Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis of high-throughput data.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33325525", "kind": "science-record", "revision": 8, "content_hash": "sha256:179dfd32105b89007e23d971d22ee789969a2ddb9b7a907bc28dd122ca9ea025", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T22:02:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis of high-throughput data.", "doi": "10.1042/BSR20193823", "pmid": "33325525", "authors": ["Bin Zuo", "JunFeng Zhu", "Fei Xiao", "ChengLong Wang", "Yun Shen", "XiaoDong Chen"], "journal": "Bioscience reports", "year": 2020, "abstract": "BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases. The present study aimed to identify hub genes involved in the pathogenesis and further explore the potential treatment targets of RA and OA.\nMETHODS: The gene expression profile of GSE12021 was downloaded from Gene Expression Omnibus (GEO). Total 31 samples (12 RA, 10 OA and 9 NC samples) were used. The differentially expressed genes (DEGs) in RA versus NC, OA versus NC and RA versus OA groups were screened using limma package. We also verified the DEGs in GSE55235 and GSE100786. Functional annotation and protein-protein interaction (PPI) network construction of OA- and RA-specific DEGs were performed. Finally, the candidate small molecules as potential drugs to treat RA and OA were predicted in CMap database.\nRESULTS: 165 up-regulated and 163 down-regulated DEGs between RA and NC samples, 73 up-regulated and 293 down-regulated DEGs between OA and NC samples, 92 up-regulated and 98 down-regulated DEGs between RA and OA samples were identified. Immune response and TNF signaling pathway were significantly enriched pathways for RA- and OA-specific DEGs, respectively. The hub genes were mainly associated with 'Primary immunodeficiency' (RA vs. NC group), 'Ribosome' (OA vs. NC group), and 'Chemokine signaling pathway' (RA vs. OA group). Arecoline and Cefamandole were the most promising small molecule to reverse the RA and OA gene expression.\nCONCLUSION: Our findings suggest new insights into the underlying pathogenesis of RA and OA, which may improve the diagnosis and treatment of these intractable chronic diseases.", "claims": [{"id": "claim-method", "statement": "We queried the Connectivity Map (CMap, http://www.broadinstitute.org/cmap/) to screen the candidate small molecule drugs based on the gene signature of RA and OA. CMap is a collection of databases that stores thousands of gene transcription-expression profiles from cultured mammalian cells exposed to active small molecule drugs. The DEGs were divided into up-regulated and down-regulated groups. The enrichment scores ranging from −1 to +1 were calculated, which represented the similarity.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33325525", "locator": "sections[9] \"Identification of small molecules\" paragraph 2", "quote": "We queried the Connectivity Map (CMap, http://www.broadinstitute.org/cmap/) to screen the candidate small molecule drugs based on the gene signature of RA and OA. CMap is a collection of databases that stores thousands of gene transcription-expression profiles from cultured mammalian cells exposed to active small molecule drugs. The DEGs were divided into up-regulated and down-regulated groups. The enrichment scores ranging from −1 to +1 were calculated, which represented the similarity."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset GSE12021 contained data of synovial tissues from 31 samples, including 9 normal control (NC), 12 RA, and 10 OA samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33325525", "locator": "sections[3] \"Data resources\" paragraph 2", "quote": "The dataset GSE12021 contained data of synovial tissues from 31 samples, including 9 normal control (NC), 12 RA, and 10 OA samples."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33325525"], "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:GSE100786"], "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:GSE100786"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33325525", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1042/BSR20193823", "sha256": "sha256:6e83a8e38e31b9ebc53210d43112fb684a8a50fe1a28770e9788dc7f80fa1fe0", "bytes": 21746, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1042/BSR20193823", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7744737", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE100786", "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=GSE100786", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE100786", "version": null, "note": "The dataset GSE12021 contained data of synovial tissues from 31 samples, including 9 normal control (NC), 12 RA, and 10 OA samples.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The dataset GSE12021 contained data of synovial tissues from 31 samples, including 9 normal control (NC), 12 RA, and 10 OA samples.