{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40211281", "kind": "science-record", "revision": 4, "content_hash": "sha256:06ce99211e9ac6290fea613442bd35bd2068831bdbc36d48bf6ea776c0f26b8b", "created_at": "2026-11-01T20:30:22Z", "updated_at": "2026-11-01T22:56:20Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The CD163 + tissue-infiltrating macrophages regulate ferroptosis in thyroid-associated ophthalmopathy orbital fibroblasts via the TGF-β/Smad2/3 signaling pathway.", "doi": "10.1186/s12967-025-06443-0", "pmid": "40211281", "authors": ["Xuemei Li", "Siyi Wang", "Hanwen Cao", "Simin Xu", "Chao Xiong", "Jinhai Yu", "Yunxiu Chen", "Zhangjun Ren", "Min Li", "Ying Hu", "Puying Gan", "Qihua Xu", "Yaohua Wang", "Hongfei Liao"], "journal": "Journal of translational medicine", "year": 2025, "abstract": "BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is a thyroid function-related, organ-specific autoimmune disease that primarily leads to specific reactive changes and tissue remodeling in the periocular region. The exact pathogenesis of TAO remains unclear.\nMETHODS: High-throughput gene expression datasets related to TAO were comprehensively retrieved from the Gene Expression Omnibus (GEO) database, selecting GSE174139 and GSE158464 for analysis. Differentially expressed genes (DEGs) between TAO patients and healthy controls were identified, and ferroptosis-related genes (FRGs) were obtained from the FerrDb database. The intersection of DEGs and FRGs yielded ferroptosis-related genes associated with TAO.The transcriptional expression of FRGs was validated using real-time quantitative polymerase chain reaction (RT-qPCR) on orbital adipose tissue samples from TAO patients and healthy controls. Single-cell sequencing of six human tissue samples further analyzed changes in cellular subpopulations within the TAO microenvironment.Additionally, a co-culture model of CD163 + macrophages and TAO orbital fibroblasts, along with an in vitro TGF-β1-induced orbital fibroblast (OF) model, was constructed to validate the role of the TGF-β1/SMAD2/3 axis in ferroptosis regulation. Finally, potential clinical drugs targeting CD163 + macrophages with high ferroptosis activity in TAO were predicted using the Random Walk with Restart (RWR) algorithm combined with the DGIdb database.\nRESULTS: We first utilized TAO-related datasets from the GEO database, combined with the FerrDb ferroptosis database, to identify changes in iron metabolism genes during TAO progression through differential expression analysis, screening 7 key ferroptosis-related proteins. In vitro validation revealed that all but AOPQ and LGMN, which were upregulated, exhibited downregulated expression.Single-cell sequencing of orbital connective tissue from 4 TAO patients and 2 healthy controls identified 16,364 cells spanning 18 cell types. Analysis of the 7 key ferroptosis-related proteins revealed that fibroblasts and macrophages displayed elevated ferroptosis signaling during TAO progression. Subcluster analysis of macrophages identified 4 distinct subpopulations, with the C2 subpopulation-characterized by high expression of CD163 and CCL18-exhibiting prominent ferroptosis activation signals.Further validation using clinical tissue samples, a co-culture model of CD163 + macrophages and TAO orbital fibroblasts, and an in vitro TGF-β1-induced orbital fibroblast (OF) model confirmed aberrant activation of the TGF-β1/SMAD2/3 pathway as a key regulator of ferroptosis. Hub gene analysis of C2 subpopulation marker genes, combined with the DGIdb database, predicted potential clinical drugs targeting the C2 macrophages.\nCONCLUSION: This study, integrating single-cell RNA-Seq and bulk transcriptome analysis, revealed the involvement of CD163 + tissue-infiltrating macrophages in regulating ferroptosis of orbital fibroblasts during TAO progression and identified therapeutic candidates targeting macrophage ferroptosis signaling in TAO. Furthermore, in vitro experiments demonstrated that activation of the TGF-β1/SMAD2/3 axis promotes ferroptosis in TAO orbital fibroblasts, highlighting a novel pathway for potential therapeutic intervention.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were identified using DESeq2 with a threshold of p.adj < 0.05 and |log2FoldChange| > 0.5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40211281", "locator": "sections[4] \"Differential gene expression analysis\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were identified using DESeq2 with a threshold of p.adj < 0.05 and |log2FoldChange| > 0.5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The primary data of the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40211281", "locator": "sections[29] \"notes\" paragraph 1", "quote": "The primary data of the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "DESeq2 analysis of TAO-related RNA-seq data from six public GEO samples identified 334 differentially expressed genes and seven ferroptosis-associated genes, indicating abnormal activation of ferroptosis signaling during TAO progression.", "kind": "quantitative", "target": {"value": 2.0, "unit": "fold change", "tolerance": null, "source": "Based on RNA-seq data related to TAO from the public GEO database, including 6 samples, differential gene expression analysis was performed using DESeq2 with the criteria padj < 0.05 and |log2FoldChange| > 0.5, identifying a total of 334 differentially expressed genes (Fig. 1A)."}, "evidence": [{"asset": "source:pmid:40211281", "locator": "sections[19] \"Identification of ferroptosis signaling activation in TAO based on bulk data\" paragraph 2", "quote": "Based on RNA-seq data related to TAO from the public GEO database, including 6 samples, differential gene expression analysis was performed using DESeq2 with the criteria padj < 0.05 and |log2FoldChange| > 0.5, identifying a total of 334 differentially expressed genes (Fig. 1A)."}, {"asset": "source:pmid:40211281", "locator": "sections[19] \"Identification of ferroptosis signaling activation in TAO based on bulk data\" paragraph 2", "quote": "A comparative analysis with the ferroptosis-related database FerrDb revealed seven ferroptosis-associated genes: the ferroptosis driver genes AQP3 and LGMN, and the suppressor genes CP, FTL, MGST1, NQO1, and TMSB4X (Fig. 1B)."