Comprehensive analysis of key genes and pathways for biological and clinical implications in thyroid-associated ophthalmopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36056316", "kind": "science-record", "revision": 5, "content_hash": "sha256:a19bf3ee35e4aa8f5653cd1a2004f9ccdb05154ca1abba05a6d13e17a1b78ef0", "created_at": "2026-11-01T18:15:14Z", "updated_at": "2026-11-01T22:49:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of key genes and pathways for biological and clinical implications in thyroid-associated ophthalmopathy.", "doi": "10.1186/s12864-022-08854-5", "pmid": "36056316", "authors": ["Yueyue Wang", "Yanfei Shao", "Haitao Zhang", "Jun Wang", "Peng Zhang", "Weizhong Zhang", "Huanhuan Chen"], "journal": "BMC genomics", "year": 2022, "abstract": "BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is a common and organ-specific autoimmune disease. Early diagnosis and novel treatments are essential to improve the prognosis of TAO patients. Therefore, the current work was performed to identify the key genes and pathways for the biological and clinical implications of TAO through comprehensive bioinformatics analysis and a series of clinical validations.\nMETHODS: GSE105149 and GSE185952 were obtained from the Gene Expression Omnibus (GEO) database for analysis. The data were normalized to identify the common differentially expressed genes (DEGs) between the two datasets, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to assess key pathways in TAO. Protein-protein interaction (PPI) networks and hub genes among the common DEGs were identified. Furthermore, we collected the general information and blood samples from 50 TAO patients and 20 healthy controls (HCs), and the expression levels of the proteins encoded by hub genes in serum were detected by enzyme-linked immunosorbent assay (ELISA). Then we further assessed the relationship between the ELISA data and the TAO development.\nRESULTS: Several common pathways, including neuroactive ligand-receptor interaction, the IL-17 signaling pathway, and the TNF signaling pathway, were identified in both datasets. In parallel, 52 common DEGs were identified. The KEGG analysis showed that these common DEGs are mainly enriched in long-term depression, the VEGF signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway, and cytokine-cytokine receptor interactions. The key hub genes PRKCG, OSM, DPP4, LRRTM1, CXCL6, and CSF3R were screened out through the PPI network. As confirmation, the ELISA results indicated that protein expression levels of PRKCG, OSM, CSF3R, and DPP4 were significantly upregulated in TAO patients compared with HCs. In addition, PRKCG and DPP4 were verified to show value in diagnosing TAO, and CSF3R was found to be a valuable diagnostic marker in distinguishing active TAO from inactive TAO.\nCONCLUSIONS: Inflammation- and neuromodulation-related pathways might be closely associated with TAO. Based on the clinical verification, OSM, CSF3R, CXCL6, DPP4, and PRKCG may serve as inflammation- or neuromodulation-related biomarkers for TAO, providing novel insights for the diagnosis and treatment of TAO.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) between the two datasets TAO and control samples were screened using the limma (linear models for microarray data) package of R software (version 4.1.0, AT&T Bell Laboratories, USA) [14].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36056316", "locator": "sections[4] \"Identification of differentially expressed genes\" paragraph 2", "quote": "Differentially expressed genes (DEGs) between the two datasets TAO and control samples were screened using the limma (linear models for microarray data) package of R software (version 4.1.0, AT&T Bell Laboratories, USA) [14]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36056316", "locator": "sections[26] \"notes\" paragraph 1", "quote": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In parallel, 52 common DEGs were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36056316", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In parallel, 52 common DEGs were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In parallel, 52 common DEGs were identified.", "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:36056316"], "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:GSE105149"], "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:GSE105149"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36056316", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12864-022-08854-5", "sha256": "sha256:488425ff61199d1cf5cb6689d6685646a304442417edb30f703f6c7d5c21ee40", "bytes": 