Identification of Key Biomarkers and Immune Infiltration in Systemic Juvenile Idiopathic Arthritis by Integrated Bioinformatic Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34336925", "kind": "science-record", "revision": 7, "content_hash": "sha256:1afb5d838e2d9b5be1cd0d8570be207a2b12945471a551a9067369b8b5809699", "created_at": "2026-11-01T15:41:46Z", "updated_at": "2026-11-01T22:04:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Key Biomarkers and Immune Infiltration in Systemic Juvenile Idiopathic Arthritis by Integrated Bioinformatic Analysis.", "doi": "10.3389/fmolb.2021.681526", "pmid": "34336925", "authors": ["Min Zhang", "Rongxin Dai", "Qin Zhao", "Lina Zhou", "Yunfei An", "Xuemei Tang", "Xiaodong Zhao"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Systemic juvenile idiopathic arthritis (sJIA) is a rare and serious type of JIA characterized by an unknown etiology and atypical manifestations in the early stage, and early diagnosis and effective treatment are needed. We aimed to identify diagnostic biomarkers, immune cells and pathways involved in sJIA pathogenesis as well as potential treatment targets. The GSE17590, GSE80060, and GSE112057 gene expression profiles from the Gene Expression Omnibus (GEO) database were screened to obtain differentially expressed genes (DEGs) between sJIA and healthy controls. Common DEGs were subjected to pathway enrichment analysis; a protein-protein interaction network was constructed, and hub genes were identified. In addition, functional annotation of hub genes was performed with GenCLiP2. Immune infiltration analysis was then conducted with xCell, and correlation analysis between immune cells and the enriched pathways identified from gene set variation analysis was performed. The Connectivity Map database was used to identify candidate molecules for treating sJIA patients. Finally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out, and the GEO dataset GSE8361 was applied for validation of hub gene expression levels in blood samples from healthy individuals with sJIA. A total of 73 common DEGs were identified, and analysis indicated enrichment of neutrophil and platelet functions and the MAPK pathway in sJIA. Six hub genes were identified, of which three had high diagnostic sensitivity and specificity; ARG1 and PGLYRP1 were validated by qRT-PCR and microarray data of the GSE8361 dataset. We found that increased megakaryocytes and decreased Th1 cells correlated positively and negatively with the MAPK pathway, respectively. Furthermore, MEK inhibitors and some kinase inhibitors of the MAPK family were identified as candidate agents for sJIA treatment. Our results indicate two candidate markers for sJIA diagnosis and reveal the important roles of platelets and the MAPK pathway in the pathogenesis of sJIA, providing a new perspective for exploring potential molecular targets for sJIA treatment.", "claims": [{"id": "claim-method", "statement": "An unpaired Student’s t-test was applied for comparison between healthy individuals and sJIA patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34336925", "locator": "sections[13] \"Statistical Analyses\" paragraph 2", "quote": "An unpaired Student’s t-test was applied for comparison between healthy individuals and sJIA patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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"GSM207211", "GSM207213", "GSM207214", "GSM207215"], "sample_count": 65, "group_sizes": null, "group_sizes_basis": null, "platform": "1291", "taxon": "Homo sapiens", "title": "Juvenile idiopathic arthritis: peripheral blood cells", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34336925:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6634c06fa0a3a0a271565f80b89ffd679997cd6983bd9dcdb7a0cfde43a53175", "bytes": 1811, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[21]/table-wrap[1]#T1", "version": null, "note": "The 20 most significant small-molecule drugs with negative connectivity scores (suggesting that they can reverse sJIA).", "structure": {"pmcid": "PMC8316978", "section_index": 21, "section_title": "Identification of Related Active Small Molecules", "row_count": 21, "column_count": 