Ferroptosis-related gene MAPK3 is associated with the neurological outcome after cardiac arrest.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38885209", "kind": "science-record", "revision": 4, "content_hash": "sha256:3a53129fad9a0dd1b4f7e88f15d5c94c99d6caa7b25389aaa6668cb7974ff3fe", "created_at": "2026-11-01T20:28:57Z", "updated_at": "2026-11-01T22:54:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ferroptosis-related gene MAPK3 is associated with the neurological outcome after cardiac arrest.", "doi": "10.1371/journal.pone.0301647", "pmid": "38885209", "authors": ["Hong Xiang Hou", "Li Pang", "Liang Zhao", "Jihong Xing"], "journal": "PloS one", "year": 2024, "abstract": "BACKGROUND: Neuronal ferroptosis is closely related to the disease of the nervous system, and the objective of the present study was to recognize and verify the potential ferroptosis-related genes to forecast the neurological outcome after cardiac arrest.\nMETHODS: Cardiac Arrest-related microarray datasets GSE29540 and GSE92696 were downloaded from GEO and batch normalization of the expression data was performed using \"sva\" of the R package. GSE29540 was analyzed to identify DEGs. Venn diagram was applied to recognize ferroptosis-related DEGs from the DEGs. Subsequently, The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed, and PPI network was applied to screen hub genes. Receiver operating characteristic (ROC) curves were adopted to determine the predictive value of the biomarkers, and the GSE92696 dataset was applied to further evaluate the diagnostic efficacy of the biomarkers. We explore transcription factors and miRNAs associated with hub genes. The \"CIBERSORT\" package of R was utilized to analyse the proportion infiltrating immune cells. Finally, validated by a series of experiments at the cellular level.\nRESULTS: 112 overlapping ferroptosis-related DEGs were further obtained via intersecting these DEGs and ferroptosis-related genes. The GO and KEGG analysis demonstrate that ferroptosis-related DEGs are mainly involved in response to oxidative stress, ferroptosis, apoptosis, IL-17 signalling pathway, autophagy, toll-like receptor signalling pathway. The top 10 hub genes were selected, including HIF1A, MAPK3, PPARA, IL1B, PTGS2, RELA, TLR4, KEAP1, SREBF1, SIRT6. Only MAPK3 was upregulated in both GSE29540 and GAE92696. The AUC values of the MAPK3 are 0.654 and 0.850 in GSE29540 and GSE92696 respectively. The result of miRNAs associated with hub genes indicates that hsa-miR-214-3p and hsa-miR-483-5p can regulate the expression of MAPK3. MAPK3 was positively correlated with naive B cells, macrophages M0, activated dendritic cells and negatively correlated with activated CD4 memory T cells, CD8 T cells, and memory B cells. Compared to the OGD4/R24 group, the OGD4/R12 group had higher MAPK3 expression at both mRNA and protein levels and more severe ferroptosis.\nCONCLUSION: In summary, the MAPK3 ferroptosis-related gene could be used as a biomarker to predict the neurological outcome after cardiac arrest. Potential biological pathways provide novel insights into the pathogenesis of cardiac arrest.", "claims": [{"id": "claim-method", "statement": "The R package “limma” was used to screen for DEGs with a threshold of FC (fold changes) > 1 and p-value < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38885209", "locator": "sections[3] \"2.1 Data normalization and differential expression analysis\" paragraph 2", "quote": "The R package “limma” was used to screen for DEGs with a threshold of FC (fold changes) > 1 and p-value < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We downloaded the CA-related microarray datasets GSE29540 and GSE92696 from GEO (Gene Expression Omnibus), including the patients’ mRNA expression profiles and clinical information (Table 1). GSE29540 and GSE92696 serve as the training datasets and verification datasets respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38885209", "locator": "sections[20] \"4.1 Differential expression analysis and ferroptosis-related differential expression genes\" paragraph 2", "quote": "We downloaded the CA-related microarray datasets GSE29540 and GSE92696 from GEO (Gene Expression Omnibus), including the patients’ mRNA expression profiles and clinical information (Table 1). GSE29540 and GSE92696 serve as the training datasets and verification datasets respectively."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MAPK3 was the only one of the 10 hub genes upregulated in both datasets, with AUC values of 0.654 in GSE29540 and 0.850 in GSE92696.