{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38883633", "kind": "science-record", "revision": 4, "content_hash": "sha256:4cae74950faa8a7718f9264f16f8ae6754a72554e6276bd1a25347dd59dc3b4c", "created_at": "2026-11-01T20:28:57Z", "updated_at": "2026-11-01T22:54:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative bioinformatics approach for identifying key genes and potential therapeutic targets in the concurrent manifestation of hypertrophic cardiomyopathy and pulmonary hypertension.", "doi": "10.21037/jtd-23-1822", "pmid": "38883633", "authors": ["Xi Zheng", "Chenyang Zhang", "Tao Yang", "Zhanyang Luo", "Junyi Xia", "Weibin Tian", "Juan Shao", "Hu Zhang", "Jingru Gong", "Xuhui Bao"], "journal": "Journal of thoracic disease", "year": 2024, "abstract": "Background: Hypertrophic cardiomyopathy (HCM), identified as a primary cause of sudden cardiac death (SCD), intertwines with pulmonary hypertension (PH) to amplify cardiovascular morbidity. This complex synergy poses significant therapeutic challenges due to the absence of drugs specifically targeting their concurrent manifestation. This study seeks to unravel the molecular intricacies linking HCM and PH, aiming to lay the groundwork for targeted therapeutic interventions.\nMethods: Through the analysis of gene expression profiles from datasets GSE36961 (HCM) and GSE113439 (PH) within the public data repository of Gene Expression Omnibus (GEO), this research systematically identified differentially expressed genes (DEGs), conducted extensive functional annotations, and constructed detailed protein-protein interaction (PPI) networks to uncover crucial hub genes. Further, co-expression analyses, alongside drug prediction and molecular docking simulations, were employed to pinpoint potential therapeutic agents that could ameliorate the combined pathology of HCM and PH.\nResults: Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub genes. Validation across three additional datasets (GSE35229, GSE32453, and GSE53408) from GEO accentuated secreted phosphoprotein 1 (SPP1) as a key gene of interest. Remarkably, the study identified tacrolimus, ponatinib, bosutinib, dasatinib, doxorubicin, and zanubrutinib as promising drugs for addressing the dual challenge of HCM and PH.\nConclusions: The findings of this investigation shed light on the genetic underpinnings of HCM and PH's simultaneous occurrence, emphasizing the central role of SPP1 in their pathogenesis. The identification of six candidate drugs offers a hopeful vista for future therapeutic strategies targeting this complex cardiovascular interplay, marking a significant stride towards mitigating the compounded morbidity of HCM and PH. Future mechanistic and clinical studies are warranted for the investigation of this potential target and therapeutics.", "claims": [{"id": "claim-method", "statement": "GEO2R based on R language “limma” package, is a function recently updated by the GEO. It was used to screen DEGs by calculating and visualizing the differential expression multiple [settings: P<0.05, absolute fold change (FC) ≥1.5].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38883633", "locator": "sections[5] \"Identification of DEGs\" paragraph 2", "quote": "GEO2R based on R language “limma” package, is a function recently updated by the GEO. It was used to screen DEGs by calculating and visualizing the differential expression multiple [settings: P<0.05, absolute fold change (FC) ≥1.5]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GSE36961 contained 106 HCM and 39 non-HCM samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38883633", "locator": "sections[4] \"Data acquisition\" paragraph 2", "quote": "GSE36961 contained 106 HCM and 39 non-HCM samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38883633", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our comprehensive analysis unearthed 79 DEGs shared between HCM and PH, highlighting fourteen as pivotal hub 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:38883633"], "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:GSE113439"], "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:GSE113439"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38883633", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/jtd-23-1822", "sha256": "sha256:ab2d9296e1471616bbfbcc429c4d997c2e5f1e05d3c6194527f330d5e8655077", "bytes": 49864, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/jtd-23-1822", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11170365", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE113439", "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=GSE113439", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE113439", "version": null, "note": "GSE36961 contained 106 HCM and 39 non-HCM samples.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE36961 contained 106 HCM and 39 non-HCM samples.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM3106326", "GSM3106327", "GSM3106328", "GSM3106329", "GSM3106330", "GSM3106331", "GSM3106332", "GSM3106333", "GSM3106334", "GSM3106335", "GSM3106336", "GSM3106337", "GSM3106338", "GSM3106339", "GSM3106340", "GSM3106341", "GSM3106342", "GSM3106343", "GSM3106344", "GSM3106345", "GSM3106346", "GSM3106347", "GSM3106348", "GSM3106349", "GSM3106350", "GSM3106351"], "sample_count": 26, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression profiling of pulmonary arterial hypertension", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE32453", "role": "raw", "format": "geo-series", "media_type": 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sapiens", "title": "Expression data from patient iPSC", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE36961", "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=GSE36961", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE36961", "version": null, "note": "GSE36961 contained 106 HCM and 39 non-HCM samples.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE36961 contained 106 HCM and 39 non-HCM samples.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM907203", "GSM907204", "GSM907205", "GSM907206", "GSM907207", "GSM907208", "GSM907209", "GSM907210", "GSM907211", 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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": ["GSE36961", "GSE35229", "GSE113439", "GSE53408", "GSE32453"], "resolved_accessions": ["GSE36961", "GSE35229", "GSE113439", "GSE53408", "GSE32453"], "statements": ["GSE36961 contained 106 HCM and 39 non-HCM samples."], "basis": "The paper names GSE36961, GSE35229, GSE113439, GSE53408, GSE32453 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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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}}}