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EgoNet: identification of human disease ego-network modules

机译:EgoNet:识别人类疾病自我网络模块

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Background Mining novel biomarkers from gene expression profiles for accurate disease classification is challenging due to small sample size and high noise in gene expression measurements. Several studies have proposed integrated analyses of microarray data and protein-protein interaction (PPI) networks to find diagnostic subnetwork markers. However, the neighborhood relationship among network member genes has not been fully considered by those methods, leaving many potential gene markers unidentified. The main idea of this study is to take full advantage of the biological observation that genes associated with the same or similar diseases commonly reside in the same neighborhood of molecular networks. Results We present EgoNet, a novel method based on egocentric network-analysis techniques, to exhaustively search and prioritize disease subnetworks and gene markers from a large-scale biological network. When applied to a triple-negative breast cancer (TNBC) microarray dataset, the top selected modules contain both known gene markers in TNBC and novel candidates, such as RAD51 and DOK1, which play a central role in their respective ego-networks by connecting many differentially expressed genes. Conclusions Our results suggest that EgoNet, which is based on the ego network concept, allows the identification of novel biomarkers and provides a deeper understanding of their roles in complex diseases.
机译:背景技术由于基因表达测量中的样本量小且噪音大,从基因表达谱中挖掘新颖的生物标记物以进行准确的疾病分类具有挑战性。一些研究提出了对微阵列数据和蛋白质-蛋白质相互作用(PPI)网络的综合分析,以发现诊断性子网标记。但是,那些方法尚未完全考虑网络成员基因之间的邻域关系,从而导致许多潜在的基因标记物尚未鉴定。这项研究的主要思想是充分利用生物学观察结果,即与相同或相似疾病相关的基因通常位于分子网络的同一邻域中。结果我们提出了一种基于自我中心网络分析技术的新颖方法EgoNet,它能够从大规模生物网络中彻底搜索疾病亚网络和基因标记并对其进行优先级排序。当应用于三阴性乳腺癌(TNBC)微阵列数据集时,选择最靠前的模块既包含TNBC中的已知基因标记,又包含新颖的候选物,例如RAD51和DOK1,它们通过连接许多在各自的自我网络中发挥核心作用差异表达基因。结论我们的研究结果表明,基于自我网络概念的EgoNet可以识别新颖的生物标志物,并使其对复杂疾病中的作用有更深入的了解。

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