{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33447134", "kind": "science-record", "revision": 5, "content_hash": "sha256:cb2ab2a8a6392ed95dbc9e8bbcb66c2f5e4d67ee8473bbd8bf4d417b87068506", "created_at": "2026-11-01T15:41:22Z", "updated_at": "2026-11-01T21:24:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Differentially Expressed Genes and Their Clinical Significance in Ischaemic Stroke: An In-Silico Study.", "doi": "10.21315/mjms2020.27.6.6", "pmid": "33447134", "authors": ["Sandeep Appunni", "Muni Rubens", "Venkataraghavan Ramamoorthy", "Hina Sharma", "Anjani Kumar Singh", "Vishnu Swarup", "Himanshu Narayan Singh"], "journal": "The Malaysian journal of medical sciences : MJMS", "year": 2020, "abstract": "BACKGROUND: Ischaemic stroke (IS), a multifactorial neurological disorder, is mediated by interplay between genes and the environment and, thus, blood-based IS biomarkers are of significant clinical value. Therefore, this study aimed to find global differentially expressed genes (DEGs) in-silico, to identify key enriched genes via gene set enrichment analysis (GSEA) and to determine the clinical significance of these genes in IS.\nMETHODS: Microarray expression dataset GSE22255 was retrieved from the Gene Expression Omnibus (GEO) database. It includes messenger ribonucleic acid (mRNA) expression data for the peripheral blood mononuclear cells of 20 controls and 20 IS patients. The bioconductor-package 'affy' was used to calculate expression and a pairwise t-test was applied to screen DEGs (P < 0.01). Further, GSEA was used to determine the enrichment of DEGs specific to gene ontology (GO) annotations.\nRESULTS: GSEA analysis revealed 21 genes to be significantly plausible gene markers, enriched in multiple pathways among all the DEGs (n = 881). Ten gene sets were found to be core enriched in specific GO annotations. JunD, NCX3 and fibroblast growth factor receptor 4 (FGFR4) were under-represented and glycoprotein M6-B (GPM6B) was persistently over-represented.\nCONCLUSION: The identified genes are either associated with the pathophysiology of IS or they affect post-IS neuronal regeneration, thereby influencing clinical outcome. These genes should, therefore, be evaluated for their utility as suitable markers for predicting IS in clinical scenarios.", "claims": [{"id": "claim-method", "statement": "GSEA results are based on the Kolmogorov-Smirnov (K-S) statistical test", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33447134", "locator": "sections[9] \"Functional Enrichment Analysis of Genomic Datasets in IS Using GSEA\" paragraph 7", "quote": "GSEA results are based on the Kolmogorov-Smirnov (K-S) statistical test"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mRNA microarray expression dataset GSE22255, which is based on the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Inc., Santa Clara, CA, USA), was retrieved from the Gene Expression Omnibus (GEO). This dataset includes mRNA expression data from the peripheral blood mononuclear cells of 20 controls and 20 IS patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33447134", "locator": "sections[3] \"Affymetrix Microarray Data\" paragraph 2", "quote": "The mRNA microarray expression dataset GSE22255, which is based on the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Inc., Santa Clara, CA, USA), was retrieved from the Gene Expression Omnibus (GEO). This dataset includes mRNA expression data from the peripheral blood mononuclear cells of 20 controls and 20 IS patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33447134"], "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:GSE22255"], "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:GSE22255"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33447134", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21315/mjms2020.27.6.6", "sha256": "sha256:18f281e6abb86547d1d7aee32b0dddeeb7be3c44c60e8c7412cb77d073c51c68", "bytes": 40091, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21315/mjms2020.27.6.6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7785266", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE22255", "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=GSE22255", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22255", "version": null, "note": "The mRNA microarray expression dataset GSE22255, which is based on the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Inc., Santa Clara, CA, USA), was retrieved from the Gene Expression Omnibus (GEO). 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE22255"], "resolved_accessions": ["GSE22255"], "statements": ["The mRNA microarray expression dataset GSE22255, which is based on the Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Inc., Santa Clara, CA, USA), was retrieved from the Gene Expression Omnibus (GEO). This dataset includes mRNA expression data from the peripheral blood mononuclear cells of 20 controls and 20 IS patients."], "basis": "The paper names GSE22255 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:33447134", "data:geo:GSE22255", "asset:table:pmid:33447134:1", "asset:table:pmid:33447134:2", "asset:table:pmid:33447134:3", "asset:table:pmid:33447134:4"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE22255"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:26:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 30722, "completion_tokens": 1416, "cached_tokens": 785}}, "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:33447134", "type": "paper", "label": "pmid:33447134"}, {"id": "source:pmid:33447134", "type": "manuscript", "label": "PMID 33447134 full text"}, {"id": "data:geo:GSE22255", "type": "dataset", "label": "GEO GSE22255"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33447134", "type": "paper", "label": "pmid:33447134"}, {"id": "source:pmid:33447134", "type": "manuscript", "label": "PMID 33447134 full text"}, {"id": "data:geo:GSE22255", "type": "dataset", "label": "GEO GSE22255"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33447134", "type": "extraction", "used": ["source:pmid:33447134"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE22255", "type": "accession_resolution", "used": ["data:geo:GSE22255"], "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:33447134", "parent_hash": "sha256:97bb7dab5b81924d7cbc556cf27659733eef90d70c8c3e9bcffc487f43908a3b", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE22255 licence not read", "asset:data:geo:GSE22255 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "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": ["significance of these genes in IS. 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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. 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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}}}