Identification of key genes and convergent pathways disrupted in autism spectrum disorder via comprehensive bioinformatic analysis. (2021)

• Record Type: Journal Article
• Authors: Rahnama, Maryam; Tehrani, Hossein Abdul; Mirzaie, Mehdi; Vahid ziaee,
• Is Part Of: Informatics in medicine unlocked. Volume 24(2021)
• Publication Date: 2021
• Subjects: ASD -- Enrichment analysis -- PPI Network -- Hub gene -- Network module; Medical informatics -- Periodicals; 610.285
• DOI: 10.1016/j.imu.2021.100589
• Languages: English
• ISSNs: 2352-9148

Abstract

Abstract: Background: Autism spectrum disorder (ASD) is a complex heterogeneous condition with multifactorial etiology. Despite hundreds of genes found to be associated with ASD, they all involve in several converging pathways. This study aims at investigating key genes and critical pathways in ASD using a bioinformatic approach. Methods: ASD risk genes were recruited from known resources. Functional enrichment analysis was performed through Enrichr to identify enriched gene ontology terms and pathways linked to ASD pathogenesis. Thereafter, the protein-protein interaction (PPI) network was constructed and analyzed using STRING database and Cytoscape software respectively. Hub genes were identified topologically. Network modules were also extracted and further analyzed to explore enriched biological processes, via WebGestalt platform. Results: It was demonstrated that ASD risk genes were mainly involved in synaptic functioning, localized mostly in dendrite, axon and membrane parts of neuronal cells and had remarkable functions in regulating ion channel activity. EP300, DLG4 and HRAS were found to be three most significant hub genes. Via network clustering, 28 modules were obtained of which 5 modules were considered significant. Module enrichment analysis revealed multisystem involvement including synaptic and immune system dysfunction in addition to dysregulation of ion channel activity and cell cycle disruption. Conclusion: Results of this study can provide more insights into the biological underpinnings of ASD. Additionally, hub genes, critical pathways and main network modules, could serve as potential targets for developing treatment strategies and biomarker discovery in ASD.