BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson's disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40594234", "kind": "science-record", "revision": 3, "content_hash": "sha256:07ef7493ae87d3eecbe2318fed3b6460ac2e6d87ce9c12ca999c9d0cf7c2f3a4", "created_at": "2026-11-01T20:30:40Z", "updated_at": "2026-11-01T22:14:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson's disease.", "doi": "10.1038/s41598-025-05580-2", "pmid": "40594234", "authors": ["Dongdong Chen", "Qingqing Huang", "Ming Ye"], "journal": "Scientific reports", "year": 2025, "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.", "claims": [{"id": "claim-method", "statement": "Sixteen intersecting genes related to circadian rhythms were obtained for further analysis. For further screening, the LASSO machine learning method was selected.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40594234", "locator": "sections[22] \"LASSO regression algorithm for screening key genes\" paragraph 2", "quote": "Sixteen intersecting genes related to circadian rhythms were obtained for further analysis. For further screening, the LASSO machine learning method was selected."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40594234", "locator": "sections[36] \"notes\" paragraph 1", "quote": "Data are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The 16 intersecting genes were further screened using least absolute shrinkage and selection operator (LASSO) regression (Fig. 7a, b), resulting in 2 differential genes: CDK5 and BSCL2.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40594234", "locator": "sections[9] \"Screening for differential genes associated with circadian rhythm disorders by LASSO regression\" paragraph 2", "quote": "The 16 intersecting genes were further screened using least absolute shrinkage and selection operator (LASSO) regression (Fig. 7a, b), resulting in 2 differential genes: CDK5 and BSCL2."}, {"asset": "source:pmid:40594234", "locator": "sections[9] \"Screening for differential genes associated with circadian rhythm disorders by LASSO regression\" paragraph 2", "quote": "Further validation using ROC curves was performed in both the test (AUC for CDK5 0.861, AUC for BSCL2 0.889) and validation sets (AUC for CDK5 0.80, AUC for BSCL2 0.867), and both were found to be significant (Fig. 7e:h)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The 16 intersecting genes were further screened using least absolute shrinkage and selection operator (LASSO) regression (Fig. 7a, b), resulting in 2 differential genes: CDK5 and BSCL2.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40594234"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Finally, immunohistochemistry and immunoblotting-related experiments were", "in levels of BSCL2 and CDK5 in the PD group. Immunohistochemistry further demonstrated reduced TH-positive neu"], "order_basis": "paper_text_order:1925", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nce in PD. Finally, immunohistochemistry and immunoblotting-related experiments were performed for furth", "nts were performed for further confirmation. 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