37506, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12864-022-08854-5", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9440526", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE105149", "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=GSE105149", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE105149", "version": null, "note": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2823303", "GSM2823304", "GSM2823305", "GSM2823306", "GSM2823307", "GSM2823308", "GSM2823309", "GSM2823310", "GSM2823311", "GSM2823312", "GSM2823313", "GSM2823314", "GSM2823315", "GSM2823316", "GSM2823317", "GSM2823318", "GSM2823319", "GSM2823320", "GSM2823321", "GSM2823322", "GSM2823323", "GSM2823324", "GSM2823325", "GSM2823326", "GSM2823327", "GSM2823328", "GSM2823329", "GSM2823330", "GSM2823331", "GSM2823332", "GSM2823333", "GSM2823334", "GSM2823335", "GSM2823336", "GSM2823337", "GSM2823338", "GSM2823339", "GSM2823340", "GSM2823341", "GSM2823342", "GSM2823343", "GSM2823344", "GSM2823345", "GSM2823346", "GSM2823347", "GSM2823348", "GSM2823349", "GSM2823350", "GSM2823351"], "sample_count": 49, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene Expression in the Human Lacrimal Gland", "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:GSE185952", "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=GSE185952", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE185952", "version": null, "note": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5627753", "GSM5627754", "GSM5627755", "GSM5627756", "GSM5627757", "GSM5627758"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "30862", "taxon": "Homo sapiens", "title": "For lncRNA, circRNA and mRNA sequencing of thyroid-associated ophthalmopathy patients and normal people", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE105149 not downloaded", "asset:data:geo:GSE105149 licence not read", "asset:data:geo:GSE185952 not downloaded", "asset:data:geo:GSE185952 licence not read"]}, "analysis": {"state": "complete", "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": "Differentially expressed genes (DEGs) between the two datasets TAO and control samples were screened using the limma (linear models for microarray data) package of R software (version 4.1.0, AT&T Bell Laboratories, USA) [14]."}}, {"id": "method-2", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "logistic regression"}}, {"id": "method-3", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman's rank correlation"}}, {"id": "method-4", "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"}}, {"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": 0.8, "band": "high", "quote": "Pathway enrichment"}}, {"id": "method-6", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-7", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "chi-square"}}], "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": ["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": ["GSE105149", "GSE185952"], "resolved_accessions": ["GSE105149", "GSE185952"], "statements": ["The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo)."], "basis": "The paper names GSE105149, GSE185952 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:36056316", "data:geo:GSE105149"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE105149"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:03:01Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10728, "completion_tokens": 1307, "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:36056316", "type": "paper", "label": "pmid:36056316"}, {"id": "source:pmid:36056316", "type": "manuscript", "label": "PMID 36056316 full text"}, {"id": "data:geo:GSE105149", "type": "dataset", "label": "GEO GSE105149"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36056316", "type": "paper", "label": "pmid:36056316"}, {"id": "source:pmid:36056316", "type": "manuscript", "label": "PMID 36056316 full text"}, {"id": "data:geo:GSE105149", "type": "dataset", "label": "GEO GSE105149"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36056316", "type": "extraction", "used": ["source:pmid:36056316"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE105149", "type": "accession_resolution", "used": ["data:geo:GSE105149"], "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:36056316", "parent_hash": "sha256:6cc7d7044a247337be64ade92a4e1e9418fa9b97d5dbbf1e6ba5ca57a3e10355", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE105149 licence not read", "asset:data:geo:GSE105149 not downloaded", "asset:data:geo:GSE185952 licence not read", "asset:data:geo:GSE185952 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tected by enzyme-linked immunosorbent assay (ELISA). Then we further assessed the relationship", "urther assessed the relationship between the ELISA data and the TAO development. RESULTS: Sever", "hrough the PPI network. As confirmation, the ELISA results indicated that protein expression le", "coded by hub genes in serum were detected by enzyme-linked immunosorbent assay (ELISA). Then we further assessed the relati"], "order_basis": "paper_text_order:1166", "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": ["Differentially expressed genes (DEGs) between the two datasets TAO and control samples were screened using the limma (linear models for microarray data) package of R software (version 4.1.0, AT&T Bell Laboratories, USA) [14]."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}