{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39713769", "kind": "science-record", "revision": 3, "content_hash": "sha256:d3839aa05977c3dd0ca841e2d38ad22d46462e8dca073ade6226b5b41f063910", "created_at": "2026-11-01T20:30:02Z", "updated_at": "2026-11-01T22:13:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Immune-related gene characterization and biological mechanisms in major depressive disorder revealed based on transcriptomics and network pharmacology.", "doi": "10.3389/fpsyt.2024.1485957", "pmid": "39713769", "authors": ["Shasha Wu", "Qing Jiang", "Jinhui Wang", "Daming Wu", "Yan Ren"], "journal": "Frontiers in psychiatry", "year": 2024, "abstract": "Background: Major depressive disorder (MDD) is a severe psychiatric disorder characterized by complex etiology, with genetic determinants that are not fully understood. The objective of this study was to investigate the pathogenesis of MDD and to explore its association with the immune system by identifying hub biomarkers using bioinformatics analyses and examining immune infiltrates in human autopsy samples.\nMethods: Gene microarray data were obtained from the Gene Expression Omnibus (GEO) datasets GSE32280, GSE76826, GSE98793, and GSE39653. Our approach included differential expression analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network analysis to identify hub genes associated with MDD. Subsequently, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Cytoscape plugin CluGO, and Gene Set Enrichment Analysis (GSEA) were utilized to identify immune-related genes. The final selection of immune-related hub genes was determined through the least absolute shrinkage and selection operator (Lasso) regression analysis and PPI analysis. Immune cell infiltration in MDD patients was analyzed using CIBERSORT, and correlation analysis was performed between key immune cells and genes. The diagnostic accuracy of the identified hub genes was evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, we conducted a study involving 10 MDD patients and 10 healthy controls (HCs) meeting specific criteria to assess the expression levels of these hub genes in their peripheral blood mononuclear cells (PBMCs). The Herbal Ingredient Target Database (HIT) was employed to screen for herbal components that target these genes, potentially identifying novel therapeutic agents.\nResults: A total of 159 down-regulated and 51 up-regulated genes were identified for further analysis. WGCNA revealed 12 co-expression modules, with modules \"darked\", \"darkurquoise\" and \"light yellow\" showing significant positive associations with MDD. Functional enrichment pathway analysis indicated that these differential genes were associated with immune functions. Integration of differential and immune-related gene analysis identified 21 common genes. The Lasso algorithm confirmed 4 hub genes as potential biomarkers for MDD. GSEA analysis suggested that these genes may be involved in biological processes such as protein export, RNA degradation, and fc gamma r mediated cytotoxis. Pathway enrichment analysis identified three highly enriched immune-related pathways associated with the 4 hub genes. ROC curve analysis indicated that these hub genes possess good diagnostic value. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) demonstrated significant expression differences of these hub genes in PBMCs between MDD patients and HCs. Immune infiltration analysis revealed significant correlations between immune cells, including Mast cells resting, T cells CD8, NK cells resting, and Neutrophils, which were significantly correlated with the hub genes expression. HIT identified one herb target related to IL7R and 14 targets related to TLR2.\nConclusions: The study identified four immune-related hub genes (TLR2, RETN, HP, and IL7R) in MDD that may impact the diagnosis and treatment of the disorder. By leveraging the GEO database, our findings contribute to the understanding of the relationship between MDD and immunity, presenting potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "The “pROC” R package was used to calculate the AUC of the receiver operating characteristic (ROC) curves to assess the predictive effect of the feature genes in the training and validation sets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39713769", "locator": "sections[10] \"Validation of the diagnostic ability of the hub genes\" paragraph 2", "quote": "The “pROC” R package was used to calculate the AUC of the receiver operating characteristic (ROC) curves to assess the predictive effect of the feature genes in the training and validation sets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39713769", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The AUC of the diagnostic model was 0.83, indicating good diagnostic performance.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39713769", "locator": "sections[22] \"Diagnostic model based on four hub genes\" paragraph 2", "quote": "The AUC of the diagnostic model was 0.83, indicating good diagnostic performance ( Figure 7F )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The AUC of the diagnostic model was 0.83, indicating good diagnostic performance.", "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:39713769"], "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:GSE32280"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_mann_whitney", "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:GSE32280"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39713769", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fpsyt.2024.1485957", "sha256": "sha256:2a824136b1195a115869aa0e25d8e9c3a735386889e3a82980f974294f8d3c72", "bytes": 51060, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fpsyt.2024.1485957", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11659238", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE32280", "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=GSE32280", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE32280", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/ Supplementary Material . 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"blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: mann_whitney."}, "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": ["GSE32280", "GSE76826", "GSE98793", "GSE39653"], "resolved_accessions": ["GSE32280", "GSE76826", "GSE98793", "GSE39653"], "statements": ["The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE32280, GSE76826, GSE98793, GSE39653 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:39713769", "data:geo:GSE32280"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_mann_whitney", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE32280"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:43:01Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12872, "completion_tokens": 1595, "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:39713769", "type": "paper", "label": "pmid:39713769"}, {"id": "source:pmid:39713769", "type": "manuscript", "label": "PMID 39713769 full text"}, {"id": "data:geo:GSE32280", "type": "dataset", "label": "GEO GSE32280"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39713769", "type": "paper", "label": "pmid:39713769"}, {"id": "source:pmid:39713769", "type": "manuscript", "label": "PMID 39713769 full text"}, {"id": "data:geo:GSE32280", "type": "dataset", "label": "GEO GSE32280"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39713769", "type": "extraction", "used": ["source:pmid:39713769"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE32280", "type": "accession_resolution", "used": ["data:geo:GSE32280"], "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:39713769", "parent_hash": "sha256:265a9eecd0e4c7f042618231518149a3d924e781ac1e1c46cf94245f1e650f46", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE32280 licence not read", "asset:data:geo:GSE32280 not downloaded", "asset:data:geo:GSE39653 licence not read", "asset:data:geo:GSE39653 not downloaded", "asset:data:geo:GSE76826 licence not read", "asset:data:geo:GSE76826 not downloaded", "asset:data:geo:GSE98793 licence not read", "asset:data:geo:GSE98793 not downloaded", "execution.not_run", "method.group_comparison_mann_whitney", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:group_comparison_mann_whitney"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ates in human autopsy samples. Methods: Gene microarray data were obtained from the Gene Expression"], "order_basis": "paper_text_order:534", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rse transcription-polymerase chain reaction (RT-qPCR) demonstrated significant expression differe", "transcription-polymerase chain reaction (RT-qPCR) demonstrated significant expression differe"], "order_basis": "paper_text_order:2838", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Mann-Whitney"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]},"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":"2026-11-04T03:05:04+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}}}