EXPLORING THE PROGNOSTIC NECROPTOSIS-RELATED GENES AND UNDERLYING MECHANISM IN SEPSIS USING BIOINFORMATICS.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38920136", "kind": "science-record", "revision": 4, "content_hash": "sha256:25a45c8f01b379b9f684341af629276d78b640fae34f8f0ed6aa761f58de0b2f", "created_at": "2026-11-01T20:29:00Z", "updated_at": "2026-11-01T22:54:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "EXPLORING THE PROGNOSTIC NECROPTOSIS-RELATED GENES AND UNDERLYING MECHANISM IN SEPSIS USING BIOINFORMATICS.", "doi": "10.1097/SHK.0000000000002414", "pmid": "38920136", "authors": ["Jie Liu", "Lin Li", "Shuyang He", "Xin Zheng", "Dan Zhu", "Guangyao Kong", "Ping Li"], "journal": "Shock (Augusta, Ga.)", "year": 2024, "abstract": "ABSTRACT: Sepsis is a life-threatening disease due to a dysregulated host response to infection, with an unknown regulatory mechanism for prognostic necroptosis-related genes (NRGs). Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers ( ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 ) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses. Afterward, the ingenuity pathway analysis (IPA) highlighted enrichment in hepatic fibrosis pathways and BEX2 protein. Moreover, we examined their regulatory targets and functional links with necroptotic signaling molecules via miRDB, TargetScan, Network analyst, and GeneMANIA. The molecular regulatory network displayed that hsa-miR-5195-3p and hsa-miR-145-5p regulated ATRX, BACH2, and CD40, while YY1 showed strong connectivity, concurrently controlling LEF1, ATRX, BCL2, BACH2, and CD40. CD40 exhibited similar expression patterns to RIPK3 and MLKL, and LEF1 was functionally associated with MLKL. Additionally, DrugBank analysis identified paclitaxel, docetaxel, and rasagiline as potential BCL2-targeting sepsis treatments. Finally, real-time quantitative PCR confirmed ATRX, TSC1, and LEF1 downregulation in sepsis samples, contrasting CD40's increased expression in CTL samples. In conclusion, ATRX , TSC1 , CD40 , BACH2 , BCL2 , and LEF1 may be critical regulatory targets of necroptosis in sepsis, providing a basis for further necroptosis-related studies in sepsis.", "claims": [{"id": "claim-method", "statement": "Then, the limma package (version 3.52.2) (14) based on |log2fold-change (FC)| > 0.5 and P value <0.05 was used to screen for differentially expressed genes (DEGs) in sepsis patients and CTL.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38920136", "locator": "sections[4] \"Identification of differentially expressed NRGs\" paragraph 2", "quote": "Then, the limma package (version 3.52.2) (14) based on |log2fold-change (FC)| > 0.5 and P value <0.05 was used to screen for differentially expressed genes (DEGs) in sepsis patients and CTL."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE65682 was the source of clinical data for sepsis patients in this study for survival analysis, containing 802 blood-derived RNA-seq from 760 sepsis patients (479 patients with survival information) and 42 control (CTL) samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38920136", "locator": "sections[3] \"Data acquisition\" paragraph 2", "quote": "The GSE65682 was the source of clinical data for sepsis patients in this study for survival analysis, containing 802 blood-derived RNA-seq from 760 sepsis patients (479 patients with survival information) and 42 control (CTL) samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers (ATRX, TSC1, CD40, BACH2, BCL2, and LEF1) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38920136", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers (ATRX, TSC1, CD40, BACH2, BCL2, and LEF1) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using GEO datasets GSE65682 and GSE134347, we identified six NRG biomarkers (ATRX, TSC1, CD40, BACH2, BCL2, and LEF1) with survival and diagnostic significance through Kaplan-Meier (KM) and receiver operating characteristic (ROC) analyses.", "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:38920136"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE134347"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE134347"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38920136", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/SHK.0000000000002414", "sha256": 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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": ["GSE65682", "GSE134347"], "resolved_accessions": ["GSE65682", "GSE134347"], "statements": ["The GSE65682 was the source of clinical data for sepsis patients in this study for survival analysis, containing 802 blood-derived RNA-seq from 760 sepsis patients (479 patients with survival information) and 42 control (CTL) samples."], "basis": "The paper names GSE65682, GSE134347 in Gene Expression Omnibus (GEO) 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:38920136", "data:geo:GSE134347"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE134347"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:22:24Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 10036, "completion_tokens": 1339, "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:38920136", "type": "paper", "label": "pmid:38920136"}, {"id": "source:pmid:38920136", "type": "manuscript", "label": "PMID 38920136 full text"}, {"id": "data:geo:GSE134347", "type": "dataset", "label": "GEO GSE134347"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38920136", "type": "paper", "label": "pmid:38920136"}, {"id": "source:pmid:38920136", "type": "manuscript", "label": "PMID 38920136 full text"}, {"id": "data:geo:GSE134347", "type": "dataset", "label": "GEO GSE134347"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38920136", "type": "extraction", "used": ["source:pmid:38920136"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE134347", "type": "accession_resolution", "used": ["data:geo:GSE134347"], "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:38920136", "parent_hash": "sha256:346448e3089f4bb342781c32de299ab09c168a456b3bd33d8fbd6fcdffd8359e", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE134347 licence not read", "asset:data:geo:GSE134347 not downloaded", "asset:data:geo:GSE65682 licence not read", "asset:data:geo:GSE65682 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": 0.93, "evidence": ["l BCL2-targeting sepsis treatments. Finally, real-time quantitative PCR confirmed ATRX, TSC1, and LEF1 downregulatio"], "order_basis": "paper_text_order:1232", "id": "assay:1"}, {"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": ["Then, the limma package (version 3.52.2) (14) based on |log2fold-change (FC)| > 0.5 and P value <0.05 was used to screen for differentially expressed genes (DEGs) in sepsis patients and CTL."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}