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Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis

机译:秀丽隐杆线虫早期胚胎发生的分子机器的预测模型。

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Although numerous fundamental aspects of development have been uncovered through the study of individual genes and proteins, system-level models are still missing for most developmental processes. The first two cell divisions of Caenorhabditis elegans embryogenesis constitute an ideal test bed for a system-level approach. Early embryogenesis, including processes such as cell division and establishment of cellular polarity, is readily amenable to large-scale functional analysis. A first step toward a system-level understanding is to provide 'first-draft' models both of the molecular assemblies involved(1) and of the functional connections between them. Here we show that such models can be derived from an integrated gene/protein network generated from three different types of functional relationship(2): protein interaction(3), expression profiling similarity(4) and phenotypic profiling similarity(5), as estimated from detailed early embryonic RNA interference phenotypes systematically recorded for hundreds of early embryogenesis genes(6). The topology of the integrated network suggests that C. elegans early embryogenesis is achieved through coordination of a limited set of molecular machines. We assessed the overall predictive value of such molecular machine models by dynamic localization of ten previously uncharacterized proteins within the living embryo.
机译:尽管通过研究单个基因和蛋白质已经发现了开发的许多基本方面,但是大多数开发过程仍缺少系统级模型。秀丽隐杆线虫胚胎发生的前两个细胞分裂构成系统级方法的理想测试平台。早期胚胎发生,包括诸如细胞分裂和细胞极性建立等过程,很容易进行大规模功能分析。迈向系统级理解的第一步是提供涉及的分子组件(1)及其之间的功能连接的“初稿”模型。在这里,我们证明了这样的模型可以从由三种不同类型的功能关系(2):蛋白质相互作用(3),表达谱相似性(4)和表型谱相似性(5)生成的整合基因/蛋白网络中获得。系统地记录了数百种早期胚胎发生基因的详细早期胚胎RNA干扰表型(6)。集成网络的拓扑结构表明,秀丽隐杆线虫的早期胚胎发生是通过协调有限的一组分子机器来实现的。我们通过动态定位活体胚胎中的十个以前未表征的蛋白质,评估了这种分子机器模型的总体预测价值。

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