是关键因素。此外,网络稀疏性、触发函数类型和输入数据中的噪声会影响推断性能。当两个因素同时变化时,发现一个参数的变化会显著影响另一个参数的动态响应。我们还使用真实的基因调控网络研究了关键因素,并获得的结果证实了使用人工数据的仿真结果。不同的初始条件也被用作一种替代的触发方法。相关结果证实,就推断性能而言,数据集的数量是最重要的参数。