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pmid:33869630

Shared Molecular Mechanisms between Alzheimer's Disease and Periodontitis Revealed by Transcriptomic Analysis.

Jieqi Jin · Mengkai Guang · Anthony Chukwunonso Ogbuehi · Simin Li · Kai Zhang · Yihong Ma · Aneesha Acharya · Bihan Guo · Zongwu Peng · Xiangqiong Liu · Yupei Deng · Zhaobi Fang · Xiongjie Zhu · Shiting Hua · Cong Li · Rainer Haak · Dirk Ziebolz · Gerhard Schmalz · Lei Liu · Baohua Xu · Xiaofeng Huang

BioMed research international · 2021 doi:10.1155/2021/6633563

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pmid:33869630
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science-record
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2026-11-01T15:41:32Z
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2026-11-01T22:46:32Z
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title
Shared Molecular Mechanisms between Alzheimer's Disease and Periodontitis Revealed by Transcriptomic Analysis.
doi
10.1155/2021/6633563
pmid
33869630
authors array · 21 items
[0]
Jieqi Jin
[1]
Mengkai Guang
[2]
Anthony Chukwunonso Ogbuehi
[3]
Simin Li
[4]
Kai Zhang
[5]
Yihong Ma
[6]
Aneesha Acharya
[7]
Bihan Guo
[8]
Zongwu Peng
[9]
Xiangqiong Liu
[10]
Yupei Deng
[11]
Zhaobi Fang
[12]
Xiongjie Zhu
[13]
Shiting Hua
[14]
Cong Li
[15]
Rainer Haak
[16]
Dirk Ziebolz
[17]
Gerhard Schmalz
[18]
Lei Liu
[19]
Baohua Xu
[20]
Xiaofeng Huang
journal
BioMed research international
year
2021
abstract
OBJECTIVE: To investigate the genetic crosstalk mechanisms that link periodontitis and Alzheimer's disease (AD). BACKGROUND: Periodontitis, a common oral infectious disease, is associated with Alzheimer's disease (AD) and considered a putative contributory factor to its progression. However, a comprehensive investigation of potential shared genetic mechanisms between these diseases has not yet been reported. METHODS: Gene expression datasets related to periodontitis were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed to identify differentially expressed genes (DEGs). Genes associated with AD were downloaded from the DisGeNET database. Overlapping genes among the DEGs in periodontitis and the AD-related genes were defined as crosstalk genes between periodontitis and AD. The Boruta algorithm was applied to perform feature selection from these crosstalk genes, and representative crosstalk genes were thus obtained. In addition, a support vector machine (SVM) model was constructed by using the scikit-learn algorithm in Python. Next, the crosstalk gene-TF network and crosstalk gene-DEP (differentially expressed pathway) network were each constructed. As a final step, shared genes among the crosstalk genes and periodontitis-related genes in DisGeNET were identified and denoted as the core crosstalk genes. RESULTS: Four datasets (GSE23586, GSE16134, GSE10334, and GSE79705) pertaining to periodontitis were included in the analysis. A total of 48 representative crosstalk genes were identified by using the Boruta algorithm. Three TFs (FOS, MEF2C, and USF2) and several pathways (i.e., JAK-STAT, MAPK, NF-kappa B, and natural killer cell-mediated cytotoxicity) were identified as regulators of these crosstalk genes. Among these 48 crosstalk genes and the chronic periodontitis-related genes in DisGeNET, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 were shared and identified as the most pivotal candidate links between periodontitis and AD. CONCLUSIONS: Exploration of available transcriptomic datasets revealed C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 as the top candidate molecular linkage genes between periodontitis and AD.
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Differential gene expression analysis of periodontitis-related datasets was carried out using the Linear Models for Microarray (limma) package [12] in the R project (version 3.0.1, http://www.r-project.org/) [13].
