Hubei Bioinformatics and Molecular Imaging Key Laboratory, Huazhong University of Science and Technology, Wuhan, Hubei, China.
PLoS One. 2012;7(8):e42517. doi: 10.1371/journal.pone.0042517. Epub 2012 Aug 3.
Bacterial pathogens continue to threaten public health worldwide today. Identification of bacterial virulence factors can help to find novel drug/vaccine targets against pathogenicity. It can also help to reveal the mechanisms of the related diseases at the molecular level. With the explosive growth in protein sequences generated in the postgenomic age, it is highly desired to develop computational methods for rapidly and effectively identifying virulence factors according to their sequence information alone. In this study, based on the protein-protein interaction networks from the STRING database, a novel network-based method was proposed for identifying the virulence factors in the proteomes of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C. jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark datasets derived from the aforementioned species, the identification accuracies achieved by the network-based method were around 0.9, significantly higher than those by the sequence-based methods such as BLAST, feature selection and VirulentPred. Further analysis showed that the functional associations such as the gene neighborhood and co-occurrence were the primary associations between these virulence factors in the STRING database. The high success rates indicate that the network-based method is quite promising. The novel approach holds high potential for identifying virulence factors in many other various organisms as well because it can be easily extended to identify the virulence factors in many other bacterial species, as long as the relevant significant statistical data are available for them.
细菌病原体如今仍在威胁着全球公共健康。鉴定细菌毒力因子有助于寻找针对致病性的新型药物/疫苗靶点。它还有助于在分子水平上揭示相关疾病的机制。在后基因组时代,蛋白质序列呈爆炸式增长,人们非常希望开发出仅根据序列信息就能快速有效地识别毒力因子的计算方法。在这项研究中,基于 STRING 数据库中的蛋白质-蛋白质相互作用网络,我们提出了一种新的基于网络的方法,用于鉴定 UPEC 536、UPEC CFT073、PAO1、费城 1、NCTC 11168 和 H37Rv 中的毒力因子。在来自上述物种的相同基准数据集上进行评估,网络方法的识别准确率约为 0.9,明显高于 BLAST、特征选择和 VirulentPred 等序列方法。进一步的分析表明,基因邻近和共现等功能关联是 STRING 数据库中这些毒力因子之间的主要关联。高成功率表明该网络方法非常有前途。由于该新方法可以轻松扩展到识别许多其他细菌物种的毒力因子,只要为它们提供相关的重要统计数据,因此它也具有在许多其他各种生物体中识别毒力因子的巨大潜力。
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