• Xu You, Yunqiao Zhang, Qing Long, Zijun Liu, Ziqiao Feng, Wengyu Zhang, Zhaowei Teng, and Yong Zeng.
• The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan, P.R. China.
• Medicine (Baltimore). 2020 Aug 28; 99 (35): e21989.

BackgroundBipolar disorder (BD), a common kind of mood disorder with frequent recurrence, high rates of additional comorbid conditions and poor compliance, has an unclear pathogenesis. The Gene Expression Omnibus (GEO) database is a gene expression database created and maintained by the National Center for Biotechnology Information. Researchers can download expression data online for bioinformatics analysis, especially for cancer research. However, there is little research on the use of such bioinformatics analysis methodologies for mental illness by downloading differential expression data from the GEO database.MethodsPublicly available data were downloaded from the GEO database (GSE12649, GSE5388 and GSE5389), and differentially expressed genes (DEGs) were extracted by using the online tool GEO2R. A Venn diagram was used to screen out common DEGs between postmortem brain tissues and normal tissues. Functional annotation and pathway enrichment analysis of DEGs were performed by using Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Furthermore, a protein-protein interaction network was constructed to identify hub genes.ResultsA total of 289 DEGs were found, among which 5 of 10 hub genes [HSP90AA1, HSP90AB 1, UBE2N, UBE3A, and CUL1] were identified as susceptibility genes whose expression was downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that variations in these 5 hub genes were obviously enriched in protein folding, protein polyubiquitination, apoptotic process, protein binding, the ubiquitin-mediated proteolysis pathway, and protein processing in the endoplasmic reticulum pathway. These findings strongly suggested that HSP90AA1, UBE3A, and CUL 1, which had large areas under the curve in receiver operator curves (P < .05), were potential diagnostic markers for BD.ConclusionAlthough there are 3 hub genes [HSP90AA1, UBE3A, and CUL 1] that are tightly correlated with the occurrence of BD, mainly based on routine bioinformatics methods for cancer-related disease, the feasibility of applying this single GEO bioinformatics approach for mental illness is questionable, given the significant differences between mental illness and cancer-related diseases.

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