{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40171845", "kind": "science-record", "revision": 4, "content_hash": "sha256:e0cccb22c8253e744cb5bbd685c5aeda610f9978e8b5bf393b8a876c7b1d16e6", "created_at": "2026-11-01T20:30:21Z", "updated_at": "2026-11-01T22:56:19Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "METTL3, an Independent Adverse Prognostic Factor for AML, Promotes the Development of AML by Modulating the PGC-1α-MAPK Pathway and PGC-1α-Antioxidant System Axis.", "doi": "10.1002/cam4.70771", "pmid": "40171845", "authors": ["Yuqian Tang", "Xiaoyan Liu", "Wu Ye", "Xiaojia Wang", "Xiaoyu Wei", "Yiwen Du", "Ying Zhang", "Yuping Gong"], "journal": "Cancer medicine", "year": 2025, "abstract": "BACKGROUND: m6A represents a prevalent epigenetic modification of mammalian mRNAs. Studies have demonstrated that m6A RNA methylation-modifying enzymes play crucial roles in the onset and progression of AML. However, their clinical relevance remains undefined, and the mechanisms underlying their modulation of AML have yet to be elucidated.\nRESULTS: The expression levels of the m6A RNA-modifying enzymes METTL3, METTL14, WTAP, FTO and ALKBH5 were elevated in AML patients. METTL3-positive AML is often accompanied by DNMT3A mutations and is also an independent poor prognostic factor for AML patients. Following METTL3 knockdown, we observed a decrease in the m6A level of the mitochondrial oxidative stress gene PGC-1α in K562 and MV4-11 cells. We analyzed the expression levels of PGC-1α and METTL3 mRNA in 105 patients with primary AML. The expression levels of PGC-1α and METTL3 mRNA were positively correlated. Similar to METTL3 knockdown, PGC-1α gene knockdown resulted in increased phosphorylation of the key signaling molecules P38, c-Jun and ERK1/2 in the MAPK signaling pathway, and decreased mRNA levels of SOD1, GPX1, catalase and UCP2 in the antioxidant system of K562 cells. Analysis of the TCGA and GSE13159 datasets, along with samples from West China Hospital, revealed that patients exhibiting high PGC-1α expression had a poor prognosis.\nCONCLUSION: The m6A methylation-modifying enzyme METTL3 is an independent prognostic factor for poor prognosis in AML patients. PGC-1α is a downstream signaling molecule of METTL3, and METTL3 affects its expression by regulating the m6A level of PGC-1α. PGC-1α acts as an oncogene in AML by affecting the MAPK pathway and antioxidant system.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate Cox regression analyses were used to evaluate the effects of various factors on survival. Survival curves were plotted using the Kaplan–Meier method and compared using the log‐rank test. Additionally, FDR (False Discovery Rate) was utilized for multiple comparisons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40171845", "locator": "sections[15] \"Data Analysis\" paragraph 2", "quote": "Univariate and multivariate Cox regression analyses were used to evaluate the effects of various factors on survival. Survival curves were plotted using the Kaplan–Meier method and compared using the log‐rank test. Additionally, FDR (False Discovery Rate) was utilized for multiple comparisons."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are openly available in the TCGA at https://www.cbioportal.org and in the GEO at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13159 reference number GSE13159 [22]. The data that support the findings of this study from patient samples are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40171845", "locator": "sections[29] \"Data Availability Statement\" paragraph 2", "quote": "The data that support the findings of this study are openly available in the TCGA at https://www.cbioportal.org and in the GEO at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13159 reference number GSE13159 [22]. The data that support the findings of this study from patient samples are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Positive METTL3 was found to be an independent adverse prognostic factor for AML (HR: 5.635, 95% CI: 1.147–27.694, p = 0.033), while positive WTAP expression was not.