Linking disease-associated genes to regulatory networks via promoter organization.
Linking disease-associated genes to regulatory networks via promoter organization.
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DOI：
10.1093/nar/gki230
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发表时间：
2005
影响因子：
14.9
通讯作者：
Schneider R
中科院分区：
文献类型：
--
作者：
Döhr S;Klingenhoff A;Maier H;Hrabé de Angelis M;Werner T;Schneider R
途径或疾病相关基因可能参与一个以上的转录共调控网络。这样的基因组可以很容易地通过文献分析或高通量技术获得，例如微阵列或蛋白质相互作用图谱。我们开发了一种策略，通过在电子启动子分析中定义调控网络，在没有先验知识的情况下找到潜在的共同调控亚群。在同源基因中(垂直方向)以及在共调控基因的启动子序列中(水平方向)保守的一对转录因子结合位点被用作种子，用于开发代表潜在协同调控的启动子模型。这一方法被应用于青年成熟发作性糖尿病(MODY)相关基因列表，该列表产生了两个连接MODY相关胰岛素/葡萄糖信号通路中功能相互作用的基因的模型。通过使用这些启动子模型进行数据库搜索，确定了与我们的初始基因列表功能相关的其他基因。因此，数据驱动的电子启动子分析允许将分子机制与细胞的生物功能相结合。
Pathway- or disease-associated genes may participate in more than one transcriptional co-regulation network. Such gene groups can be readily obtained by literature analysis or by high-throughput techniques such as microarrays or protein-interaction mapping. We developed a strategy that defines regulatory networks by in silico promoter analysis, finding potentially co-regulated subgroups without a priori knowledge. Pairs of transcription factor binding sites conserved in orthologous genes (vertically) as well as in promoter sequences of co-regulated genes (horizontally) were used as seeds for the development of promoter models representing potential co-regulation. This approach was applied to a Maturity Onset Diabetes of the Young (MODY)-associated gene list, which yielded two models connecting functionally interacting genes within MODY-related insulin/glucose signaling pathways. Additional genes functionally connected to our initial gene list were identified by database searches with these promoter models. Thus, data-driven in silico promoter analysis allowed integrating molecular mechanisms with biological functions of the cell.
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DOI：
10.1073/pnas.1032913100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Patti, ME;Butte, AJ;Mandarino, LJ
通讯作者：
Mandarino, LJ
影响因子：
6.8
作者：
Altman, RB;Raychaudhuri, S
通讯作者：
Raychaudhuri, S
影响因子：
5.8
作者：
Klingenhoff, A;Frech, K;Werner, T
通讯作者：
Werner, T
影响因子：
2.5
作者：
Gailus-Durner, V;Scherf, M;Werner, T
通讯作者：
Werner, T
影响因子：
14.9
作者：
Hamosh, A;Scott, AF;McKusick, VA
通讯作者：
McKusick, VA