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2693242", "GSM2693243", "GSM2693244", "GSM2693245", "GSM2693246", "GSM2693247", "GSM2693248", "GSM2693249", "GSM2693250", "GSM2693251", "GSM2693252", "GSM2693253", "GSM2693254", "GSM2693255", "GSM2693256", "GSM2693257", "GSM2693258", "GSM2693259", "GSM2693260", "GSM2693261", "GSM2693262", "GSM2693263", "GSM2693264", "GSM2693265", "GSM2693266", "GSM2693267", "GSM2693268", "GSM2693269"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data of bone marrow and blood monocytes from patients with rheumatoid arthritis (RA) and osteoarthritis (OA)", "resolution_checked_at": 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"15", "ITGAX", "24"], ["CD2", "22", "DICER1", "8", "CTLA4", "23"], ["CD27", "22", "SIL1", "7", "CCL5", "21"], ["CXCL10", "19", "TLR7", "7", "CXCL10", "20"], ["CCL5", "19", "DHX9", "7", "STAT1", "20"], ["CD79A", "18", "RPL27A", "7", "CXCR3", "18"], ["CD79B", "18", "SOCS3", "6", "APOE", "17"], ["CXCL9", "17", "RPL35A", "6", "CXCL9", "16"], ["IL2RG", "17", "INSR", "6", "IL7R", "15"]], "row_count": 11, "column_count": 6, "numeric_cells": 38, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T4"}}, {"id": "asset:table:pmid:33325525:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c0f9ef6b374b3abd15f47d186ab42b403937e72ea19ac6e38d28b70eda0fbe82", "bytes": 1095, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T5", "version": null, "note": "List of the 10 most significant small molecule drugs that can reverse the tumoral status of RA and OA", "structure": {"pmcid": "PMC7744737", "section_index": 15, "section_title": "Identification of related active small molecules", "row_count": 21, "column_count": 4}, "table": {"label": "Table 5", "caption": "List of the 10 most significant small molecule drugs that can reverse the tumoral status of RA and OA", "rows": [["Arthritic tissue", "CMap name", "enrichment", "p value"], ["RA versus NC", "Cefamandole", "-0.939", "0"], ["", "Arachidonyltrifluoromethane", "-0.869", "0.03438"], ["", "Quipazine", "-0.85", "0.00095"], ["", "Isometheptene", "-0.847", "0.00101"], ["", "Nadolol", "-0.825", "0.00177"], ["", "3-Acetamidocoumarin", "-0.824", "0.00185"], ["", "Prestwick-1082", "-0.815", "0.0125"], ["", "Aciclovir", "-0.809", "0.00014"], ["", "Canadine", "-0.809", "0.00259"], ["", "Gentamicin", "-0.783", "0.00444"], ["OA versus NC", "Arecoline", "-0.889", "0.00034"], ["", "Sulmazole", "-0.885", "0.00298"], ["", "Prestwick-983", "-0.875", "0.00393"], ["", "Ciclopirox", "-0.853", 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"data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We queried the Connectivity Map (CMap, http://www.broadinstitute.org/cmap/) to screen the candidate small molecule drugs based on the gene signature of RA and OA. CMap is a collection of databases that stores thousands of gene transcription-expression profiles from cultured mammalian cells exposed to active small molecule drugs. The DEGs were divided into up-regulated and down-regulated groups. The enrichment scores ranging from −1 to +1 were calculated, which represented the similarity."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["GSE12021", "GSE55235", "GSE100786"], "resolved_accessions": ["GSE12021", "GSE55235", "GSE100786"], "statements": ["The dataset GSE12021 contained data of synovial tissues from 31 samples, including 9 normal control (NC), 12 RA, and 10 OA samples."], "basis": "The paper names GSE12021, GSE55235, GSE100786 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:33325525", "data:geo:GSE100786", "asset:table:pmid:33325525:1", "asset:table:pmid:33325525:2", "asset:table:pmid:33325525:3", "asset:table:pmid:33325525:4", "asset:table:pmid:33325525:5"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE100786"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:25:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 16857, "completion_tokens": 2425, "cached_tokens": 716}}, "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:33325525", "type": "paper", "label": "pmid:33325525"}, {"id": "source:pmid:33325525", "type": "manuscript", "label": "PMID 33325525 full text"}, {"id": "data:geo:GSE100786", "type": "dataset", "label": "GEO GSE100786"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33325525", "type": "paper", "label": "pmid:33325525"}, {"id": "source:pmid:33325525", "type": "manuscript", "label": "PMID 33325525 full text"}, {"id": "data:geo:GSE100786", "type": "dataset", "label": "GEO GSE100786"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33325525", "type": "extraction", "used": ["source:pmid:33325525"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE100786", "type": "accession_resolution", "used": ["data:geo:GSE100786"], "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:33325525", "parent_hash": "sha256:f146073748b4c834c3f3c32fe20bdf433390053434cca11a2cecf4de834f33a3", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE100786 licence not read", "asset:data:geo:GSE100786 not downloaded", "asset:data:geo:GSE12021 licence not read", "asset:data:geo:GSE12021 not downloaded", "asset:data:geo:GSE55235 licence not read", "asset:data:geo:GSE55235 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": 0.7, "evidence": ["limma"], "order_basis": "analysis_only", "id": "assay:1"}]}