Riquelme Medina Ignacio, Lubovac-Pilav Zelmina
Bioinformatics research group, School of Biosciences, University of Skövde, Skövde, Sweden.
PLoS One. 2016 Jun 3;11(6):e0156006. doi: 10.1371/journal.pone.0156006. eCollection 2016.
Type 1 diabetes (T1D) is a complex disease, caused by the autoimmune destruction of the insulin producing pancreatic beta cells, resulting in the body's inability to produce insulin. While great efforts have been put into understanding the genetic and environmental factors that contribute to the etiology of the disease, the exact molecular mechanisms are still largely unknown. T1D is a heterogeneous disease, and previous research in this field is mainly focused on the analysis of single genes, or using traditional gene expression profiling, which generally does not reveal the functional context of a gene associated with a complex disorder. However, network-based analysis does take into account the interactions between the diabetes specific genes or proteins and contributes to new knowledge about disease modules, which in turn can be used for identification of potential new biomarkers for T1D. In this study, we analyzed public microarray data of T1D patients and healthy controls by applying a systems biology approach that combines network-based Weighted Gene Co-Expression Network Analysis (WGCNA) with functional enrichment analysis. Novel co-expression gene network modules associated with T1D were elucidated, which in turn provided a basis for the identification of potential pathways and biomarker genes that may be involved in development of T1D.
1型糖尿病(T1D)是一种复杂的疾病,由产生胰岛素的胰腺β细胞的自身免疫性破坏引起,导致身体无法产生胰岛素。尽管人们在了解导致该疾病病因的遗传和环境因素方面付出了巨大努力,但确切的分子机制在很大程度上仍然未知。T1D是一种异质性疾病,该领域以前的研究主要集中在单个基因的分析上,或者使用传统的基因表达谱分析,而这通常无法揭示与复杂疾病相关基因的功能背景。然而,基于网络的分析确实考虑了糖尿病特异性基因或蛋白质之间的相互作用,并有助于获得有关疾病模块的新知识,进而可用于识别T1D潜在的新生物标志物。在本研究中,我们通过应用一种系统生物学方法来分析T1D患者和健康对照的公共微阵列数据,该方法将基于网络的加权基因共表达网络分析(WGCNA)与功能富集分析相结合。阐明了与T1D相关的新型共表达基因网络模块,这反过来为识别可能参与T1D发病机制的潜在途径和生物标志物基因提供了基础。