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sections[5] "2.3. Differential Gene Expression Analysis" paragraph 2
quote
Differential gene expression analysis of periodontitis-related datasets was carried out using the Linear Models for Microarray (limma) package [12] in the R project (version 3.0.1, http://www.r-project.org/) [13].
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The data used to support the findings of this study are available from the corresponding author upon request.
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sections[27] "Data Availability" paragraph 2
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The data used to support the findings of this study are available from the corresponding author upon request.
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Details of the included periodontitis-related GEO datasets.
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3.1. Included Periodontitis-Related Datasets
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Table 1
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Details of the included periodontitis-related GEO datasets.
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Included four datasets
[1]
Type of periodontitis
[2]
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[3]
Number of examined genes
[4]
Number of inflamed gingival tissue samples
[5]
Number of healthy control samples
[6]
Number of total samples
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GSE23586
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3 patients with severe chronic periodontitis
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23,518
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120 patients (65 with chronic periodontitis and 55 with aggressive periodontitis)
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241
[5]
69
[6]
310
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GSE10334
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63 with chronic periodontitis and 27 with aggressive periodontitis
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24,441
[4]
183
[5]
64
[6]
247
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Generalized aggressive periodontitis (GAgP): n = 4; chronic periodontitis (CP): n = 4
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8
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4
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The number of up/downregulated DEGs identified in the four periodontitis-related datasets GSE23586, GSE16134, GSE10334, and GSE79705 at thresholds set for defining DEGs.
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3.2. Identification of Periodontitis-Related DEGs and Their Functions
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Table 2
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The number of up/downregulated DEGs identified in the four periodontitis-related datasets GSE23586, GSE16134, GSE10334, and GSE79705 at thresholds set for defining DEGs.
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Data
[1]
Number of upregulated DEGs
[2]
Number of downregulated DEGs
[3]
Number of total DEGs
[4]
∣log2 FC∣
[5]
p value
[6]
Expression scale (if the data normalization was performed)
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GSE23586
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7
[2]
69
[3]
76
[4]
>1
[5]
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True
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GSE16134
[1]
188
[2]
48
[3]
236
[4]
>1
[5]
<0.05
[6]
False
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GSE10334
[1]
152
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42
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194
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>1
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GSE79705
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219
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291
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510
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section[16]/table-wrap[1]#tab2
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Topological characteristics of the top 30 nodes in the periodontitis-related PPI network, ranked in descending order of degree.
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PMC8032519
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17
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3.3. The Hub Genes Identified by the Periodontitis-Related PPI Network
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Table 3
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Topological characteristics of the top 30 nodes in the periodontitis-related PPI network, ranked in descending order of degree.
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[7]
Topological coefficient
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MYC
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0.379066
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0.00278
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0.374864
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0.004283
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0.005425
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2.112
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0.473485
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0.004524
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0.007004
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DEG_up
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2.864727
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0.046792
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0.349073
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0.000791
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0.006306
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2.705212
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0.005251
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0.007732
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0.015773
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0.362956
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0.024541
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0.011238
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DEG_down
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2.885091
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0.030011
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0.34661
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0.002144
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0.009614
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DEG_up
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2.880727
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0.024538
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0.347135
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0.003265
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0.009974
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The 51 crosstalk genes that were upregulated and 41 crosstalk genes which were downregulated in periodontitis.
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PMC8032519
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18
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3.4. Crosstalk Genes Bridging Alzheimer's Disease and Periodontitis
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Table 4
caption
The 51 crosstalk genes that were upregulated and 41 crosstalk genes which were downregulated in periodontitis.
