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pmid:32355739
Analysis of potential hub genes involved in the pathogenesis of Chinese type 1 diabetic patients.
Shuting Yang · Chuqing Cao · Zhiguo Xie · Zhiguang Zhou
Annals of translational medicine · 2020 doi:10.21037/atm.2020.02.171
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Complete file
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Although studies on T1D susceptibility genes have achieved great progress, the molecular mechanism of T1D remains to be explained.\nMETHODS: To explore the underlying mechanisms of T1D, bioinformatic analysis based on a microarray database was used to determine the key biomarkers of T1D as well as their biofunctions and interactions. The microarray database GSE55100 was downloaded from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were processed by packages in R Software. The database for Annotation, Visualization, and Integrated Discovery (DAVID, version 6.8) was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The protein-protein interaction network was analyzed with the Search Tool for the Retrieval of Interacting Genes (STRING), and the module analysis was performed using Cytoscape.\nRESULTS: Seventy-eight DEGs and 13 hub genes were identified. The biofunctions and pathways of these DEGs were enriched in immune response, extracellular exosome, cytokine activity and antigen processing and presentation. Thirteen DEGs with MCODE score ≥2 were selected as hub genes including MMP9, ARG1, CAMP, CHI3L1, CRISP3, SLPI, LCN2, PGLYRP1, LTF, RETN, CEACAM1, CEACAM8 and MS4A3.\nCONCLUSIONS: The identification and analyses of the DEGs and hub genes from database GSE55100 provide novel prospectives of the pathogenesis of T1D.", "claims": [{"id": "claim-method", "statement": "The affy package in R Software was used for data normalization, and limma package was applied for the remaining processes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32355739", "locator": "sections[4] \"DEG identification\" paragraph 2", "quote": "The affy package in R Software was used for data normalization, and limma package was applied for the remaining processes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mRNA expression file of GSE55100 was downloaded from GEO database (http://www.ncbi.nlm.nih.gov/geo), a public data source recoding genetic information (11). 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"version": null, "note": "Results of GO and KEGG pathway enrichment analysis of DEGs", "structure": {"pmcid": "PMC7186604", "section_index": 9, "section_title": "Enrichment analyses", "row_count": 18, "column_count": 4}, "table": {"label": "Table 1", "caption": "Results of GO and KEGG pathway enrichment analysis of DEGs", "rows": [["Term", "Description", "Count in gene set", "P value"], ["GO:0006955", "Immune response", "11", "4.61E-06"], ["GO:0045087", "Innate immune response", "10", "3.91E-05"], ["GO:0007155", "Cell adhesion", "9", "3.78E-04"], ["GO:0006954", "Inflammatory response", "8", "6.38E-04"], ["GO:0008284", "Positive regulation of cell proliferation", "7", "0.009180343"], ["GO:0070062", "Extracellular exosome", "28", "7.73E-07"], ["GO:0005615", "Extracellular space", "22", "7.20E-09"], ["GO:0005576", "Extracellular region", "14", "0.005261967"], ["GO:0005887", "Integral component of plasma membrane", "12", "0.013566932"], ["GO:0005125", "Cytokine activity", "5", "0.004714656"], ["GO:0005506", "Iron ion binding", "4", "0.021178215"], ["GO:0030246", "Carbohydrate binding", "4", "0.039835718"], ["GO:0004888", "Transmembrane signaling receptor activity", "4", "0.049477271"], ["GO:0004252", "Serine-type endopeptidase activity", "4", "0.075232402"], ["hsa04612", "Antigen processing and presentation", "5", "3.45E-04"], ["hsa05164", "Influenza A", "5", "0.007298983"], ["hsa05168", "Herpes simplex infection", "5", "0.008696934"]], "row_count": 18, "column_count": 4, "numeric_cells": 51, "header_rows": 1, "locator": "section[9]/table-wrap[1]#t1"}}, {"id": "asset:table:pmid:32355739:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8d5c6044f3378ab971bfb866c462dc9fb2bf891d615b4f5438e650bf8c53541d", "bytes": 1798, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t2", "version": null, "note": "Information of 13 hub genes in T1D", "structure": {"pmcid": "PMC7186604", "section_index": 11, "section_title": "Hub gene selection", "row_count": 14, "column_count": 3}, "table": {"label": "Table 2", "caption": "Information of 13 hub genes in T1D", "rows": [["Gene symbol", "Full name", "Implications"], ["MMP9", "Matrix metallopeptidase 