{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40855347", "kind": "science-record", "revision": 2, "content_hash": "sha256:bb9dd4ccb63a94010d1249056ec4ec357c99ac86b9f59560664305f5ac74dc14", "created_at": "2026-11-01T20:30:57Z", "updated_at": "2026-11-01T21:35:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Potential novel diagnostic biomarkers of atrial fibrillation: four ferroptosis-related genes linking immune infiltration.", "doi": "10.1186/s40001-025-03092-3", "pmid": "40855347", "authors": ["Yao-Zong Guan", "Huai Wang", "Huan-Jie Huang", "Dong-Yan Liang", "Xiu-Yuan Liang", "De-Sheng Lu", "Hao Liu"], "journal": "European journal of medical research", "year": 2025, "abstract": "BACKGROUND: Atrial fibrillation (AF) is a common atrial arrhythmia in clinic, regulated by the immune system and associated with ferroptosis. We hypothesized that combining the analysis of ferroptosis and immune infiltration in AF will help identify more precise diagnostic biomarkers.\nMETHODS: We analyzed two gene expression omnibus (GEO) data sets (GSE41177 and GSE122188) and extracted characteristic ferroptosis-related genes related to sinus rhythm and AF via bioinformatic analysis. CIBERSORT was used to identify ferroptosis/immune-related genes (FIRGs) in AF. LASSO model analysis was used to identify novel FIRGs. The GSE79768 data set and qRT-PCR were used to validate the FIRGs. ROC curves were then drawn to evaluate the diagnostic power of the FIRGs, and GSEA was used to detect the pathways enriched with the validated FIRGs.\nRESULTS: A total of eight FIRGs were identified between the healthy and AF groups through LASSO model analysis. Four FIRGs (ALOX15, SNX5, CA9, and PROK2) were subsequently validated as novel FIRGs with high diagnostic power for AF (AUC = 0.851-0.911). They were enriched mainly in cytokine-cytokine receptor interactions, ascorbate and aldarate metabolism, the nod-like receptor signaling pathway, and the intestinal immune network for IgA production. In addition, ceRNA networks (mRNA-miRNA-lncRNA) such as SNX5-hsa-miR-185-3p-LINC01165 and PROK2-hsa-miR-125b-2-3p-RP11-333E1.2 were constructed. Candidate drugs, such as linoleic acid, which is targeted by ALOX15, and sulfamide, targeted by CA9, were also identified.\nCONCLUSIONS: Our findings reveal the significant ferroptosis/immune-related genes and the potential pathways and biofunctions enriched with these genes in AF and provide new insights for the diagnosis and interference of AF.", "claims": [{"id": "claim-method", "statement": "A total of 138 genes intersecting ferroptosis-related genes and 782 immune-related genes were utilized for LASSO regression analysis (Fig. 4a).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40855347", "locator": "sections[16] \"Further screening of characteristic genes with LASSO regression\" paragraph 2", "quote": "A total of 138 genes intersecting ferroptosis-related genes and 782 immune-related genes were utilized for LASSO regression analysis (Fig. 4a)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analysed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40855347", "locator": "sections[32] \"Data availability\" paragraph 2", "quote": "No datasets were generated or analysed during the current study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Four FIRGs (ALOX15, SNX5, CA9, and PROK2) were subsequently validated as novel FIRGs with high diagnostic power for AF (AUC = 0.851–0.911).", "kind": "quantitative", "target": {"value": 0.851, "unit": "auc", "tolerance": null, "source": "Four FIRGs (ALOX15, SNX5, CA9, and PROK2) were subsequently validated as novel FIRGs with high diagnostic power for AF (AUC = 0.851–0.911)."}, "evidence": [{"asset": "source:pmid:40855347", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Four FIRGs (ALOX15, SNX5, CA9, and PROK2) were subsequently validated as novel FIRGs with high diagnostic power for AF (AUC = 0.851–0.911)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Four FIRGs (ALOX15, SNX5, CA9, and PROK2) were subsequently validated as novel FIRGs with high diagnostic power for AF (AUC = 0.851–0.911).", "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:40855347"], "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:GSE122188"], "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:GSE122188"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40855347", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s40001-025-03092-3", "sha256": 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study.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "No datasets were generated or analysed during the current study.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1005418", "GSM1005419", "GSM1005420", "GSM1005421", "GSM1005422", "GSM1005423", "GSM1005424", "GSM1005425", "GSM1005426", "GSM1005427", "GSM1005428", "GSM1005429", "GSM1005430", "GSM1005431", "GSM1005432", "GSM1005433", "GSM1005434", "GSM1005435", "GSM1005436", "GSM1005437", "GSM1005438", "GSM1005439", "GSM1005440", "GSM1005441", "GSM1005442", "GSM1005443", "GSM1005444", "GSM1005445", "GSM1006245", "GSM1006246", "GSM1006247", "GSM1006248", "GSM1006249", "GSM1006250", "GSM1006251", "GSM1006252", "GSM1006253", "GSM1006254"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Region-specific gene expression profiles in left atria of patients with valvular atrial fibrillation", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE79768", "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=GSE79768", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE79768", "version": null, "note": "No datasets were generated or analysed during the current study.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "No datasets were generated or analysed during the current study.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2102184", "GSM2102185", "GSM2102186", "GSM2102187", "GSM2102188", "GSM2102189", "GSM2102190", "GSM2102191", "GSM2102192", 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No tolerance is published because the paper states none."}], "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": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (LASSO regression analysis), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "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": ["GSE41177", "GSE122188", "GSE79768"], "resolved_accessions": ["GSE41177", "GSE122188", "GSE79768"], "statements": ["No datasets were generated or analysed during the current study."], "basis": "The paper names GSE41177, GSE122188, GSE79768 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": [], "assets": ["source:pmid:40855347", "data:geo:GSE122188"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE122188"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:00:21Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 17373, "completion_tokens": 1881, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40855347", "type": "paper", "label": "pmid:40855347"}, {"id": "source:pmid:40855347", "type": "manuscript", "label": "PMID 40855347 full text"}, {"id": "data:geo:GSE122188", "type": "dataset", "label": "GEO GSE122188"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40855347", "type": "paper", "label": "pmid:40855347"}, {"id": "source:pmid:40855347", "type": "manuscript", "label": "PMID 40855347 full text"}, {"id": "data:geo:GSE122188", "type": "dataset", "label": "GEO GSE122188"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40855347", "type": "extraction", "used": ["source:pmid:40855347"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE122188", "type": "accession_resolution", "used": ["data:geo:GSE122188"], "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:40855347", "parent_hash": "sha256:4b50693b81bce71ee7b8780647fda289004c3b7e0b686074f40425bb99017670", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE122188 licence not read", "asset:data:geo:GSE122188 not downloaded", "asset:data:geo:GSE41177 licence not read", "asset:data:geo:GSE41177 not downloaded", "asset:data:geo:GSE79768 licence not read", "asset:data:geo:GSE79768 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["Methods Quantitative real-time PCR (qRT-PCR) validation of FIRGs in normal subj", "rom Sep 2023 to November 2023, respectively. Real-time PCR was performed to validate the expression of", "expressions were determined by utilized fast real-time PCR set (LightCycler480 II, Rotkreuz, Switzerlan"], "order_basis": "paper_text_order:1908", "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": ["re associated with cell cycle regulation and apoptosis. Supplementary Materials Supplementary Mater"], "order_basis": "paper_text_order:3789", "id": "assay:2"}]},"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":"2026-11-04T01:34:21+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}}}