}, {"asset": "source:pmid:40211281", "locator": "sections[19] \"Identification of ferroptosis signaling activation in TAO based on bulk data\" paragraph 3", "quote": "These findings suggest abnormal activation of the ferroptosis signaling pathway during TAO progression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "DESeq2 analysis of TAO-related RNA-seq data from six public GEO samples identified 334 differentially expressed genes and seven ferroptosis-associated genes, indicating abnormal activation of ferroptosis signaling during TAO progression.", "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:40211281"], "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:GSE158464"], "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:GSE158464"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40211281", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-025-06443-0", "sha256": "sha256:b0a2055d0b09e4b6dc19d6af2dd8b7df3fc150234ab72ecd980db1941e8f8d4a", "bytes": 50816, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12967-025-06443-0", "version": null, "note": "Full article fetched from PMC; 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Homo sapiens", "title": "Temperature-dependent induction of browning in retrobulbar fat", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE174139", "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=GSE174139", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE174139", "version": null, "note": "The primary data of the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The primary data of the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5287845", "GSM5287846", "GSM5287847", "GSM5287848", "GSM5287849", "GSM5287850", "GSM5287851", "GSM5287852", "GSM5287853", "GSM5287854"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "24676;18573", "taxon": "Homo sapiens", "title": "Transcriptomic profiling of human orbital fat and differentiating orbital fibroblasts", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE158464 not downloaded", "asset:data:geo:GSE158464 licence not read", "asset:data:geo:GSE174139 not downloaded", "asset:data:geo:GSE174139 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "deseq2", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differentially expressed genes (DEGs) were identified using DESeq2 with a threshold of p.adj < 0.05 and |log2FoldChange| > 0.5."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "differential_expression_fit", "expected_value": 2.0, "unit": "fold change", "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."}], "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: deseq2."}, "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": ["GSE174139", "GSE158464"], "resolved_accessions": ["GSE174139", "GSE158464"], "statements": ["The primary data of the current study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE174139, GSE158464 in Gene Expression Omnibus (GEO) database 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:40211281", "data:geo:GSE158464"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE158464"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:49:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13316, "completion_tokens": 1897, "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:40211281", "type": "paper", "label": "pmid:40211281"}, {"id": "source:pmid:40211281", "type": "manuscript", "label": "PMID 40211281 full text"}, {"id": "data:geo:GSE158464", "type": "dataset", "label": "GEO GSE158464"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40211281", "type": "paper", "label": "pmid:40211281"}, {"id": "source:pmid:40211281", "type": "manuscript", "label": "PMID 40211281 full text"}, {"id": "data:geo:GSE158464", "type": "dataset", "label": "GEO GSE158464"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40211281", "type": "extraction", "used": ["source:pmid:40211281"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE158464", "type": "accession_resolution", "used": ["data:geo:GSE158464"], "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:40211281", "parent_hash": "sha256:87499087c66d0ef4f38b18618f5708a69710b073a3ed9aa611293c66142b7fee", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE158464 licence not read", "asset:data:geo:GSE158464 not downloaded", "asset:data:geo:GSE174139 licence not read", "asset:data:geo:GSE174139 not downloaded", "execution.not_run", "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": ["time quantitative polymerase chain reaction (RT-qPCR) on orbital adipose tissue samples from TAO", "e quantitative polymerase chain reaction (RT-qPCR) on orbital adipose tissue samples from TAO"], "order_basis": "paper_text_order:944", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ophages. CONCLUSION: This study, integrating single-cell RNA-Seq and bulk transcriptome analysis, revealed th", "gnaling during TAO progression, we performed single-cell RNA sequencing on eye tissues from 2 normal volunteers and"], "order_basis": "paper_text_order:2967", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["CLUSION: This study, integrating single-cell RNA-Seq and bulk transcriptome analysis, revealed th", "ng TAO progression, we performed single-cell RNA sequencing on eye tissues from 2 normal volunteers and", "dy, integrating single-cell RNA-Seq and bulk transcriptome analysis, revealed the involvement of CD163", "Analysis of cell proportions in single-cell transcriptome data was performed to show changes in cell p"], "order_basis": "paper_text_order:2979", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["y terms displayed We validated, using tissue immunofluorescence, that the infiltration of CD163 + macrophage"], "order_basis": "paper_text_order:8892", "id": "assay:4"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ther validation was conducted via RT-PCR and flow cytometry (Fig. 5D, E, G-J). RT-PCR results showed a s", "3 + macrophage marker CD163 mRNA expression. Flow cytometry analysis revealed a rightward shift in the f"], "order_basis": "paper_text_order:9238", "id": "assay:5"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["sue. (A-C) Morphology of CD163 + macrophages cultured in vitro.(D, G, H) Identification of M0 macroph"], "order_basis": "paper_text_order:9892", "id": "assay:6"}, {"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": ["Differentially expressed genes (DEGs) were identified using DESeq2 with a threshold of p.adj < 0.05 and |log2FoldChange| > 0.5."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]},"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":"2026-11-04T00:47:20+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}}}