When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases.
When the human viral infectome and diseasome networks collide: towards a systems biology platform for the aetiology of human diseases.
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DOI：
10.1186/1752-0509-5-13
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发表时间：
2011-01-21
影响因子：
--
通讯作者：
Lotteau V
中科院分区：
文献类型：
--
作者：
Navratil V;de Chassey B;Combe CR;Lotteau V
全面了解病毒感染的分子机制是发现新的抗病毒药物和人类疾病易感因素的主要挑战。预计该领域的新进展将来自系统级建模和不断涌现的高通量“组学”数据的整合。在这里，我们描述了人类基因组蛋白相互作用网络，一个新的系统病毒学模型的虚拟病毒感染的人类细胞涉及110种病毒。该计算机模型被应用于全面探索病毒及其相关疾病之间的分子关系。这是通过将病毒-宿主和宿主-宿主物理蛋白质-蛋白质相互作用组与病毒复制所必需的一组基因合并来完成的，这些基因与人类遗传疾病有关。这种系统水平的方法提供了强有力的证据，证明病毒蛋白质组靶向广泛的功能和相互连接的蛋白质模块，以及人类相互作用组内的高度中心和桥接蛋白质。使用功能性基因组RNAi数据，靶向蛋白的高中心性与它们对病毒生命周期的重要性相关。通过模拟细胞网络扰动，证明了病毒对桥接细胞功能的蛋白质的隐形攻击，这一特性可能是某些人类疾病的分子病因学中必不可少的。将人类基因组和疾病体联网揭示了病毒与各种疾病的联系，并概述了丙型肝炎病毒引起的疾病的分子基础，以及涉及1型糖尿病的38个新的候选遗传易感因素。这里描述的人类基因组和疾病体网络为全面建模和分析与病毒感染相关的系统水平特性以及潜在参与人类疾病分子病因学的候选基因提供了独特的途径。
Comprehensive understanding of molecular mechanisms underlying viral infection is a major challenge towards the discovery of new antiviral drugs and susceptibility factors of human diseases. New advances in the field are expected from systems-level modelling and integration of the incessant torrent of high-throughput "-omics" data. Here, we describe the Human Infectome protein interaction Network, a novel systems virology model of a virtual virus-infected human cell concerning 110 viruses. This in silico model was applied to comprehensively explore the molecular relationships between viruses and their associated diseases. This was done by merging virus-host and host-host physical protein-protein interactomes with the set of genes essential for viral replication and involved in human genetic diseases. This systems-level approach provides strong evidence that viral proteomes target a wide range of functional and inter-connected modules of proteins as well as highly central and bridging proteins within the human interactome. The high centrality of targeted proteins was correlated to their essentiality for viruses' lifecycle, using functional genomic RNAi data. A stealth-attack of viruses on proteins bridging cellular functions was demonstrated by simulation of cellular network perturbations, a property that could be essential in the molecular aetiology of some human diseases. Networking the Human Infectome and Diseasome unravels the connectivity of viruses to a wide range of diseases and profiled molecular basis of Hepatitis C Virus-induced diseases as well as 38 new candidate genetic predisposition factors involved in type 1 diabetes mellitus. The Human Infectome and Diseasome Networks described here provide a unique gateway towards the comprehensive modelling and analysis of the systems level properties associated to viral infection as well as candidate genes potentially involved in the molecular aetiology of human diseases.
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影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN
影响因子：
64.8
作者：
Krishnan, Manoj N.;Ng, Aylwin;Sukumaran, Bindu;Gilfoy, Felicia D.;Uchil, Pradeep D.;Sultana, Hameeda;Brass, Abraham L.;Adametz, Rachel;Tsui, Melody;Qian, Feng;Montgomery, Ruth R.;Lev, Sima;Mason, Peter W.;Koski, Raymond A.;Elledge, Stephen J.;Xavier, Ramnik J.;Agaisse, Herve;Fikrig, Erol
通讯作者：
Fikrig, Erol
影响因子：
15.9
作者：
Filippi, Christophe M.;Estes, Elizabeth A.;von Herrath, Matthias G.
通讯作者：
von Herrath, Matthias G.
影响因子：
3.7
作者：
Childs, Kay;Stock, Nicola;Goodbourn, Stephen
通讯作者：
Goodbourn, Stephen
DOI：
10.1073/pnas.0407639101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Andrejeva, J;Childs, KS;Randall, RE
通讯作者：
Randall, RE