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CrossHub: a tool for multi-way analysis of The Cancer Genome Atlas (TCGA) in the context of gene expression regulation mechanisms

机译:CrossHub:在基因表达调控机制中对癌症基因组图谱(TCGA)进行多路分析的工具

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摘要

The contribution of different mechanisms to the regulation of gene expression varies for different tissues and tumors. Complementation of predicted mRNA–miRNA and gene–transcription factor (TF) relationships with the results of expression correlation analyses derived for specific tumor types outlines the interactions with functional impact in the current biomaterial. We developed CrossHub software, which enables two-way identification of most possible TF–gene interactions: on the basis of ENCODE ChIP-Seq binding evidence or Jaspar prediction and co-expression according to the data of The Cancer Genome Atlas (TCGA) project, the largest cancer omics resource. Similarly, CrossHub identifies mRNA–miRNA pairs with predicted or validated binding sites (TargetScan, mirSVR, PicTar, DIANA microT, miRTarBase) and strong negative expression correlations. We observed partial consistency between ChIP-Seq or miRNA target predictions and gene–TF/miRNA co-expression, demonstrating a link between these indicators. Additionally, CrossHub expression-methylation correlation analysis can be used to identify hypermethylated CpG sites or regions with the greatest potential impact on gene expression. Thus, CrossHub is capable of outlining molecular portraits of a specific gene and determining the three most common sources of expression regulation: promoter/enhancer methylation, miRNA interference and TF-mediated activation or repression. CrossHub generates formatted Excel workbooks with the detailed results. CrossHub is freely available at .
机译:对于不同的组织和肿瘤,不同机制对基因表达调节的贡献也不同。预测的mRNA–miRNA和基因转录因子(TF)关系与针对特定肿瘤类型得出的表达相关分析结果的补充,概述了当前生物材料中具有功能影响的相互作用。我们开发了CrossHub软件,该软件可双向识别大多数可能的TF基因相互作用:根据癌症基因组图谱(TCGA)项目的数据,基于ENCODE ChIP-Seq结合证据或Jaspar预测和共表达,最大的癌症组学资源。同样,CrossHub可以识别具有预测或验证的结合位点(TargetScan,mirSVR,PicTar,DIANA microT,miRTarBase)和强烈的负表达相关性的mRNA-miRNA对。我们观察到ChIP-Seq或miRNA靶标预测与基因–TF / miRNA共表达之间的部分一致性,表明了这些指标之间的联系。另外,CrossHub表达-甲基化相关分析可用于鉴定对基因表达影响最大的超甲基化CpG位点或区域。因此,CrossHub能够概述特定基因的分子画像并确定三种最常见的表达调控来源:启动子/增强子甲基化,miRNA干扰和TF介导的激活或抑制。 CrossHub生成格式化的Excel工作簿以及详细结果。 CrossHub在以下位置免费提供。

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