Tissue Specificity of Human Disease Module.
Tissue Specificity of Human Disease Module.
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DOI：
10.1038/srep35241
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发表时间：
2016-10-17
影响因子：
4.6
通讯作者：
Barabási AL
中科院分区：
文献类型：
--
作者：
Kitsak M;Sharma A;Menche J;Guney E;Ghiassian SD;Loscalzo J;Barabási AL
携带与遗传疾病相关的突变的基因存在于所有人类细胞中;然而，遗传疾病的临床表现通常具有高度组织特异性。尽管某些疾病基因只在特定组织中表达，但仅疾病基因的表达模式不能解释所观察到的人类疾病的组织特异性。在这里，我们假设一种疾病要在特定的组织中表现出来，需要在该组织中表达一个完整的基因功能子网络（疾病模块）。在这一假设的驱动下，我们对人类相互作用组中疾病基因的表达模式进行了系统的研究。我们发现，在特定组织中表达的基因倾向于定位在相互作用组的相同邻域中。相比之下，在不同组织中表达的基因被分离在不同的网络邻域中。最重要的是，我们表明，这是完整性和完整性的疾病模块的表达，决定疾病的表现在选定的组织。这种方法使我们能够构建一个疾病组织网络，确认已知的和预测意想不到的疾病组织协会。
Genes carrying mutations associated with genetic diseases are present in all human cells; yet, clinical manifestations of genetic diseases are usually highly tissue-specific. Although some disease genes are expressed only in selected tissues, the expression patterns of disease genes alone cannot explain the observed tissue specificity of human diseases. Here we hypothesize that for a disease to manifest itself in a particular tissue, a whole functional subnetwork of genes (disease module) needs to be expressed in that tissue. Driven by this hypothesis, we conducted a systematic study of the expression patterns of disease genes within the human interactome. We find that genes expressed in a specific tissue tend to be localized in the same neighborhood of the interactome. By contrast, genes expressed in different tissues are segregated in distinct network neighborhoods. Most important, we show that it is the integrity and the completeness of the expression of the disease module that determines disease manifestation in selected tissues. This approach allows us to construct a disease-tissue network that confirms known and predicts unexpected disease-tissue associations.
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影响因子：
4.3
作者：
Barshir R;Shwartz O;Smoly IY;Yeger-Lotem E
通讯作者：
Yeger-Lotem E
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
12.3
作者：
Hart GT;Ramani AK;Marcotte EM
通讯作者：
Marcotte EM
影响因子：
14.9
作者：
López-Bigas, N;Ouzounis, CA
通讯作者：
Ouzounis, CA
影响因子：
4.6
作者：
Friese, MA;Hellwage, J;Zipfel, PF
通讯作者：
Zipfel, PF