Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy.
Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy.
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DOI：
10.1186/1752-0509-4-138
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发表时间：
2010-10-15
影响因子：
--
通讯作者：
Huang HC
中科院分区：
文献类型：
--
作者：
Lin CC;Hsiang JT;Wu CY;Oyang YJ;Juan HF;Huang HC
分子网络是细胞内分子活动的支柱，为理解疾病机制提供了契机。虽然蛋白质 - 蛋白质相互作用数据构成了静态网络图，但特定条件下共表达信息的整合为这些网络的动态特征提供了线索。扩张型心肌病是心力衰竭的主要病因。尽管先前的研究已经确定了心力衰竭的假定生物标志物或治疗靶点，但扩张型心肌病的潜在分子机制仍不清楚。
我们开发了一种基于网络的比较分析方法，该方法将蛋白质 - 蛋白质相互作用与基因表达谱以及生物学功能注释相结合，以揭示不同生物学状态下的动态功能模块。我们发现，特定条件下共表达的蛋白质相互作用网络中的枢纽蛋白在不同生物学状态之间往往存在差异表达。将这种方法应用于一组心力衰竭患者，我们从相互作用网络中确定了两个显著出现的功能模块。这些模块在正常和疾病状态之间的动态变化进一步提示了一种扩张型心肌病的潜在分子模型。
我们提出了一个新的框架来分析不同生物学状态下的相互作用网络。它成功地揭示了与心力衰竭密切相关的网络模块；更重要的是，这些网络动态为扩张型心肌病的病因提供了新的见解。所揭示的分子模块可能被用作潜在的药物靶点，并为心力衰竭治疗提供新的方向。
Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy.
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影响因子：
14.9
作者：
Keshava Prasad TS;Goel R;Kandasamy K;Keerthikumar S;Kumar S;Mathivanan S;Telikicherla D;Raju R;Shafreen B;Venugopal A;Balakrishnan L;Marimuthu A;Banerjee S;Somanathan DS;Sebastian A;Rani S;Ray S;Harrys Kishore CJ;Kanth S;Ahmed M;Kashyap MK;Mohmood R;Ramachandra YL;Krishna V;Rahiman BA;Mohan S;Ranganathan P;Ramabadran S;Chaerkady R;Pandey A
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Pandey A
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影响因子：
7.8
作者：
Lampugnani, MG;Zanetti, A;Corada, M;Takahashi, T;Balconi, G;Breviario, F;Orsenigo, F;Cattelino, A;Kemler, R;Daniel, TO;Dejana, E
通讯作者：
Dejana, E
影响因子：
24
作者：
Barth, Andreas S.;Kuner, Ruprecht;Sueltmann, Holger
通讯作者：
Sueltmann, Holger
影响因子：
12.3
作者：
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通讯作者：
Elofsson A
影响因子：
9.9
作者：
通讯作者：
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