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Positive METTL3 was found to be an independent adverse prognostic factor for AML (HR: 5.635, 95% CI: 1.147–27.694, p = 0.033), while positive WTAP expression was not."}, "evidence": [{"asset": "source:pmid:40171845", "locator": "sections[18] \"METTL3 and WTAP Indicate Poor Prognosis, With METTL3 as an Independent Prognostic Factor\" paragraph 4", "quote": "Positive METTL3 was found to be an independent adverse prognostic factor for AML (HR: 5.635, 95% CI: 1.147–27.694, p = 0.033), while positive WTAP expression was not."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Positive METTL3 was found to be an independent adverse prognostic factor for AML (HR: 5.635, 95% CI: 1.147–27.694, p = 0.033), while positive WTAP expression was not.", "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:40171845"], "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:GSE13159"], "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:GSE13159"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40171845", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/cam4.70771", "sha256": "sha256:db83304aff28cff40f6cf2c6aff2570128df816875d08a0d76816a10b5716f5c", "bytes": 56712, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/cam4.70771", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11962650", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13159", "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=GSE13159", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13159", "version": null, "note": "The data that support the findings of this study are openly available in the TCGA at https://www.cbioportal.org and in the GEO at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13159 reference number GSE13159 [22]. The data that support the findings of this study from patient samples are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings of this study are openly available in the TCGA at https://www.cbioportal.org and in the GEO at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13159 reference number GSE13159 [22]. The data that support the findings of this study from patient samples are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM329407", "GSM329408", "GSM329409", "GSM329410", "GSM329411", "GSM329412", "GSM329413", "GSM329414", "GSM329415", "GSM329416", "GSM329417", "GSM329418", "GSM329419", "GSM329420", "GSM329421", "GSM329422", "GSM329423", "GSM329424", "GSM329425", "GSM329426", "GSM329427", "GSM329428", "GSM329429", "GSM329430", "GSM329431", "GSM329432", "GSM329433", "GSM329434", "GSM329435", "GSM329436", "GSM329437", "GSM329438", "GSM329439", "GSM329440", "GSM329441", "GSM329442", "GSM329443", "GSM329444", "GSM329445", "GSM329446", "GSM329447", "GSM329448", "GSM329449", "GSM329450", "GSM329451", "GSM329452", "GSM329453", "GSM329454", "GSM329455", "GSM329456", "GSM329457", "GSM329458", "GSM329459", "GSM329460", "GSM329461", "GSM329462", "GSM329463", "GSM329464", "GSM329465", "GSM329466", 