Gu Jianying, Wang Yufeng, Lilburn Timothy
Department of Biology, City University of New York, Staten Island, New York 10314, USA.
J Bacteriol. 2009 Oct;191(20):6262-72. doi: 10.1128/JB.00475-09. Epub 2009 Aug 7.
Our views of the genes that drive phenotypes have generally been built up one locus or operon at a time. However, a given phenotype, such as virulence, is a multilocus phenomenon. To gain a more comprehensive view of the genes and interactions underlying a phenotype, we propose an approach that incorporates information from comparative genomics and network biology and illustrate it by examining the virulence phenotype of Vibrio cholerae O1 El Tor N16961. We assessed the associations among the virulence-associated proteins from Vibrio cholerae and all the other proteins from this bacterium using a functional-association network map. In the context of this map, we were able to identify 262 proteins that are functionally linked to the virulence-associated genes more closely than is typical of the proteins in this strain and 240 proteins that are functionally linked to the virulence-associated proteins with a confidence score greater than 0.9. The roles of these genes were investigated using functional information from online data sources, comparative genomics, and the relationships shown by the protein association map. We also incorporated core proteome data from the family Vibrionaceae; 35% of the virulence-associated proteins have orthologs among the 1,822 orthologous groups of proteins in the core proteome, indicating that they may be dual-role virulence genes or encode functions that have value outside the human host. This approach is a valuable tool in searching for novel functional associations and in investigating the relationship between genotype and phenotype.
我们对驱动表型的基因的认识通常是一次建立一个基因座或操纵子。然而，特定的表型，如毒力，是一种多基因座现象。为了更全面地了解表型背后的基因及其相互作用，我们提出了一种整合比较基因组学和网络生物学信息的方法，并通过研究霍乱弧菌O1 El Tor N16961的毒力表型来进行说明。我们使用功能关联网络图评估了霍乱弧菌中与毒力相关的蛋白质和该细菌所有其他蛋白质之间的关联。在这张图的背景下，我们能够识别出262种蛋白质，它们与毒力相关基因的功能联系比该菌株中的典型蛋白质更为紧密，以及240种蛋白质，它们与毒力相关蛋白质的功能联系的置信度得分大于0.9。利用在线数据源的功能信息、比较基因组学以及蛋白质关联图所显示的关系，对这些基因的作用进行了研究。我们还纳入了弧菌科的核心蛋白质组数据；在核心蛋白质组的1822个直系同源蛋白质组中，35%的毒力相关蛋白质有直系同源物，这表明它们可能是具有双重作用的毒力基因，或者编码在人类宿主之外具有价值的功能。这种方法是寻找新的功能关联以及研究基因型和表型之间关系的宝贵工具。
