An integrated bioinformatics strategy to elucidate the function of hub genes linked to Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a degenerative and the most common cause of dementia. Dementia is a collective term for a set of symptoms that can be caused by a variety of factors. It is characterised by memory and vocabulary lapse, problem-solving, and other cognitive abilities that impair a person's ability to perform daily tasks. These complications arise due to the loss of neurons involved in cognitive activity. People who are in the critical stages of this disease are bedridden and need 24-hour attention and treatment. The aim of our present study is to identify differentially expressed genes (DEGs) using various bioinformatic tools to know about the molecular mechanism responsible for AD. For this study, we used 7 different microarray datasets to identify the main DEGs. Initially, 3686 upregulated and 2487 downregulated DEGs were identified on the basis of cut off criteria [i.e., p –value < 0.05 and absolute log 2 (fold change) >0.5]. After the network analysis, 191 genes, 122 upregulated and 79 downregulated were identified. Consequently, we get 7 key genes, six upregulated (ATP5B, CTNNB1, DYNC1H1, GDI2, ITGB1 and HIST1H2BK) and one downregulated (PAK3) after submitting these 191 genes to string database. Moreover, AD specific miRNA-mRNA regulatory network was determined using these hub genes. Subsequently, 4 mRNAs three upregulated (CTNNB1, DYNC1H1, ITGB1) and one downregulated (PAK3) + 11 associated miRNAs (hsa-miR-186-3p, hsa-miR-29a-5p, hsa-miR-16-5p, hsa-miR-15a-5p, hsa-miR-93-5p, hsa-miR-24,3p, hsa-miR-17-5p, has-let-7b-5p, has-miR-23b-3p, has-miR-145-5p and hsa-miR-20a-3p)] were identified. In FFL study (Feed Forward Loop) two genes among the seven key genes were identified to play regulatory and inhibitory role. Finally, we reported that these genes can act as a substantial biomarker in AD based on prioritization of candidate gene.