{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36358600", "kind": "science-record", "revision": 4, "content_hash": "sha256:6941d5f3ef7229ad80318bf5276a91d0c93029e7d64976b6dc66fba8890f0ef0", "created_at": "2026-11-01T18:15:48Z", "updated_at": "2026-11-01T22:08:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Heterogeneity and Differentiation Trajectories of Infiltrating CD8+ T Cells in Lung Adenocarcinoma.", "doi": "10.3390/cancers14215183", "pmid": "36358600", "authors": ["Xiaojie Song", "Guanghui Zhao", "Guangqiang Wang", "Haidong Gao"], "journal": "Cancers", "year": 2022, "abstract": "CD8+ T cells infiltrating the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) are critical for establishing antitumor immunity. Nevertheless, the global landscape of their numbers, functional status, and differentiation trajectories remains unclear. In the single-cell RNA-sequencing (scRNA-seq) dataset GSE131907 of LUAD, the CD8+T cells were selected for TSNE clustering, and the results showed that they could be divided into ten subsets. The cell differentiation trajectory showed the presence of abundant transition-state CD8+ T cells during the differentiation of naive-like CD8+ T cells into cytotoxic CD8+ T cells and exhausted CD8+ T cells. The differentially expressed marker genes among subsets were used to construct the gene signature matrix, and the proportion of each subset was identified and calculated in The Cancer Genome Atlas (TCGA) samples. Survival analysis showed that the higher the proportion of the exhausted CD8+ T lymphocyte (ETL) subset, the shorter the overall survival (OS) time of LUAD patients (p = 0.0098). A total of 61 genes were obtained by intersecting the differentially expressed genes (DEGs) of the ETL subset, and the DEGs of the TCGA samples were divided into a high and a low group according to the proportion of the ETL subset. Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes. Our study further deepens the understanding of the heterogeneity and functional exhaustion of infiltrating CD8+ T cells in LUAD. The screened prognostic marker genes provide potential targets for targeted therapy and immunotherapy in LUAD patients.", "claims": [{"id": "claim-method", "statement": "Survival analysis was performed on candidate hub genes using the R ‘survival’ package, and the genes with a significant effect on prognosis were selected as hub genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36358600", "locator": "sections[13] \"2.11. Construction of PPI Network and Identification of Hub Genes\" paragraph 2", "quote": "Survival analysis was performed on candidate hub genes using the R ‘survival’ package, and the genes with a significant effect on prognosis were selected as hub genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE131907 dataset is available from the GEO database. TCGA-LUAD sample data can be obtained from the TCGA database. Additional information is available from articles or supplementary files. 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Please access it from the following link: https://github.com/qilugaohaidong/R_script, accessed on 10 October 2022."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36358600", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes.", "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:36358600"], "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:GSE131907"], "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:GSE131907"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36358600", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/cancers14215183", "sha256": "sha256:096dd72808e139f43579667e635a7c3f6d8569049fe97936a784fb2a9dfdb72b", "bytes": 39510, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/cancers14215183", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9658355", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE131907", "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=GSE131907", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE131907", "version": null, "note": "The GSE131907 dataset is available from the GEO database. TCGA-LUAD sample data can be obtained from the TCGA database. Additional information is available from articles or supplementary files. The codes used for analysis have uploaded to the GitHub website. Please access it from the following link: https://github.com/qilugaohaidong/R_script, accessed on 10 October 2022.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GSE131907 dataset is available from the GEO database. TCGA-LUAD sample data can be obtained from the TCGA database. Additional information is available from articles or supplementary files. The codes used for analysis have uploaded to the GitHub website. 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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}}}