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"GSM330307", "GSM330308", "GSM330309", "GSM330310", "GSM330317", "GSM330318", "GSM330319", "GSM330320", "GSM330321", "GSM330322", "GSM330323", "GSM330324", "GSM330325", "GSM330326", "GSM330327", "GSM330328", "GSM330329", "GSM330330", "GSM330331", "GSM330332", "GSM330333", "GSM330334", "GSM330335", "GSM330336", "GSM330337", "GSM330338", "GSM330339", "GSM330340", "GSM330341", "GSM330342", "GSM330343", "GSM330344", "GSM330345", "GSM330346", "GSM330347", "GSM330348", "GSM330349", "GSM330350", "GSM330351", "GSM330352", "GSM330353", "GSM330354", "GSM330355", "GSM330356", "GSM330357", "GSM330358", "GSM330359", "GSM330360", "GSM330361", "GSM330362", "GSM330363", "GSM330364", "GSM330365", "GSM330366", "GSM330367", "GSM330368", "GSM330369", "GSM330370", "GSM330371", "GSM330372", "GSM330373", "GSM330374", "GSM330375", "GSM330376", "GSM330377", "GSM330378", "GSM330379", "GSM330380", "GSM330381", "GSM330382", "GSM330383", "GSM330384", "GSM330385", "GSM330386", "GSM330387", "GSM330388", "GSM330389", "GSM330390", "GSM330391", "GSM330392", "GSM330393", "GSM330394", "GSM330395", "GSM330396", "GSM330397", "GSM330398", "GSM330399", "GSM330400", "GSM330401", "GSM330402", "GSM330403", "GSM330404", "GSM330405", "GSM330406", "GSM330407", "GSM330408", "GSM330409", "GSM330410", "GSM330411", "GSM330412", "GSM330413", "GSM330414", "GSM330415", "GSM330416", "GSM330417", "GSM330418", "GSM330419", "GSM330420", "GSM330421", "GSM330422", "GSM330423", "GSM330424", "GSM330425", "GSM330426", "GSM330427", "GSM330428", "GSM330429", "GSM330430", "GSM330431", "GSM330432", "GSM330433", "GSM330434", "GSM330435", "GSM330436", "GSM330437", "GSM330438", "GSM330439", "GSM330440", "GSM330441", "GSM330442", "GSM330443", "GSM330444", "GSM330445", "GSM330446", "GSM330447", "GSM330448", "GSM330449", "GSM330450", "GSM330451", "GSM330452", "GSM330453", "GSM330454", "GSM330455", "GSM330456", "GSM330457", "GSM330458", "GSM330459", "GSM330460", "GSM330461", "GSM330462", "GSM330463", "GSM330464", "GSM330465", "GSM330466", "GSM330467", "GSM330468", "GSM330469", "GSM330470", "GSM330471", "GSM330472", "GSM330473", "GSM330474", "GSM330475", "GSM330476", "GSM330477", "GSM330478", "GSM330479", "GSM330480", "GSM330481", "GSM330482", "GSM330483", "GSM330484", "GSM330485", "GSM330486", "GSM330487", "GSM330488", "GSM330489", "GSM330490", "GSM330491", "GSM330492", "GSM330493", "GSM330494", "GSM330495", "GSM330496", "GSM330497", "GSM330498", "GSM330499", "GSM330500", "GSM330501", "GSM330502", "GSM330503", "GSM330504", "GSM330505", "GSM330506", "GSM330507", "GSM330508", "GSM330509", "GSM330510", "GSM330511", "GSM330512", "GSM330513", "GSM330514", "GSM330515", "GSM330516", "GSM330517", "GSM330518", "GSM330519", "GSM330520", "GSM330521", "GSM330522", "GSM330523", "GSM330524", "GSM330525", "GSM330526", "GSM330527", "GSM330528", "GSM330529", "GSM330530", "GSM330531", "GSM330532", "GSM330533", "GSM330534", "GSM330535", "GSM330536", "GSM330537", "GSM330538", "GSM330539", "GSM330540", "GSM330541", "GSM330542", "GSM330543", "GSM330544", "GSM330545", "GSM330546", "GSM330547", "GSM330548", "GSM330549", "GSM330550", "GSM330551", "GSM330552", "GSM330553", "GSM330554", "GSM330555", "GSM330556", "GSM330557", "GSM330558", "GSM330559", "GSM330560", "GSM330561", "GSM330562", "GSM330563", "GSM330564", "GSM330565", "GSM330566", "GSM330567", "GSM330568", "GSM330569", "GSM330570", "GSM330571", "GSM330572", "GSM330573", "GSM330574", "GSM330575", "GSM330576", "GSM330577", "GSM330578", "GSM330579", "GSM330580", "GSM330581", "GSM330582", "GSM330583", "GSM330584", "GSM330585", "GSM330586", "GSM330587", "GSM330588", "GSM330589", "GSM330590", "GSM330591", "GSM330592", "GSM330593", "GSM330594", "GSM330595", "GSM330596", "GSM330597", "GSM330598", "GSM330599", "GSM330600", "GSM330601", "GSM330602", "GSM330603", "GSM330604", "GSM330605", "GSM330606", "GSM330607", "GSM330608", "GSM330609", "GSM330610", "GSM330611", "GSM330612", "GSM330613", "GSM330614", "GSM330615", "GSM330616", "GSM330617", "GSM330618", "GSM330619", "GSM330620", "GSM330621", "GSM330622", "GSM330623", "GSM330624", "GSM330625", "GSM330626", "GSM330627", "GSM330628", "GSM330629", "GSM330630", "GSM330631", "GSM330632", "GSM330633", "GSM330634", "GSM330635", "GSM330636", "GSM330637", "GSM330638", "GSM330639