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Meta-analysis approach identifies candidate genes and associated molecular networks for Type-2 Diabetes Mellitus

机译:meta分析方法确定了2型糖尿病的候选基因和相关分子网络

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摘要

Background Multiple functional genomics data for complex human diseases have been published and made available by researchers worldwide. The main goal of these studies is the detailed analysis of a particular aspect of the disease. Complementary, meta-analysis approaches try to extract supersets of disease genes and interaction networks by integrating and combining these individual studies using statistical approaches. Results Here we report on a meta-analysis approach that integrates data of heterogeneous origin in the domain of type-2 diabetes mellitus (T2DM). Different data sources such as DNA microarrays and, complementing, qualitative data covering several human and mouse tissues are integrated and analyzed with a Bootstrap scoring approach in order to extract disease relevance of the genes. The purpose of the meta-analysis is two-fold: on the one hand it identifies a group of genes with overall disease relevance indicating common, tissue-independent processes related to the disease; on the other hand it identifies genes showing specific alterations with respect to a single study. Using a random sampling approach we computed a core set of 213 T2DM genes across multiple tissues in human and mouse, including well-known genes such as Pdk4, Adipoq, Scd, Pik3r1, Socs2 that monitor important hallmarks of T2DM, for example the strong relationship between obesity and insulin resistance, as well as a large fraction (128) of yet barely characterized novel candidate genes. Furthermore, we explored functional information and identified cellular networks associated with this core set of genes such as pathway information, protein-protein interactions and gene regulatory networks. Additionally, we set up a web interface in order to allow users to screen T2DM relevance for any – yet non-associated – gene. Conclusion In our paper we have identified a core set of 213 T2DM candidate genes by a meta-analysis of existing data sources. We have explored the relation of these genes to disease relevant information and – using enrichment analysis – we have identified biological networks on different layers of cellular information such as signaling and metabolic pathways, gene regulatory networks and protein-protein interactions. The web interface is accessible via http://t2dm-geneminer.molgen.mpg.de webcite.
机译:背景技术复杂的人类疾病的多功能基因组学数据已经发表,并已被全世界的研究人员提供。这些研究的主要目标是对该疾病特定方面的详细分析。互补的荟萃分析方法试图通过使用统计方法整合和组合这些个体研究来提取疾病基因和相互作用网络的超集。结果在这里,我们报告了一种荟萃分析方法,该方法整合了2型糖尿病(T2DM)领域中异类来源的数据。为了提取基因的疾病相关性,使用Bootstrap评分方法整合并分析了不同的数据源,例如DNA微阵列以及覆盖几种人类和小鼠组织的补充性定性数据。荟萃分析的目的有两个方面:一方面,它鉴定出一组与总体疾病相关的基因,这些基因表明与该疾病相关的常见,组织独立的过程。另一方面,它可以鉴定出单项研究显示出特定变化的基因。使用随机抽样方法,我们计算了人类和小鼠中多个组织的213个T2DM基因的核心集,包括监测T2DM的重要标志(例如紧密关系)的著名基因,例如Pdk4,Adipoq,Scd,Pik3r1,Socs2。肥胖与胰岛素抵抗之间的关系,以及很大一部分(128)尚未表征的新候选基因。此外,我们探索了功能信息,并确定了与该核心基因集相关的细胞网络,例如通路信息,蛋白质-蛋白质相互作用和基因调控网络。此外,我们设置了一个Web界面,以便允许用户筛选任何(但尚未关联)基因的T2DM相关性。结论在我们的论文中,我们通过对现有数据源的荟萃分析确定了213个T2DM候选基因的核心集。我们已经研究了这些基因与疾病相关信息之间的关系,并且通过富集分析,我们已经在细胞信息的不同层上确定了生物网络,例如信号传导和代谢途径,基因调控网络以及蛋白质-蛋白质相互作用。可通过http://t2dm-geneminer.molgen.mpg.de Webcite访问Web界面。

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