Identifying differentially expressed genes, miRNAs and TFs in major depressive disorder by bioinformatics analysis of next generation sequencing data

Major depressive disorder (MDD) is a neuropsychiatric disorder with a high risk of suicide. This study aimed to examine the key genes, microRNAs and TFs associated with MDD. Next generation sequancing dataset (GSE275676) was downloaded from the Gene expression omnibus (GEO) database. The DEGs were screened using DESeq2 in R bioconductor tool. We next performed gene ontology (GO) analysis and REACTOME pathway enrichment analysis using the g:Profiler. Moreover, Cytoscape with IMex interactome was utilized to visualize protein-protein interaction (PPI) network and modules of these DEGs. Subsequantely, miRNA-hub gene regulatory network and TF-hub gene regulatory network were built by Cytoscape to predict the underlying microRNAs (miRNAs) and transcription factors (TFs) associated with hub genes. Finally, top 10 hub genes in the PPI network were validated by receiver operating characteristic (ROC) curve analysis. We screened 958 DEGs, containing 479 up regulated genes and 479 down regulated genes. GO and REACTOME pathway enrichment analyses revealed that DEGs are mainly enriched in cell communication, synapse, enzyme binding, response to stimulus, cell periphery, signaling receptor binding, neuronal system and immune system. YWHAG, ONECUT1, CALM2, ARRB1, PIK3R1, CDK2, VCAM1, HLA-B, VIM and ERBB2 are the topb hub genes in PPI network and modules. The predicted miRNA-hub gene regulatory network identified miRNAs (hsa-miR-548j-5p, hsa-mir-466, hsa-miR-523-5p and hsa-mir-6829-3p) targeting hub genes and predicted TF-hub gene regulatory network identified TFs (PAX2, JUND, FEV and PPARG). In conclusion, this bioinformatics analysis of NGS data demonstrated that hub genes, miRNAs and TFs might regulate the development of MDD. These hub genes, miRNAs and TFs could be used as new biomarkers for diagnosis and to guide the combination medicine of MDD.