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38885209", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Only MAPK3 was upregulated in both GSE29540 and GAE92696."}, {"asset": "source:pmid:38885209", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The AUC values of the MAPK3 are 0.654 and 0.850 in GSE29540 and GSE92696 respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "MAPK3 was the only one of the 10 hub genes upregulated in both datasets, with AUC values of 0.654 in GSE29540 and 0.850 in GSE92696.", "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:38885209"], "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:GSE29540"], "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": {"fold_change": "ackage “limma”, using a fold-change threshold greater than"}, "inputs": ["data:geo:GSE29540"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38885209", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0301647", "sha256": "sha256:a2a6faabb674c35bf80185409a9f6fe9ad057520b1fc53bfc9e053199fc424ee", "bytes": 42829, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0301647", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11182507", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE29540", "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=GSE29540", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE29540", "version": null, "note": "We downloaded the CA-related microarray datasets GSE29540 and GSE92696 from GEO (Gene Expression Omnibus), including the patients’ mRNA expression profiles and clinical information (Table 1). GSE29540 and GSE92696 serve as the training datasets and verification datasets respectively.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We downloaded the CA-related microarray datasets GSE29540 and GSE92696 from GEO (Gene Expression Omnibus), including the patients’ mRNA expression profiles and clinical information (Table 1). GSE29540 and GSE92696 serve as the training datasets and verification datasets respectively.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM731311", "GSM731312", "GSM731313", "GSM731314", "GSM731315", "GSM731316", "GSM731317", "GSM731318", "GSM731319", "GSM731320", "GSM731321", "GSM731322", "GSM731323", "GSM731324", "GSM731325", "GSM731326", "GSM731327", "GSM731328", "GSM731329", "GSM731330", "GSM731331", "GSM731332", "GSM731333", "GSM731334", "GSM731335", "GSM731336", "GSM731337", "GSM731338", "GSM731339", "GSM731340", "GSM731341", "GSM731342", "GSM731343", "GSM731344", "GSM731345", "GSM731346", "GSM731347", "GSM731348", "GSM731349", "GSM731350", "GSM731351", "GSM731352", "GSM731353", "GSM731354", "GSM731355", "GSM731356", "GSM731357", "GSM731358", "GSM731359", "GSM731360", "GSM731361", "GSM731362", "GSM731363", "GSM731364", "GSM731365", "GSM731366", "GSM731367", "GSM731368", "GSM731369", "GSM731370", "GSM731371", "GSM731372", "GSM731373", "GSM731374", "GSM731375", "GSM731376", "GSM731377", "GSM731378", "GSM731379", "GSM731380", "GSM731381", "GSM731382", "GSM731383", "GSM731384", "GSM731385", "GSM731386", "GSM731387", "GSM731388", "GSM731389", "GSM731390", "GSM731391", "GSM731392", "GSM731393", "GSM731394", "GSM731395", "GSM731396", "GSM731397", "GSM731398", "GSM731399", "GSM731400", "GSM731401", "GSM731402", "GSM731403", "GSM731404", "GSM731405", "GSM731406", "GSM731407", "GSM731408", "GSM731409", "GSM731410", "GSM731411", "GSM731412", "GSM731413", "GSM731414", "GSM731415", "GSM731416", "GSM731417", "GSM731418", "GSM731419", "GSM731420", "GSM731421", "GSM731422", "GSM731423", "GSM731424", "GSM731425", "GSM731426", "GSM731427", "GSM731428", "GSM731429", "GSM731430", "GSM731431", "GSM731432", "GSM731433", "GSM731434", "GSM731435", "GSM731436", "GSM731437", "GSM731438", "GSM731439", "GSM731440", "GSM731441", "GSM731442", "GSM731443", "GSM731444", "GSM731445", "GSM731446", "GSM731447", "GSM731448", "GSM731449", "GSM731450"], "sample_count": 140, "group_sizes": null, "group_sizes_basis": null, "platform": "13218", "taxon": "Homo sapiens", "title": "Prediction of neurological outcomes shortly after cardiac arrest", "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:GSE92696", "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=GSE92696", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE92696", "version": null, "note": "We downloaded the CA-related microarray datasets GSE29540 and GSE92696 from GEO (Gene Expression Omnibus), including the patients’ mRNA expression profiles and clinical information (Table 1). GSE29540 and GSE92696 serve as the training datasets and verification datasets respectively.