{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36836779", "kind": "science-record", "revision": 4, "content_hash": "sha256:71cddf92b9fed4f69fdd945a7c553539a90aa6f3bfe98c44502653adee8b820a", "created_at": "2026-11-01T19:01:27Z", "updated_at": "2026-11-01T22:51:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "In Silico Analysis of Publicly Available Transcriptomic Data for the Identification of Triple-Negative Breast Cancer-Specific Biomarkers.", "doi": "10.3390/life13020422", "pmid": "36836779", "authors": ["Rachid Kaddoura", "Fatma Alqutami", "Mohamed Asbaita", "Mahmood Hachim"], "journal": "Life (Basel, Switzerland)", "year": 2023, "abstract": "BACKGROUND: Breast cancer is the most common type of cancer among women and is classified into multiple subtypes. Triple-negative breast cancer (TNBC) is the most aggressive subtype, with high mortality rates and limited treatment options such as chemotherapy and radiation. Due to the heterogeneity and complexity of TNBC, there is a lack of reliable biomarkers that can be used to aid in the early diagnosis and prognosis of TNBC in a non-invasive screening method.\nAIM: This study aims to use in silico methods to identify potential biomarkers for TNBC screening and diagnosis, as well as potential therapeutic markers.\nMETHODS: Publicly available transcriptomic data of breast cancer patients published in the NCBI's GEO database were used in this analysis. Data were analyzed with the online tool GEO2R to identify differentially expressed genes (DEGs). Genes that were differentially expressed in more than 50% of the datasets were selected for further analysis. Metascape, Kaplan-Meier plotter, cBioPortal, and the online tool TIMER were used for functional pathway analysis to identify the biological role and functional pathways associated with these genes. Breast Cancer Gene-Expression Miner v4.7 was used to validify the obtained results in a larger cohort of datasets.\nRESULTS: A total of 34 genes were identified as differentially expressed in more than half of the datasets. The DEG GATA3 had the highest degree of regulation, and it plays a role in regulating other genes. The estrogen-dependent pathway was the most enriched pathway, involving four crucial genes, including GATA3. The gene FOXA1 was consistently down-regulated in TNBC in all datasets.\nCONCLUSIONS: The shortlisted 34 DEGs will aid clinicians in diagnosing TNBC more accurately as well as developing targeted therapies to improve patient prognosis. In vitro and in vivo studies are further recommended to validate the results of the current study.", "claims": [{"id": "claim-method", "statement": "Each dataset was processed individually to identify DEGs using the GEO2R online tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/, accessed on 1 October 2021). Samples were assigned to groups based on their subtype and analyzed using the standardized parameters of the tool. These standardized parameters include automated log2 transformation of non-transformed data, empirical Bayes method of calculation through the limma statistical package, and adjustment of p value using the default Benjamini and Hochberg (false discovery rate) method. p-value < 0.05 was used to indicate statistical significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36836779", "locator": "sections[4] \"2.2. Identification of Differentially Expressed Genes\" paragraph 2", "quote": "Each dataset was processed individually to identify DEGs using the GEO2R online tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/, accessed on 1 October 2021). Samples were assigned to groups based on their subtype and analyzed using the standardized parameters of the tool. These standardized parameters include automated log2 transformation of non-transformed data, empirical Bayes method of calculation through the limma statistical package, and adjustment of p value using the default Benjamini and Hochberg (false discovery rate) method. p-value < 0.05 was used to indicate statistical significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets supporting the conclusion of this article are available in the NCBI repository, (https://www.ncbi.nlm.nih.gov/geo/, accessed on 1 October 2021), with their accession codes in Table 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36836779", "locator": "sections[29] \"Data Availability Statement\" paragraph 2", "quote": "The datasets supporting the conclusion of this article are available in the NCBI repository, (https://www.ncbi.nlm.nih.gov/geo/, accessed on 1 October 2021), with their accession codes in Table 1."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The re-analysis of these datasets revealed a total of 1217 DEGs in all datasets (Supplementary Files S1–S9), 34 of which are consistent across five of the nine datasets (50%) (Figure 2, Table 2, Supplementary File S10), with these genes being either up- or down-regulated.", "kind": "quantitative", "target": {"value": 50.0, "unit": "per cent", "tolerance": null, "source": "The re-analysis of these datasets revealed a total of 1217 DEGs in all datasets (Supplementary Files S1–S9), 34 of which are consistent across five of the nine datasets (50%) (Figure 2, Table 2, Supplementary File S10), with these genes being either up- or down-regulated."