Zamanian-Azodi M, Rezaei-Tavirani M, Rezaei Tavirani M. Obsessive-Compulsive Disorder Interactome Profile Analysis: A Perspective From Molecular Mechanism. BCN 2021; 12 (2) :187-198
URL:
http://bcn.iums.ac.ir/article-1-1590-en.html
1- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Introduction: Obsessive-Compulsive Disorder (OCD) is one of the complex neuropsychiatric conditions. This disorder disables individuals in many different aspects of their personal and social life. Interactome analysis may provide a better understanding of this disorder’s molecular origin and its underlying mechanisms.
Methods: In this study, the OCD-associated genes were extracted from the literature. The criterion for gene selection was to choose genes with at least one significant report. Furthermore, by applying Cytoscape and its plugins, protein-protein interaction network, and gene ontology of the 31 candidate genes related to OCD from genetic association studies is examined. The cross-validation method was used for network centrality assessment.
Results: A scale-free network, including 1940 nodes and 3269 edges for 31 genes, was constructed. According to the network centrality evaluation, ESR1, TNFα, DRD2, DRD4, HTR1B, HTR2A, and CDH2 showed the highest values and can be considered hub-bottlenecks elements. It is also confirmed by the number of 123 cross-validation tests that the frequency of these essential genes remains unaltered against the initial seed genes’ changes with the accuracy of 0.962. Besides, enrichment analysis identified four highlighted biological processes related to the 31 candidate genes. The top biological processes are determined as dopamine transport, learning, memory, and monoamine transport.
Conclusion: Among 31 initial genes, 7 were introduced as crucial elements for onset and development in OCD and can be suggested for further investigations. Furthermore, the complex molecular origin of OCD requires high-throughput screening for diagnosis and treatment goals. The findings are a possible valuable source to establish molecular-based diagnostic tools for OCD.
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Highlights
● Seven genes were suggested to have topological features in the Obsessive-Compulsive Disorder (OCD) interaction network.
● Dopamine transport, learning, memory, and monoamine transport were the critical contributing biological processes in the OCD network.
● ESR1 could play an indenciple role in a specific subtype of OCD for women.
● The presence of OCD in different subtypes could be linked to the combination of malfunction of gene groups.
Plain Language Summary
The results of this study suggest that topological information of interactome profile of OCD reported genes from genetic studies; however, it is in its initial phase. Our PPI network analysis can serve as a paradigm for later experiments such as genomic, proteomic, and metabolomic investigations.
Type of Study:
Original |
Subject:
Clinical Neuroscience Received: 2020/08/23 | Accepted: 2020/12/2 | Published: 2021/03/1