Yeger-Lotem Esti, Sattath Shmuel, Kashtan Nadav, Itzkovitz Shalev, Milo Ron, Pinter Ron Y, Alon Uri, Margalit Hanah
Department of Molecular Genetics and Biotechnology, Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel.
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5934-9. doi: 10.1073/pnas.0306752101. Epub 2004 Apr 12.
Genes and proteins generate molecular circuitry that enables the cell to process information and respond to stimuli. A major challenge is to identify characteristic patterns in this network of interactions that may shed light on basic cellular mechanisms. Previous studies have analyzed aspects of this network, concentrating on either transcription-regulation or protein-protein interactions. Here we search for composite network motifs: characteristic network patterns consisting of both transcription-regulation and protein-protein interactions that recur significantly more often than in random networks. To this end we developed algorithms for detecting motifs in networks with two or more types of interactions and applied them to an integrated data set of protein-protein interactions and transcription regulation in Saccharomyces cerevisiae. We found a two-protein mixed-feedback loop motif, five types of three-protein motifs exhibiting coregulation and complex formation, and many motifs involving four proteins. Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions.
基因和蛋白质生成分子电路，使细胞能够处理信息并对刺激做出反应。一个主要挑战是在这个相互作用网络中识别出可能揭示基本细胞机制的特征模式。先前的研究分析了这个网络的各个方面，要么专注于转录调控，要么专注于蛋白质 - 蛋白质相互作用。在这里，我们寻找复合网络基序：由转录调控和蛋白质 - 蛋白质相互作用组成的特征网络模式，其出现频率比随机网络中显著更高。为此，我们开发了用于检测具有两种或更多种相互作用类型的网络中基序的算法，并将其应用于酿酒酵母中蛋白质 - 蛋白质相互作用和转录调控的综合数据集。我们发现了一个双蛋白混合反馈环基序、五种表现出共调控和复合物形成的三蛋白基序，以及许多涉及四种蛋白质的基序。几乎所有四蛋白基序都由较小基序的组合组成。这项研究提出了一个用于检测具有多种相互作用类型的网络构建模块的基本框架。
