Zhan Ming
Bioinformatics Unit, Research Resources Branch, National Institute on Aging, NIH, 333 Cassell Drive, Baltimore, MD, 21224, USA,
Genomic Med. 2007;1(1-2):19-28. doi: 10.1007/s11568-007-9004-7. Epub 2007 May 11.
The coordinated and dynamic modulation or interaction of genes or proteins acts as an important mechanism used by a cell in functional regulation. Recent studies have shown that many transcriptional networks exhibit a scale-free topology and hierarchical modular architecture. It has also been shown that transcriptional networks or pathways are dynamic and behave only in certain ways and controlled manners in response to disease development, changing cellular conditions, and different environmental factors. Moreover, evolutionarily conserved and divergent transcriptional modules underline fundamental and species-specific molecular mechanisms controlling disease development or cellular phenotypes. Various computational algorithms have been developed to explore transcriptional networks and modules from gene expression data. In silico studies have also been made to mimic the dynamic behavior of regulatory networks, analyzing how disease or cellular phenotypes arise from the connectivity or networks of genes and their products. Here, we review the recent development in computational biology research on deciphering modular and dynamic behaviors of transcriptional networks, highlighting important findings. We also demonstrate how these computational algorithms can be applied in systems biology studies as on disease, stem cells, and drug discovery.
基因或蛋白质的协同动态调控或相互作用是细胞进行功能调节的重要机制。最近的研究表明,许多转录网络呈现出无标度拓扑结构和层次模块化架构。研究还表明,转录网络或途径是动态的,仅在特定方式和受控方式下响应疾病发展、细胞条件变化和不同环境因素而发挥作用。此外,进化上保守和不同的转录模块是控制疾病发展或细胞表型的基本和物种特异性分子机制的基础。已经开发了各种计算算法来从基因表达数据中探索转录网络和模块。还进行了计算机模拟研究,以模拟调控网络的动态行为,分析疾病或细胞表型如何从基因及其产物的连接性或网络中产生。在此,我们综述了计算生物学研究在破译转录网络的模块化和动态行为方面的最新进展,突出重要发现。我们还展示了这些计算算法如何应用于疾病、干细胞和药物发现等系统生物学研究。