Lin Wen-Hsien, Liu Wei-Chung, Hwang Ming-Jing
Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
BMC Syst Biol. 2009 Mar 11;3:32. doi: 10.1186/1752-0509-3-32.
Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure.
Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined.
Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.
尽管各种组织类型的人类细胞拥有相同的遗传信息集，但它们在形态上却有很大差异。一些基因在所有细胞类型中都有表达以执行维持细胞基本功能的任务，而一些基因则选择性表达以执行组织特异性功能。在本研究中，我们希望阐明人类维持细胞基本功能的基因和组织特异性基因所编码的蛋白质是如何在人类蛋白质 - 蛋白质相互作用网络中组织的。我们使用两个基因表达数据集和一个蛋白质 - 蛋白质相互作用数据库构建了不同组织类型的蛋白质 - 蛋白质相互作用网络。然后，我们计算了三个具有拓扑重要性的网络指标，即度中心性、紧密中心性和中介中心性，以衡量维持细胞基本功能的基因和组织特异性基因所编码蛋白质的网络位置，并量化它们的局部连接结构。
与随机选择的蛋白质相比，维持细胞基本功能的基因所编码的蛋白质往往有更多直接相互作用的邻居，并在蛋白质对之间的几条最短相互作用路径中占据网络位置，而组织特异性基因所编码的蛋白质则不然。此外，维持细胞基本功能的基因所编码的蛋白质在所有组织类型中都倾向于与其他由维持细胞基本功能的基因所编码的蛋白质相连，而组织特异性基因所编码的蛋白质也倾向于与其他由组织特异性基因所编码的蛋白质相连，但仅在所检查的大约一半组织类型中如此。
我们的分析表明，维持细胞基本功能的基因所编码的蛋白质倾向于占据重要的网络位置，而组织特异性基因所编码的蛋白质则不然。我们讨论了研究结果的生物学意义，并提出了一个关于细胞如何在蛋白质 - 蛋白质相互作用网络中组织其蛋白质工具的假设。我们的结果使我们推测，维持细胞基本功能的基因所编码的蛋白质可能在人类蛋白质 - 蛋白质相互作用网络中形成一个核心，而组织特异性基因所编码的蛋白质簇则附着在网络更外围位置的核心上。
