谷氨酸棒杆菌调控网络的功能结构和全局特性：来自高基因组覆盖数据集的新见解
Functional architecture and global properties of the Corynebacterium glutamicum regulatory network: novel insights from a dataset with a high genomic coverage
摘要：
谷氨酸棒杆菌是一种革兰氏阳性、厌氧、棒状土壤细菌，能够在多种碳源如糖和有机酸上生长。由于其高效生物合成氨基酸如L-谷氨酸和L-赖氨酸的能力，其是生物技术相关的生物体。在这里，我们重建了最完整的C。对迄今为止的谷氨酸调控网络进行了系统的研究，全面分析了谷氨酸调控网络的全球组织性质、系统级特征和功能架构。我们的分析显示了Abasy Atlas在研究调控网络的功能组织方面的巨大力量。我们创建了C的两个模型。谷氨酸调控网络：所有证据（包含弱支持和强支持的相互作用，基因组覆盖率= 73%）和强支持（仅考虑强支持的证据，基因组覆盖率= 71%）。使用国家的最先进的方法，我们证明了幂律行为真正统治的连接和聚类系数分布。我们发现了一个以前没有报道过的电路基序，我们命名为复杂的前馈基序。我们强调了反馈回路对功能架构的重要性，而不仅仅是它们在网络中是否在统计上过度代表。我们发现，以前报道的自上而下的方法是不足以推断的层次结构的调控网络，因为反馈桥不同的层次结构层，和自上而下的方法忽视了存在的模块间基因塑造的整合层。我们的研究结果进一步支持了一个菱形的，三层的层次结构，表现出一些反馈之间的处理和协调层，这是由四类系统级元素：全球监管机构，本地自主模块，基础机械和模块间基因。
英文摘要：
Corynebacterium glutamicum is a Gram-positive, anaerobic, rod-shaped soil bacterium able to grow on a diversity of carbon sources like sugars and organic acids. It is a biotechnological relevant organism because of its highly efficient ability to biosynthesize amino acids, such as L-glutamic acid and L-lysine. Here, we reconstructed the most complete C. glutamicum regulatory network to date and comprehensively analyzed its global organizational properties, systems-level features and functional architecture. Our analyses show the tremendous power of Abasy Atlas to study the functional organization of regulatory networks. We created two models of the C. glutamicum regulatory network: all-evidences (containing both weak and strong supported interactions, genomic coverage = 73%) and strongly-supported (only accounting for strongly supported evidences, genomic coverage = 71%). Using state-of-the-art methodologies, we prove that power-law behaviors truly govern the connectivity and clustering coefficient distributions. We found a non-previously reported circuit motif that we named complex feed-forward motif. We highlighted the importance of feedback loops for the functional architecture, beyond whether they are statistically over-represented or not in the network. We show that the previously reported top-down approach is inadequate to infer the hierarchy governing a regulatory network because feedback bridges different hierarchical layers, and the top-down approach disregards the presence of intermodular genes shaping the integration layer. Our findings all together further support a diamond-shaped, three-layered hierarchy exhibiting some feedback between processing and coordination layers, which is shaped by four classes of systems-level elements: global regulators, locally autonomous modules, basal machinery and intermodular genes.
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