Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis.
<h4>Background</h4>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a rising global prevalence. Mutations in the CHD8 gene have been implicated in ASD, yet the underlying molecular mechanisms remain insufficiently understood.<h4>Methods</h4>We anal...
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0325893 |
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| author | Hewei Zhang Shenghao Hua Daiyan Jiao Dong Chen Qin Gu Chao Bao |
| author_facet | Hewei Zhang Shenghao Hua Daiyan Jiao Dong Chen Qin Gu Chao Bao |
| author_sort | Hewei Zhang |
| collection | DOAJ |
| description | <h4>Background</h4>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a rising global prevalence. Mutations in the CHD8 gene have been implicated in ASD, yet the underlying molecular mechanisms remain insufficiently understood.<h4>Methods</h4>We analyzed transcriptomic data from the CHD8A and CHD8B allelic deletion sample dataset GSE236993 to identify differentially expressed genes (DEGs). We intersected these DEGs with genes related to the Notch signaling pathway and performed functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as protein-protein interaction (PPI) analyses, to identify key genes. These key genes were validated using the CHD8-deficient sample dataset GSE85417, resulting in the identification of seven common key genes. We then constructed drug-gene interaction networks and microRNA (miRNA) regulatory networks to further elucidate the mechanisms by which CHD8 impacts ASD.<h4>Results</h4>Seven hub genes-IGF2, FN1, CXCR4, COL11A1, ITGA6, LOX, and FBN2-were identified, all involved in the Notch signaling pathway and playing significant roles in neurodevelopment and extracellular matrix regulation. Among these, IGF2 and CXCR4 were particularly crucial in ASD pathogenesis, suggesting their potential as diagnostic biomarkers and therapeutic targets. MiRNA regulatory network analysis revealed several miRNAs that may modulate these hub genes, offering new insights into ASD pathogenesis. Drug-gene interaction analysis suggested possible therapeutic small-molecule compounds, such as AMD3100 and IGF-1R inhibitors.<h4>Conclusions</h4>Our multi-level bioinformatics analysis identified key genes and regulatory networks potentially involved in ASD associated with CHD8 deficiency. These findings enhance the understanding of ASD's molecular mechanisms and highlight potential therapeutic targets, paving the way for future diagnostic and treatment strategies. |
| format | Article |
| id | doaj-art-ff1494d41b5e472bb504e21810ba89a6 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-ff1494d41b5e472bb504e21810ba89a62025-08-20T03:22:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032589310.1371/journal.pone.0325893Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis.Hewei ZhangShenghao HuaDaiyan JiaoDong ChenQin GuChao Bao<h4>Background</h4>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a rising global prevalence. Mutations in the CHD8 gene have been implicated in ASD, yet the underlying molecular mechanisms remain insufficiently understood.<h4>Methods</h4>We analyzed transcriptomic data from the CHD8A and CHD8B allelic deletion sample dataset GSE236993 to identify differentially expressed genes (DEGs). We intersected these DEGs with genes related to the Notch signaling pathway and performed functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as protein-protein interaction (PPI) analyses, to identify key genes. These key genes were validated using the CHD8-deficient sample dataset GSE85417, resulting in the identification of seven common key genes. We then constructed drug-gene interaction networks and microRNA (miRNA) regulatory networks to further elucidate the mechanisms by which CHD8 impacts ASD.<h4>Results</h4>Seven hub genes-IGF2, FN1, CXCR4, COL11A1, ITGA6, LOX, and FBN2-were identified, all involved in the Notch signaling pathway and playing significant roles in neurodevelopment and extracellular matrix regulation. Among these, IGF2 and CXCR4 were particularly crucial in ASD pathogenesis, suggesting their potential as diagnostic biomarkers and therapeutic targets. MiRNA regulatory network analysis revealed several miRNAs that may modulate these hub genes, offering new insights into ASD pathogenesis. Drug-gene interaction analysis suggested possible therapeutic small-molecule compounds, such as AMD3100 and IGF-1R inhibitors.<h4>Conclusions</h4>Our multi-level bioinformatics analysis identified key genes and regulatory networks potentially involved in ASD associated with CHD8 deficiency. These findings enhance the understanding of ASD's molecular mechanisms and highlight potential therapeutic targets, paving the way for future diagnostic and treatment strategies.https://doi.org/10.1371/journal.pone.0325893 |
| spellingShingle | Hewei Zhang Shenghao Hua Daiyan Jiao Dong Chen Qin Gu Chao Bao Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis. PLoS ONE |
| title | Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis. |
| title_full | Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis. |
| title_fullStr | Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis. |
| title_full_unstemmed | Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis. |
| title_short | Identification of Therapeutic Targets in Autism Spectrum Disorder through CHD8-Notch Pathway Interaction Analysis. |
| title_sort | identification of therapeutic targets in autism spectrum disorder through chd8 notch pathway interaction analysis |
| url | https://doi.org/10.1371/journal.pone.0325893 |
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