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Regulation pattern in periodontitis
[1]
Crosstalk genes linking periodontitis and Alzheimer's disease
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Upregulated
[1]
AMIGO1 (adhesion molecule with Ig-like domain 1; gene ID: 57463)ARG2 (arginase 2; gene ID: 384)BDKRB2 (bradykinin receptor B2; gene ID: 624)BRI3 (brain protein I3; gene ID: 25798)C1D (C1D nuclear receptor corepressor; gene ID: 10438)C3 (complement C3; gene ID: 718)C4A (complement C4A (Rodgers blood group); gene ID: 720)C4B (complement C4B; gene ID: 721)C4B_2 (complement component 4B (Chido blood group), copy 2; gene ID: 100293534)CASP7 (caspase 7; gene ID: 840)CD177 (CD177 molecule; gene ID: 57126)CD38 (CD38 molecule; gene ID: 952)CHCHD10 (coiled-coil-helix-coiled-coil-helix domain containing 10; gene ID: 400916)COX8A (cytochrome c oxidase subunit 8A; gene ID: 1351)CSF3 (colony-stimulating factor 3; gene ID: 1440)CTGF (cellular communication network factor 2; gene ID: 1490)CTSS (cathepsin S; gene ID: 1520)CXCL1 (C-X-C motif chemokine ligand 1; gene ID: 2919)CXCL12 (C-X-C motif chemokine ligand 12; gene ID: 6387)CXCL8 (C-X-C motif chemokine ligand 8; gene ID: 3576)CXCR4 (C-X-C motif chemokine receptor 4; gene ID: 7842)ENPP2 (ectonucleotide pyrophosphatase/phosphodiesterase 2; gene ID: 5168)FCGR3A (Fc fragment of IgG receptor IIIa; gene ID: 2214)FCGR3B (Fc fragment of IgG receptor IIIb; gene ID: 2215)FHL2 (four and a half LIM domains 2; gene ID: 2274)FOS (Fos proto-oncogene, AP-1 transcription factor subunit; gene ID: 2353)FOXO1 (forkhead box O1; gene ID: 2308)GSTK1 (glutathione S-transferase kappa 1; gene ID: 373156)GSTO1 (glutathione S-transferase omega 1; gene ID: 9446)HCLS1 (hematopoietic cell-specific Lyn substrate 1; gene ID: 3059)IGFBP7 (insulin-like growth factor binding protein 7; gene ID: 3490)IL1B (interleukin-1 beta; gene ID: 3553)LYZ (lysozyme; gene ID: 4069)MAK16 (MAK16 homolog; gene ID: 84549)MEF2C (myocyte-specific enhancer factor 2C; gene ID: 4208)MME (membrane metalloendopeptidase; gene ID: 4311)MMP1 (matrix metallopeptidase 1; gene ID: 4312)MMP3 (matrix metallopeptidase 3; gene ID: 4314)MS4A1 (membrane-spanning 4-domains A1; gene ID: 931)MSRA (methionine sulfoxide reductase A; gene ID: 4482)MZB1 (marginal zone B and B1 cell-specific protein; gene ID: 51237)NDUFB8 (NADH:ubiquinone oxidoreductase subunit B8; gene ID: 4714)PECAM1 (platelet endothelial cell adhesion molecule 1; gene ID: 5175)PLAT (plasminogen activator, tissue type; gene ID: 5327)PSENEN (presenilin enhancer, gamma-secretase subunit; gene ID: 55851)SEL1L (SEL1L adaptor subunit of ERAD E3 ubiquitin ligase; gene ID: 6400)SERPINI1 (serpin family I member 1; gene ID: 5274)ST6GAL1 (ST6 beta-galactoside alpha-2,6-sialyltransferase 1; gene ID: 6480)VCAN (versican; gene ID: 1462)VIM (vimentin; gene ID: 7431)WARS2 (tryptophanyl tRNA synthetase 2, mitochondrial; gene ID: 10352)
