Interactions between transcription factors and target genes form regulatory networks that control target gene expression. Regulatory networks contain canonical motifs, including the feed forward loop (FFL), single input module (SIM), and multiple input module (MIM) (Fig. 1). A challenge for network analysis is to identify and enumerate the motifs, required to illuminate their biological significance. Although there is consensus about the definition of the FFL, published definitions of the SIM and MIM are unclear and often used inconsistently. Here, we provide, for the first time, a complete and consistent definition of SIM and MIM, and algorithms for enumerating SIMs and MIMs in any network. From the algorithmic point of view, enumeration of SIMs and MIMs is substantially harder than enumerating FFLs. We compare the distributions of motifs in the Yeast regulatory network under different physiological conditions, reported earlier by the landmark paper of Luscombe et al. (Nature 2004, 431: 308-312). Our reanalysis shows major differences in the number of motifs compared with the results of those authors, requiring significant revision of some of their conclusions.

译文

转录因子与靶基因之间的相互作用形成控制靶基因表达的调节网络。监管网络包含规范主题,包括前馈环路(FFL),单输入模块(SIM)和多输入模块(MIM)(图1)。网络分析的一个挑战是识别并枚举阐明其生物学意义所需的基序。尽管对FFL的定义已达成共识,但已发布的SIM和MIM的定义尚不清楚,并且经常使用不一致。在这里,我们首次提供了完整和一致的SIM卡和MIM定义,以及用于枚举任何网络中的SIM卡和MIM的算法。从算法的角度来看,SIM和MIM的枚举比枚举FFL的难度大得多。我们比较了不同生理条件下酵母调节网络中基序的分布,这是由Luscombe等人的地标性论文较早报道的。 (Nature 2004,431:308-312)。我们的重新分析表明,与那些作者的结果相比,母题的数量存在重大差异,需要对他们的某些结论进行重大修改。

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