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Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process

机译:计算系统生物学方法预测细胞凋亡过程中微RNA及其基因组热点的调控因子和靶标。

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Novel computational systems biology tools such as common targets analysis, common regulators analysis, pathway discovery, and transcriptomic-based hotspot discovery provide new opportunities in understanding of apoptosis molecular mechanisms. In this study, after measuring the global contribution of microRNAs in the course of apoptosis by Affymetrix platform, systems biology tools were utilized to obtain a comprehensive view on the role of microRNAs in apoptosis process. Network analysis and pathway discovery highlighted the crosstalk between transcription factors and microRNAs in apoptosis. Within the transcription factors, PRDM1 showed the highest upregulation during the course of apoptosis, with more than 9-fold expression increase compared to non-apoptotic condition. Within the microRNAs, MIR1208 showed the highest expression in non-apoptotic condition and downregulated by more than 6 fold during apoptosis. Common regulators algorithm showed that TNF receptor is the key upstream regulator with a high number of regulatory interactions with the differentially expressed microRNAs. BCL2 and AKT1 were the key downstream targets of differentially expressed microRNAs. Enrichment analysis of the genomic locations of differentially expressed microRNAs led us to the discovery of chromosome bands which were highly enriched (p < 0.01) with the apoptosis-related microRNAs, such as 13q31.3, 19p13.13, and Xq27.3 This study opens a new avenue in understanding regulatory mechanisms and downstream functions in the course of apoptosis as well as distinguishing genomic-enriched hotspots for apoptosis process.
机译:新颖的计算系统生物学工具,例如共同靶标分析,共同调节剂分析,途径发现和基于转录组学的热点发现,为了解凋亡分子机制提供了新的机会。在这项研究中,在通过Affymetrix平台测量了microRNA在凋亡过程中的总体贡献后,利用系统生物学工具全面了解了microRNA在凋亡过程中的作用。网络分析和途径发现突显了凋亡中转录因子和microRNA之间的串扰。在转录因子中,PRDM1在凋亡过程中显示出最高的上调,与非凋亡条件相比,表达增加了9倍以上。在microRNA中,MIR1208在非凋亡条件下显示最高表达,在凋亡过程中被下调6倍以上。常用的调节剂算法显示,TNF受体是关键的上游调节剂,与差异表达的microRNA具有大量的调节相互作用。 BCL2和AKT1是差异表达的microRNA的关键下游目标。对差异表达的microRNA基因组位置的富集分析导致我们发现了与凋亡相关的microRNA(例如13q31.3、19p13.13和Xq27.3)高度富集(p <0.01)的染色体带。为了解凋亡过程中的调控机制和下游功能,以及为凋亡过程区分基因组富集的热点开辟了一条新途径。

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