Integrated Bioinformatic Analysis Reveals TXNRD1 as a Novel Biomarker and Potential Therapeutic Target in Idiopathic Pulmonary Arterial Hypertension.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35646965", "kind": "science-record", "revision": 5, "content_hash": "sha256:6560bb9aa35b8386dad66ef993c1e50b76690101c20dde7dff3908bfbb327e2b", "created_at": "2026-11-01T18:14:34Z", "updated_at": "2026-11-01T22:49:11Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Bioinformatic Analysis Reveals TXNRD1 as a Novel Biomarker and Potential Therapeutic Target in Idiopathic Pulmonary Arterial Hypertension.", "doi": "10.3389/fmed.2022.894584", "pmid": "35646965", "authors": ["Wenchao Lin", "Yiyang Tang", "Mengqiu Zhang", "Benhui Liang", "Meijuan Wang", "Lihuang Zha", "Zaixin Yu"], "journal": "Frontiers in medicine", "year": 2022, "abstract": "Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening cardiopulmonary disease lacking specific diagnostic markers and targeted therapy, and its mechanism of development remains to be elucidated. The present study aimed to explore novel diagnostic biomarkers and therapeutic targets in IPAH by integrated bioinformatics analysis. Four eligible datasets (GSE117261, GSE15197, GSE53408, GSE48149) was firstly downloaded from GEO database and subsequently integrated by Robust rank aggregation (RRA) method to screen robust differentially expressed genes (DEGs). Then functional annotation of robust DEGs was performed by GO and KEGG enrichment analysis. The protein-protein interaction (PPI) network was constructed followed by using MCODE and CytoHubba plug-in to identify hub genes. Finally, 10 hub genes were screened including ENO1, TALDO1, TXNRD1, SHMT2, IDH1, TKT, PGD, CXCL10, CXCL9, and CCL5. The GSE113439 dataset was used as a validation cohort to appraise these hub genes and TXNRD1 was selected for verification at the protein level. The experiment results confirmed that serum TXNRD1 concentration was lower in IPAH patients and the level of TXNRD1 had great predictive efficiency (AUC:0.795) as well as presents negative correlation with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Consistently, the expression of TXNRD1 was proved to be inhibited in animal and cellular model of PAH. In addition, GSEA analysis was performed to explore the functions of TXNRD1 and the results revealed that TXNRD1 was closely correlated with mTOR signaling pathway, MYC targets, and unfolded protein response. Finally, knockdown of TXNRD1 was shown to exacerbate proliferative disorder, migration and apoptosis resistance in PASMCs. In conclusion, our study demonstrates that TXNRD1 is a promising candidate biomarker for diagnosis of IPAH and plays an important role in PAH pathogenesis, although further research is necessary.", "claims": [{"id": "claim-method", "statement": "To determine DEGs between IPAH and control group, we utilized limma R package to analyze with the cut-off criteria of | log2 fold-change (FC)| > 0.5 and P-value < 0.05. Identified DEGs from each dataset were integrated using the Robust Rank Aggregation (RRA) method to minimize the inconsistency.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35646965", "locator": "sections[4] \"Identification of Robust Differentially Expressed Genes Among Each Gene Expression Omnibus Dataset\" paragraph 2", "quote": "To determine DEGs between IPAH and control group, we utilized limma R package to analyze with the cut-off criteria of | log2 fold-change (FC)| > 0.5 and P-value < 0.05. Identified DEGs from each dataset were integrated using the Robust Rank Aggregation (RRA) method to minimize the inconsistency."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors declare that all data supporting the findings of this study are available in Zenodo (DOI: 10.5281/zenodo.5840973). If any other requirements were requested, please contact the author at convenience.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35646965", "locator": "sections[15] \"Data Availability\" paragraph 2", "quote": "The authors declare that all data supporting the findings of this study are available in Zenodo (DOI: 10.5281/zenodo.5840973). If any other requirements were requested, please contact the author at convenience."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Integration of four GEO lung-tissue datasets by robust rank aggregation identified TXNRD1 as a downregulated candidate in IPAH, with serum TXNRD1 showing an AUC of 0.795 for diagnosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35646965", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Four eligible datasets (GSE117261, GSE15197, GSE53408, GSE48149) was firstly downloaded from GEO database and subsequently integrated by Robust rank aggregation (RRA) method to screen robust differentially expressed genes (DEGs)."}, {"asset": "source:pmid:35646965", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The experiment results confirmed that serum TXNRD1 concentration was lower in IPAH patients and the level of TXNRD1 had great predictive efficiency (AUC:0.795) as well as presents negative correlation with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Integration of four GEO lung-tissue datasets by robust rank aggregation identified TXNRD1 as a downregulated candidate in IPAH, with serum TXNRD1 showing an AUC of 0.795 for diagnosis.", "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:35646965"], "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:35646965", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmed.2022.894584", "sha256": "sha256:d5ee4ff62e94dd237053ce7275fe673273f17cb12fa6a5fe883a914c4c498124", "bytes": 39663, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmed.2022.894584", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9133447", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "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 authors declare that all data supporting the findings of this study are available in Zenodo (DOI: 10.5281/zenodo.5840973). 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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": ["GSE117261", "GSE53408", "GSE48149", "GSE15197", "GSE113439"], "resolved_accessions": ["GSE117261", "GSE53408", "GSE48149", "GSE15197", "GSE113439"], "statements": ["The authors declare that all data supporting the findings of this study are available in Zenodo (DOI: 10.5281/zenodo.5840973). If any other requirements were requested, please contact the author at convenience."], "basis": "The paper names GSE117261, GSE53408, GSE48149, GSE15197, GSE113439 in Gene Expression Omnibus (GEO) database 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:35646965", "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": "2026-11-01T17:48:23Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11130, "completion_tokens": 2496, "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:35646965", "type": "paper", "label": "pmid:35646965"}, {"id": "source:pmid:35646965", "type": "manuscript", "label": "PMID 35646965 full text"}, {"id": "data:geo:GSE113439", "type": "dataset", "label": "GEO GSE113439"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35646965", "type": "paper", "label": "pmid:35646965"}, {"id": "source:pmid:35646965", "type": "manuscript", "label": "PMID 35646965 full text"}, {"id": "data:geo:GSE113439", "type": "dataset", "label": "GEO GSE113439"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35646965", "type": "extraction", "used": ["source:pmid:35646965"], "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:35646965", "parent_hash": "sha256:0939b25afd7f017af69eb67fbe796d0a051017157ebc9ef7e5fbec885a53959b", "fork_of": null, "generation": 4}, "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:GSE15197 licence not read", "asset:data:geo:GSE15197 not downloaded", "asset:data:geo:GSE48149 licence not read", "asset:data:geo:GSE48149 not downloaded", "asset:data:geo:GSE53408 licence not read", "asset:data:geo:GSE53408 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": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ets, and unfolded protein response. Finally, knockdown of TXNRD1 was shown to exacerbate proliferat", "h. For gene knockdown in PASMCs, cells were transfected with control siRNA or si-TXNRD1 in antibioti", "Hill, NJ, United States) for 24 h. For gene knockdown in PASMCs, cells were transfected with contr", "PASMCs, cells were transfected with control siRNA or si-TXNRD1 in antibiotic-free medium for 4"], "order_basis": "paper_text_order:1774", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["erbate proliferative disorder, migration and apoptosis resistance in PASMCs. In conclusion, our stu"], "order_basis": "paper_text_order:1856", "id": "assay:2"}, {"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": ["South University. Fourteen 180–200 g male SD rats were raised under standard laboratory conditions", "for the care and use of rat. One week later, rats were randomly divided into control group and MCT", "ted States) respectively. After 21 days, the rats were anesthetized and the right ventricle systoli", "rough right heart catheterization. Then, the rats were sacrificed, and lung and heart tissues were"], "order_basis": "paper_text_order:2255", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were collected for histological analysis and western blotting. The RV hypertrophy index was calculated as", "ples, TXNRD1 expression was also verified by Western blotting using lung homogenate of monocrotaline (MCT)", "g homogenates from MCT rats were measured by Western blot analysis and the results indicated TXNRD1 wa", "ue in animal experiments. (B) Representative Western blots and quantification of TXNRD1 and β-actin in"], "order_basis": "paper_text_order:2850", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ing confluence. Cell purity was confirmed by immunofluorescence with smooth muscle cell actin (1:400, 67735-", "Figure 6B). The result was also confirmed by immunofluorescence staining in which TXNRD1 was predominantly e", "lated the rat PASMCs which were confirmed by immunofluorescence with alpha-sma (see Supplementary Figure 3)", "t t-test was used to compare two groups. (C) Immunofluorescence images of lung distal PA from MCT rats and c"], "order_basis": "paper_text_order:3714", "id": "assay:5"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["mental validation. Firstly, we collected the blood samples from 9 IPAH patients and 13 healthy controls to d"], "order_basis": "paper_text_order:7196", "id": "assay:6"}, {"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": ["To determine DEGs between IPAH and control group, we utilized limma R package to analyze with the cut-off criteria of | log2 fold-change (FC)| > 0.5 and P-value < 0.05. Identified DEGs from each dataset were integrated using the Robust Rank Aggregation (RRA) method to minimize the inconsistency."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}