[2] array · 1 item
[0]
[3] array · 2 items
[0]
Downregulated
[1]
ABCA12 (ATP binding cassette subfamily A member 12; gene ID: 26154)ACE (angiotensin I converting enzyme; gene ID: 1636)ADRB1 (adrenoceptor beta 1; gene ID: 153)BCL2L2 (BCL2-like 2; gene ID: 599)BRSK1 (BR serine/threonine kinase 1; gene ID: 84446)CALML5 (calmodulin-like 5; gene ID: 51806)CALR (calreticulin; gene ID: 811)CD36 (CD36 molecule; gene ID: 948)CDH1 (cadherin 1; gene ID: 999)CDK5R1 (cyclin-dependent kinase 5 regulatory subunit 1; gene ID: 8851)CTDSP2 (CTD small phosphatase 2; gene ID: 10106)DNM1 (dynamin 1; gene ID: 1759)DSG1 (desmoglein 1; gene ID: 1828)FLG (filaggrin; gene ID: 2312)GJA1 (gap junction protein alpha 1; gene ID: 2697)GRHL3 (grainyhead-like transcription factor 3; gene ID: 57822)GRIN3B (glutamate ionotropic receptor NMDA type subunit 3B; gene ID: 116444)HM13 (histocompatibility minor 13; gene ID: 81502)HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase; gene ID: 3156)HSPB1 (heat shock protein family B (small) member 1; gene ID: 3315)KAT5 (lysine acetyltransferase 5; gene ID: 10524)MAP3K12 (mitogen-activated protein kinase kinase kinase 12; gene ID: 7786)MED12 (mediator complex subunit 12; gene ID: 9968)MFN2 (mitofusin 2; gene ID: 9927)MYC (MYC proto-oncogene, bHLH transcription factor; gene ID: 4609)NEFL (neurofilament light; gene ID: 4747)NES (exportin 1; gene ID: 7514)NGF (nerve growth factor; gene ID: 4803)NOS3 (nitric oxide synthase 3; gene ID: 4846)NPTXR (neuronal pentraxin receptor; gene ID: 23467)PLXNA3 (plexin A3; gene ID: 55558)PPIL2 (peptidylprolyl isomerase-like 2; gene ID: 23759)PTGS1 (prostaglandin-endoperoxide synthase 1; gene ID: 5742)RPL13 (ribosomal protein L13; gene ID: 6137)SCIMP (SLP adaptor and CSK interacting membrane protein; gene ID: 388325)SPPL2B (signal peptide peptidase-like 2B; gene ID: 56928)TIAF1 (TGFB1-induced antiapoptotic factor 1; gene ID: 9220)TP73 (tumor protein P73; gene ID: 7161)TYRP1 (tyrosinase-related protein 1; gene ID: 7306)USF2 (upstream transcription factor 2, C-Fos interacting; gene ID: 7392)VEGFA (vascular endothelial growth factor A; gene ID: 7422)
locator
section[18]/table-wrap[1]#tab4
[5] object · 16 fields
id
asset:table:pmid:33869630:5
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:699dcaca7aea84f98b3863785d4eb056eebf920dbc3103f234b87a17a6b695c4
bytes
2844
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[18]/table-wrap[2]#tab5
version
null
note
Topological characteristics of the top 30 nodes in the crosstalk gene-related PPI network, ranked in descending order of degree.
structure object · 5 fields
pmcid
PMC8032519
section_index
18
section_title
3.4. Crosstalk Genes Bridging Alzheimer's Disease and Periodontitis
row_count
31
column_count
8
table object · 8 fields
label
Table 5
caption
Topological characteristics of the top 30 nodes in the crosstalk gene-related PPI network, ranked in descending order of degree.