", "GSM330640", "GSM330641", "GSM330642", "GSM330643", "GSM330644", "GSM330645", "GSM330646", "GSM330647", "GSM330648", "GSM330649", "GSM330650", "GSM330651", "GSM330652", "GSM330653", "GSM330654", "GSM330655", "GSM330656", "GSM330657", "GSM330658", "GSM330659", "GSM330660", "GSM330661", "GSM330662", "GSM330663", "GSM330664", "GSM330665", "GSM330666", "GSM330667", "GSM330668", "GSM330669", "GSM330670", "GSM330671", "GSM330672", "GSM330673", "GSM330674", "GSM330675", "GSM330676", "GSM330677", "GSM330678", "GSM330679", "GSM330680", "GSM330681", "GSM330682", "GSM330683", "GSM330684", "GSM330685", "GSM330686", "GSM330687", "GSM330688", "GSM330689", "GSM330690", "GSM330691", "GSM330692", "GSM330693", "GSM330694", "GSM330695", "GSM330696", "GSM330697", "GSM330698", "GSM330699", "GSM330700", "GSM330701", "GSM330702", "GSM330703", "GSM330704", "GSM330705", "GSM330706", "GSM330707", "GSM330708", "GSM330709", "GSM330710", "GSM330711", "GSM330712", "GSM330713", "GSM330714", "GSM330715", "GSM330716", "GSM330717", "GSM330718", "GSM330719", "GSM330720", "GSM330721", "GSM330722", "GSM330723", "GSM330724", "GSM330725", "GSM330726", "GSM330727", "GSM330728", "GSM330729", "GSM330730", "GSM330731", "GSM330732", "GSM330733", "GSM330734", "GSM330735", "GSM330736", "GSM330737", "GSM330738", "GSM330739", "GSM330740", "GSM330741", "GSM330742", "GSM330743", "GSM330744", "GSM330745", "GSM330746", "GSM330747", "GSM330748", "GSM330749", "GSM330750", "GSM330751", "GSM330752", "GSM330753", "GSM330754", "GSM330755", "GSM330756", "GSM330757", "GSM330758", "GSM330759", "GSM330760", "GSM330761", "GSM330762", "GSM330763", "GSM330764", "GSM330765", "GSM330766", "GSM330767", "GSM330768", "GSM330769", "GSM330770", "GSM330771", "GSM330772", "GSM330773", "GSM330774", "GSM330775", "GSM330776", "GSM330777", "GSM330778", "GSM330779", "GSM330780", "GSM330781", "GSM330782", "GSM330783", "GSM330784", "GSM330785", "GSM330786", "GSM330787", "GSM330788", "GSM330789", "GSM330790", "GSM330791", "GSM330792", "GSM330793", "GSM330794", "GSM330795", "GSM330796", "GSM330797", "GSM330798", "GSM330799", "GSM330800", "GSM330801", "GSM330802", "GSM330803", "GSM330804", "GSM330805", "GSM330806", "GSM330807", "GSM330808", "GSM330809", "GSM330810", "GSM330811", "GSM330812", "GSM330813", "GSM330814", "GSM330815", "GSM330816", "GSM330817", "GSM330818", "GSM330819", "GSM330820", "GSM330821", "GSM330822", "GSM330823", "GSM330824", "GSM330825", "GSM330826", "GSM330827", "GSM330828", "GSM330829", "GSM330830", "GSM330831", "GSM330832", "GSM330833", "GSM330834", "GSM330835", "GSM330836", "GSM330837", "GSM330838", "GSM330839", "GSM330840", "GSM330841", "GSM330842", "GSM330843", "GSM330844", "GSM330845", "GSM330846", "GSM330847", "GSM330848", "GSM330849", "GSM330850", "GSM330851", "GSM330852", "GSM330853", "GSM330854", "GSM330855", "GSM330856", "GSM330857", "GSM330858", "GSM330859", "GSM330860", "GSM330861", "GSM330862", "GSM330863", "GSM330864", "GSM330865", "GSM330866", "GSM330867", "GSM330868", "GSM330869", "GSM330870", "GSM330871", "GSM330872", "GSM330873", "GSM330874", "GSM330875", "GSM330876", "GSM330877", "GSM330878", "GSM330879", "GSM330880", "GSM330881", "GSM330882", "GSM330883", "GSM330884", "GSM330885", "GSM330886", "GSM330887", "GSM330888", "GSM330889", "GSM330890", "GSM330891", "GSM330892", "GSM330893", "GSM330894", "GSM330895", "GSM330896", "GSM330897", "GSM330898", "GSM330899", "GSM330900", "GSM330901", "GSM330902", "GSM330903", "GSM330904", "GSM330905", "GSM330906", "GSM330907", "GSM330908", "GSM330909", "GSM330910", "GSM330911", "GSM330912", "GSM330913", "GSM330914", "GSM330915", "GSM330916", "GSM330917", "GSM330918", "GSM330919", "GSM330920", "GSM330921", "GSM330922", "GSM330923", "GSM330924", "GSM330925", "GSM330926", "GSM330927", "GSM330928", "GSM330929", "GSM330930", "GSM330931", "GSM330932", "GSM330933", "GSM330934", "GSM330935", "GSM330936", "GSM330937", "GSM330938", "GSM330939", "GSM330940", "GSM330941", "GSM330942", "GSM330943", "GSM330944", "GSM330945", "GSM330946", "GSM330947", "GSM330948", "GSM330949", "GSM330950", "GSM330951", "GSM330952", "GSM330953", "GSM330954", "GSM330955", "GSM330956", "GSM330957", "GSM330958", "GSM330959", "GSM330960", "GSM330961", "GSM330962", "GSM330963", "GSM330964", "GSM330965", "GSM330966", "GSM330967", "GSM330968", "GSM330969", "GSM330970", "GSM330971", "GSM330972", "GSM330973", "GSM330974", "GSM330975", "GSM330976", "GSM330977", "GSM330978", "GSM330979", "GSM330980", "GSM330981", "GSM330982", "GSM330983", "GSM330984", "GSM330985", "GSM330986", "GSM330987", "GSM330988", "GSM330989", "GSM330990", "GSM330991", "GSM330992", "GSM330993", "GSM330994", "GSM330995", "GSM330996", "GSM330997", "GSM330998", "GSM330999", "GSM331000", "GSM331001", "GSM331002", "GSM331003", "GSM331004", "GSM331005", "GSM331006", "GSM331007", "GSM331008", "GSM331009", "GSM331010", "GSM331011", "GSM331012", "GSM331013", "GSM331014", "GSM331015", "GSM331016", "GSM331017", "GSM331018", "GSM331019", "GSM331020", "GSM331021", "GSM331022", "GSM331023", "GSM331024", "GSM331025", "GSM331026", "GSM331027", "GSM331028", "GSM331029", "GSM331030", "GSM331031", "GSM331032", "GSM331033", "GSM331034", "GSM331035", "GSM331036", "GSM331037", "GSM331038", "GSM331039", "GSM331040", "GSM331041", "GSM331042", "GSM331043", "GSM331044", "GSM331045", "GSM331046", "GSM331047", "GSM331048", "GSM331049", "GSM331050", "GSM331051", "GSM331052", "GSM331053", "GSM331054", "GSM331055", "GSM331056", "GSM331057", "GSM331058", "GSM331059", "GSM331060", "GSM331061", "GSM331062", "GSM331063", "GSM331064", "GSM331065", "GSM331066", "GSM331067", "GSM331068", "GSM331069", "GSM331070", "GSM331071", "GSM331072", "GSM331073", "GSM331074", "GSM331075", "GSM331076", "GSM331077", "GSM331078", "GSM331079", "GSM331080", "GSM331081", "GSM331082", "GSM331083", "GSM331084", "GSM331085", "GSM331086", "GSM331087", "GSM331088", "GSM331089", "GSM331090", "GSM331091", "GSM331092", "GSM331093", "GSM331094", "GSM331095", "GSM331096", "GSM331097", "GSM331098", "GSM331099", "GSM331100", "GSM331101", "GSM331102", "GSM331103", "GSM331104", "GSM331105", "GSM331106", "GSM331107", "GSM331108", "GSM331109", "GSM331110", "GSM331111", "GSM331112", "GSM331113", "GSM331114", "GSM331115", "GSM331116", "GSM331117", "GSM331118", "GSM331119", "GSM331120", "GSM331121", "GSM331122", "GSM331123", "GSM331124", "GSM331125", "GSM331126", "GSM331127", "GSM331128", "GSM331129", "GSM331130", "GSM331131", "GSM331132", "GSM331133", "GSM331134", "GSM331135", "GSM331136", "GSM331137", "GSM331138", "GSM331139", "GSM331140", "GSM331141", "GSM331142", "GSM331143", "GSM331144", "GSM331145", "GSM331146", "GSM331147", "GSM331148", "GSM331149", "GSM331150", "GSM331151", "GSM331152", "GSM331153", "GSM331154", "GSM331155", "GSM331156", "GSM331157", "GSM331158", "GSM331159", "GSM331160", "GSM331161", "GSM331162", "GSM331163", "GSM331164", "GSM331165", "GSM331166", "GSM331167", "GSM331168", "GSM331169", "GSM331170", "GSM331171", "GSM331172", "GSM331173", "GSM331174", "GSM331175", "GSM331176", "GSM331177", "GSM331178", "GSM331179", "GSM331180", "GSM331181", "GSM331182", "GSM331183", "GSM331184", "GSM331185", "GSM331186", "GSM331187", "GSM331188", "GSM331189", "GSM331190", "GSM331191", "GSM331192", "GSM331193", "GSM331194", "GSM331195", "GSM331196", "GSM331197", "GSM331198", "GSM331199", "GSM331200", "GSM331201", "GSM331202", "GSM331203", "GSM331204", "GSM331205", "GSM331206", "GSM331207", "GSM331208", "GSM331209", "GSM331210", "GSM331211", "GSM331212", "GSM331213", "GSM331214", "GSM331215", "GSM331216", "GSM331217", "GSM331218", "GSM331219", "GSM331220", "GSM331221", "GSM331222", "GSM331223", "GSM331224", "GSM331225", "GSM331226", "GSM331227", "GSM331228", "GSM331229", "GSM331230", "GSM331231", "GSM331232", "GSM331233", "GSM331234", "GSM331235", "GSM331236", "GSM331237", "GSM331238", "GSM331239", "GSM331240", "GSM331241", "GSM331242", "GSM331243", "GSM331244", "GSM331245", "GSM331246", "GSM331247", "GSM331248", "GSM331249", "GSM331250", "GSM331251", "GSM331252", "GSM331253", "GSM331254", "GSM331255", "GSM331256", "GSM331257", "GSM331258", "GSM331259", "GSM331260", "GSM331261", "GSM331262", "GSM331263", "GSM331264", "GSM331265", "GSM331266", "GSM331267", "GSM331268", "GSM331269", "GSM331270", "GSM331271", "GSM331272", "GSM331273", "GSM331274", "GSM331275", "GSM331276", "GSM331277", "GSM331278", "GSM331279", "GSM331280", "GSM331281", "GSM331282", "GSM331283", "GSM331284", "GSM331285", "GSM331286", "GSM331287", "GSM331288", "GSM331289", "GSM331290", "GSM331291", "GSM331292", "GSM331293", "GSM331294", "GSM331295", "GSM331296", "GSM331297", "GSM331298", "GSM331299", "GSM331300", "GSM331301", "GSM331302", "GSM331303", "GSM331304", "GSM331305", "GSM331306", "GSM331307", "GSM331308", "GSM331309", "GSM331310", "GSM331311", "GSM331312", "GSM331313", "GSM331314", "GSM331315", "GSM331316", "GSM331317", "GSM331318", "GSM331319", "GSM331320", "GSM331321", "GSM331322", "GSM331323", "GSM331324", "GSM331325", "GSM331326", "GSM331327", "GSM331328", "GSM331329", "GSM331330", "GSM331331", "GSM331332", "GSM331333", "GSM331334", "GSM331335", "GSM331336", "GSM331337", "GSM331338", "GSM331339", "GSM331340", "GSM331341", "GSM331342", "GSM331343", "GSM331344", "GSM331345", "GSM331346", "GSM331347", "GSM331348", "GSM331349", "GSM331350", "GSM331351", "GSM331352", "GSM331353", "GSM331354", "GSM331355", "GSM331356", "GSM331357", "GSM331358", "GSM331359", "GSM331360", "GSM331361", "GSM331362", "GSM331363", "GSM331364", "GSM331365", "GSM331366", "GSM331367", "GSM331368", "GSM331369", "GSM331370", "GSM331371", "GSM331372", "GSM331373", "GSM331374", "GSM331375", "GSM331376", "GSM331377", "GSM331378", "GSM331379", "GSM331380", "GSM331381", "GSM331382", "GSM331383", "GSM331384", "GSM331385", "GSM331386", "GSM331387", "GSM331388", "GSM331389", "GSM331390", "GSM331391", "GSM331392", "GSM331393", "GSM331394", "GSM331395", "GSM331396", "GSM331397", "GSM331398", "GSM331399", "GSM331400", "GSM331401", "GSM331402", "GSM331403", "GSM331404", "GSM331405", "GSM331406", "GSM331407", "GSM331408", "GSM331409", "GSM331410", "GSM331411", "GSM331412", "GSM331413", "GSM331414", "GSM331415", "GSM331416", "GSM331417", "GSM331418", "GSM331419", "GSM331420", "GSM331421", "GSM331422", "GSM331423", "GSM331424", "GSM331425", "GSM331426", "GSM331427", "GSM331428", "GSM331429", "GSM331430", "GSM331431", "GSM331432", "GSM331433", "GSM331434", "GSM331435", "GSM331436", "GSM331437", "GSM331438", "GSM331439", "GSM331440", "GSM331441", "GSM331442", "GSM331443", "GSM331444", "GSM331445", "GSM331446", "GSM331447", "GSM331448", "GSM331449", "GSM331450", "GSM331451", "GSM331452", "GSM331453", "GSM331454", "GSM331455", "GSM331456", "GSM331457", "GSM331458", "GSM331459", "GSM331460", "GSM331461", "GSM331462", "GSM331463", "GSM331464", "GSM331465", "GSM331466", "GSM331467", 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"resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE13159 not downloaded", "asset:data:geo:GSE13159 licence not read", "asset:data:geo:GSE282987 not downloaded", "asset:data:geo:GSE282987 licence not read", "asset:data:geo:GSE76009 not downloaded", "asset:data:geo:GSE76009 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate and multivariate Cox regression analyses were used to evaluate the effects of various factors on survival. Survival curves were plotted using the Kaplan–Meier method and compared using the log‐rank test. Additionally, FDR (False Discovery Rate) was utilized for multiple comparisons."