Chen Chieh-Chun, Zhong Sheng
Department of Bioengineering, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA.
BMC Genomics. 2008 Sep 16;9 Suppl 2(Suppl 2):S19. doi: 10.1186/1471-2164-9-S2-S19.
To date, the reconstruction of gene regulatory networks from gene expression data has primarily relied on the correlation between the expression of transcription regulators and that of target genes.
We developed a network reconstruction method based on quantities that are closely related to the biophysical properties of TF-TF interaction, TF-DNA binding and transcriptional activation and repression. The Network-Identifier method utilized a thermodynamic model for gene regulation to infer regulatory relationships from multiple time course gene expression datasets. Applied to five datasets of differentiating embryonic stem cells, Network-Identifier identified a gene regulatory network among 87 transcription regulator genes. This network suggests that Oct4, Sox2 and Klf4 indirectly repress lineage specific differentiation genes by activating transcriptional repressors of Ctbp2, Rest and Mtf2.
迄今为止，从基因表达数据重建基因调控网络主要依赖于转录调节因子与靶基因表达之间的相关性。
我们基于与转录因子-转录因子相互作用、转录因子-DNA结合以及转录激活和抑制的生物物理特性密切相关的量，开发了一种网络重建方法。网络识别方法利用基因调控的热力学模型从多个时间进程基因表达数据集中推断调控关系。应用于五个分化胚胎干细胞数据集，网络识别方法在87个转录调节因子基因中识别出一个基因调控网络。该网络表明，Oct4、Sox2和Klf4通过激活Ctbp2、Rest和Mtf2的转录抑制因子间接抑制谱系特异性分化基因。