rows array · 31 items
[0] array · 8 items
[0]
Node
[1]
Label
[2]
Degree
[3]
Average shortest path length
[4]
Betweenness centrality
[5]
Closeness centrality
[6]
Clustering coefficient
[7]
Topological coefficient
[1] array · 8 items
[0]
MYC
[1]
DEG_AD_down
[2]
1027
[3]
2.127525
[4]
0.466698
[5]
0.47003
[6]
5.03E − 04
[7]
0.001842
[2] array · 8 items
[0]
HSPB1
[1]
DEG_AD_down
[2]
433
[3]
2.36959
[4]
0.184598
[5]
0.422014
[6]
0.001636
[7]
0.003351
[3] array · 8 items
[0]
VIM
[1]
DEG_AD_up
[2]
320
[3]
2.663301
[4]
0.116611
[5]
0.375474
[6]
0.001763
[7]
0.005783
[4] array · 8 items
[0]
KAT5
[1]
DEG_AD_down
[2]
245
[3]
2.566359
[4]
0.089476
[5]
0.389657
[6]
0.003011
[7]
0.005621
[5] array · 8 items
[0]
RPL13
[1]
DEG_AD_down
[2]
234
[3]
2.589729
[4]
0.089708
[5]
0.386141
[6]
0.001394
[7]
0.005672
[6] array · 8 items
[0]
FOS
[1]
DEG_AD_up
[2]
226
[3]
2.883151
[4]
0.083642
[5]
0.346843
[6]
1.97E − 04
[7]
0.017606
[7] array · 8 items
[0]
CDH1
[1]
DEG_AD_down
[2]
171
[3]
2.93191
[4]
0.058428
[5]
0.341075
[6]
0
[7]
0.025911
[8] array · 8 items
[0]
TP73
[1]
DEG_AD_down
[2]
137
[3]
2.61483
[4]
0.046781
[5]
0.382434
[6]
0.006333
[7]
0.009173
[9] array · 8 items
[0]
FHL2
[1]
DEG_AD_up
[2]
136
[3]
2.641085
[4]
0.057192
[5]
0.378632
[6]
0.004031
[7]
0.00889
[10] array · 8 items
[0]
CALR
[1]
DEG_AD_down
[2]
135
[3]
2.812464
[4]
0.046142
[5]
0.35556
[6]
0.002764
[7]
0.010949
[11] array · 8 items
[0]
GSTK1
[1]
DEG_AD_up
[2]
111
[3]
2.988459
[4]
0.035152
[5]
0.334621
[6]
0
[7]
0.026289
[12] array · 8 items
[0]
MME
[1]
DEG_AD_up
[2]
104
[3]
2.836988
[4]
0.040386
[5]
0.352487
[6]
0.001307
[7]
0.011694
[13] array · 8 items
[0]
MED12
[1]
DEG_AD_down
[2]
91
[3]
2.695615
[4]
0.030682
[5]
0.370973
[6]
0.006105
[7]
0.012517
[14] array · 8 items
[0]
CASP7
[1]
DEG_AD_up
[2]
90
[3]
2.901039
[4]
0.027131
[5]
0.344704
[6]
0.005243
[7]
0.015603
[15] array · 8 items
[0]
DNM1
[1]
DEG_AD_down
[2]
84
[3]
2.960185
[4]
0.029086
[5]
0.337817
[6]
0.001147
[7]
0.023716
[16] array · 8 items
[0]
FOXO1
[1]
DEG_AD_up
[2]
67
[3]
2.977784
[4]
0.017403
[5]
0.33582
[6]
0.004071
[7]
0.026586
[17] array · 8 items
[0]
CXCR4
[1]
DEG_AD_up
[2]
65
[3]
2.998557
[4]
0.020851
[5]
0.333494
[6]
0.003846
[7]
0.028808
[18] array · 8 items
[0]
NOS3
[1]
DEG_AD_down
[2]
62
[3]
2.963647
[4]
0.018786
[5]
0.337422
[6]
0.002644
[7]
0.027957
[19] array · 8 items
[0]
NDUFB8
[1]
DEG_AD_up
[2]
56
[3]
3.042412
[4]
0.02136
[5]
0.328687
[6]
0
[7]
0.027447
[20] array · 8 items
[0]
UBC
[1]
Other gene
[2]
53
[3]
2.084824
[4]
0.149265
[5]
0.479657
[6]
0.015965
[7]
0.027336
[21] array · 8 items
[0]
NES
[1]
DEG_AD_down
[2]
53
[3]
2.920946
[4]
0.017012
[5]
0.342355
[6]
0.007983
[7]
0.022954
[22] array · 8 items
[0]
CDK5R1
[1]
DEG_AD_down
[2]
50
[3]
3.0176
[4]
0.0133
[5]
0.331389
[6]
0.002449
[7]
0.037222
[23] array · 8 items
[0]
NEFL
[1]
DEG_AD_down
[2]
