Identification of bipolar disorder related biomarkers, signaling pathways and potential therapeutic compounds based on bioinformatics methods and molecular docking technology

Abstract

Bipolar disorder (BD), also known as psychiatric disorder, affects millions of people all over the world. The aim of this investigation was to screen and verify hub genes involved in BD as well as to explore potential molecular mechanisms. The next generation sequencing (NGS) dataset GSE124326 was downloaded from the Gene Expression Omnibus (GEO) database, which contained 480 samples, including 240 BD and 240 normal controls. Differentially expressed genes (DEGs) were filtered and subjected to gene ontology (GO) and pathway enrichment analyses. A Protein-Protein Interaction (PPI) network and modules were constructed and analyzed. We predicted regulatory miRNAs and TFs of hub-genes through miRNet and NetworkAnalyst online database. Drug predicted for BD treatment was screened out from the DrugBank through NetworkAnalyst. Molecular docking studies were carried out for predicting novel drug molecules. Receiver operating characteristic curve (ROC) curves was drawn to elucidate the diagnostic value of hub genes. In this investigation, total of 957 DEGs, including 477 up regulated and 480 down regulated genes. The GO and pathway enrichment analyses of the DEGs showed that the up regulated genes were enriched in the neutrophil degranulation, immune system, transport, cytoplasm and enzyme regulator activity, and the down regulated genes were enriched in extracellular matrix organization, diseases of metabolism, multicellular organismal process, cell periphery and metal ion binding. We screened hub genes include UBB, UBE2D1, TUBA1A, RPL11, RPS24, NOTCH3, CAV1, CNBD2, CCNA1 and MYH11. We also predicted miRNAs, TFs and drugs include hsa-mir-8085, hsa-mir-4514, HMG20B, STAT3, phenserine and roflumilast. Molecular docking technology screened out three small molecule compounds, including Kakkalide, Divaricatol and Brucine small molecule compounds. The current investigation illustrates a characteristic NGS data in BD, which might contribute to the interpretation of the progression of BD and provide novel biomarkers and therapeutic targets for BD.