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Transcription factor and microRNA-regulated network motifs for cancer and signal transduction networks

机译:癌症和信号转导网络的转录因子和MicroRNA调节网络图案

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Background: Molecular networks are the basis of biological processes. Such networks can be decomposed into smaller modules, also known as network motifs. These motifs show interesting dynamical behaviors, in which co-operativity effects between the motif components play a critical role in human diseases. We have developed a motif-searching algorithm, which is able to identify common motif types from the cancer networks and signal transduction networks (STNs). Some of the network motifs are interconnected which can be merged together and form more complex structures, the so-called coupled motif structures (CMS). These structures exhibit mixed dynamical behavior, which may lead biological organisms to perform specific functions.Results: In this study, we integrate transcription factors (TFs), microRNAs (miRNAs), miRNA targets and network motifs information to build the cancer-related TF-miRNA-motif networks (TMMN). This allows us to examine the role of network motifs in cancerformation at different levels of regulation, i.e. transcription initiation (TF -> miRNA) gene-gene interaction (CMS), and post-transcriptional regulation (miRNA —> target genes). Among the cancer networks and STNs we considered, it is found that there is a substantial amount of crosstalking through motif interconnections, in particular, the crosstalk between prostate cancer network and PI3K-Akt STN.Conclusions: To validate the role of network motifs in cancer formation, several examples are presented which demonstrated the effectiveness of the present approach. A web-based platform has been set up which can be accessed at: http://ppi.bioinfo.asia.edu.tw/pathway/. It is very likely that our results can supply very specific CMS missing information for certain cancer types, it is an indispensable tool for cancer biology research.
机译:背景:分子网络是生物过程的基础。这种网络可以分解成较小的模块,也称为网络图案。这些图案显示有趣的动态行为,其中基序组分之间的合作效应在人类疾病中发挥着关键作用。我们开发了一种主题搜索算法,能够从癌症网络和信号转导网络(STN)中识别公共图案类型。一些网络图案是互连的,可以合并在一起并形成更复杂的结构,即所谓的耦合图案结构(CMS)。这些结构表现出混合动态行为,这可能导致生物生物来进行特定的功能。结果:在本研究中,我们整合转录因子(TFS),Micrornas(MiRNA),MiRNA靶和网络主题信息,以构建与癌症相关的TF- miRNA-MOTIF网络(TMMN)。这使我们能够检查网络图案在不同调节水平的癌症中的作用,即转录开始(TF - > miRNA)基因相互作用(CMS)和转录后调节(miRNA - >靶基因)。在我们考虑的癌症网络和STN中,发现通过主题互连存在大量的串扰,特别是前列腺癌网络和PI3K-AKT STN的串扰:验证网络图案在癌症中的作用形成,提出了几个例子,其证明了本方法的有效性。已设置基于Web的平台,可以访问:http://ppi.bioinfo.asia.edu.tw/patpway/。我们的结果很可能可以为某些癌症类型提供非常具体的CMS缺失信息,这是癌症生物学研究的不可或缺的工具。

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