Bioinformatics and Network-based Approaches for Determining Pathways, Signature Molecules, and Drug Substances connected to Genetic Basis of Schizophrenia etiology

Author:- Umama Khan, Md Habibur Rahman, Md. Salauddin Khan, Md. Shahadat Hossain, Md Morsaline Billah
Category:- Journal; Year:- 2022
Discipline:- Biotechnology & Genetic Engineering Discipline
School:- Life Science School


Knowledge of heterogeneous etiology and pathophysiology of schizophrenia (SZP) is reasonably inadequate and non-deterministic due to its inherent complexity and underlying vast dynamics related to genetic mechanisms. The evolution of large-scale transcriptome-wide datasets and subsequent development of relevant, robust technologies for their analyses show promises toward elucidating the genetic basis of disease pathogenesis, its early risk prediction, and predicting drug molecule targets for therapeutic intervention. In this research, we have scrutinized the genetic basis of SZP through functional annotation and network-based system biology approaches. We have determined 96 overlapping differentially expressed genes (DEGs) from 2 microarray datasets and subsequently identified their interconnecting networks to reveal transcriptome signatures like hub proteins (FYN, RAD51, SOCS3, XIAP, AKAP13, PIK3C2A, CBX5, GATA3, EIF3K, and CDKN2B), transcription factors and miRNAs. In addition, we have employed gene set enrichment to highlight significant gene ontology (e.g., positive regulation of microglial cell activation) and relevant pathways (such as axon guidance and focal adhesion) interconnected to the genes associated with SZP. Finally, we have suggested candidate drug substances like Luteolin HL60 UP as a possible therapeutic target based on these key molecular signatures.

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