Identification of biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in alcoholic hepatitis by bioinformatics and experimental verification.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37090703", "kind": "science-record", "revision": 4, "content_hash": "sha256:e261fef9095949827ff017db160ad74d50a3f1b185fe1e35532980da01f6b06b", "created_at": "2026-11-01T19:01:45Z", "updated_at": "2026-11-01T22:51:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in alcoholic hepatitis by bioinformatics and experimental verification.", "doi": "10.3389/fimmu.2023.1146693", "pmid": "37090703", "authors": ["Shasha Hou", "Dan Wang", "Xiaxia Yuan", "Xiaohuan Yuan", "Qi Yuan"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Backgrounds: Alcoholic hepatitis (AH) is a major health problem worldwide. There is increasing evidence that immune cells, iron metabolism and copper metabolism play important roles in the development of AH. We aimed to explore biomarkers that are co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.\nMethods: GSE28619 and GSE103580 datasets were integrated, CIBERSORT algorithm was used to analyze the infiltration of 22 types of immune cells and GSVA algorithm was used to calculate ferroptosis and cuproptosis scores. Using the \"WGCNA\" R package, we established a gene co-expression network and analyzed the correlation between M1 macrophages, ferroptosis and cuproptosis scores and module characteristic genes. Subsequently, candidate genes were screened by WGCNA and differential expression gene analysis. The LASSO-SVM analysis was used to identify biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis. Finally, we validated these potential biomarkers using GEO datasets (GSE155907, GSE142530 and GSE97234) and a mouse model of AH.\nResults: The infiltration level of M1 macrophages was significantly increased in AH patients. Ferroptosis and cuproptosis scores were also increased in AH patients. In addition, M1 macrophages, ferroptosis and cuproptosis were positively correlated with each other. Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.\nConclusion: We identified 5 potential biomarkers that are promising new targets for the treatment and diagnosis of AH patients.", "claims": [{"id": "claim-method", "statement": "By WGCNA and LASSO-SVM analysis, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 were potential biomarkers in AH patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37090703", "locator": "sections[25] \"Discussion\" paragraph 2", "quote": "By WGCNA and LASSO-SVM analysis, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 were potential biomarkers in AH patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37090703", "locator": "sections[27] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37090703", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Combining bioinformatics analysis with a mouse model of AH, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 may be potential biomarkers co-associated with M1 macrophages, ferroptosis and cuproptosis in AH patients.", "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:37090703"], "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:GSE103580"], "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:GSE103580"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37090703", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1146693", "sha256": "sha256:8f169c52e05a4d3b2840eac26867ea3a94caa9d11605d841b8b24e23dafa8268", "bytes": 48005, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1146693", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10117880", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE103580", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103580", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE103580", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2774700", "GSM2774701", "GSM2774702", "GSM2774703", "GSM2774704", "GSM2774705", "GSM2774706", "GSM2774707", "GSM2774708", "GSM2774709", "GSM2774710", "GSM2774711", "GSM2774712", "GSM2774713", "GSM2774714", "GSM2774715", "GSM2774716", "GSM2774717", "GSM2774718", "GSM2774719", "GSM2774720", "GSM2774721", "GSM2774722", "GSM2774723", "GSM2774724", "GSM2774725", "GSM2774726", "GSM2774727", "GSM2774728", "GSM2774729", "GSM2774730", "GSM2774731", "GSM2774732", "GSM2774733", "GSM2774734", "GSM2774735", "GSM2774736", "GSM2774737", "GSM2774738", "GSM2774739", "GSM2774740", "GSM2774741", "GSM2774742", "GSM2774743", "GSM2774744", "GSM2774745", "GSM2774746", "GSM2774747", "GSM2774748", "GSM2774749", "GSM2774750", "GSM2774751", "GSM2774752", "GSM2774753", "GSM2774754", "GSM2774755", "GSM2774756", "GSM2774757", "GSM2774758", "GSM2774759", "GSM2774760", "GSM2774761", "GSM2774762", "GSM2774763", "GSM2774764", "GSM2774765", "GSM2774766", "GSM2774767", "GSM2774768", "GSM2774769", "GSM2774770", "GSM2774771", "GSM2774772", "GSM2774773", "GSM2774774", "GSM2774775", "GSM2774776", "GSM2774777", "GSM2774778", "GSM2774779", "GSM2774780", "GSM2774781", "GSM2774782", "GSM2774783", "GSM2774784", "GSM2774785"], "sample_count": 86, "group_sizes": null, "group_sizes_basis": null, "platform": "13667", "taxon": "Homo sapiens", "title": "Transcriptome profiles of liver biopsy tissues from patients with various stages of alcoholic liver disease", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE142530", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE142530", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE142530", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4231368", "GSM4231369", "GSM4231370", "GSM4231371", "GSM4231372", "GSM4231373", "GSM4231374", "GSM4231375", "GSM4231376", "GSM4231377", "GSM4231378", "GSM4231379", "GSM4231380", "GSM4231381", "GSM4231382", "GSM4231383", "GSM4231384", "GSM4231385", "GSM4231386", "GSM4231387", "GSM4231388", "GSM4231389", "GSM4231390", "GSM4231391", "GSM4231392", "GSM4231393", "GSM4231394", "GSM4231395"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Integrated