9", "The activation of MMP9 is related with the severity of stroke in T1D"], ["ARG1", "Arginase 1", "ARG1 expression increases in T1D patients with complications"], ["CAMP", "Cathelicidin antimicrobial peptide", "CAMP was upregulated in the jejunum in low-antigen hydrolyzed casein diet T1D rats"], ["CHI3L1", "Chitinase 3 like 1", "The serum level of CHI3L1 was elevated in subjects with diabetic retinopathy"], ["CRISP3", "Cysteine-rich secretory protein 3", "The association between CRISP3 and T1D has not been reported"], ["SLPI", "Secretory leukocyte peptidase inhibitor", "The association between SLPI and T1D has not been reported"], ["LCN2", "Lipocalin 2", "The serum concentration of LCN2 correlated positively with systolic arterial pressure but negatively with eGRF in T1D patients"], ["PGLYRP1", "Peptidoglycan recognition protein 1", "The association between PGLYRP1 and T1D has not been reported"], ["LTF", "Lactotransferrin", "The association between LTF and T1D has not been reported"], ["RETN", "Resistin", "The resistin levels were elevated in T1DM patients and normalized by islet transplantation"], ["CEACAM1", "Carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)", "The association between CEACAM1 and T1D has not been reported"], ["CEACAM8", "Carcinoembryonic antigen-related cell adhesion molecule 8", "The association between CEACAM8 and T1D has not been reported"], ["MS4A3", "Membrane-spanning 4-domains, subfamily A, member 3 (hematopoietic cell-specific)", "The association between MS4A3 and T1D has not been reported"]], "row_count": 14, "column_count": 3, "numeric_cells": 9, "header_rows": 1, "locator": "section[11]/table-wrap[1]#t2"}}], "gaps": ["asset:data:geo:GSE55100 not downloaded", "asset:data:geo:GSE55100 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": "The affy package in R Software was used for data normalization, and limma package was applied for the remaining processes."}}, {"id": "method-2", "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"}}], "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": ["GSE55100"], "resolved_accessions": ["GSE55100"], "statements": ["The mRNA expression file of GSE55100 was downloaded from GEO database (http://www.ncbi.nlm.nih.gov/geo), a public data source recoding genetic information (11). Transcriptome data were obtained from the GPL570 platform, Affymetrix Human Genome U133 Plus 2.0 Array. The annotation file in the platform matches the probes with the corresponding genes. GSE55100 contains the mRNA information of PBMCs from 12 patients with newly diagnosed T1D and 10 normal controls. The affy package in R Software was used for data normalization, and limma package was applied for the remaining processes. Genes with the P<0.05 and |log Fc| (fold change) >1 were considered as DEGs."], "basis": "The paper names GSE55100 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:32355739", "data:geo:GSE55100", "asset:table:pmid:32355739:1", "asset:table:pmid:32355739:2", "asset:table:pmid:32355739:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE55100"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:19:39Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 24168, "completion_tokens": 1382, "cached_tokens": 776}}, "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:32355739", "type": "paper", "label": "pmid:32355739"}, {"id": "source:pmid:32355739", "type": "manuscript", "label": "PMID 32355739 full text"}, {"id": "data:geo:GSE55100", "type": "dataset", "label": "GEO GSE55100"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32355739", "type": "paper", "label": "pmid:32355739"}, {"id": "source:pmid:32355739", "type": "manuscript", "label": "PMID 32355739 full text"}, {"id": "data:geo:GSE55100", "type": "dataset", "label": "GEO GSE55100"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32355739", "type": "extraction", "used": ["source:pmid:32355739"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE55100", "type": "accession_resolution", "used": ["data:geo:GSE55100"], "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:32355739", "parent_hash": "sha256:2618a63c6ef2b9599f7c374bcc618b3a1a5f39572a8bc19242906e482b342a2c", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE55100 licence not read", "asset:data:geo:GSE55100 not downloaded", "execution.not_run", "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": 0.99, "evidence": ["ms of T1D, bioinformatic analysis based on a microarray database was used to determine the key bioma", "as their biofunctions and interactions. 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