49
[3]
2.913445
[4]
0.014886
[5]
0.343236
[6]
0.008503
[7]
0.024673
[24] array · 8 items
[0]
C3
[1]
DEG_AD_up
[2]
43
[3]
3.043278
[4]
0.01705
[5]
0.328593
[6]
0
[7]
0.042101
[25] array · 8 items
[0]
SEL1L
[1]
DEG_AD_up
[2]
42
[3]
3.036065
[4]
0.013066
[5]
0.329374
[6]
0
[7]
0.045635
[26] array · 8 items
[0]
DSG1
[1]
DEG_AD_down
[2]
41
[3]
3.046163
[4]
0.00857
[5]
0.328282
[6]
0
[7]
0.068464
[27] array · 8 items
[0]
GJA1
[1]
DEG_AD_down
[2]
41
[3]
3.035199
[4]
0.015703
[5]
0.329468
[6]
0
[7]
0.04037
[28] array · 8 items
[0]
MEF2C
[1]
DEG_AD_up
[2]
41
[3]
3.039238
[4]
0.008676
[5]
0.32903
[6]
0
[7]
0.068892
[29] array · 8 items
[0]
LYZ
[1]
DEG_AD_up
[2]
40
[3]
3.042123
[4]
0.008578
[5]
0.328718
[6]
0
[7]
0.065086
[30] array · 8 items
[0]
GSTO1
[1]
DEG_AD_up
[2]
38
[3]
2.820254
[4]
0.010905
[5]
0.354578
[6]
0.019915
[7]
0.030356
locator
section[18]/table-wrap[2]#tab5
[6] object · 16 fields
id
asset:table:pmid:33869630:6
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:e5016c42dafee984b459ade3ec4011b61633300aa9be2d437be4c041eb70b170
bytes
810
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[20]/table-wrap[1]#tab6
version
null
note
Classification performance of the 48 feature selection-obtained crosstalk genes in the four periodontitis-related datasets.
structure object · 5 fields
pmcid
PMC8032519
section_index
20
section_title
3.6. Classification Accuracy Using the Feature Selection-Obtained Crosstalk Genes
row_count
5
column_count
13
table object · 8 fields
label
Table 6
caption
Classification performance of the 48 feature selection-obtained crosstalk genes in the four periodontitis-related datasets.
rows array · 5 items
[0] array · 5 items
[0]
[1]
GSE16134
[2]
GSE10334
[3]
GSE23586
[4]
GSE79705
[1] array · 12 items
[0]
Samples: test set
[1]
Samples: SVM model predicts accurately
[2]
Accuracy
[3]
Samples: validation set
[4]
Samples: SVM model predicts accurately
[5]
Accuracy
[6]
Samples: validation set
[7]
Samples: SVM model predicts accurately
[8]
Accuracy
[9]
Samples: validation set
[10]
Samples: SVM model predicts accurately
[11]
Accuracy
[2] array · 13 items
[0]
Case
[1]
93
[2]
92
[3]
91.94%
[4]
183
[5]
177
[6]
88.26%
[7]
3
[8]
3
[9]
50%
[10]
8
[11]
8
[12]
66.66%
[3] array · 9 items
[0]
Control
[1]
31
[2]
22
[3]
64
[4]
41
[5]
3
[6]
0
[7]
4
[8]
0
[4] array · 9 items
[0]
Total
[1]
124
[2]
114
[3]
247
[4]
218
[5]
6
[6]
3
[7]
12
[8]
8
locator
section[20]/table-wrap[1]#tab6
[7] object · 16 fields
id
asset:table:pmid:33869630:7
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:6b26688de2b9f9f5c8a5c9f539bf15b911079933e6317bd93caf7b149dad922f
bytes
2817
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[22]/table-wrap[1]#tab7
version
null
note
Topological characteristics of the top 30 nodes in the TF-crosstalk gene target network, ranking in descending order.
