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The Integrative Method Based on the Module-Network for Identifying Driver Genes in Cancer Subtypes

机译:基于模块网络的癌症亚型驱动基因识别方法

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摘要

With advances in next-generation sequencing(NGS) technologies, a large number of multiple types of high-throughput genomics data are available. A great challenge in exploring cancer progression is to identify the driver genes from the variant genes by analyzing and integrating multi-types genomics data. Breast cancer is known as a heterogeneous disease. The identification of subtype-specific driver genes is critical to guide the diagnosis, assessment of prognosis and treatment of breast cancer. We developed an integrated frame based on gene expression profiles and copy number variation (CNV) data to identify breast cancer subtype-specific driver genes. In this frame, we employed statistical machine-learning method to select gene subsets and utilized an module-network analysis method to identify potential candidate driver genes. The final subtype-specific driver genes were acquired by paired-wise comparison in subtypes. To validate specificity of the driver genes, the gene expression data of these genes were applied to classify the patient samples with 10-fold cross validation and the enrichment analysis were also conducted on the identified driver genes. The experimental results show that the proposed integrative method can identify the potential driver genes and the classifier with these genes acquired better performance than with genes identified by other methods.
机译:随着下一代测序(NGS)技术的进步,可获得大量多种类型的高通量基因组数据。探索癌症进展的一项巨大挑战是通过分析和整合多种类型的基因组数据,从变异基因中识别驱动基因。乳腺癌被称为异质性疾病。亚型特异性驱动基因的鉴定对于指导乳腺癌的诊断,预后和治疗至关重要。我们基于基因表达谱和拷贝数变异(CNV)数据开发了一个集成框架,以识别乳腺癌亚型特异性驱动基因。在此框架中,我们采用统计机器学习方法来选择基因子集,并利用模块网络分析方法来识别潜在的候选驱动基因。通过亚型的成对比较获得了最终的亚型特异性驱动基因。为了验证驱动基因的特异性,将这些基因的基因表达数据应用10倍交叉验证对患者样品进行分类,并对鉴定出的驱动基因进行富集分析。实验结果表明,所提出的整合方法可以识别潜在的驱动基因,并且这些分类器的分类器性能优于其他方法。

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