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pmid:26334995
Genes related to inflammation and bone loss process in periodontitis suggested by bioinformatics methods.
Liang Song · Jueqi Yao · Zhijing He · Bin Xu
BMC oral health · 2015 doi:10.1186/s12903-015-0086-7
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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This study aimed to have an expression profiling comparison between periodontitis and normal control and to identify more candidate genes involved in periodontitis and to gain more insights into the molecular mechanisms of periodontitis progression.\nMETHODS: The gene expression profile of GSE16134, comprising 241 gingival tissue specimens and 69 healthy samples as control which were obtained from 120 systemically healthy patients with periodontitis (65 with chronic and 55 with aggressive periodontitis), was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in periodontitis samples were screened using the limma package in R compared with control samples. Gene Ontology (GO) and pathway enrichment analysis upon the DEGs were carried out using Hypergeometric Distribution test. Protein-protein interaction (PPI) network of the DEGs was constructed using Cytoscape, followed by module selection from the PPI network using MCODE plugin. Moreover, transcription factors (TFs) of these DEGs were identified based on TRANSFAC database and then a regulatory network was constructed.\nRESULTS: Totally, 762 DEGs (507 up- and 255 down-regulated) in periodontitis samples were identified. DEGs were enriched in different GO terms and pathways, such as immune system process, cell activation biological processes, cytokine-cytokine receptor interaction, and metabolic pathways. Cathepsin S (CTSS) and pleckstrin (PLEK) were the hub proteins in the PPI network and 3 significant modules were selected. Moreover, 19 TFs were identified including interferon regulatory factor 8 (IRF8), and FBJ murine osteosarcoma viral oncogene homolog B (FOSB).\nCONCLUSION: This study identified genes (CTSS, PLEK, IRF-8, PTGS2, and FOSB) that may be involved in the development and progression of periodontitis.", "claims": [{"id": "claim-method", "statement": "GO categories such as biological process (BP), molecular function (MF), and cellular component (CC) upon the identified DEGs were enriched from GO databases using the Hypergeometric Distribution test [18]. Also, the pathways that the DEGs involved in were enriched using the Hypergeometric Distribution test from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database [19], which had not been used by Kebschull et al. [12].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26334995", "locator": "sections[5] \"Function and pathway enrichment analysis of DEGs\" paragraph 2", "quote": "GO categories such as biological process (BP), molecular function (MF), and cellular component (CC) upon the identified DEGs were enriched from GO databases using the Hypergeometric Distribution test [18]. Also, the pathways that the DEGs involved in were enriched using the Hypergeometric Distribution test from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database [19], which had not been used by Kebschull et al. [12]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile data of GSE16134 [11] was downloaded from the Gene Expression Omnibus (GEO) in NCBI (http://www.ncbi.nlm.nih.gov/geo/) based on the platform of GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. This dataset included 241 ‘diseased’ gingival tissue specimens (bleeding on probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 3 mm) and 69 ‘healthy’ gingival tissue samples (no bleeding on probing, probing depth ≤ 4 mm, and clinical attachment loss ≤ 4 mm), obtained from 120 systemically healthy, non-smoking individuals with moderate/severe periodontitis (65 with chronic and 55 with aggressive periodontitis), as previously described [11, 12].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26334995", "locator": "sections[3] \"Microarray data and data preprocessing\" paragraph 2", "quote": "The gene expression profile data of GSE16134 [11] was downloaded from the Gene Expression Omnibus (GEO) in NCBI (http://www.ncbi.nlm.nih.gov/geo/) based on the platform of GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. This dataset included 241 ‘diseased’ gingival tissue specimens (bleeding on probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 3 mm) and 69 ‘healthy’ gingival tissue samples (no bleeding on probing, probing depth ≤ 4 mm, and clinical attachment loss ≤ 4 mm), obtained from 120 systemically healthy, non-smoking individuals with moderate/severe periodontitis (65 with chronic and 55 with aggressive periodontitis), as previously described [11, 12]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using limma-based differential expression analysis of GSE16134 downloaded from GEO, the study identified 762 periodontitis-associated DEGs relative to healthy controls.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26334995", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The gene expression profile of GSE16134, comprising 241 gingival tissue specimens and 69 healthy samples as control which were obtained from 120 systemically healthy patients with periodontitis (65 with chronic and 55 with aggressive periodontitis), was downloaded from the Gene Expression Omnibus (GEO) database."}, {"asset": "source:pmid:26334995", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed genes (DEGs) in periodontitis samples were screened using the limma package in R compared with control samples."}, {"asset": "source:pmid:26334995", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Totally, 762 DEGs (507 up- and 255 down-regulated) in periodontitis samples were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using limma-based differential expression analysis of GSE16134 downloaded from GEO, the study identified 762 periodontitis-associated DEGs relative to healthy controls.", "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:26334995"], "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. 