Coordinated modular functionality and prognostic potential of a heart failure biomarker-driven interaction network.
Coordinated modular functionality and prognostic potential of a heart failure biomarker-driven interaction network.
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DOI：
10.1186/1752-0509-4-60
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发表时间：
2010-05-12
影响因子：
--
通讯作者：
Wagner DR
中科院分区：
文献类型：
--
作者：
Azuaje F;Devaux Y;Wagner DR
通过实施基于生物网络的分析，可以增强对潜在相关生物标志物的识别和对心力衰竭（HF）发展相关分子机制的更深入理解。为了支持这些努力，在这里，我们报告了一个全球网络的蛋白质-蛋白质相互作用（PPI）相关的HF，其特征在于通过综合生物信息学分析的多个来源的“组学”信息。我们发现这个PPI网络的结构和功能架构是高度模块化的。这些网络模块可以被分配到专门的过程，特定的细胞区域，它们的功能角色往往部分重叠。我们的研究结果表明，HF生物标志物可以被定义为模块内和模块间通信的关键协调者。一般来说，推定的生物标志物可以被区分为该网络中的“信息流量”介质。最高的高流量蛋白质由在HF和非HF患者中不高度差异表达的基因编码。然而，我们提出的证据表明，整合高流量基因的表达模式可能支持准确预测HF。我们定量地证明，内部和模块间的功能活动可能是由一个家庭的转录因子已知与预防肥大控制。本文报告的系统驱动分析为识别潜在的新型生物标志物和以更全面和综合的方式了解HF相关机制提供了基础。
The identification of potentially relevant biomarkers and a deeper understanding of molecular mechanisms related to heart failure (HF) development can be enhanced by the implementation of biological network-based analyses. To support these efforts, here we report a global network of protein-protein interactions (PPIs) relevant to HF, which was characterized through integrative bioinformatic analyses of multiple sources of "omic" information. We found that the structural and functional architecture of this PPI network is highly modular. These network modules can be assigned to specialized processes, specific cellular regions and their functional roles tend to partially overlap. Our results suggest that HF biomarkers may be defined as key coordinators of intra- and inter-module communication. Putative biomarkers can, in general, be distinguished as "information traffic" mediators within this network. The top high traffic proteins are encoded by genes that are not highly differentially expressed across HF and non-HF patients. Nevertheless, we present evidence that the integration of expression patterns from high traffic genes may support accurate prediction of HF. We quantitatively demonstrate that intra- and inter-module functional activity may be controlled by a family of transcription factors known to be associated with the prevention of hypertrophy. The systems-driven analysis reported here provides the basis for the identification of potentially novel biomarkers and understanding HF-related mechanisms in a more comprehensive and integrated way.
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影响因子：
12.3
作者：
Auffray C;Chen Z;Hood L
通讯作者：
Hood L
影响因子：
9.9
作者：
通讯作者：
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影响因子：
37.8
作者：
Heidecker, Bettina;Kasper, Edward K.;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
3.7
作者：
Azuaje F;Devaux Y;Wagner DR
通讯作者：
Wagner DR
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