Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network.
Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network.
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作者：
Zhang LV;King OD;Wong SL;Goldberg DS;Tong AH;Lesage G;Andrews B;Bussey H;Boone C;Roth FP
大规模的研究揭示了多种生物相互作用类型的网络，如蛋白质-蛋白质相互作用、遗传相互作用、转录调控、序列同源性和表达相关性。相互联系的重复模式，或“网络基序”，揭示了包含一种或两种相互作用类型的网络的生物学见解。为了研究涉及多种生物相互作用类型的更复杂关系，我们组装了一个集成的酿酒酵母网络，其中节点代表基因（或其蛋白质产物），不同颜色的链接代表上述五种生物相互作用类型。我们研究了包含多种相互作用类型的三节点和四节点互连模式，发现了许多丰富的多色网络基序。此外，我们发现大多数母题形成了“网络主题”——一类包含多次出现的网络母题的高阶重复互连模式。网络主题可以与特定的生物现象联系在一起，并可能代表更基本的网络设计原则。网络主题的例子包括一对具有许多复杂遗传相互作用的蛋白质复合物-“补偿复合物”主题。主题地图——根据这些主题绘制的网络——可以简化原本令人困惑的生物关系。我们通过根据两个特定的网络主题绘制S. cerevisiae网络来证明这一点。在一个完整的S. cerevisiae相互作用网络中，显著丰富的基序通常是网络主题的标志，这是与生物现象相对应的高阶网络结构。用网络主题来表示网络为复杂的生物关系提供了一种有用的简化。
Large-scale studies have revealed networks of various biological interaction types, such as protein-protein interaction, genetic interaction, transcriptional regulation, sequence homology, and expression correlation. Recurring patterns of interconnection, or 'network motifs', have revealed biological insights for networks containing either one or two types of interaction. To study more complex relationships involving multiple biological interaction types, we assembled an integrated Saccharomyces cerevisiae network in which nodes represent genes (or their protein products) and differently colored links represent the aforementioned five biological interaction types. We examined three- and four-node interconnection patterns containing multiple interaction types and found many enriched multi-color network motifs. Furthermore, we showed that most of the motifs form 'network themes' – classes of higher-order recurring interconnection patterns that encompass multiple occurrences of network motifs. Network themes can be tied to specific biological phenomena and may represent more fundamental network design principles. Examples of network themes include a pair of protein complexes with many inter-complex genetic interactions – the 'compensatory complexes' theme. Thematic maps – networks rendered in terms of such themes – can simplify an otherwise confusing tangle of biological relationships. We show this by mapping the S. cerevisiae network in terms of two specific network themes. Significantly enriched motifs in an integrated S. cerevisiae interaction network are often signatures of network themes, higher-order network structures that correspond to biological phenomena. Representing networks in terms of network themes provides a useful simplification of complex biological relationships.