在9月26日的《美国科学院院刊》杂志上，来自耶鲁大学的华裔学者俞海源（Haiyuan Yu，分子生物物理和生物化学博士后）和同事Mark Gerstein公布了他们对基因调节网络分级结构的基因组分析结果。
生物学中的一个基础问题就是细胞如何根据不同的刺激，利用转录因子来协调成千上万个基因的表达。转录因子和它们的靶标基因之间的关系能够根据定向调节网络被模拟出来。这些关系与社会网络中的“指令链”结构类似，这种结构的特点是具有分级层次特征。
在这项新的研究中，俞博士和同事研究出了确定普遍化的层次的运算方法，并且利用这些方法阐明了存在俞典型原核生物（大肠杆菌）和真核生物（酵母）的调节网络中的广泛的金字塔形层次结构——大部分转录因子处于金字塔底部，只有少数转录因子处于顶部。
这些处于顶部的主控因子处于蛋白质－蛋白质相互作用网络的中央，它们能够通过蛋白质相互作用接受来自整个调节层次的信息输入。而且，它们还对其他基因具有最大的影响力。但是，令人惊讶的是，处于调节层次底部的转录因子对细胞的生存更为重要。
研究人员曾经认为主控转录因子通过直接调节许多基因来产生广泛的影响，但事实上具有最多直接的调节靶标的转录因子处于这种层次网络的中间。俞博士发现这些中等转录因子是整个层次网络的“控制瓶颈”，这种中级管理者的控制程度与不同企业和政府机构中的社会结构非常相似。
在这项研究中，俞博士和M. G.共同完成了实验设计，俞博士进行了实验并完成资料分析。
原始出处：
Haiyuan Yu and Mark Gerstein
Genomic analysis of the hierarchical structure of regulatory networks
PNAS published September 26, 2006, 10.1073/pnas.0508637103 [Abstract] [PDF] [Supporting Information]
A fundamental question in biology is how the cell uses transcription factors (TFs) to coordinate the expression of thousands of genes in response to various stimuli. The relationships between TFs and their target genes can be modeled in terms of directed regulatory networks. These relationships, in turn, can be readily compared with commonplace "chain-of-command" structures in social networks, which have characteristic hierarchical layouts. Here, we develop algorithms for identifying generalized hierarchies (allowing for various loop structures) and use these approaches to illuminate extensive pyramid-shaped hierarchical structures existing in the regulatory networks of representative prokaryotes (Escherichia coli) and eukaryotes (Saccharomyces cerevisiae), with most TFs at the bottom levels and only a few master TFs on top. These masters are situated near the center of the protein-protein interaction network, a different type of network from the regulatory one, and they receive most of the input for the whole regulatory hierarchy through protein interactions. Moreover, they have maximal influence over other genes, in terms of affecting expression-level changes. Surprisingly, however, TFs at the bottom of the regulatory hierarchy are more essential to the viability of the cell. Finally, one might think master TFs achieve their wide influence through directly regulating many targets, but TFs with most direct targets are in the middle of the hierarchy. We find, in fact, that these midlevel TFs are "control bottlenecks" in the hierarchy, and this great degree of control for "middle managers" has parallels in efficient social structures in various corporate and governmental settings.
