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Topological and statistical analyses of gene regulatory networks reveal unifying yet quantitatively different emergent properties

机译:基因调控网络的拓扑和统计分析揭示了统一但数量上不同的新兴特性

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摘要

Understanding complexity in physical, biological, social and information systems is predicated on describing interactions amongst different components. Advances in genomics are facilitating the high-throughput identification of molecular interactions, and graphs are emerging as indispensable tools in explaining how the connections in the network drive organismal phenotypic plasticity. Here, we describe the architectural organization and associated emergent topological properties of gene regulatory networks (GRNs) that describe protein-DNA interactions (PDIs) in several model eukaryotes. By analyzing GRN connectivity, our results show that the anticipated scale-free network architectures are characterized by organism-specific power law scaling exponents. These exponents are independent of the fraction of the GRN experimentally sampled, enabling prediction of properties of the complete GRN for an organism. We further demonstrate that the exponents describe inequalities in transcription factor (TF)-target gene recognition across GRNs. These observations have the important biological implication that they predict the existence of an intrinsic organism-specific trans and/or cis regulatory landscape that constrains GRN topologies. Consequently, architectural GRN organization drives not only phenotypic plasticity within a species, but is also likely implicated in species-specific phenotype.
机译:了解物理,生物,社会和信息系统的复杂性是基于描述不同组件之间的相互作用。基因组学的进步促进了分子相互作用的高通量鉴定,并且图表正在成为解释网络中的连接如何驱动生物表型可塑性的必不可少的工具。在这里,我们描述了基因调节网络(GRN)的体系结构组织和相关的新兴拓扑特性,这些基因描述了几种模型真核生物中的蛋白质-DNA相互作用(PDI)。通过分析GRN连通性,我们的结果表明,预期的无标度网络体系结构具有特定于有机体的幂律定标指数。这些指数与实验采样的GRN的分数无关,从而可以预测生物体完整GRN的特性。我们进一步证明,该指数描述了跨GRN的转录因子(TF)-靶标基因识别中的不等式。这些观察结果具有重要的生物学意义,即它们预测了约束GRN拓扑的内在生物体特有的反式和/或顺式调控态势的存在。因此,建筑GRN组织不仅驱动物种内部的表型可塑性,而且还可能与物种特定的表型有关。

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