Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Sci Rep. 2021 Jan 13;11(1):1168. doi: 10.1038/s41598-020-80745-9.
Molecular interactions are studied as independent networks in systems biology. However, molecular networks do not exist independently of each other. In a network of networks approach (called multiplex), we study the joint organization of transcriptional regulatory network (TRN) and protein-protein interaction (PPI) network. We find that TRN and PPI are non-randomly coupled across five different eukaryotic species. Gene degrees in TRN (number of downstream genes) are positively correlated with protein degrees in PPI (number of interacting protein partners). Gene-gene and protein-protein interactions in TRN and PPI, respectively, also non-randomly overlap. These design principles are conserved across the five eukaryotic species. Robustness of the TRN-PPI multiplex is dependent on this coupling. Functionally important genes and proteins, such as essential, disease-related and those interacting with pathogen proteins, are preferentially situated in important parts of the human multiplex with highly overlapping interactions. We unveil the multiplex architecture of TRN and PPI. Multiplex architecture may thus define a general framework for studying molecular networks. This approach may uncover the building blocks of the hierarchical organization of molecular interactions.
在系统生物学中，分子相互作用被作为独立的网络进行研究。然而，分子网络并不是相互独立存在的。在网络的网络方法（称为多重网络）中，我们研究转录调控网络（TRN）和蛋白质-蛋白质相互作用（PPI）网络的联合组织。我们发现，TRN 和 PPI 在五个不同的真核生物物种之间是非随机耦合的。TRN 中的基因度（下游基因的数量）与 PPI 中的蛋白质度（相互作用的蛋白质伙伴的数量）呈正相关。TRN 和 PPI 中的基因-基因和蛋白质-蛋白质相互作用也存在非随机重叠。这些设计原则在五个真核生物物种中都是保守的。TRN-PPI 多重网络的稳健性依赖于这种耦合。功能重要的基因和蛋白质，如必需基因、与疾病相关的基因以及与病原体蛋白相互作用的基因，优先位于人类多重网络中具有高度重叠相互作用的重要部分。我们揭示了 TRN 和 PPI 的多重网络结构。因此，多重网络结构可能定义了研究分子网络的一般框架。这种方法可能揭示分子相互作用的层次组织的构建块。
