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pmid:41212877
Identification and validation of the important role of tryptophan-related gene CYP1B1 in the development and progression of sepsis.
Li-Hong Chen · Wei-Ru Lin · Hui-Rong Hu · Zhi-Yuan Chen · Yan-Hui Wang
PloS one · 2025 doi:10.1371/journal.pone.0335944
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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However, the function of tryptophan metabolism in the immune characteristics of sepsis still needs to be elucidated.\nMETHODS: We collected the datasets from the GEO database to extract data of blood samples RNA of patients with or without sepsis in GSE28750, GSE65682, GSE69528, and GSE137342. A serials of bioinformatics analysis, including batch normalization, differential analysis, and single-cell sequencing analysis were finished through R software. Finally, the effects of the candidate differential gene on sepsis progression were evaluated using transcription-quantitative polymerase chain reaction (RT-qPCR), transwell assays, western blot, and immunofluorescence staining.\nRESULTS: One tryptophan metabolism-related DEG for sepsis were obtained, namely CYP1B1. The transcriptional and translational level of CYP1B1 were obviously increased in the blood tissues. Notably, CYP1B1 exhibited great discriminative ability for the diagnosis of sepsis. Furthermore, single-cell sequencing analysis further indicated that CYP1B1 was primarily expressed in monocytes, and its' expression level was significantly upregulated in monocytes activated by sepsis/LPS. Knockdown of CYP1B1 dramatically decreased the proinflammatory cytokines expression, blocked the migration of monocytes, and inhibited the expression of tryptophan metabolism-related protein TDO2.\nCONCLUSION: CYP1B1 is involved in tryptophan metabolism and its upregulation can promote the progression and development of sepsis through activating monocytes.", "claims": [{"id": "claim-method", "statement": "After merging the four datasets, differential analysis was performed using the Limma R package to screen differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41212877", "locator": "sections[4] \"Selection of differentially expressed genes\" paragraph 2", "quote": "After merging the four datasets, differential analysis was performed using the Limma R package to screen differentially expressed genes (DEGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the paper and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41212877", "locator": "sections[22] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the paper and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "One tryptophan metabolism-related DEG for sepsis were obtained, namely CYP1B1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41212877", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "One tryptophan metabolism-related DEG for sepsis were obtained, namely CYP1B1."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "One tryptophan metabolism-related DEG for sepsis were obtained, namely CYP1B1.", "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:41212877"], "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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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE28750", "GSE65682", "GSE69528", "and GSE137342", "GSE167363", "GSE69063", "GSE95233", "and GSE131761"], "resolved_accessions": ["GSE28750", "GSE65682", "GSE69528", "GSE167363", "GSE69063", "GSE95233"], "statements": ["All relevant data are within the paper and its Supporting Information files."], "basis": "The paper names GSE28750, GSE65682, GSE69528, GSE167363, GSE69063, GSE95233 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:41212877", "data:geo:GSE167363"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE167363"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:05:15Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10897, "completion_tokens": 2067, "cached_tokens": 188}}, "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:41212877", "type": "paper", "label": "pmid:41212877"}, {"id": "source:pmid:41212877", "type": "manuscript", "label": "PMID 41212877 full text"}, {"id": "data:geo:GSE167363", "type": "dataset", "label": "GEO GSE167363"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41212877", "type": "paper", "label": "pmid:41212877"}, {"id": "source:pmid:41212877", "type": "manuscript", "label": "PMID 41212877 full text"}, {"id": "data:geo:GSE167363", "type": "dataset", "label": "GEO GSE167363"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41212877", "type": "extraction", "used": ["source:pmid:41212877"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE167363", "type": "accession_resolution", "used": ["data:geo:GSE167363"], "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:41212877", "parent_hash": "sha256:0d9cd05fa3779745c8abe3393145ecb8c7be4049d3177f201c88186d59158d35", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE167363 licence not read", "asset:data:geo:GSE167363 not downloaded", "asset:data:geo:GSE28750 licence not read", "asset:data:geo:GSE28750 not downloaded", "asset:data:geo:GSE65682 licence not read", "asset:data:geo:GSE65682 not downloaded", "asset:data:geo:GSE69063 licence not read", "asset:data:geo:GSE69063 not downloaded", "asset:data:geo:GSE69528 licence not read", "asset:data:geo:GSE69528 not downloaded", "asset:data:geo:GSE95233 licence not read", "asset:data:geo:GSE95233 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": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tion-quantitative polymerase chain reaction (RT-qPCR), transwell assays, western blot, and immuno", "n-quantitative polymerase chain reaction (RT-qPCR), transwell assays, western blot, and immuno"], "order_basis": "paper_text_order:803", "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": 0.93, "evidence": ["chain reaction (RT-qPCR), transwell assays, western blot, and immunofluorescence staining. RESULTS: O"], "order_basis": "paper_text_order:832", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["T-qPCR), transwell assays, western blot, and immunofluorescence staining. RESULTS: One tryptophan metabolism"], "order_basis": "paper_text_order:849", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ulated in monocytes activated by sepsis/LPS. Knockdown of CYP1B1 dramatically decreased the proinfl", "Methods and material Cell culture and transfection Human monocyte lines THP-1 was purchased fro", "ma Genetics (Shanghai, China). For transient transfection, THP-1 cells were transfected with siRNA usi", "For transient transfection, THP-1 cells were transfected with siRNA using a transfection reagent (Lip"], "order_basis": "paper_text_order:1358", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["Sciences (Shanghai, China). THP-1 cells were cultured in RPMI 1640 medium (Gibco, ThermoFisher Scient"], "order_basis": "paper_text_order:1898", "id": "assay:5"}, {"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": ["After merging the four datasets, differential analysis was performed using the Limma R package to screen differentially expressed genes (DEGs)."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}