Bioinformatics reveals diagnostic potential of cuproptosis-related genes in the pathogenesis of sepsis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38163157", "kind": "science-record", "revision": 3, "content_hash": "sha256:6b753e59e259c19581c3b0ce586bd51fedcabc5a73b1c299392b11cba6a270f4", "created_at": "2026-11-01T19:20:05Z", "updated_at": "2026-11-01T22:10:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics reveals diagnostic potential of cuproptosis-related genes in the pathogenesis of sepsis.", "doi": "10.1016/j.heliyon.2023.e22664", "pmid": "38163157", "authors": ["Zhongyi Sun", "Qiuyue Zhao", "Jiahao Zhang", "Yanan Hu", "Jiachen Qu", "Han Gao", "Zhiyong Peng"], "journal": "Heliyon", "year": 2024, "abstract": "Background: Multiple modes of cell death occur during the development of sepsis. Among these patterns, cuproptosis has recently been identified as a regulated form of cell death. However, its impact on the onset and progression of sepsis remains unclear.\nMethod: We screened a dataset of gene expression profiles from patients with sepsis using the GEO database. Survival analysis was performed to analyze the relationship between cuproptosis-related genes (CRGs) and prognosis. Hub genes were identified through univariate Cox regression analysis. The diagnostic value of hub genes in sepsis was tested in both training sets (GSE65682) and validation sets (GSE134347). To examine the association between hub genes and immune cells, single-sample gene set enrichment analysis (ssGSEA) and Pearson correlation analysis were employed. Additionally, the CRGs were validated in a septic mouse model using real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC).\nResults: In sepsis, most CRGs were upregulated, with only DLD and MTF1 downregulated. High expression of three genes (GLE, LIAS, and PDHB) was associated with better prognosis, but only two hub genes (LIAS, PDHB) reached statistical significance. The receiver operating characteristic (ROC) analysis for diagnosing sepsis showed LIAS had a range of 0.793-0.906, while PDHB achieved values of 0.882 and 0.975 in the training and validation sets, respectively. ssGSEA analysis revealed a lower number of immune cells in the sepsis group, and there was a correlation between immune cell population and CRGs (LIAS, PDHB). Analysis in the septic mouse model demonstrated no significant difference in mRNA expression levels and IHC staining between LIAS and PDHB in heart and liver tissues, but up-regulation was observed in lung tissues. Furthermore, the mRNA expression levels and IHC staining of LIAS and PDHB were down-regulated in renal tissues.\nConclusions: Cuproptosis is emerging as a significant factor in the development of sepsis. LIAS and PDHB, identified as potential diagnostic biomarkers for cuproptosis-associated sepsis, are believed to play crucial roles in the initiation and progression of cuproptosis-induced sepsis.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis was used to estimate the hazard ratio (HR) of survival.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38163157", "locator": "sections[21] \"Prognosis-related analysis\" paragraph 2", "quote": "Univariate Cox regression analysis was used to estimate the hazard ratio (HR) of survival."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data associated with this study has been deposited at https://www.ncbi.nlm.nih.gov/gds under the accession number GSE65682 and GSE134347.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38163157", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "Data associated with this study has been deposited at https://www.ncbi.nlm.nih.gov/gds under the accession number GSE65682 and GSE134347."}], "state": "complete"}, {"id": "claim-target-result", "statement": "LIAS and PDHB showed diagnostic performance for sepsis in the training and validation datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38163157", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The receiver operating characteristic (ROC) analysis for diagnosing sepsis showed LIAS had a range of 0.793–0.906, while PDHB achieved values of 0.882 and 0.975 in the training and validation sets, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "LIAS and PDHB showed diagnostic performance for sepsis in the training and validation datasets.", "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:38163157"], "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:38163157", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2023.e22664", "sha256": 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"evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate Cox regression analysis was used to estimate the hazard ratio (HR) of survival."}}, {"id": "method-2", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-4", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", 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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": ["Data associated with this study has been deposited at https://www.ncbi.nlm.nih.gov/gds under the accession number GSE65682 and GSE134347."], "basis": "The paper names GSE65682, GSE134347 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": ["cox_ph"], "assets": ["source:pmid:38163157", "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": "2026-11-01T19:03:51Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13400, "completion_tokens": 1365, "cached_tokens": 256}}, "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:38163157", "type": "paper", "label": "pmid:38163157"}, {"id": "source:pmid:38163157", "type": "manuscript", "label": "PMID 38163157 full text"}, {"id": "data:geo:GSE134347", "type": "dataset", "label": "GEO GSE134347"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38163157", "type": "paper", "label": "pmid:38163157"}, {"id": "source:pmid:38163157", "type": "manuscript", "label": "PMID 38163157 full text"}, {"id": "data:geo:GSE134347", "type": "dataset", "label": "GEO GSE134347"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38163157", "type": "extraction", "used": ["source:pmid:38163157"], "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:38163157", "parent_hash": "sha256:e9fa5eb95d49f5900019ec775aed006bb5496f2d9e95f2c690279ce975376af8", "fork_of": null, "generation": 2}, "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": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ionally, the CRGs were validated in a septic mouse model using real-time quantitative PCR (qRT-PCR) a", "nd CRGs (LIAS, PDHB). Analysis in the septic mouse model demonstrated no significant difference in mR", "ionally, the CRGs were validated in a septic mouse model using real-time quantitative PCR (qRT-", "nd CRGs (LIAS, PDHB). Analysis in the septic mouse model demonstrated no significant difference"], "order_basis": "paper_text_order:942", "id": "assay:1"}, {"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": ["were validated in a septic mouse model using real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC). Re"], "order_basis": "paper_text_order:960", "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": 0.99, "evidence": ["ing real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC). Results: In sepsis, most CRGs were up", "tive PCR (qRT-PCR) and immunohistochemistry (IHC). Results: In sepsis, most CRGs were upregul", "ant difference in mRNA expression levels and IHC staining between LIAS and PDHB in heart and", "Furthermore, the mRNA expression levels and IHC staining of LIAS and PDHB were down-regulate"], "order_basis": "paper_text_order:1001", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Univariate Cox regression analysis was used to estimate the hazard ratio (HR) of survival."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}