Detection of type 2 diabetes related modules and genes based on epigenetic networks.
Detection of type 2 diabetes related modules and genes based on epigenetic networks.
复制标题
基于表观遗传网络检测2型糖尿病相关模块和基因
DOI：
10.1186/1752-0509-8-s1-s5
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发表时间：
2014
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Liu H;Wang T;Liu H;Wei Y;Zhao G;Su J;Wu Q;Qiao H;Zhang Y
背景2型糖尿病（T2D）是一种以胰岛素抵抗和胰岛素分泌减少为特征的最常见的慢性代谢性疾病。遗传变异只能解释T2D的部分遗传力，因此需要新的方法来检测疾病的易感基因。表观遗传学可以建立环境因素与T2D病理机制之间的接口。结果基于网络理论，结合表观遗传特征和人类相互作用组，构建了加权人类DNA甲基化网络（WMPN），并通过t2d相关差异甲基化基因获得了t2d相关子网络（TMSN）。研究发现，TMSN具有T2D特异性的网络结构，非致死性代谢性疾病致病基因往往位于网络的拓扑和功能外围。结合染色质修饰，构建加权染色质修饰网络（WCPN），利用TMSN基因集获得t2d相关的染色质修饰模式子网络。TCSN具有紧密连接的网络社区，表明TMSN和TCSN可能代表了t2d相关表观遗传失调子通路的集合。使用累积超几何测试，鉴定了DNA甲基化和染色质修饰的24个相互作用模块。通过对人T2D胰岛组织中基因表达的分析，发现存在由DNA甲基化异常和（或）染色质修饰引起的表达水平变异的基因，这些基因可能影响和促进T2D的发展。结论我们已经检测到T2D的DNA甲基化和染色质修饰的潜在相互作用模块。T2D表观遗传网络的研究为理解由表观遗传疾病引起的T2D发病机制提供了新的途径。
BackgroundType 2 diabetes (T2D) is one of the most common chronic metabolic diseases characterized by insulin resistance and the decrease of insulin secretion. Genetic variation can only explain part of the heritability of T2D, so there need new methods to detect the susceptibility genes of the disease. Epigenetics could establish the interface between the environmental factor and the T2D Pathological mechanism.ResultsBased on the network theory and by combining epigenetic characteristics with human interactome, the weighted human DNA methylation network (WMPN) was constructed, and a T2D-related subnetwork (TMSN) was obtained through T2D-related differentially methylated genes. It is found that TMSN had a T2D specific network structure that non-fatal metabolic disease causing genes were often located in the topological and functional periphery of network. Combined with chromatin modifications, the weighted chromatin modification network (WCPN) was built, and a T2D-related chromatin modification pattern subnetwork was obtained by the TMSN gene set. TCSN had a densely connected network community, indicating that TMSN and TCSN could represent a collection of T2D-related epigenetic dysregulated sub-pathways. Using the cumulative hypergeometric test, 24 interplay modules of DNA methylation and chromatin modifications were identified. By the analysis of gene expression in human T2D islet tissue, it is found that there existed genes with the variant expression level caused by the aberrant DNA methylation and (or) chromatin modifications, which might affect and promote the development of T2D.ConclusionsHere we have detected the potential interplay modules of DNA methylation and chromatin modifications for T2D. The study of T2D epigenetic networks provides a new way for understanding the pathogenic mechanism of T2D caused by epigenetic disorders.