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["BP", "GO:0002684", "positive regulation of immune system process", "73", "<1.00E-16"], ["CC", "GO:0005576", "extracellular region", "138", "<1.00E-16"], ["CC", "GO:0005615", "extracellular space", "70", "<1.00E-16"], ["CC", "GO:0044421", "extracellular region part", "86", "<1.00E-16"], ["CC", "GO:0071944", "cell periphery", "191", "2.64E-14"], ["CC", "GO:0005886", "plasma membrane", "186", "1.49E-13"], ["MF", "GO:0008009", "chemokine activity", "10", "2.35E-07"], ["MF", "GO:0003823", "antigen binding", "12", "4.64E-07"], ["MF", "GO:0032403", "protein complex binding", "26", "4.85E-07"], ["MF", "GO:0042379", "chemokine receptor binding", "10", "1.11E-06"], ["MF", "GO:0005178", "integrin binding", "12", "1.41E-06"], ["B: the top 5 GO terms of the down-regulated DEGs"], ["BP", "GO:0043588", "skin development", "311", "2.33E-14"], ["BP", "GO:0008544", "epidermis development", "280", "1.18E-12"], ["BP", "GO:0030216", "keratinocyte differentiation", "108", "1.09E-09"], ["BP", "GO:0009913", 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"4.40E-12"], ["5144", "Malaria", "51", "2.12E-09"], ["4060", "Cytokine-cytokine receptor interaction", "265", "2.39E-08"], ["4141", "Protein processing in endoplasmic reticulum", "165", "5.11E-07"], ["4640", "Hematopoietic cell lineage", "88", "5.53E-07"], ["5323", "Rheumatoid arthritis", "91", "8.66E-07"], ["5140", "Leishmaniasis", "72", "1.64E-06"], ["4670", "Leukocyte transendothelial migration", "116", "4.30E-06"], ["4514", "Cell adhesion molecules (CAMs)", "133", "6.18E-06"], ["4062", "Chemokine signaling pathway", "189", "1.71E-05"], ["B: the top 10 enriched pathways of the down-regulated DEGs"], ["590", "Arachidonic acid metabolism", "59", "0.002776062"], ["980", "Metabolism of xenobiotics by cytochrome P450", "71", "0.005420335"], ["982", "Drug metabolism - cytochrome P450", "73", "0.005982341"], ["350", "Tyrosine metabolism", "41", "0.007842248"], ["1100", "Metabolic pathways", "1130", "0.012102847"], ["5144", "Malaria", "51", "0.014274311"], ["5014", "Amyotrophic lateral 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"PPI network construction and modules selection", "row_count": 16, "column_count": 4}, "table": {"label": "Table 3", "caption": "The top 5 DEGs with higher degrees in the selected modules", "rows": [["Module", "Gene", "Expression changes", "Degree"], ["module 1", "CTSS", "up", "20"], ["", "CCL5", "up", "19"], ["", "PLEK", "up", "19"], ["", "CCR1", "up", "19"], ["", "FPR1", "up", "19"], ["Module 2", "IL6", "up", "17"], ["", "LCK", "up", "14"], ["", "FCER1G", "up", "13"], ["", "CD19", "up", "13"], ["", "CSF1R", "up", "13"], ["Module 3", "IL8", "up", "13"], ["", "IL1B", "up", "12"], ["", "MMP9", "up", "11"], ["", "PTGS2", "up", "11"], ["", "PLAT", "up", "10"]], "row_count": 16, "column_count": 4, "numeric_cells": 19, "header_rows": 1, "locator": "section[11]/table-wrap[1]#Tab3"}}], "gaps": ["asset:data:geo:GSE16134 not downloaded", "asset:data:geo:GSE16134 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": 0.7, "band": "medium", "quote": "limma"}}, {"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"}}, {"id": "method-3", "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": 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Also, the pathways that the DEGs involved in were enriched using the Hypergeometric Distribution test from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database [19], which had not been used by Kebschull et al. [12]."}}], "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": ["GSE16134"], "resolved_accessions": ["GSE16134"], "statements": ["The gene expression profile data of GSE16134 [11] was downloaded from the Gene Expression Omnibus (GEO) in NCBI (http://www.ncbi.nlm.nih.gov/geo/) based on the platform of GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. This dataset included 241 ‘diseased’ gingival tissue specimens (bleeding on probing, probing depth ≥ 4 mm, and clinical attachment loss ≥ 3 mm) and 69 ‘healthy’ gingival tissue samples (no bleeding on probing, probing depth ≤ 4 mm, and clinical attachment loss ≤ 4 mm), obtained from 120 systemically healthy, non-smoking individuals with moderate/severe periodontitis (65 with chronic and 55 with aggressive periodontitis), as previously described [11, 12]."], "basis": "The paper names GSE16134 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:26334995", "data:geo:GSE16134", "asset:table:pmid:26334995:1", "asset:table:pmid:26334995:2", "asset:table:pmid:26334995:3"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE16134"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:24:41Z", "independence": "same_provider"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 8, "usage": {"prompt_tokens": 71745, "completion_tokens": 3650, "cached_tokens": 2104}}, "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:26334995", "type": "paper", "label": "pmid:26334995"}, {"id": "source:pmid:26334995", "type": "manuscript", "label": "PMID 26334995 full text"}, {"id": "data:geo:GSE16134", "type": "dataset", "label": "GEO GSE16134"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:26334995", "type": "paper", "label": "pmid:26334995"}, {"id": "source:pmid:26334995", "type": "manuscript", "label": "PMID 26334995 full text"}, {"id": "data:geo:GSE16134", "type": "dataset", "label": "GEO GSE16134"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-26334995", "type": "extraction", "used": ["source:pmid:26334995"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE16134", "type": "accession_resolution", "used": ["data:geo:GSE16134"], "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:26334995", "parent_hash": "sha256:9681c505fd84c5b2450bc7d5274783ba2af60813d854ed8411836fd2b9a45db2", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE16134 licence not read", "asset:data:geo:GSE16134 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["terferon regulatory factor 8 (IRF8), and FBJ murine osteosarcoma viral oncogene homolog B (FOSB)"], "order_basis": "paper_text_order:1842", "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": 0.7, "evidence": ["limma"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}