Bioinformatics reveals the potential mechanisms and biomarkers of necroptosis in neuroblastoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39145050", "kind": "science-record", "revision": 4, "content_hash": "sha256:5753ea6a2f94fe041110388850075104453d49794d9e27433c3d035b5bcd789b", "created_at": "2026-11-01T20:29:15Z", "updated_at": "2026-11-01T22:54:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics reveals the potential mechanisms and biomarkers of necroptosis in neuroblastoma.", "doi": "10.21037/tcr-24-14", "pmid": "39145050", "authors": ["Bing Gao", "Shaochun Yan", "Wei Xie", "Guo Shao"], "journal": "Translational cancer research", "year": 2024, "abstract": "Background: Neuroblastoma (NB) is a malignant tumor primarily found in children, presenting significant challenges in its development and prognosis. The role of necroptosis in the pathogenesis of NB has been acknowledged as crucial for treatment. This study aimed to investigate the key genes and functional pathways associated with necroptosis, as well as immune infiltration analysis, in NB. Furthermore, we aimed to evaluate the diagnostic significance of these genes for prognostic assessment and explore their potential immunological characteristics.\nMethods: The NB dataset (GSE19274, GSE73517, and GSE85047) was obtained from the Gene Expression Omnibus (GEO) database, and genes associated with necroptosis were collected from GeneCards and previous literature. First, we conducted differential expression analysis and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We employed gene set enrichment analysis (GSEA) to identify overlapping enriched functional pathways from the NB dataset. In addition, we constructed a protein-protein interaction (PPI) network, predicting relevant microRNAs (miRNAs) and transcription factors (TFs), as well as their corresponding drug predictions. Furthermore, the diagnostic value was assessed using receiver operating characteristic (ROC) curves. Finally, an immune infiltration analysis was performed.\nResults: We identified six necroptosis-related differentially expressed genes (NRDEGs) closely associated with necroptosis in NB. They were enriched in Tuberculosis, Apoptosis-multiple species, Salmonella infection, legionellosis, and platinum drug resistance. GSEA and PPI network analyses, along with mRNA-drug interaction network, revealed 38 potential drugs corresponding to BIRC2, CAMK2G, CASP3, and IL8. ROC curve analysis showed that in GSE19274, FLOT2 with area under the ROC curve (AUC) of 0.850 and DAPK1 with AUC of 0.789.\nConclusions: Our study elucidates the key genes and functional pathways associated with necroptosis in NB, offering valuable insights to enhance our comprehension of the pathogenesis of NB, and improve prognosis assessment.", "claims": [{"id": "claim-method", "statement": "To investigate the pathways, potential mechanisms, and biological features associated with DEGs in NB, we first performed normalization using the limma package (21) on GSE19274, GSE73517, and GSE85047 datasets, and subsequently conducted differential analysis to find the DEGs between the low-risk group and high-risk groups in the three NB datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39145050", "locator": "sections[7] \"NB-related differentially expressed genes\" paragraph 2", "quote": "To investigate the pathways, potential mechanisms, and biological features associated with DEGs in NB, we first performed normalization using the limma package (21) on GSE19274, GSE73517, and GSE85047 datasets, and subsequently conducted differential analysis to find the DEGs between the low-risk group and high-risk groups in the three NB datasets."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Six necroptosis-related differentially expressed genes were identified in neuroblastoma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39145050", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified six necroptosis-related differentially expressed genes (NRDEGs) closely associated with necroptosis in NB."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Six necroptosis-related differentially expressed genes were identified in neuroblastoma.", "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:39145050"], "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:GSE19274"], "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:GSE19274"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39145050", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tcr-24-14", "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": ["GSE19274", "GSE73517", "GSE85047"], "resolved_accessions": ["GSE19274", "GSE73517", "GSE85047"], "statements": ["The expression profile datasets GSE19274 (11), GSE73517 (12), and GSE85047 (13) of NB patients were downloaded from the GEO database (14) using the R package GEOquery (15)."], "basis": "The paper names GSE19274, GSE73517, GSE85047 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:39145050", "data:geo:GSE19274"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE19274"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:28:21Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 11477, "completion_tokens": 1522, "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:39145050", "type": "paper", "label": "pmid:39145050"}, {"id": "source:pmid:39145050", "type": "manuscript", "label": "PMID 39145050 full text"}, {"id": "data:geo:GSE19274", "type": "dataset", "label": "GEO GSE19274"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39145050", "type": "paper", "label": "pmid:39145050"}, {"id": "source:pmid:39145050", "type": "manuscript", "label": "PMID 39145050 full text"}, {"id": "data:geo:GSE19274", "type": "dataset", "label": "GEO GSE19274"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39145050", "type": "extraction", "used": ["source:pmid:39145050"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE19274", "type": "accession_resolution", "used": ["data:geo:GSE19274"], "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:39145050", "parent_hash": "sha256:154e9df530241daaf1755ea0d23187d98ca94b95501ffff93c2a1887ad74785a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE19274 licence not read", "asset:data:geo:GSE19274 not downloaded", "asset:data:geo:GSE73517 licence not read", "asset:data:geo:GSE73517 not downloaded", "asset:data:geo:GSE85047 licence not read", "asset:data:geo:GSE85047 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": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["s in NB. They were enriched in Tuberculosis, Apoptosis-multiple species, Salmonella infection, legi", "iched in KEGG pathways such as tuberculosis, apoptosis-multiple species, Salmonella infection, legi"], "order_basis": "paper_text_order:1598", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["latform GPL16876 Agilent-020382 Human Custom Microarray 44k (Feature Number version). GSE85047 consi", "he data platform being GPL5175 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) v"], "order_basis": "paper_text_order:2881", "id": "assay:2"}, {"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": ["To investigate the pathways, potential mechanisms, and biological features associated with DEGs in NB, we first performed normalization using the limma package (21) on GSE19274, GSE73517, and GSE85047 datasets, and subsequently conducted differential analysis to find the DEGs between the low-risk group and high-risk groups in the three NB datasets."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}