structure object · 5 fields
pmcid
PMC8032519
section_index
22
section_title
3.8. The Identification of Transcription Factors Regulating the Crosstalk Genes
row_count
33
column_count
8
table object · 8 fields
label
Table 7
caption
Topological characteristics of the top 30 nodes in the TF-crosstalk gene target network, ranking in descending order.
rows array · 33 items
[0] array · 8 items
[0]
Node
[1]
Label
[2]
Degree
[3]
Average shortest path length
[4]
Betweenness centrality
[5]
Closeness centrality
[6]
Clustering coefficient
[7]
Topological coefficient
[1] array · 8 items
[0]
FOS
[1]
DEG_up&TF
[2]
89
[3]
2.178295
[4]
0.206101
[5]
0.459075
[6]
0.020429
[7]
0.03825
[2] array · 8 items
[0]
VEGFA
[1]
DEG_down
[2]
77
[3]
2.211886
[4]
0.197219
[5]
0.452103
[6]
0.010936
[7]
0.038456
[3] array · 8 items
[0]
MEF2C
[1]
DEG_up&TF
[2]
76
[3]
2.328165
[4]
0.159945
[5]
0.429523
[6]
0.004211
[7]
0.044258
[4] array · 8 items
[0]
CDH1
[1]
DEG_down
[2]
69
[3]
2.540052
[4]
0.159392
[5]
0.393693
[6]
0
[7]
0.086634
[5] array · 8 items
[0]
CXCR4
[1]
DEG_up
[2]
47
[3]
2.596899
[4]
0.075105
[5]
0.385075
[6]
9.25E − 04
[7]
0.083836
[6] array · 8 items
[0]
MME
[1]
DEG_up
[2]
44
[3]
2.664083
[4]
0.04365
[5]
0.375364
[6]
0
[7]
0.131313
[7] array · 8 items
[0]
C4A
[1]
DEG_up
[2]
38
[3]
2.661499
[4]
0.029742
[5]
0.375728
[6]
0.01138
[7]
0.118617
[8] array · 8 items
[0]
VIM
[1]
DEG_up
[2]
38
[3]
2.521964
[4]
0.060293
[5]
0.396516
[6]
0.012802
[7]
0.065789
[9] array · 8 items
[0]
CSF3
[1]
DEG_up
[2]
36
[3]
2.550388
[4]
0.031734
[5]
0.392097
[6]
0.019048
[7]
0.075137
[10] array · 8 items
[0]
C4B
[1]
DEG_up
[2]
34
[3]
2.679587
[4]
0.018887
[5]
0.373192
[6]
0.012478
[7]
0.122037
[11] array · 8 items
[0]
VCAN
[1]
DEG_up
[2]
34
[3]
2.726098
[4]
0.030567
[5]
0.366825
[6]
0
[7]
0.143717
[12] array · 8 items
[0]
IL1B
[1]
DEG_up
[2]
33
[3]
2.741602
[4]
0.05746
[5]
0.36475
[6]
0
[7]
0.134602
[13] array · 8 items
[0]
BRSK1
[1]
DEG_down
[2]
30
[3]
2.741602
[4]
0.030404
[5]
0.36475
[6]
0
[7]
0.153788
[14] array · 8 items
[0]
SERPINI1
[1]
DEG_up
[2]
29
[3]
2.793282
[4]
0.019014
[5]
0.358002
[6]
0
[7]
0.127586
[15] array · 8 items
[0]
USF2
[1]
DEG_down&TF
[2]
27
[3]
2.591731
[4]
0.027575
[5]
0.385842
[6]
0.045584
[7]
0.081607
[16] array · 8 items
[0]
GRHL3
[1]
DEG_down
[2]
27
[3]
2.775194
[4]
0.027067
[5]
0.360335
[6]
0
[7]
0.150732
[17] array · 8 items
[0]
HSPB1
[1]
DEG_down
[2]
26
[3]
2.780362
[4]
0.017981
[5]
0.359665
[6]
0
[7]
0.155678
[18] array · 8 items
[0]
MMP3
[1]
DEG_up
[2]
26
[3]
2.607235
[4]
0.024377
[5]
0.383548
[6]
0.036923
[7]
0.074984
[19] array · 8 items
[0]
CTGF
[1]
DEG_up
[2]
25
[3]
2.788114
[4]
0.020669
[5]
0.358665
[6]
0
[7]
0.161905
[20] array · 8 items
[0]
HMGCR
[1]
DEG_down
[2]
25
[3]
2.767442
[4]
0.041119
[5]
0.361345
[6]
0
[7]
0.16
[21] array · 8 items
[0]
GATA2
[1]
TF
[2]
24
[3]
2.095607
[4]
0.052687
[5]
0.477189
[6]
0.018116
[7]
0.104678
[22] array · 8 items
[0]
PLAT
[1]
DEG_up
[2]
24
[3]
2.762274
[4]
0.028075
[5]
0.362021
[6]
0
[7]
0.173148
[23] array · 8 items
[0]
ETS1
[1]
TF
[2]
22
[3]
2.273902
[4]
0.03767
[5]
0.439773
[6]
0.012987
[7]
0.092022
[24] array · 8 items
