{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38993569", "kind": "science-record", "revision": 4, "content_hash": "sha256:357a28bcebc26a1fff2c550ed32946ae7d8f75833fb34143060982dbf0a4429b", "created_at": "2026-11-01T20:29:04Z", "updated_at": "2026-11-01T22:54:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A High Immune-Related Index with the Suppression of cGAS-STING Pathway is a Key Determinant to Herceptin Resistance in HER2+ Breast Cancer.", "doi": "10.7150/ijbs.94868", "pmid": "38993569", "authors": ["Ruizhao Cai", "Qingshan Chen", "Dechang Zhao", "Yan Wang", "Ling Zhou", "Kaiming Zhang", "Jialu Shan", "Zhiling Li", "Yuhong Chen", "Hailiang Zhang", "Gongkan Feng", "Xiaofeng Zhu", "Rong Deng", "Jun Tang"], "journal": "International journal of biological sciences", "year": 2024, "abstract": "Resistance to HER2-targeted therapy is the major cause of treatment failure in patients with HER2+ breast cancer (BC). Given the key role of immune microenvironment in tumor development, there is a lack of an ideal prognostic model that fully accounts for immune infiltration. In this study, WGCNA analysis was performed to discover the relationship between immune-related signaling and prognosis of HER2+ BC. After Herceptin-resistant BC cell lines established, transcriptional profiles of resistant cell line and RNA-sequencing data from GSE76360 cohort were analyzed for candidate genes. 85 samples of HER2+ BC from TCGA database were analyzed by the Cox regression, XGBoost and Lasso algorithm to generalize a credible immune-related prognostic index (IRPI). Correlations between the IRPI signature and tumor microenvironment were further analyzed by multiple algorithms, including single-cell RNA sequencing data analysis. Patients with high IRPI had suppressive tumor immune microenvironment and worse prognosis. The suppression of type I interferon signaling indicated by the IRPI in Herceptin-resistant HER2+ BC was validated. And we elucidated that the suppression of cGAS-STING pathway is the key determinant underlying immune escape in Herceptin-resistant BC with high IRPI. A combination of STING agonist and DS-8201 could serve as a new strategy for Herceptin-resistant HER2+ BC.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis of OS was performed to identify prognostic genes with p <0.05 using TCGA HER2+ BC cohort. XGBoost algorithm was performed to identify immune-related genes. Finally, the Lasso Cox regression method was used to shrink the candidates to construct the most suitable signature with “glmnet” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38993569", "locator": "sections[7] \"Construction of the immune-related prognostic index (IRPI)\" paragraph 2", "quote": "Univariate Cox regression analysis of OS was performed to identify prognostic genes with p <0.05 using TCGA HER2+ BC cohort. XGBoost algorithm was performed to identify immune-related genes. Finally, the Lasso Cox regression method was used to shrink the candidates to construct the most suitable signature with “glmnet” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "RNA expression and corresponding clinical data of HER2+ BC patients enrolled on the 03-311 trial were obtained from GSE76360 cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38993569", "locator": "sections[20] \"Down-regulation of type I IFN signaling is associated with poor prognosis in HER2+ BC patients\" paragraph 2", "quote": "RNA expression and corresponding clinical data of HER2+ BC patients enrolled on the 03-311 trial were obtained from GSE76360 cohort."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The three-gene IRPI showed strong time-dependent prognostic performance in HER2+ breast cancer, with OS AUC values of 0.89, 0.78, and 0.82 at 1, 3, and 5 years and PFS AUC values of 0.81, 0.80, and 0.83 at 1, 3, and 5 years.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38993569", "locator": "sections[21] \"Construction of an immune-related prognostic index (IRPI) for HER2+ BC\" paragraph 4", "quote": "The time-dependent area under ROC curve (AUC) for OS reached 0.89 at 1 year, 0.78 at 3 years, and 0.82 at 5 years, while the time-dependent AUC for PFS reached 0.81 at 1 year, 0.80 at 3 years, and 0.83 at 5 years (Figure 2B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The three-gene IRPI showed strong time-dependent prognostic performance in HER2+ breast cancer, with OS AUC values of 0.89, 0.78, and 0.82 at 1, 3, and 5 years and PFS AUC values of 0.81, 0.80, and 0.83 at 1, 3, and 5 years.", "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:38993569"], "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:GSE176078"], "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:GSE176078"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38993569", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/ijbs.94868", "sha256": 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"identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE191230", "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=GSE191230", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE191230", "version": null, "note": "RNA expression and corresponding clinical data of HER2+ BC patients enrolled on the 03-311 trial were obtained from GSE76360 cohort.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "RNA expression and corresponding clinical data of HER2+ BC patients enrolled on the 03-311 trial were obtained from GSE76360 cohort.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM5741915", "GSM5741916", "GSM5741917", "GSM5741918", "GSM5741919", 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XGBoost algorithm was performed to identify immune-related genes. Finally, the Lasso Cox regression method was used to shrink the candidates to construct the most suitable signature with “glmnet” R package."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "student's t-test"}}, {"id": "method-3", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-5", "family": "machine_learning", "specific": "gradient_boosting", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "XGBoost"}}, {"id": "method-6", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:38993569", "data:geo:GSE176078"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE176078"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:24:14Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 12916, "completion_tokens": 2540, "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:38993569", "type": "paper", "label": "pmid:38993569"}, {"id": "source:pmid:38993569", "type": "manuscript", "label": "PMID 38993569 full text"}, {"id": "data:geo:GSE176078", "type": "dataset", "label": "GEO GSE176078"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38993569", "type": "paper", "label": "pmid:38993569"}, {"id": "source:pmid:38993569", "type": "manuscript", "label": "PMID 38993569 full text"}, {"id": "data:geo:GSE176078", "type": "dataset", "label": "GEO GSE176078"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38993569", "type": "extraction", "used": ["source:pmid:38993569"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE176078", "type": "accession_resolution", "used": ["data:geo:GSE176078"], "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:38993569", "parent_hash": "sha256:39556723362199d5585c094c9d06b4f098c49a042d0ec12ab7f098e3ae6798dc", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE176078 licence not read", "asset:data:geo:GSE176078 not downloaded", "asset:data:geo:GSE191230 licence not read", "asset:data:geo:GSE191230 not downloaded", "asset:data:geo:GSE76360 licence not read", "asset:data:geo:GSE76360 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["iptional profiles of resistant cell line and RNA-sequencing data from GSE76360 cohort were analyzed for", "y multiple algorithms, including single-cell RNA sequencing data analysis. Patients with high IRPI had s"], "order_basis": "paper_text_order:610", "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": 0.93, "evidence": ["r analyzed by multiple algorithms, including single-cell RNA sequencing data analysis. Patients with high IRPI had s"], "order_basis": "paper_text_order:981", "id": "assay:2"}, {"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 Cox regression analysis of OS was performed to identify prognostic genes with p <0.05 using TCGA HER2+ BC cohort. XGBoost algorithm was performed to identify immune-related genes. Finally, the Lasso Cox regression method was used to shrink the candidates to construct the most suitable signature with “glmnet” R package."], "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. 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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}}}