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A network-based pathway-extending approach using DNA methylation and gene expression data to identify altered pathways

机译:一种基于网络的途径扩展方法使用DNA甲基化和基因表达数据来识别改变的途径

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摘要

Pathway analysis allows us to gain insights into a comprehensive understanding of the molecular mechanisms underlying cancers. Currently, high-throughput multi-omics data and various types of large-scale biological networks enable us to identify cancer-related pathways by comprehensively analyzing these data. Combining information from multidimensional data, pathway databases and interaction networks is a promising strategy to identify cancer-related pathways. Here we present a novel network-based approach for integrative analysis of DNA methylation and gene expression data to extend original pathways. The results show that the extension of original pathways can provide a basis for discovering new components of the original pathway and understanding the crosstalk between pathways in a large-scale biological network. By inputting the gene lists of the extended pathways into the classical gene set analysis (ORA and FCS), we effectively identified the altered pathways which are correlated well with the corresponding cancer. The method is evaluated on three datasets retrieved from TCGA (BRCA, LUAD and COAD). The results show that the integration of DNA methylation and gene expression data through a network of known gene interactions is effective in identifying altered pathways.
机译:途径分析使我们能够洞悉癌症的分子机制。当前,高通量多组学数据和各种类型的大规模生物网络使我们能够通过全面分析这些数据来识别与癌症相关的途径。将来自多维数据,途径数据库和相互作用网络的信息相结合是识别癌症相关途径的一种有前途的策略。在这里,我们提出了一种基于网络的新颖方法,可对DNA甲基化和基因表达数据进行综合分析以扩展原始途径。结果表明,原始途径的扩展可以为发现原始途径的新成分和理解大规模生物网络中途径之间的串扰提供基础。通过将扩展途径的基因清单输入经典基因集分析(ORA和FCS),我们有效地鉴定了与相应癌症相关性良好的改变途径。对从TCGA检索的三个数据集(BRCA,LUAD和COAD)进行了评估。结果表明,通过已知基因相互作用的网络整合DNA甲基化和基因表达数据可有效识别途径的改变。

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