Center for Complex Networks Research-CCNR and Department of Physics, Northeastern University, Boston, Massachusetts, United States of America.
PLoS Comput Biol. 2012;8(6):e1002531. doi: 10.1371/journal.pcbi.1002531. Epub 2012 Jun 28.
Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia.
许多人类疾病是由疾病易感性基因（遗传疾病）的突变引起的，也与病毒感染（病毒相关疾病）有关，无论是直接因果关系还是间接关联。在这里，我们研究了宿主相互作用组的病毒扰动是否可能是这种病毒相关疾病关系的基础。我们使用两种不同的人类病毒，即 EBV 和 HPV，作为模型，发现病毒蛋白的宿主靶标位于疾病易感性基因产物的网络附近。病毒相关疾病组织中的表达变化和合并症模式在病毒靶标的网络附近显著聚类。在病毒蛋白的细胞靶标和疾病基因之间发现的拓扑接近度被用来揭示 HPV 与范可尼贫血之间的新通路。