5}, "table": {"label": "TABLE 1", "caption": "The 20 most significant small-molecule drugs with negative connectivity scores (suggesting that they can reverse sJIA).", "rows": [["Rank", "Name", "Score", "Target", "MOA"], ["1", "JAK3-inhibitor-I*", "-99.89", "JAK3", "JAK inhibitor"], ["2", "Cyclo-[Arg-Gly-Asp-D-Phe-Val]", "-99.89", "ITGAV, ITGB3", "Integrin antagonist"], ["3", "Phenazone", "-99.89", "PTGS1, PTGS2", "Cyclooxygenase inhibitor"], ["4", "SC-68376*", "-99.82", "MAPK14", "p38 MAPK inhibitor"], ["5", "PD-123319", "-99.77", "AGTR2", "Angiotensin receptor antagonist"], ["6", "CG-930*", "-99.72", "MAPK8", "JNK inhibitor"], ["7", "Lapatinib", "-99.7", "EGFR, ERBB2, CYP3A5", "EGFR inhibitor, ErbB2 inhibitor"], ["8", "Tipifarnib", "-99.68", "FNTA, FNTB", "Farnesyltransferase inhibitor"], ["9", "PKCbeta-inhibitor", "-99.68", "PRKCB", "PKC inhibitor"], ["10", "MK-1775", "-99.61", "WEE1", "WEE1 kinase inhibitor"], ["11", "T-0070907", "-99.58", "PPARG", "PPAR receptor antagonist"], ["12", "QL-XI-92", "-99.44", "DDR1", "DDR1 inhibitor"], ["13", "AS-703026*", "-99.22", "MAP2K1, MAP2K2", "MEK inhibitor"], ["14", "PD-98059*", "-99.12", "MAP2K1, MAP2K2, MAPK1, MAPK11, MAPK12, MAPK14, MAPK3, MAPK8", "MEK inhibitor, MAP kinase inhibitor"], ["15", "Selumetinib*", "-99.05", "MAP2K1, MAP2K2", "MEK inhibitor"], ["16", "Palonosetron", "-99.01", "HTR3A", "Serotonin receptor antagonist"], ["17", "Cisapride", "-98.96", "HTR4, KCNH2, CYP2B6, CYP2C8, CYP3A5, CYP3A7", "Serotonin receptor agonist"], ["18", "Terazosin", "-98.91", "ADRA1D, ADRA1A, ADRA1B, KCNH2, KCNH6,", "Adrenergic receptor antagonist"], ["19", "PD-0325901*", "-98.91", "MAP2K1, MAP2K2", "MEK inhibitor, MAP kinase inhibitor"], ["20", "LY-303511", "-98.87", "CSNK2A1, CSNK2A2, CSNK2B, MTOR", "Casein kinase inhibitor, MTOR inhibitor, PI3K inhibitor"]], "row_count": 21, "column_count": 5, "numeric_cells": 53, 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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": ["GSE17590", "GSE80060", "GSE112057", "GSE8361"], "resolved_accessions": ["GSE17590", "GSE80060", "GSE112057", "GSE8361"], "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 GSE17590, GSE80060, GSE112057, GSE8361 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": ["pca_fit"], "assets": ["source:pmid:34336925", "data:geo:GSE112057", "asset:table:pmid:34336925:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE112057"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:33:10Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 42763, "completion_tokens": 1713, "cached_tokens": 792}}, "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:34336925", "type": "paper", "label": "pmid:34336925"}, {"id": "source:pmid:34336925", "type": "manuscript", "label": "PMID 34336925 full text"}, {"id": "data:geo:GSE112057", "type": "dataset", "label": "GEO GSE112057"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34336925", "type": "paper", "label": "pmid:34336925"}, {"id": "source:pmid:34336925", "type": "manuscript", "label": "PMID 34336925 full text"}, {"id": "data:geo:GSE112057", "type": "dataset", "label": "GEO GSE112057"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34336925", "type": "extraction", "used": ["source:pmid:34336925"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE112057", "type": "accession_resolution", "used": ["data:geo:GSE112057"], "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:34336925", "parent_hash": "sha256:02c37c6ca839505468a78feefb19feb4cbc13d2d3a708147fb70399132fa9f5b", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE112057 licence not read", "asset:data:geo:GSE112057 not downloaded", "asset:data:geo:GSE17590 licence not read", "asset:data:geo:GSE17590 not downloaded", "asset:data:geo:GSE80060 licence not read", "asset:data:geo:GSE80060 not downloaded", "asset:data:geo:GSE8361 licence not read", "asset:data:geo:GSE8361 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": ["G1 and PGLYRP1 were validated by qRT-PCR and microarray data of the GSE8361 dataset. We found that i"], "order_basis": "paper_text_order:1694", "id": "assay:1"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["PCA"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}