Prognostic signature and therapeutic drug identification for dilated cardiomyopathy based on necroptosis via bioinformatics and experimental validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39747333", "kind": "science-record", "revision": 3, "content_hash": "sha256:5c636d18fdca506d0b6365238e89892720bc48abcca1ac7867c213a60f3d2108", "created_at": "2026-11-01T20:30:04Z", "updated_at": "2026-11-01T22:13:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic signature and therapeutic drug identification for dilated cardiomyopathy based on necroptosis via bioinformatics and experimental validation.", "doi": "10.1038/s41598-024-83455-8", "pmid": "39747333", "authors": ["Han Yang", "Zhenwei Wang", "Yawei Xu", "Yimei Du", "Haibo Yang", "Yang Lu"], "journal": "Scientific reports", "year": 2025, "abstract": "Necroptosis, a type of programmed cell death, has been increasingly linked to cardiovascular disease development, yet its role in dilated cardiomyopathy (DCM) remains unclear. In this study, we analyzed the GSE5406 dataset from the GEO database to explore necroptosis-related prognostic signatures in DCM using LASSO regression. We identified five necroptosis-related genes (BID, CAMK2B, GLUL, HSP90AB1, CHMP5) that define a necroptosis-related signature with strong predictive value, evidenced by ROC curve areas of 0.852 and 0.957 in training and test sets, respectively. Our analyses, including GO and GSEA enrichment, focused on pathways associated with high necroptosis-related scores (NRS) and revealed significant immune cell infiltration. Notably, nTreg and iTreg cells were enriched in the high NRS group, while CD8 naive T cells and CD8 T cells positively correlated with NRS. Small molecule drugs fenofibrate, procyclidine, and tienilic acid emerged as potential therapeutic agents for high-risk patients, with fenofibrate showing efficacy in inhibiting DCM progression in an inflammatory animal model. These findings underscore the clinical relevance of necroptosis-related genes in assessing DCM progression and prognosis and highlight their potential for targeted therapeutic development.", "claims": [{"id": "claim-method", "statement": "In this study, we analyzed the GSE5406 dataset from the GEO database to explore necroptosis-related prognostic signatures in DCM using LASSO regression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39747333", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In this study, we analyzed the GSE5406 dataset from the GEO database to explore necroptosis-related prognostic signatures in DCM using LASSO regression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset supporting the conclusions of this article are available in the GEO repository [GSE5406].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39747333", "locator": "sections[35] \"notes\" paragraph 1", "quote": "The dataset supporting the conclusions of this article are available in the GEO repository [GSE5406]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified five necroptosis-related genes (BID, CAMK2B, GLUL, HSP90AB1, CHMP5) that define a necroptosis-related signature with strong predictive value, evidenced by ROC curve areas of 0.852 and 0.957 in training and test sets, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39747333", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified five necroptosis-related genes (BID, CAMK2B, GLUL, HSP90AB1, CHMP5) that define a necroptosis-related signature with strong predictive value, evidenced by ROC curve areas of 0.852 and 0.957 in training and test sets, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We identified five necroptosis-related genes (BID, CAMK2B, GLUL, HSP90AB1, CHMP5) that define a necroptosis-related signature with strong predictive value, evidenced by ROC curve areas of 0.852 and 0.957 in training and test sets, respectively.", "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:39747333"], "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:GSE5406"], "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:GSE5406"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39747333", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-024-83455-8", "sha256": "sha256:a222d8ea45846cd9968e1d3a4b2d9537c794341fd3858e62fcb58fdf63eca5bc", "bytes": 38764, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-024-83455-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11696111", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE5406", "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=GSE5406", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE5406", "version": null, "note": "The dataset supporting the conclusions of this article are available in the GEO repository [GSE5406].", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The dataset supporting the conclusions of this article are available in the GEO repository [GSE5406].", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM123518", "GSM123519", "GSM123520", "GSM123521", "GSM123522", "GSM123523", "GSM123524", "GSM123525", "GSM123526", "GSM123527", "GSM123528", "GSM123529", "GSM123530", "GSM123531", "GSM123532", "GSM123533", "GSM123534", "GSM123535", "GSM123536", "GSM123537", "GSM123538", "GSM123539", "GSM123540", "GSM123541", "GSM123542", "GSM123543", "GSM123544", "GSM123545", "GSM123546", "GSM123547", "GSM123548", "GSM123549", "GSM123550", "GSM123551", "GSM123552", "GSM123553", "GSM123554", "GSM123555", "GSM123556", "GSM123557", "GSM123558", "GSM123559", "GSM123560", "GSM123561", "GSM123562", "GSM123563", "GSM123564", "GSM123565", "GSM123566", "GSM123567", "GSM123568", "GSM123569", "GSM123570", "GSM123571", "GSM123572", "GSM123573", "GSM123574", "GSM123575", "GSM123576", "GSM123577", "GSM123578", "GSM123579", "GSM123580", "GSM123581", "GSM123582", "GSM123583", "GSM123584", "GSM123585", "GSM123586", "GSM123587", "GSM123588", "GSM123589", "GSM123590", "GSM123591", "GSM123592", "GSM123593", "GSM123594", "GSM123595", "GSM123596", "GSM123597", "GSM123598", "GSM123599", "GSM123600", "GSM123601", "GSM123602", "GSM123603", "GSM123604", "GSM123605", "GSM123606", "GSM123607", "GSM123608", "GSM123609", "GSM123610", "GSM123611", "GSM123612", "GSM123613", "GSM123614", "GSM123615", "GSM123616", "GSM123617", "GSM123618", "GSM123619", "GSM123620", "GSM123621", "GSM123622", "GSM123623", "GSM123624", "GSM123625", "GSM123626", "GSM123627", "GSM123628", "GSM123629", "GSM123630", "GSM123631", "GSM123632", "GSM123633", "GSM123634", "GSM123635", "GSM123636", "GSM123637", "GSM123638", "GSM123639", "GSM123640", "GSM123641", "GSM123642", "GSM123643", "GSM123644", "GSM123645", "GSM123646", "GSM123647", "GSM123648", "GSM123649", "GSM123650", "GSM123651", "GSM123652", "GSM123653", "GSM123654", "GSM123655", "GSM123656", "GSM123657", "GSM123658", "GSM123659", "GSM123660", "GSM123661", "GSM123662", "GSM123663", "GSM123664", "GSM123665", "GSM123666", "GSM123667", "GSM123668", "GSM123669", "GSM123670", "GSM123671", "GSM123672", "GSM123673", "GSM123674", "GSM123675", "GSM123676", "GSM123677", "GSM123678", "GSM123679", "GSM123680", "GSM123681", "GSM123682", "GSM123683", "GSM123684", "GSM123685", "GSM123686", "GSM123687", "GSM123688", "GSM123689", "GSM123690", "GSM123691", "GSM123692", "GSM123693", "GSM123694", "GSM123695", "GSM123696", "GSM123697", "GSM123698", "GSM123699", "GSM123700", "GSM123701", "GSM123702", "GSM123703", "GSM123704", "GSM123705", "GSM123706", "GSM123707", "GSM123708", "GSM123709", "GSM123710", "GSM123711", "GSM123712", "GSM123713", "GSM123714", "GSM123715", "GSM123716", "GSM123717", "GSM123718", "GSM123719", "GSM123720", "GSM123721", "GSM123722", "GSM123723", "GSM123724", "GSM123725", "GSM123726", "GSM123727"], "sample_count": 210, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Human ischemic cardiomyopathy, idiopathic cardiomyopathy, and nonfailing controls", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE5406 not downloaded", "asset:data:geo:GSE5406 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-2", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.7, "band": "medium", "quote": "ROC curve"}}, {"id": "method-3", "family": "model_calibration", "specific": "decision_curve", "label": "Model calibration / clinical utility", "dsl_operations": ["calibration_bins", "net_benefit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictions_and_outcomes"], "evidence": {"score": 0.8, "band": "high", "quote": "Decision curve analysis"}}, {"id": "method-4", "family": null, "specific": null, "label": "LASSO regression", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "In this study, we analyzed the GSE5406 dataset from the GEO database to explore necroptosis-related prognostic signatures in DCM using LASSO regression."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": ["GSE5406"], "resolved_accessions": ["GSE5406"], "statements": ["The dataset supporting the conclusions of this article are available in the GEO repository [GSE5406]."], "basis": "The paper names GSE5406 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:39747333", "data:geo:GSE5406"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE5406"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:44:00Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10737, "completion_tokens": 1432, "cached_tokens": 128}}, "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:39747333", "type": "paper", "label": "pmid:39747333"}, {"id": "source:pmid:39747333", "type": "manuscript", "label": "PMID 39747333 full text"}, {"id": "data:geo:GSE5406", "type": "dataset", "label": "GEO GSE5406"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39747333", "type": "paper", "label": "pmid:39747333"}, {"id": "source:pmid:39747333", "type": "manuscript", "label": "PMID 39747333 full text"}, {"id": "data:geo:GSE5406", "type": "dataset", "label": "GEO GSE5406"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39747333", "type": "extraction", "used": ["source:pmid:39747333"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE5406", "type": "accession_resolution", "used": ["data:geo:GSE5406"], "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:39747333", "parent_hash": "sha256:8a59d77d5b02b123d1d0107118eee738930d9b6b50eb432e6758cd5c7005efb7", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE5406 licence not read", "asset:data:geo:GSE5406 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": ["for the Care and Use of Laboratory Animals. Mice were randomly divided into three groups: control", "fibrate group. For the control group, BALB/c mice were not administrated with anything. The other t", "rated with anything. The other two groups of mice were injected with α-myosin heavy chain at days 0", "rate (30 mg/kg per mouse), respectively. All mice were anesthetized with 2% pentobarbital and eutha"], "order_basis": "paper_text_order:3024", "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": 0.99, "evidence": ["ial necroptosis-related genes in DCM mice by RT-qPCR and found that the expression of Ripk1, Ripk", "necroptosis-related genes in DCM mice by RT-qPCR and found that the expression of Ripk1, Ripk"], "order_basis": "paper_text_order:6106", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["ANOVA"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}