Multi-Omics Analysis Reveals Glucose Metabolic Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE155907", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155907", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE155907", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4715485", "GSM4715486", "GSM4715487", "GSM4715488", "GSM4715489", "GSM4715490", "GSM4715491", "GSM4715492", "GSM4715493"], "sample_count": 9, "group_sizes": null, "group_sizes_basis": null, "platform": "21290", "taxon": "Homo sapiens", "title": "Super Enhancer Regulation of Cytokine-Induced Chemokine Production in Alcoholic Hepatitis [RNA-Seq]", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE28619", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE28619", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE28619", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM709348", "GSM709349", "GSM709350", "GSM709351", "GSM709352", "GSM709353", "GSM709354", "GSM709355", "GSM709356", "GSM709357", "GSM709358", "GSM709359", "GSM709360", "GSM709361", "GSM709362", "GSM709363", "GSM709364", "GSM709365", "GSM709366", "GSM709367", "GSM709368", "GSM709369"], "sample_count": 22, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Transcriptome Analysis Identifies Fn14, a TNF Superfamily Receptor Member, as a Therapeutic Target in Alcoholic Hepatitis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE97234", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97234", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE97234", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2559987", "GSM2559988", "GSM2559989", "GSM2559990", "GSM2559991", "GSM2559992", "GSM2559993", "GSM2559994", "GSM2559995", "GSM2559996"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "13112", "taxon": "Mus musculus", "title": "Pyroptosis by Caspase11/4-Gasdermin-D Pathway in Alcoholic Hepatitis", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE103580 not downloaded", "asset:data:geo:GSE103580 licence not read", "asset:data:geo:GSE142530 not downloaded", "asset:data:geo:GSE142530 licence not read", "asset:data:geo:GSE155907 not downloaded", "asset:data:geo:GSE155907 licence not read", "asset:data:geo:GSE28619 not downloaded", "asset:data:geo:GSE28619 licence not read", "asset:data:geo:GSE97234 not downloaded", "asset:data:geo:GSE97234 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "By WGCNA and LASSO-SVM analysis, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 were potential biomarkers in AH patients."}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "principal component analysis"}}, {"id": "method-3", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-5", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "hierarchical clustering"}}, {"id": "method-6", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: support_vector_machine."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE28619", "GSE103580", "GSE155907", "GSE142530", "GSE97234"], "resolved_accessions": ["GSE28619", "GSE103580", "GSE155907", "GSE142530", "GSE97234"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE28619, GSE103580, GSE155907, GSE142530, GSE97234 in Gene Expression Integrated Database (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "assets": ["source:pmid:37090703", "data:geo:GSE103580"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE103580"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:37:28Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14345, "completion_tokens": 1833, "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:37090703", "type": "paper", "label": "pmid:37090703"}, {"id": "source:pmid:37090703", "type": "manuscript", "label": "PMID 37090703 full text"}, {"id": "data:geo:GSE103580", "type": "dataset", "label": "GEO GSE103580"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37090703", "type": "paper", "label": "pmid:37090703"}, {"id": "source:pmid:37090703", "type": "manuscript", "label": "PMID 37090703 full text"}, {"id": "data:geo:GSE103580", "type": "dataset", "label": "GEO GSE103580"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37090703", "type": "extraction", "used": ["source:pmid:37090703"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE103580", "type": "accession_resolution", "used": ["data:geo:GSE103580"], "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:37090703", "parent_hash": "sha256:169d52a380266e61f77fb6b34993d7dfa34e4d45b4cb04e9e939fc392145595f", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE103580 licence not read", "asset:data:geo:GSE103580 not downloaded", "asset:data:geo:GSE142530 licence not read", "asset:data:geo:GSE142530 not downloaded", "asset:data:geo:GSE155907 licence not read", "asset:data:geo:GSE155907 not downloaded", "asset:data:geo:GSE28619 licence not read", "asset:data:geo:GSE28619 not downloaded", "asset:data:geo:GSE97234 licence not read", "asset:data:geo:GSE97234 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "machine_learning", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["train_classifier", "cross_validate", "roc_auc"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["By WGCNA and LASSO-SVM analysis, we found that ALDOA, COL3A1, LUM, THBS2 and TIMP1 were potential biomarkers in AH patients."], "order_basis": "analysis_only", "id": "assay:1"}]}