Systematic analysis of pleiotropy in C. elegans early embryogenesis.
Systematic analysis of pleiotropy in C. elegans early embryogenesis.
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DOI：
10.1371/journal.pcbi.1000003
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发表时间：
2008-02-29
影响因子：
4.3
通讯作者：
Ge H
中科院分区：
文献类型：
--
作者：
Zou L;Sriswasdi S;Ross B;Missiuro PV;Liu J;Ge H
多效性是指一个基因控制几个不同的，似乎无关的，表型效应的现象。我们使用C。以线虫早期胚胎发生为模型进行系统的多效性研究。我们分析了来自C. elegans和识别“表型签名”，这是一组细胞缺陷，指示某些生物功能。通过将表型特征与我们识别的特征相匹配，我们将具有复杂表型特征的基因分配给多个功能类。总之，我们观察到，多效性广泛发生在早期胚胎发生的基因，这些基因中的一小部分是高度多效性的。我们假设，参与早期胚胎发生的基因被组织成部分重叠的功能模块，多效性基因代表这些模块之间的“连接器”。为了支持这一假设，我们发现，高度多效性基因往往驻留在蛋白质-蛋白质相互作用网络的中心位置，这表明多效性基因作为不同的蛋白质复合物或途径之间的连接点。在一个生物系统中，有些基因扮演单一角色，而另一些则执行多种功能。我们如何确定哪些基因是多功能的？探测基因功能的一种信息方式是消除给定基因的表达并观察表型结果。RNAi技术使得能够产生全基因组表型数据。常规地，基因根据RNAi后观察到的缺陷被聚类为互斥的类别。然而，将可能发挥多种作用的基因专门分配到一个类别中是任意的。本文提出了一种计算方法，可以对基因进行分类，同时允许将具有复杂表型的基因分配到多个类别中。我们将这种方法应用于C. elegans早期胚胎，并发现这些基因中约有一半可以分配给一个以上的功能类别。这种方法允许识别以前未发现的基因功能。我们还发现，在早期胚胎中发挥多种作用的基因往往位于蛋白质网络的中心位置。我们的方法可用于在其他系统中基于表型数据进行功能注释，并识别协调多种生物功能的基因。
Pleiotropy refers to the phenomenon in which a single gene controls several distinct, and seemingly unrelated, phenotypic effects. We use C. elegans early embryogenesis as a model to conduct systematic studies of pleiotropy. We analyze high-throughput RNA interference (RNAi) data from C. elegans and identify “phenotypic signatures”, which are sets of cellular defects indicative of certain biological functions. By matching phenotypic profiles to our identified signatures, we assign genes with complex phenotypic profiles to multiple functional classes. Overall, we observe that pleiotropy occurs extensively among genes involved in early embryogenesis, and a small proportion of these genes are highly pleiotropic. We hypothesize that genes involved in early embryogenesis are organized into partially overlapping functional modules, and that pleiotropic genes represent “connectors” between these modules. In support of this hypothesis, we find that highly pleiotropic genes tend to reside in central positions in protein-protein interaction networks, suggesting that pleiotropic genes act as connecting points between different protein complexes or pathways. In a biological system, some genes play single roles while others perform multiple functions. How can we determine which genes are multi-functional? An informative way for probing gene functions is to eliminate the expression of a given gene and observe the phenotypic consequences. RNAi techniques have enabled the generation of genome-wide phenotypic data. Conventionally, genes are clustered into mutually exclusive categories according to the observed defects following RNAi. However, assigning genes that may play multiple roles exclusively into a single category is arbitrary. This paper works out a computational approach that categorizes genes while allowing assignment of genes with complex phenotypes into multiple categories. We apply this approach to genes involved in cell divisions of C. elegans early embryos, and find that about half of these genes can be assigned to more than one functional category. This approach has allowed the identification of previously undiscovered gene functions. We also find that genes playing many roles in early embryos tend to reside in central positions in protein networks. Our approach can be used to perform functional annotations based on phenotypic data in other systems and to identify genes that coordinate multiple biological functions.
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影响因子：
64.8
作者：
Foster, KR;Shaulsky, G;Thompson, CRL
通讯作者：
Thompson, CRL
酵母蛋白相互作用网络中的高比分蛋白。
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