MiRNA-miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features.
MiRNA-miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features.
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DOI：
10.1093/nar/gkq832
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发表时间：
2011-02
影响因子：
14.9
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Xu J;Li CX;Li YS;Lv JY;Ma Y;Shao TT;Xu LD;Wang YY;Du L;Zhang YP;Jiang W;Li CQ;Xiao Y;Li X
多种microrna （mirna）之间的协同调控对于理解人类复杂的转录后调控机制非常重要。复杂疾病受多种miRNA而不是单一miRNA影响。因此，确定miRNA的协同作用，从而进一步确定miRNA在全系统水平上的功能，并从新的角度研究miRNA - miRNA协同网络中的疾病miRNA特征是一个挑战。本研究通过共调节功能模块构建了miRNA - miRNA功能协同网络（MFSN），该功能模块具有三个特点：对应miRNA对的共同靶点、丰富于同一基因本体类别、在蛋白质相互作用网络中接近。预测的miRNA协同作用通过功能模块的显著高共表达和对功能模块的显著负调控得到验证。我们发现MFSN具有无尺度、小世界和模块化结构。此外，MFSN中疾病mirna的拓扑特征与非疾病mirna不同。它们具有更强的协同作用，表明它们具有更高的功能复杂性，是MFSN的全局核心。此外，与同一疾病相关的mirna彼此接近。MFSN的结构和疾病miRNA的特征通过不同的miRNA目标数据集被验证是稳健的。
Synergistic regulations among multiple microRNAs (miRNAs) are important to understand the mechanisms of complex post-transcriptional regulations in humans. Complex diseases are affected by several miRNAs rather than a single miRNA. So, it is a challenge to identify miRNA synergism and thereby further determine miRNA functions at a system-wide level and investigate disease miRNA features in the miRNA–miRNA synergistic network from a new view. Here, we constructed a miRNA–miRNA functional synergistic network (MFSN) via co-regulating functional modules that have three features: common targets of corresponding miRNA pairs, enriched in the same gene ontology category and close proximity in the protein interaction network. Predicted miRNA synergism is validated by significantly high co-expression of functional modules and significantly negative regulation to functional modules. We found that the MFSN exhibits a scale free, small world and modular architecture. Furthermore, the topological features of disease miRNAs in the MFSN are distinct from non-disease miRNAs. They have more synergism, indicating their higher complexity of functions and are the global central cores of the MFSN. In addition, miRNAs associated with the same disease are close to each other. The structure of the MFSN and the features of disease miRNAs are validated to be robust using different miRNA target data sets.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
30.8
作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z
影响因子：
5.7
作者：
Blower, Paul E.;Verducci, Joseph S.;Sadee, Wolfgang
通讯作者：
Sadee, Wolfgang
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP