Fudan University, Shanghai, China.
Bioprocess Biosyst Eng. 2010 May;33(4):495-505. doi: 10.1007/s00449-009-0358-1. Epub 2009 Aug 6.
Genome-wide transcriptional regulatory networks (TRNs) specify the interactions between transcription factors (TFs) and their target genes. Many methods have been proposed to reconstruct regulatory networks from gene expression datasets and/or genome sequences, but most of them can only infer qualitative regulation relationships. Thus, developing a quantitative model that can estimate the kinetic parameters of transcriptional regulatory functions is an urgent and important task. In this paper I propose REMBE, a regulatory model based on binding energy, to quantify transcriptional regulatory networks. My model combines multiple kinetic quantities, including binding strength, TF-DNA's binding energy, transcription productivity with respect to each binding state, and hidden TFs' concentration, into a general learning model. Experimental results show that my model can effectively learn these kinetic parameters and TFs' concentration from genome sequences and gene expression data. Moreover, these learned parameters and TFs' concentration provide more informative biological senses than merely qualitative regulatory relationships can do.
全基因组转录调控网络(TRNs)指定了转录因子(TFs)与其靶基因之间的相互作用。已经提出了许多方法来从基因表达数据集和/或基因组序列中重建调控网络,但大多数方法只能推断定性的调控关系。因此,开发一种能够估计转录调控功能的动力学参数的定量模型是一个紧迫而重要的任务。在本文中,我提出了 REMBE,一种基于结合能的调控模型,用于量化转录调控网络。我的模型将多个动力学参数,包括结合强度、TF-DNA 的结合能、每个结合状态的转录产率以及隐藏 TF 的浓度,组合到一个通用的学习模型中。实验结果表明,我的模型可以有效地从基因组序列和基因表达数据中学习这些动力学参数和 TF 的浓度。此外,这些学习到的参数和 TF 的浓度比仅仅定性的调控关系提供了更有信息量的生物学意义。