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.033, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE13159", "GSE282987", "GSE76009"], "resolved_accessions": ["GSE13159", "GSE282987", "GSE76009"], "statements": ["The data that support the findings of this study are openly available in the TCGA at https://www.cbioportal.org and in the GEO at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13159 reference number GSE13159 [22]. The data that support the findings of this study from patient samples are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE13159, GSE282987, GSE76009 in GEO 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:40171845", "data:geo:GSE13159"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13159"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:49:41Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17564, "completion_tokens": 2595, "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:40171845", "type": "paper", "label": "pmid:40171845"}, {"id": "source:pmid:40171845", "type": "manuscript", "label": "PMID 40171845 full text"}, {"id": "data:geo:GSE13159", "type": "dataset", "label": "GEO GSE13159"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40171845", "type": "paper", "label": "pmid:40171845"}, {"id": "source:pmid:40171845", "type": "manuscript", "label": "PMID 40171845 full text"}, {"id": "data:geo:GSE13159", "type": "dataset", "label": "GEO GSE13159"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40171845", "type": "extraction", "used": ["source:pmid:40171845"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13159", "type": "accession_resolution", "used": ["data:geo:GSE13159"], "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:40171845", "parent_hash": "sha256:01f9453e1fe2e23de673d34d1b1df7ef939a418f8f4fcb4f17964531a7efb1a2", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE13159 licence not read", "asset:data:geo:GSE13159 not downloaded", "asset:data:geo:GSE282987 licence not read", "asset:data:geo:GSE282987 not downloaded", "asset:data:geo:GSE76009 licence not read", "asset:data:geo:GSE76009 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ic factor for AML patients. Following METTL3 knockdown, we observed a decrease in the m6A level of", "ere positively correlated. Similar to METTL3 knockdown, PGC-1α gene knockdown resulted in increased", "ed. Similar to METTL3 knockdown, PGC-1α gene knockdown resulted in increased phosphorylation of the"], "order_basis": "paper_text_order:740", "id": "assay:1"}, {"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": ["itochondrial oxidative stress gene PGC-1α in K562 and MV4-11 cells. We analyzed the expression", "talase and UCP2 in the antioxidant system of K562 cells. Analysis of the TCGA and GSE13159 dat", "n DMEM medium supplemented with 10% FBS. All cell lines were maintained at 37°C in a humidified atmosphere with 5% C", "tology, West China Hospital. K562 cells were cultured in RPMI 1640 medium supplemented with 10% FBS;"], "order_basis": "paper_text_order:844", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["AML patients (n = 112); (B) A representative Western blot (WB) image demonstrating the expression of m", "China Hospital (n = 108); (D) Representative Western Blot analysis showing PGC‐1α protein expression;"], "order_basis": "paper_text_order:3802", "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 and multivariate Cox regression analyses were used to evaluate the effects of various factors on survival. Survival curves were plotted using the Kaplan–Meier method and compared using the log‐rank test. Additionally, FDR (False Discovery Rate) was utilized for multiple comparisons."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T02:11:59+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}