Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37732317", "kind": "science-record", "revision": 4, "content_hash": "sha256:552265a9025b82775c4678a19801670ac18e5023dad0a95dd8a575a7e3ee45bd", "created_at": "2026-11-01T19:02:34Z", "updated_at": "2026-11-01T22:52:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analyses of m6A RNA methylation patterns and related immune microenvironment in idiopathic pulmonary arterial hypertension.", "doi": "10.3389/fgene.2023.1222368", "pmid": "37732317", "authors": ["Gufeng Gao", "Ai Chen", "Jin Gong", "Weijun Lin", "Weibin Wu", "Sagor Mohammad Ismail Hajary", "Guili Lian", "Li Luo", "Liangdi Xie"], "journal": "Frontiers in genetics", "year": 2023, "abstract": "Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease with a poor prognosis and high heritability, characterized by elevated pulmonary vascular resistance (PVR) and pulmonary artery pressure. N6-methyladenosine (m6A) RNA modification influences many RNA metabolism pathways. However, the position of m6A methylation regulators in IPAH remains unknown. Therefore, the study aims to disclose the function m6A regulators exert in the pathological mechanisms of IPAH and the immune microenvironment involved. The GSE117261 dataset was downloaded from the Gene Expression Omnibus (GEO) to screen the differentially expressed genes (DEGs) between normal and IPAH samples. Functional and pathway enrichment analyses of DEGs were then conducted by Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also identified the differentially-expressed m6A (DEm6A) regulators between normal and IPAH samples. Key m6A regulators related to the prediction of IPAH were selected using the random forest model. The results showed that FMR1, RBM15, HNRNPA2B1 and IGFBP3 were upregulated in IPAH. In contrast, LRPPRC was downregulated. The single sample gene set enrichment analysis (ssGSEA) method was then adopted to estimate the immune microenvironment in distinct m6A clusters and m6A phenotype-related genes (PRGs) clusters, respectively. Furthermore, we calculated the m6A score via principal component analysis (PCA), and the Sankey diagram was selected to present the correlation among the m6A clusters, m6A PRGs clusters and m6A score. Finally, quantitative RT-PCR and Western blotting were used to validate the key genes in human pulmonary artery smooth muscle cells (HPASMCs) treated by human platelet-derived growth factor-BB (PDGF-BB). The relative mRNA and protein expression levels of FMR1 were significantly elevated, however, the relative mRNA and protein expression levels of LRPPRC were downregulated. Besides, the relative mRNA level of HNRNPA2B1 was increased. Generally, this bioinformatics analysis might provoke more insights into diagnosing and treating IPAH.", "claims": [{"id": "claim-method", "statement": "Genes with different expression levels between normal and IPAH lung tissues were collected via the “limma” package with the criterion of adjusted p-value <0.05 and |logFC| >1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37732317", "locator": "sections[3] \"2.1 Data collection and process\" paragraph 2", "quote": "Genes with different expression levels between normal and IPAH lung tissues were collected via the “limma” package with the criterion of adjusted p-value <0.05 and |logFC| >1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117261.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37732317", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117261."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The results showed that FMR1, RBM15, HNRNPA2B1 and IGFBP3 were upregulated in IPAH. In contrast, LRPPRC was downregulated.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37732317", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The results showed that FMR1, RBM15, HNRNPA2B1 and IGFBP3 were upregulated in IPAH. In contrast, LRPPRC was downregulated."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The results showed that FMR1, RBM15, HNRNPA2B1 and IGFBP3 were upregulated in IPAH. In contrast, LRPPRC was downregulated.", "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:37732317"], "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:GSE117261"], "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:GSE117261"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37732317", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2023.1222368", "sha256": "sha256:7c26c3134faf5cd0f48a779992eae6a560b3eccfbdd370992c1fb9fa8158277e", "bytes": 38121, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2023.1222368", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10507408", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"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": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117261.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117261.", "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}}], "gaps": ["asset:data:geo:GSE117261 not downloaded", "asset:data:geo:GSE117261 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Genes with different expression levels between normal and IPAH lung tissues were collected via the “limma” package with the criterion of adjusted p-value <0.05 and |logFC| >1."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "analysis of variance"}}, {"id": "method-3", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "principal component analysis"}}, {"id": "method-4", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "random forest"}}, {"id": "method-5", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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"], "resolved_accessions": ["GSE117261"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117261."], "basis": "The paper names GSE117261 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37732317", "data:geo:GSE117261"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE117261"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:54:01Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11463, "completion_tokens": 1035, "cached_tokens": 128}}, "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:37732317", "type": "paper", "label": "pmid:37732317"}, {"id": "source:pmid:37732317", "type": "manuscript", "label": "PMID 37732317 full text"}, {"id": "data:geo:GSE117261", "type": "dataset", "label": "GEO GSE117261"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37732317", "type": "paper", "label": "pmid:37732317"}, {"id": "source:pmid:37732317", "type": "manuscript", "label": "PMID 37732317 full text"}, {"id": "data:geo:GSE117261", "type": "dataset", "label": "GEO GSE117261"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37732317", "type": "extraction", "used": ["source:pmid:37732317"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE117261", "type": "accession_resolution", "used": ["data:geo:GSE117261"], "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:37732317", "parent_hash": "sha256:885699af258b30cd6e4d5867f108f2a560d93fefafa3521b0ed3de50fb33b42a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE117261 licence not read", "asset:data:geo:GSE117261 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": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["m6A score. Finally, quantitative RT-PCR and Western blotting were used to validate the key genes in human"], "order_basis": "paper_text_order:1707", "id": "assay:1"}, {"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": ["Genes with different expression levels between normal and IPAH lung tissues were collected via the “limma” package with the criterion of adjusted p-value <0.05 and |logFC| >1."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}