BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s disease
Abstract There is a close relationship between Parkinson’s disease (PD) and circadian rhythm disturbances. To investigate genes linked to circadian rhythm disruption in PD, we analyzed the PD dataset via bioinformatic techniques. We downloaded 2 datasets from the GEO database; one dataset (GSE20163)...
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Nature Portfolio
2025-07-01
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| author | Dongdong Chen Qingqing Huang Ming Ye |
| author_facet | Dongdong Chen Qingqing Huang Ming Ye |
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| description | Abstract There is a close relationship between Parkinson’s disease (PD) and circadian rhythm disturbances. To investigate genes linked to circadian rhythm disruption in PD, we analyzed the PD dataset via bioinformatic techniques. We downloaded 2 datasets from the GEO database; one dataset (GSE20163) was used as an internal training set, whereas the other dataset (GSE20164) was used as an external set. We first performed differential gene expression analysis on the GSE20163 dataset to identify differentially expressed genes (DEGs). We then conducted weighted gene co-expression network analysis on this dataset to select the most significant modules (turquoise modules) and took the intersection of the two to obtain crossover genes (85 genes), which were functionally enriched in the Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). These 85 crossover genes were again taken to intersect with circadian rhythm-related genes (2531) to form circadian rhythm-related genes (16). Box plot presentation was performed and found that all p-values were significant. Least absolute shrinkage and selection operator (LASSO) regression analysis was carried out to find 2 representative genes (CDK5, BSCL2). ROC curve analysis was conducted in both the cohort and the validation set, demonstrating statistically significant in each group. Gene set enrichment analysis (GSEA) was conducted on these 2 genes in the internal training set. Analysis of these two genes revealed that they are involved in the regulation of biological processes and synaptic signaling. The diagnostic and predictive model for Parkinson’s disease (PD), which relies on circadian-related genes (BSCL2 and CDK5), has excellent diagnostic and predictive performance. This model could serve as a valuable device in the diagnosis of circadian disturbance in PD. Finally, immunohistochemistry and immunoblotting-related experiments were performed for further confirmation. Immunoblot analysis revealed decreased protein levels of BSCL2 and CDK5 in the PD group. Immunohistochemistry further demonstrated reduced TH-positive neuron counts in this experimental cohort. Taking these findings together, BSCL2 and CDK5 are important genes associated with circadian rhythm disturbance in PD. |
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| institution | Kabale University |
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| language | English |
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| spelling | doaj-art-fb8eeaedbe1d42c6967e38ec91fadb592025-08-20T04:01:41ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-05580-2BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s diseaseDongdong Chen0Qingqing Huang1Ming Ye2Department of Neurosurgery, The Affiliated Hospital of Jiang Nan UniversityDeparment of Thyroid Surgery, Jiangsu Institute of Nuclear MedicineDepartment of Neurosurgery & Brain and Nerve Research Laboratory , The First Affiliated Hospital of Soochow UniversityAbstract There is a close relationship between Parkinson’s disease (PD) and circadian rhythm disturbances. To investigate genes linked to circadian rhythm disruption in PD, we analyzed the PD dataset via bioinformatic techniques. We downloaded 2 datasets from the GEO database; one dataset (GSE20163) was used as an internal training set, whereas the other dataset (GSE20164) was used as an external set. We first performed differential gene expression analysis on the GSE20163 dataset to identify differentially expressed genes (DEGs). We then conducted weighted gene co-expression network analysis on this dataset to select the most significant modules (turquoise modules) and took the intersection of the two to obtain crossover genes (85 genes), which were functionally enriched in the Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). These 85 crossover genes were again taken to intersect with circadian rhythm-related genes (2531) to form circadian rhythm-related genes (16). Box plot presentation was performed and found that all p-values were significant. Least absolute shrinkage and selection operator (LASSO) regression analysis was carried out to find 2 representative genes (CDK5, BSCL2). ROC curve analysis was conducted in both the cohort and the validation set, demonstrating statistically significant in each group. Gene set enrichment analysis (GSEA) was conducted on these 2 genes in the internal training set. Analysis of these two genes revealed that they are involved in the regulation of biological processes and synaptic signaling. The diagnostic and predictive model for Parkinson’s disease (PD), which relies on circadian-related genes (BSCL2 and CDK5), has excellent diagnostic and predictive performance. This model could serve as a valuable device in the diagnosis of circadian disturbance in PD. Finally, immunohistochemistry and immunoblotting-related experiments were performed for further confirmation. Immunoblot analysis revealed decreased protein levels of BSCL2 and CDK5 in the PD group. Immunohistochemistry further demonstrated reduced TH-positive neuron counts in this experimental cohort. Taking these findings together, BSCL2 and CDK5 are important genes associated with circadian rhythm disturbance in PD.https://doi.org/10.1038/s41598-025-05580-2Parkinson’s diseaseCircadian rhythm disturbanceBSCL2CDK5Bioinformatics |
| spellingShingle | Dongdong Chen Qingqing Huang Ming Ye BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s disease Scientific Reports Parkinson’s disease Circadian rhythm disturbance BSCL2 CDK5 Bioinformatics |
| title | BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s disease |
| title_full | BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s disease |
| title_fullStr | BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s disease |
| title_full_unstemmed | BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s disease |
| title_short | BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson’s disease |
| title_sort | bscl2 and cdk5 are two genes associated with circadian rhythm disturbance in parkinson s disease |
| topic | Parkinson’s disease Circadian rhythm disturbance BSCL2 CDK5 Bioinformatics |
| url | https://doi.org/10.1038/s41598-025-05580-2 |
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