Goemann Bjoern, Potapov Anatolij P, Ante Michael, Wingender Edgar
Department of Bioinformatics, University Medical Center Goettingen, Georg August University Goettingen, Goldschmidtstr. 1, D-37077 Goettingen, Germany.
Genome Inform. 2009 Oct;23(1):32-45.
We have systematically analyzed various topological patterns comprising 1, 2 or 3 nodes in the mammalian metabolic, signal transduction and transcription networks: These patterns were analyzed with regard to their frequency and statistical over-representation in each network, as well as to their topological significance for the coherence of the networks. The latter property was evaluated using the pairwise disconnectivity index, which we have recently introduced to quantify how critical network components are for the internal connectedness of a network. The 1-node pattern made up by a vertex with a self-loop has been found to exert particular properties in all three networks. In general, vertices with a self-loop tend to be topologically more important than other vertices. Moreover, self-loops have been found to be attached to most 2-node and 3-node patterns, thereby emphasizing a particular role of self-loop components in the architectural organization of the networks. For none of the networks, a positive correlation between the mean topological significance and the Z-score of a pattern could be observed. That is, in general, motifs are not per se more important for the overall network coherence than patterns that are not over-represented. All 2- and 3-node patterns that are over-represented and thus qualified as motifs in all three networks exhibit a loop structure. This intriguing observation can be viewed as an advantage of loop-like structures in building up the regulatory circuits of the whole cell. The transcription network has been found to differ from the other networks in that (i) self-loops play an even higher role, (ii) its binary loops are highly enriched with self-loops attached, and (iii) feed-back loops are not over-represented. Metabolic networks reveal some particular topological properties which may reflect the fact that metabolic paths are, to a large extent, reversible. Interestingly, some of the most important 3-node patterns of both the transcription and the signaling network can be concatenated to subnetworks comprising many genes that play a particular role in the regulation of cell proliferation.
我们系统地分析了哺乳动物代谢、信号转导和转录网络中包含1个、2个或3个节点的各种拓扑模式：分析了这些模式在每个网络中的出现频率和统计上的过度代表性，以及它们对网络连贯性的拓扑意义。使用我们最近引入的成对不连通性指数评估了后一种特性，该指数用于量化网络组件对网络内部连通性的关键程度。由带有自环的顶点组成的1节点模式在所有三个网络中都具有特殊性质。一般来说，带有自环的顶点在拓扑上往往比其他顶点更重要。此外，已发现自环附着于大多数2节点和3节点模式，从而强调了自环组件在网络架构组织中的特殊作用。在任何一个网络中，均未观察到模式的平均拓扑意义与Z分数之间存在正相关。也就是说，一般而言，基序本身对于整体网络连贯性并不比未过度代表性的模式更重要。所有在所有三个网络中过度代表性并因此被视为基序的2节点和3节点模式都呈现出环结构。这一有趣的观察结果可被视为环状结构在构建整个细胞调节回路方面的一个优势。已发现转录网络与其他网络的不同之处在于：（i）自环发挥着更高的作用；（ii）其二元环高度富集有附着的自环；（iii）反馈环未过度代表性。代谢网络揭示了一些特殊的拓扑性质，这可能反映了代谢途径在很大程度上是可逆的这一事实。有趣地是，转录网络和信号网络中一些最重要的3节点模式可以连接成包含许多在细胞增殖调节中起特定作用的基因的子网络。