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We downloaded the CA-related microarray datasets GSE29540 and GSE92696 from GEO (Gene Expression Omnibus), including the patients’ mRNA expression profiles and clinical information (Table 1). GSE29540 and GSE92696 serve as the training datasets and verification datasets respectively.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2435438", "GSM2435439", "GSM2435440", "GSM2435441", "GSM2435442", "GSM2435443", "GSM2435444", "GSM2435445", "GSM2435446", "GSM2435447", "GSM2435448", "GSM2435449", "GSM2435450", "GSM2435451", "GSM2435452", "GSM2435453", "GSM2435454", "GSM2435455", "GSM2435456", "GSM2435457", "GSM2435458", "GSM2435459"], "sample_count": 22, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Identification of novel biomarkers for prediction of neurological prognosis following cardiac arrest", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE29540 not downloaded", "asset:data:geo:GSE29540 licence not read", "asset:data:geo:GSE92696 not downloaded", "asset:data:geo:GSE92696 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"fold_change": "ackage “limma”, using a fold-change threshold greater than"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The R package “limma” was used to screen for DEGs with a threshold of FC (fold changes) > 1 and p-value < 0.05."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}, {"id": "method-4", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-5", "family": "network_analysis", "specific": "centrality", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "centrality"}}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE29540", "GSE92696"], "resolved_accessions": ["GSE29540", "GSE92696"], "statements": ["We downloaded the CA-related microarray datasets GSE29540 and GSE92696 from GEO (Gene Expression Omnibus), including the patients’ mRNA expression profiles and clinical information (Table 1). GSE29540 and GSE92696 serve as the training datasets and verification datasets respectively."], "basis": "The paper names GSE29540, GSE92696 in GEO (Gene Expression Omnibus) 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:38885209", "data:geo:GSE29540"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE29540"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:21:26Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 12746, "completion_tokens": 1390, "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:38885209", "type": "paper", "label": "pmid:38885209"}, {"id": "source:pmid:38885209", "type": "manuscript", "label": "PMID 38885209 full text"}, {"id": "data:geo:GSE29540", "type": "dataset", "label": "GEO GSE29540"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38885209", "type": "paper", "label": "pmid:38885209"}, {"id": "source:pmid:38885209", "type": "manuscript", "label": "PMID 38885209 full text"}, {"id": "data:geo:GSE29540", "type": "dataset", "label": "GEO GSE29540"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38885209", "type": "extraction", "used": ["source:pmid:38885209"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE29540", "type": "accession_resolution", "used": ["data:geo:GSE29540"], "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:38885209", "parent_hash": "sha256:e5eaf728ff3afc7373c6855f181ac896496cb7e74db650024528b9cc92f01522", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE29540 licence not read", "asset:data:geo:GSE29540 not downloaded", "asset:data:geo:GSE92696 licence not read", "asset:data:geo:GSE92696 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": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["diac arrest. METHODS: Cardiac Arrest-related microarray datasets GSE29540 and GSE92696 were download"], "order_basis": "paper_text_order:340", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["n response to oxidative stress, ferroptosis, apoptosis, IL-17 signalling pathway, autophagy, toll-l"], "order_basis": "paper_text_order:1501", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["y Laboratory of Cerebrovascular Disease were cultured in high-glucose DMEM medium (Procell, Wu Han, C", "n and reperfusion Human neuroblastoma cells, SH-SY5Y, derived from human bone marrow, can differe", "notypes and express neuron-specific markers. SH-SY5Y has been widely used in the in vitro study o", "jury and other diseases [39–41]. So we chose SH-SY5Y to construct an in vitro OGD/R model. SH-SY5"], "order_basis": "paper_text_order:3485", "id": "assay:3"}, {"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": ["The R package “limma” was used to screen for DEGs with a threshold of FC (fold changes) > 1 and p-value < 0.05."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}