}, "evidence": [{"asset": "source:pmid:36836779", "locator": "sections[7] \"3. Results\" paragraph 2", "quote": "The re-analysis of these datasets revealed a total of 1217 DEGs in all datasets (Supplementary Files S1–S9), 34 of which are consistent across five of the nine datasets (50%) (Figure 2, Table 2, Supplementary File S10), with these genes being either up- or down-regulated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The re-analysis of these datasets revealed a total of 1217 DEGs in all datasets (Supplementary Files S1–S9), 34 of which are consistent across five of the nine datasets (50%) (Figure 2, Table 2, Supplementary File S10), with these genes being either up- or down-regulated.", "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:36836779"], "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. 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"differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Each dataset was processed individually to identify DEGs using the GEO2R online tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/, accessed on 1 October 2021). Samples were assigned to groups based on their subtype and analyzed using the standardized parameters of the tool. These standardized parameters include automated log2 transformation of non-transformed data, empirical Bayes method of calculation through the limma statistical package, and adjustment of p value using the default Benjamini and Hochberg (false discovery rate) method. p-value < 0.05 was used to indicate statistical significance."}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "differential_expression_fit", "expected_value": 50.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "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": ["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: limma_voom."}, "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": ["GSE2741", "GSE18864", "GSE19615", "GSE30682", "GSE36295", "GSE37751", "GSE40115", "GSE45255", "GSE97177"], "resolved_accessions": ["GSE2741", "GSE18864", "GSE19615", "GSE30682", "GSE36295", "GSE37751", "GSE40115", "GSE45255", "GSE97177"], "statements": ["The datasets supporting the conclusion of this article are available in the NCBI repository, (https://www.ncbi.nlm.nih.gov/geo/, accessed on 1 October 2021), with their accession codes in Table 1."], "basis": "The paper names GSE2741, GSE18864, GSE19615, GSE30682, GSE36295, GSE37751, GSE40115, GSE45255, GSE97177 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36836779", "data:geo:GSE18864"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE18864"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:31:37Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14297, "completion_tokens": 2560, "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:36836779", "type": "paper", "label": "pmid:36836779"}, {"id": "source:pmid:36836779", "type": "manuscript", "label": "PMID 36836779 full text"}, {"id": "data:geo:GSE18864", "type": "dataset", "label": "GEO GSE18864"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36836779", "type": "paper", "label": "pmid:36836779"}, {"id": "source:pmid:36836779", "type": "manuscript", "label": "PMID 36836779 full text"}, {"id": "data:geo:GSE18864", "type": "dataset", "label": "GEO GSE18864"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36836779", "type": "extraction", "used": ["source:pmid:36836779"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE18864", "type": "accession_resolution", "used": ["data:geo:GSE18864"], "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:36836779", "parent_hash": "sha256:893df51cffd83ea6e32a034c0aaef4eca114311cc0aaa9be0e42e6e8ec3f36e0", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE18864 licence not read", "asset:data:geo:GSE18864 not downloaded", "asset:data:geo:GSE19615 licence not read", "asset:data:geo:GSE19615 not downloaded", "asset:data:geo:GSE2741 licence not read", "asset:data:geo:GSE2741 not downloaded", "asset:data:geo:GSE30682 licence not read", "asset:data:geo:GSE30682 not downloaded", "asset:data:geo:GSE36295 licence not read", "asset:data:geo:GSE36295 not downloaded", "asset:data:geo:GSE37751 licence not read", "asset:data:geo:GSE37751 not downloaded", "asset:data:geo:GSE40115 licence not read", "asset:data:geo:GSE40115 not downloaded", "asset:data:geo:GSE45255 licence not read", "asset:data:geo:GSE45255 not downloaded", "asset:data:geo:GSE97177 licence not read", "asset:data:geo:GSE97177 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": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["s to improve patient prognosis. In vitro and in vivo studies are further recommended to validate"], "order_basis": "paper_text_order:1939", "id": "assay:1"}, {"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": ["Each dataset was processed individually to identify DEGs using the GEO2R online tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/, accessed on 1 October 2021). Samples were assigned to groups based on their subtype and analyzed using the standardized parameters of the tool. These standardized parameters include automated log2 transformation of non-transformed data, empirical Bayes method of calculation through the limma statistical package, and adjustment of p value using the default Benjamini and Hochberg (false discovery rate) method. p-value < 0.05 was used to indicate statistical significance."], "order_basis": "consumes_earlier_output", "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":"2026-11-04T03:10:33+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}}}