Department of Pediatrics, J J M Medical College, Davangere, Karnataka, 577004, India.
Department of Pharmaceutical Chemistry, K.L.E. College of Pharmacy, Gadag, Karnataka, 582101, India.
Sci Rep. 2022 Jun 1;12(1):9157. doi: 10.1038/s41598-022-13291-1.
Type 1 diabetes mellitus (T1DM) is a metabolic disorder for which the underlying molecular mechanisms remain largely unclear. This investigation aimed to elucidate essential candidate genes and pathways in T1DM by integrated bioinformatics analysis. In this study, differentially expressed genes (DEGs) were analyzed using DESeq2 of R package from GSE162689 of the Gene Expression Omnibus (GEO). Gene ontology (GO) enrichment analysis, REACTOME pathway enrichment analysis, and construction and analysis of protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network, and validation of hub genes were performed. A total of 952 DEGs (477 up regulated and 475 down regulated genes) were identified in T1DM. GO and REACTOME enrichment result results showed that DEGs mainly enriched in multicellular organism development, detection of stimulus, diseases of signal transduction by growth factor receptors and second messengers, and olfactory signaling pathway. The top hub genes such as MYC, EGFR, LNX1, YBX1, HSP90AA1, ESR1, FN1, TK1, ANLN and SMAD9 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. Receiver operating characteristic curve (ROC) analysis confirmed that these genes were significantly associated with T1DM. In conclusion, the identified DEGs, particularly the hub genes, strengthen the understanding of the advancement and progression of T1DM, and certain genes might be used as candidate target molecules to diagnose, monitor and treat T1DM.
1 型糖尿病(T1DM)是一种代谢紊乱疾病,其潜在的分子机制仍很大程度上不清楚。本研究通过综合生物信息学分析,旨在阐明 T1DM 的关键候选基因和途径。在这项研究中,使用 R 包中的 DESeq2 分析了来自 GEO 的 GSE162689 的差异表达基因(DEGs)。进行了基因本体论(GO)富集分析、REACTOME 途径富集分析,以及构建和分析蛋白质-蛋白质相互作用(PPI)网络、模块、miRNA-枢纽基因调控网络和 TF-枢纽基因调控网络,并对枢纽基因进行了验证。在 T1DM 中鉴定出 952 个差异表达基因(477 个上调和 475 个下调基因)。GO 和 REACTOME 富集结果表明,DEGs 主要富集在多细胞生物发育、刺激检测、生长因子受体和第二信使信号转导疾病以及嗅觉信号通路。从 PPI 网络、模块、miRNA-枢纽基因调控网络和 TF-枢纽基因调控网络中筛选出 MYC、EGFR、LNX1、YBX1、HSP90AA1、ESR1、FN1、TK1、ANLN 和 SMAD9 等顶级枢纽基因作为 DEGs 中的关键基因。接收器操作特征曲线(ROC)分析证实这些基因与 T1DM 显著相关。总之,鉴定出的 DEGs,特别是枢纽基因,加深了对 T1DM 进展和进展的理解,某些基因可能被用作诊断、监测和治疗 T1DM 的候选靶分子。