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pmid:39779759
Tryptophan metabolism-related gene CYP1B1 serves as a shared biomarker for both Parkinson's disease and insomnia.
Xin-Yu Li · Wen-Kai Yu · Jing-Hao Wu · Wen-Jun He · Yu-Nan Cheng · Kai Gao · Yi-Han Wei · Yu-Sheng Li
Scientific reports · 2025 doi:10.1038/s41598-024-84362-8
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Experiment
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Complete file
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However, the precise mechanisms by which TRP metabolism contributes to these conditions remain insufficiently elucidated. This study explores shared tryptophan metabolism-related genes (TMRGs) and molecular mechanisms underlying PD and insomnia, aiming to provide insights into their shared pathogenesis. We analyzed datasets for PD (GSE100054) and insomnia (GSE208668) obtained from the Gene Expression Omnibus (GEO) database. TMRGs were obtained from the Molecular Signatures Database (MSigDB) and the Genecards database. Tryptophan metabolism-related differentially expressed genes (TM-DEGs) were identified by intersecting TMRGs with shared differentially expressed genes (DEGs) from these datasets. Through Protein-Protein Interaction (PPI) network analysis, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) , and Extreme Gradient Boosting (XGBoost) machine learning, we identified Cytochrome P4501B1 (CYP1B1) and Electron Transfer Flavoprotein Alpha (ETFA) as key hub genes. Subsequently, we employed CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) to further investigate the association between hub genes and peripheral immune activation and inflammatory response. Additionally, gene interaction, Drug-mRNA, Transcription Factor (TF)-mRNA, and competing endogenous RNA (ceRNA) networks centered on these hub genes were constructed to explore regulatory mechanisms and potential drug interactions. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:39779759", "data:geo:GSE100054"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE100054"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:44:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11818, "completion_tokens": 1724, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:39779759", "type": "paper", "label": "pmid:39779759"}, {"id": "source:pmid:39779759", "type": "manuscript", "label": "PMID 39779759 full text"}, {"id": "data:geo:GSE100054", "type": "dataset", "label": "GEO GSE100054"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39779759", "type": "paper", "label": "pmid:39779759"}, {"id": "source:pmid:39779759", "type": "manuscript", "label": "PMID 39779759 full text"}, {"id": "data:geo:GSE100054", "type": "dataset", "label": "GEO GSE100054"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39779759", "type": "extraction", "used": ["source:pmid:39779759"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE100054", "type": "accession_resolution", "used": ["data:geo:GSE100054"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:39779759", "parent_hash": "sha256:63d026504e83d09d449320466d2054e4fe76789fe84f9559005f4c241ef67f02", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE100054 licence not read", "asset:data:geo:GSE100054 not downloaded", "asset:data:geo:GSE165082 licence not read", "asset:data:geo:GSE165082 not downloaded", "asset:data:geo:GSE198273 licence not read", "asset:data:geo:GSE198273 not downloaded", "asset:data:geo:GSE208668 licence not read", "asset:data:geo:GSE208668 not downloaded", "asset:data:geo:GSE49036 licence not read", "asset:data:geo:GSE49036 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ession in a PD model. Ten-week-old C57BL/6 J mice were obtained from Beijing Vital River Laboratory", "ogy Co., Ltd. (Beijing, China). Six of these mice were subjected to a chronic sleep deprivation app", "one week to model clinical insomnia. Control mice were housed in identical apparatuses to maintain", "al apparatuses to maintain normal sleep. All mice were kept under standard laboratory conditions: 2"], "order_basis": "paper_text_order:2429", "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": ["ate our conclusions, we employed qRT-PCR and Western blotting to assess transcriptional changes in CYP1B1", "pheral blood compared to controls (Fig. 8A). Western blotting similarly confirmed increased protein expres", "d compared to controls (Fig. 8C). Subsequent Western blotting confirmed these results, consistent with the", "genes in mouse peripheral blood samples. (B) Western blot validation of differential protein expressio"], "order_basis": "paper_text_order:7047", "id": "assay:2"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["DEGs were identified using the ‘limma’ package (v3.54.2)32, with selection criteria of p-value < 0.05 and absolute log2 fold change (|log2FC|) > 0.5."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}