Integrating proteomic, transcriptional, and interactome data reveals hidden components of signaling and regulatory networks.

Integrating proteomic, transcriptional, and interactome data reveals hidden components of signaling and regulatory networks.
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DOI:
10.1126/scisignal.2000350
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发表时间:
2009-07-28
期刊:
影响因子:
7.3
通讯作者:
Fraenkel E
Fraenkel E
中科院分区:
生物学1区
文献类型:
--
作者:
Huang SS;Fraenkel E

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细胞信号传导和调控网络是基本生物学过程的基础,如生长、分化和对环境的反应。虽然现在有各种高通量的方法来研究这些过程,他们的知识仍然是零碎的。通常,通过转录、蛋白质组学和遗传测定鉴定的绝大多数命中位于预期途径之外。细胞反应的这些意想不到的成分通常是最有趣的,因为它们可以提供对生物过程的新见解,并可能揭示新的治疗方法。然而,它们也是最难解释的。我们提出了一种技术,基于Steiner树问题,使用以前报道的蛋白质-蛋白质和蛋白质-DNA相互作用,以确定这些命中是如何组织成功能连贯的途径,揭示了许多组件的细胞反应是不容易明显的原始数据。同时适用于磷酸化蛋白质组学和转录数据的酵母信息素反应,它确定的变化,在不同的细胞过程中,远远超出了预期的途径。
Cellular signaling and regulatory networks underlie fundamental biological processes such as growth, differentiation, and response to the environment. Although there are now various high-throughput methods for studying these processes, knowledge of them remains fragmentary. Typically, the vast majority of hits identified by transcriptional, proteomic, and genetic assays lie outside of the expected pathways. These unexpected components of the cellular response are often the most interesting, because they can provide new insights into biological processes and potentially reveal new therapeutic approaches. However, they are also the most difficult to interpret. We present a technique, based on the Steiner tree problem, that uses previously reported protein-protein and protein-DNA interactions to determine how these hits are organized into functionally coherent pathways, revealing many components of the cellular response that are not readily apparent in the original data. Applied simultaneously to phosphoproteomic and transcriptional data for the yeast pheromone response, it identifies changes in diverse cellular processes that extend far beyond the expected pathways.
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