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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

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Experiment

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Data

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title
Genes related to inflammation and bone loss process in periodontitis suggested by bioinformatics methods.
doi
10.1186/s12903-015-0086-7
pmid
26334995
authors array · 4 items
[0]
Liang Song
[1]
Jueqi Yao
[2]
Zhijing He
[3]
Bin Xu
journal
BMC oral health
year
2015
abstract
BACKGROUND: Despite of numerous studies on periodontitis, the mechanism underlying the progression of periodontitis still remains largely unknown. 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. METHODS: 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. RESULTS: 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). CONCLUSION: This study identified genes (CTSS, PLEK, IRF-8, PTGS2, and FOSB) that may be involved in the development and progression of periodontitis.
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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].
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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].
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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].
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sections[3] "Microarray data and data preprocessing" paragraph 2
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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].
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Using limma-based differential expression analysis of GSE16134 downloaded from GEO, the study identified 762 periodontitis-associated DEGs relative to healthy controls.
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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.
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Differentially expressed genes (DEGs) in periodontitis samples were screened using the limma package in R compared with control samples.
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Totally, 762 DEGs (507 up- and 255 down-regulated) in periodontitis samples were identified.
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Using limma-based differential expression analysis of GSE16134 downloaded from GEO, the study identified 762 periodontitis-associated DEGs relative to healthy controls.
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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].
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The functional analysis of the DEGs
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GO and pathway enrichment analysis of DEGs
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The functional analysis of the DEGs
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[4]
1.49E-13
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chemokine activity
[3]
10
[4]
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antigen binding
[3]
12
[4]
4.64E-07
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protein complex binding
[3]
26
[4]
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10
[4]
1.11E-06
[16] array · 5 items
[0]
MF
[1]
GO:0005178
[2]
integrin binding
[3]
12
[4]
1.41E-06
[17] array · 1 item
[0]
B: the top 5 GO terms of the down-regulated DEGs
[18] array · 5 items
[0]
BP
[1]
GO:0043588
[2]
skin development
[3]
311
[4]
2.33E-14
[19] array · 5 items
[0]
BP
[1]
GO:0008544
[2]
epidermis development
[3]
280
[4]
1.18E-12
[20] array · 5 items
[0]
BP
[1]
GO:0030216
[2]
keratinocyte differentiation
[3]
108
[4]
1.09E-09
[21] array · 5 items
[0]
BP
[1]
GO:0009913
[2]
epidermal cell differentiation
[3]
154
[4]
1.01E-08
[22] array · 5 items
[0]
BP
[1]
GO:0009888
[2]
tissue development
[3]
1479
[4]
2.09E-08
[23] array · 5 items
[0]
CC
[1]
GO:0030057
[2]
desmosome
[3]
22
[4]
5.73E-06
[24] array · 5 items
[0]
CC
[1]
GO:0005882
[2]
intermediate filament
[3]
191
[4]
2.33E-05
[25] array · 5 items
[0]
CC
[1]
GO:0045111
[2]
intermediate filament cytoskeleton
[3]
231
[4]
2.76E-05
[26] array · 5 items
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CC
[1]
GO:0045095
[2]
keratin filament
[3]
93
[4]
0.00096928
[27] array · 5 items
[0]
CC
[1]
GO:0005911
[2]
cell-cell junction
[3]
297
[4]
0.00108577
[28] array · 5 items
[0]
MF
[1]
GO:0005198
[2]
structural molecule activity
[3]
627
[4]
2.89E-05
[29] array · 5 items
[0]
MF
[1]
GO:0005200
[2]
structural constituent of cytoskeleton
[3]
94
[4]
0.00104197
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[0]
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[1]
GO:0016755
[2]
transferase activity, transferring amino-acyl groups
[3]
24
[4]
0.003031659
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[0]
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[1]
GO:0016702
[2]
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
[3]
25
[4]
0.003414279
[32] array · 5 items
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MF
[1]
GO:0016701
[2]
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen
[3]
26
[4]
0.003825148
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The pathway enrichment analysis of the DEGs
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GO and pathway enrichment analysis of DEGs
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The pathway enrichment analysis of the DEGs
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[3]
4.40E-12
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51
[3]
2.12E-09
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[1]
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265
[3]
2.39E-08
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[1]
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165
[3]
5.11E-07
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[1]
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[3]
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[3]
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[1]
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[3]
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[1]
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[3]
4.30E-06
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[1]
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[3]
6.18E-06
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[1]
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[2]
189
[3]
1.71E-05
[12] array · 1 item
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[0]
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[1]
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[2]
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[3]
0.002776062
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[1]
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[2]
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[3]
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[15] array · 4 items
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[1]
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[2]
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[3]
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[1]
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[2]
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[3]
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[1]
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[2]
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[3]
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[3]
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[3]
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[1]
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[2]
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[3]
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[1]
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[3]
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[1]
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[3]
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The top 5 DEGs with higher degrees in the selected modules
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PPI network construction and modules selection
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Table 3
caption
The top 5 DEGs with higher degrees in the selected modules
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[0] array · 4 items
[0]
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[2]
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[3]
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20
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11
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PTGS2
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section[11]/table-wrap[1]#Tab3
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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].
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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.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:26334995", "kind": "science-record", "revision": 8, "content_hash": "sha256:c8cc1dcb720e059c98da7f5895d1842376b2b6b3769eeb100101c91dfc1db01e", "created_at": "2026-11-01T15:40:10Z", "updated_at": "2026-11-01T21:58:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Genes related to inflammation and bone loss process in periodontitis suggested by bioinformatics methods.", "doi": "10.1186/s12903-015-0086-7", "pmid": "26334995", "authors": ["Liang Song", "Jueqi Yao", "Zhijing He", "Bin Xu"], "journal": "BMC oral health", "year": 2015, "abstract": "BACKGROUND: Despite of numerous studies on periodontitis, the mechanism underlying the progression of periodontitis still remains largely unknown. 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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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. 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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": ["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"}]}