Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35712711", "kind": "science-record", "revision": 4, "content_hash": "sha256:0adb38235613cbd0f9e6f41cd211e7a9c18985f564d948c89b17780bbb8cc946", "created_at": "2026-11-01T18:14:42Z", "updated_at": "2026-11-01T22:06:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension.", "doi": "10.3389/fphar.2022.908783", "pmid": "35712711", "authors": ["Yan Liu", "Jun-Zhuo Shi", "Rong Jiang", "Shao-Fei Liu", "Yang-Yang He", "Emiel P C van der Vorst", "Christian Weber", "Yvonne Döring", "Yi Yan"], "journal": "Frontiers in pharmacology", "year": 2022, "abstract": "Objective: Regulatory T cells (Tregs) are critical immune modulators to maintain immune homeostasis and limit pulmonary hypertension (PH). This study was aimed to identify Treg-related genes (TRGs) in PH. Methods: The gene expression profile from lungs of PH patients was retrieved from the Gene Expression Omnibus (GEO) database. The abundance of Tregs was estimated by the xCell algorithm, the correlation of which with differentially expressed genes (DEGs) was performed. DEGs with a |Pearson correlation coefficient| >0.4 were identified as TRGs. Functional annotation and the protein-protein interaction (PPI) network were analyzed. A gene signature for 25 hub TRGs (TRGscore) was generated by a single sample scoring method to determine its accuracy to distinguish PH from control subjects. TRGs were validated in datasets of transcriptional profiling of PH cohorts and in lung tissues of experimental PH mice. Results: A total of 819 DEGs were identified in lungs of 58 PAH patients compared to that of 25 control subjects of dataset GSE117261. In total, 165 of all these DEGs were correlated with the abundance of Tregs and identified as TRGs, with 90 upregulated genes and 75 downregulated genes compared to that of control subjects. The upregulated TRGs were enriched in negative regulation of multiple pathways, such as cAMP-mediated signaling and I-kappaB kinase/NF-kappaB signaling, and regulated by multiple genes encoding transcriptional factors including HIF1A. Furthermore, 25 hub genes categorized into three clusters out of 165 TRGs were derived, and we identified 27 potential drugs targeting 10 hub TRGs. The TRGscore based on 25 hub TRGs was higher in PH patients and could distinguish PH from control subjects (all AUC >0.7). Among them, 10 genes including NCF2, MNDA/Ifi211, HCK, FGR, CSF3R, AQP9, S100A8, G6PD/G6pdx, PGD, and TXNRD1 were significantly reduced in lungs of severe PH patients of dataset GSE24988 as well as in lungs of hypoxic PH mice compared to corresponding controls. Conclusion: Our finding will shed some light on the Treg-associated therapeutic targets in the progression of PH and emphasize on TRGscore as a novel indicator for PH.", "claims": [{"id": "claim-method", "statement": "The relationship of all DEGs with the abundance of Tregs was further investigated by Pearson correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35712711", "locator": "sections[5] \"Identification of Treg-Related Genes and the Functional Enrichment\" paragraph 2", "quote": "The relationship of all DEGs with the abundance of Tregs was further investigated by Pearson correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35712711", "locator": "sections[25] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The TRGscore based on 25 hub TRGs was higher in PH patients and could distinguish PH from control subjects (all AUC >0.7).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35712711", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The TRGscore based on 25 hub TRGs was higher in PH patients and could distinguish PH from control subjects (all AUC >0.7)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The TRGscore based on 25 hub TRGs was higher in PH patients and could distinguish PH from control subjects (all AUC >0.7).", "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:35712711"], "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:35712711", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphar.2022.908783", "sha256": "sha256:7fa0d44fc213939ad8b2674c8b3df6bae2cadc1c6e9944b3bf1e08ea56cff8db", "bytes": 52249, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphar.2022.908783", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9197497", "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": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_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:GSE117261", "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=GSE117261", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE117261", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3290067", "GSM3290068", "GSM3290069", "GSM3290070", "GSM3290071", "GSM3290072", "GSM3290073", "GSM3290074", "GSM3290075", "GSM3290076", "GSM3290077", "GSM3290078", "GSM3290079", "GSM3290080", "GSM3290081", "GSM3290082", "GSM3290083", "GSM3290084", "GSM3290085", "GSM3290086", "GSM3290087", "GSM3290088", "GSM3290089", "GSM3290090", "GSM3290091", "GSM3290092", "GSM3290093", "GSM3290094", "GSM3290095", "GSM3290096", "GSM3290097", "GSM3290098", "GSM3290099", "GSM3290100", "GSM3290101", "GSM3290102", "GSM3290103", "GSM3290104", "GSM3290105", "GSM3290106", "GSM3290107", "GSM3290108", "GSM3290109", "GSM3290110", "GSM3290111", "GSM3290112", "GSM3290113", "GSM3290114", "GSM3290115", "GSM3290116", "GSM3290117", "GSM3290118", "GSM3290119", "GSM3290120", "GSM3290121", "GSM3290122", "GSM3290123", "GSM3290124", "GSM3290125", "GSM3290126", "GSM3290127", "GSM3290128", "GSM3290129", "GSM3290130", "GSM3290131", "GSM3290132", "GSM3290133", "GSM3290134", "GSM3290135", "GSM3290136", "GSM3290137", "GSM3290138", "GSM3290139", "GSM3290140", "GSM3290141", "GSM3290142", "GSM3290143", "GSM3290144", "GSM3290145", "GSM3290146", "GSM3290147", "GSM3290148", "GSM3290149"], "sample_count": 83, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Systems Analysis of the Human Pulmonary Arterial Hypertension Lung Transcriptome", "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:GSE24988", "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=GSE24988", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE24988", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM613638", "GSM613639", "GSM613640", "GSM613641", "GSM613642", "GSM613643", "GSM613644", "GSM613645", "GSM613646", "GSM613647", "GSM613648", "GSM613649", "GSM613650", "GSM613651", "GSM613652", "GSM613653", "GSM613654", "GSM613655", "GSM613656", "GSM613657", "GSM613658", "GSM613659", "GSM613660", "GSM613661", "GSM613662", "GSM613663", "GSM613664", "GSM613665", "GSM613666", "GSM613667", "GSM613668", "GSM613669", "GSM613670", "GSM613671", "GSM613672", "GSM613673", "GSM613674", "GSM613675", "GSM613676", "GSM613677", "GSM613678", "GSM613679", "GSM613680", "GSM613681", "GSM613682", "GSM613683", "GSM613684", "GSM613685", "GSM613686", "GSM613687", "GSM613688", "GSM613689", "GSM613690", "GSM613691", "GSM613692", "GSM613693", "GSM613694", "GSM613695", "GSM613696", "GSM613697", "GSM613698", "GSM613699", "GSM613700", "GSM613701", "GSM613702", "GSM613703", "GSM613704", "GSM613705", "GSM613706", "GSM613707", "GSM613708", "GSM613709", "GSM613710", "GSM613711", "GSM613712", "GSM613713", "GSM613714", "GSM613715", "GSM613716", "GSM613717", "GSM613718", "GSM613719", "GSM613720", "GSM613721", "GSM613722", "GSM613723", "GSM613724", "GSM613725", "GSM613726", "GSM613727", "GSM613728", "GSM613729", "GSM613730", "GSM613731", "GSM613732", "GSM613733", "GSM613734", "GSM613735", "GSM613736", "GSM613737", "GSM613738", "GSM613739", "GSM613740", "GSM613741", "GSM613742", "GSM613743", "GSM613744", "GSM613745", "GSM613746", "GSM613747", "GSM613748", "GSM613749", "GSM613750", "GSM613751", "GSM613752", "GSM613753"], "sample_count": 116, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression profiles based on Pulmonary Artery Pressures in Pulmonary Fibrosis", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE113439 not downloaded", "asset:data:geo:GSE113439 licence not read", "asset:data:geo:GSE117261 not downloaded", "asset:data:geo:GSE117261 licence not read", "asset:data:geo:GSE24988 not downloaded", "asset:data:geo:GSE24988 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The relationship of all DEGs with the abundance of Tregs was further investigated by Pearson correlation analysis."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "targets": [], "gaps": []}, "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": ["pearson_r"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson."}, "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": ["GSE117261", "GSE24988", "GSE113439"], "resolved_accessions": ["GSE117261", "GSE24988", "GSE113439"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE117261, GSE24988, GSE113439 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": ["pearson_r"], "assets": ["source:pmid:35712711", "data:geo:GSE113439"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE113439"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:51:07Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15867, "completion_tokens": 1327, "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:35712711", "type": "paper", "label": "pmid:35712711"}, {"id": "source:pmid:35712711", "type": "manuscript", "label": "PMID 35712711 full text"}, {"id": "data:geo:GSE113439", "type": "dataset", "label": "GEO GSE113439"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35712711", "type": "paper", "label": "pmid:35712711"}, {"id": "source:pmid:35712711", "type": "manuscript", "label": "PMID 35712711 full text"}, {"id": "data:geo:GSE113439", "type": "dataset", "label": "GEO GSE113439"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35712711", "type": "extraction", "used": ["source:pmid:35712711"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE113439", "type": "accession_resolution", "used": ["data:geo:GSE113439"], "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:35712711", "parent_hash": "sha256:43d42891ff513d98319cada2202a9b9e344773829b142ea4f111579eacaf06eb", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE113439 licence not read", "asset:data:geo:GSE113439 not downloaded", "asset:data:geo:GSE117261 licence not read", "asset:data:geo:GSE117261 not downloaded", "asset:data:geo:GSE24988 licence not read", "asset:data:geo:GSE24988 not downloaded", "execution.not_run", "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": 0.99, "evidence": ["2020). A total of 16 male 8-week-old C57BL/6 mice were provided by Vital River Laboratories Co., Lt", "5 ± 2°C, and 50 ± 5% relative humidity). The mice were randomly kept either in the hypoxia chamber", "ondition). The feeding, water, and cages for mice were changed twice a week. Identification of TRGs"], "order_basis": "paper_text_order:2681", "id": "assay:1"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The relationship of all DEGs with the abundance of Tregs was further investigated by Pearson correlation analysis."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}