Department of Endocrinology, HwaMei Hospital, University of Chinese Academy of Sciences, 41 Northwest Street Zhejiang Province, Ningbo, 315010, China.
Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, 315010, China.
Hum Genomics. 2022 Sep 8;16(1):38. doi: 10.1186/s40246-022-00412-0.
Thyroid eye disease (TED) is the most common orbital pathology that occurs in up to 50% of patients with Graves' disease. Herein, we aimed at discovering the possible hub genes and pathways involved in TED based on bioinformatical approaches.
The GSE105149 and GSE58331 datasets were downloaded from the Gene Expression Omnibus (GEO) database and merged for identifying TED-associated modules by weighted gene coexpression network analysis (WGCNA) and local maximal quasi-clique merger (lmQCM) analysis. EdgeR was run to screen differentially expressed genes (DEGs). Transcription factor (TF), microRNA (miR) and drug prediction analyses were performed using ToppGene suite. Function enrichment analysis was used to investigate the biological function of genes. Protein-protein interaction (PPI) analysis was performed based on the intersection between the list of genes obtained by WGCNA, lmQCM and DEGs, and hub genes were identified using the MCODE plugin. Based on the overlap of 497 genes retrieved from the different approaches, a robust TED coexpression network was constructed and 11 genes (ATP6V1A, PTGES3, PSMD12, PSMA4, METAP2, DNAJA1, PSMA1, UBQLN1, CCT2, VBP1 and NAA50) were identified as hub genes. Key TFs regulating genes in the TED-associated coexpression network, including NFRKB, ZNF711, ZNF407 and MORC2, and miRs including hsa-miR-144, hsa-miR-3662, hsa-miR-12136 and hsa-miR-3646, were identified. Genes in the coexpression network were enriched in the biological processes including proteasomal protein catabolic process and proteasome-mediated ubiquitin-dependent protein catabolic process and the pathways of endocytosis and ubiquitin-mediated proteolysis. Drugs perturbing genes in the coexpression network were also predicted and included enzyme inhibitors, chlorodiphenyl and finasteride.
For the first time, TED-associated coexpression network was constructed and key genes and their functions, as well as TFs, miRs and drugs, were predicted. The results of the present work may be relevant in the treatment and diagnosis of TED and may boost molecular studies regarding TED.
甲状腺眼病（TED）是最常见的眼眶病理学，在高达 50%的格雷夫斯病患者中发生。在此，我们旨在通过生物信息学方法发现 TED 中可能涉及的枢纽基因和途径。
从基因表达综合数据库（GEO）下载 GSE105149 和 GSE58331 数据集，并通过加权基因共表达网络分析（WGCNA）和局部最大拟准簇合并（lmQCM）分析合并以识别 TED 相关模块。使用 EdgeR 筛选差异表达基因（DEGs）。使用 ToppGene 套件进行转录因子（TF）、microRNA（miR）和药物预测分析。进行功能富集分析以研究基因的生物学功能。基于 WGCNA、lmQCM 和 DEGs 获得的基因列表之间的交集进行蛋白质-蛋白质相互作用（PPI）分析，并使用 MCODE 插件识别枢纽基因。基于从不同方法中检索到的 497 个基因的重叠，构建了一个稳健的 TED 共表达网络，并确定了 11 个基因（ATP6V1A、PTGES3、PSMD12、PSMA4、METAP2、DNAJA1、PSMA1、UBQLN1、CCT2、VBP1 和 NAA50）为枢纽基因。调节 TED 相关共表达网络中基因的关键 TF，包括 NFRKB、ZNF711、ZNF407 和 MORC2，以及包括 hsa-miR-144、hsa-miR-3662、hsa-miR-12136 和 hsa-miR-3646 在内的 miRs 也被鉴定出来。共表达网络中的基因富集于包括蛋白酶体蛋白分解代谢和蛋白酶体介导的泛素依赖性蛋白分解代谢以及内吞作用和泛素介导的蛋白水解途径在内的生物学过程中。还预测了干扰共表达网络中基因的药物，包括酶抑制剂、氯二苯和非那雄胺。
首次构建了 TED 相关共表达网络，并预测了关键基因及其功能，以及 TF、miR 和药物。本研究结果可能与 TED 的治疗和诊断相关，并可能推动 TED 的分子研究。
