Bridging topological and functional information in protein interaction networks by short loops profiling.
Bridging topological and functional information in protein interaction networks by short loops profiling.
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DOI：
10.1038/srep08540
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发表时间：
2015-02-23
影响因子：
4.6
通讯作者：
Fraternali F
中科院分区：
文献类型：
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作者：
Chung SS;Pandini A;Annibale A;Coolen AC;Thomas NS;Fraternali F
蛋白质-蛋白质相互作用网络（PPINs）已被用于识别蛋白质之间潜在的新相互联系以及关键的细胞功能。在这项研究中，我们通过分析短环的网络基序来确定PPIN拓扑结构的基本原理，短环是3到6个蛋白质之间的小循环相互作用。我们将30个PPINs与相应的随机零模型进行了比较，并检查了从622个人类蛋白质复合物的交叉验证高置信度数据集中提取的环中常见生物学功能的发生情况。我们证明了环是PPINs的固有特征，并且特定的细胞功能主要由不同长度的环执行。拓扑学上，我们发现循环与PPINs的准确性密切相关，并定义了具有高弹性的交互核心。该核心的识别和环路组成的分析是评估PPIN质量和发现实验检测方法可能存在的偏差的有前途的工具。超过96%的环具有至少一种生物学功能，富集了与mRNA代谢加工和细胞周期相关的细胞功能。我们的分析表明，这些基序可以用于功能表型检测的靶向实验设计。
Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.