Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Biochem Biophys Res Commun. 2010 Oct 8;401(1):112-6. doi: 10.1016/j.bbrc.2010.09.021. Epub 2010 Sep 15.
The centrality-lethality rule, i.e., high-degree proteins or hubs tend to be more essential than low-degree proteins in the yeast protein interaction network, reveals that a protein's central position indicates its important function, but whether and why hubs tend to be more essential have been heavily debated. Here, we integrated gene expression and functional module data to classify hubs into four types: non-co-expressed non-co-cluster hubs, non-co-expressed co-cluster hubs, co-expressed non-co-cluster hubs and co-expressed co-cluster hubs. We found that all the four hub types are more essential than non-hubs, but they also show different enrichments in essential proteins. Non-co-expressed non-co-cluster hubs play key role in organizing different modules formed by the other three hub types, but they are less important to the survival of the yeast cell. Among the four hub types, co-expressed co-cluster hubs, which likely correspond to the core components of stable protein complexes, are the most essential. These results demonstrated that our classification of hubs into four types could better improve the understanding of gene essentiality.
核心致死性法则，即高程度蛋白质或枢纽蛋白在酵母蛋白互作网络中比低程度蛋白质更具核心地位，这表明蛋白质的核心位置表明其具有重要的功能，但枢纽蛋白是否以及为何更具核心地位一直存在激烈的争论。在这里，我们整合了基因表达和功能模块数据，将枢纽蛋白分为四类：非共表达非共聚类枢纽蛋白、非共表达共聚类枢纽蛋白、共表达非共聚类枢纽蛋白和共表达共聚类枢纽蛋白。我们发现，所有这四类枢纽蛋白都比非枢纽蛋白更具核心地位，但它们在必需蛋白中的富集程度也不同。非共表达非共聚类枢纽蛋白在组织由其他三种枢纽蛋白形成的不同模块方面起着关键作用，但对酵母细胞的生存不太重要。在这四种枢纽蛋白中，共表达共聚类枢纽蛋白可能对应于稳定蛋白质复合物的核心组件，是最具核心地位的。这些结果表明，我们将枢纽蛋白分为四类的方法可以更好地提高对基因核心地位的理解。
