Li Cheng-Wei, Chen Bor-Sen
Laboratory of Systems Biology, National Tsing Hua University, Hsinchu, 300, Taiwan.
Gene Regul Syst Bio. 2009 Oct 19;3:191-210.
In order to investigate the possible mechanisms for eve stripe formation of Drosophila embryo, a spatio-temporal gene/protein interaction network model is proposed to mimic dynamic behaviors of protein synthesis, protein decay, mRNA decay, protein diffusion, transcription regulations and autoregulation to analyze the interplay of genes and proteins at different compartments in early embryogenesis. In this study, we use the maximum likelihood (ML) method to identify the stochastic 3-D Embryo Space-Time (3-DEST) dynamic model for gene/protein interaction network via 3-D mRNA and protein expression data and then use the Akaike Information Criterion (AIC) to prune the gene/protein interaction network. The identified gene/protein interaction network allows us not only to analyze the dynamic interplay of genes and proteins on the border of eve stripes but also to infer that eve stripes are established and maintained by network motifs built by the cooperation between transcription regulations and diffusion mechanisms in early embryogenesis. Literature reference with the wet experiments of gene mutations provides a clue for validating the identified network. The proposed spatio-temporal dynamic model can be extended to gene/protein network construction of different biological phenotypes, which depend on compartments, e.g. postnatal stem/progenitor cell differentiation.
为了研究果蝇胚胎中偶数条纹形成的可能机制,提出了一个时空基因/蛋白质相互作用网络模型,以模拟蛋白质合成、蛋白质降解、mRNA降解、蛋白质扩散、转录调控和自动调控的动态行为,从而分析早期胚胎发育中不同区域基因和蛋白质的相互作用。在本研究中,我们使用最大似然(ML)方法通过三维mRNA和蛋白质表达数据识别基因/蛋白质相互作用网络的随机三维胚胎时空(3-DEST)动态模型,然后使用赤池信息准则(AIC)修剪基因/蛋白质相互作用网络。所识别的基因/蛋白质相互作用网络不仅使我们能够分析偶数条纹边界上基因和蛋白质的动态相互作用,还能推断出偶数条纹是在早期胚胎发育过程中由转录调控和扩散机制协同构建的网络基序建立和维持的。与基因突变的湿实验相关的文献参考为验证所识别的网络提供了线索。所提出的时空动态模型可以扩展到不同生物表型的基因/蛋白质网络构建,这些生物表型取决于区域,例如出生后干细胞/祖细胞分化。