[0]
NPTXR
[1]
DEG_down
[2]
22
[3]
2.826873
[4]
0.020478
[5]
0.353748
[6]
0
[7]
0.154545
[25] array · 8 items
[0]
AR
[1]
TF
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21
[3]
2.24031
[4]
0.040698
[5]
0.446367
[6]
0.02381
[7]
0.105465
[26] array · 8 items
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YBX1
[1]
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[3]
2.315245
[4]
0.037801
[5]
0.43192
[6]
0.004762
[7]
0.098928
[27] array · 8 items
[0]
BCL2L2
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DEG_down
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[3]
2.813953
[4]
0.018179
[5]
0.355372
[6]
0
[7]
0.144048
[28] array · 8 items
[0]
FCGR3A
[1]
DEG_up
[2]
21
[3]
2.81137
[4]
0.020521
[5]
0.355699
[6]
0
[7]
0.192799
[29] array · 8 items
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ABCA12
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DEG_down
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20
[3]
2.79845
[4]
0.010961
[5]
0.357341
[6]
0
[7]
0.2
[30] array · 8 items
[0]
SP1
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[3]
2.191214
[4]
0.037362
[5]
0.456368
[6]
0.026316
[7]
0.109167
[31] array · 8 items
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CDK5R1
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DEG_down
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20
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2.824289
[4]
0.017878
[5]
0.354071
[6]
0
[7]
0.156098
[32] array · 8 items
[0]
FLG
[1]
DEG_down
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[3]
2.653747
[4]
0.012281
[5]
0.376826
[6]
0.042105
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0.093043
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section[22]/table-wrap[1]#tab7
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The number of crosstalk gene-related DEPs within the four periodontitis-related datasets.
structure object · 5 fields
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PMC8032519
section_index
23
section_title
3.9. Signaling Pathways Enriched in the Crosstalk Genes
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6
column_count
7
table object · 8 fields
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Table 8
caption
The number of crosstalk gene-related DEPs within the four periodontitis-related datasets.
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[0] array · 7 items
[0]
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[1]
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[2]
DEP
[3]
DEP
[4]
DEP
[5]
Log FC
[6]
p value
[1] array · 4 items
[0]
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[1]
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[2]
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[3]
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[2] array · 7 items
[0]
GSE23586
[1]
6
[2]
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[3]
12
[4]
13
[5]
>1
[6]
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[0]
GSE16134
[1]
310
[2]
84
[3]
2
[4]
86
[5]
>1
[6]
<0.05
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[0]
GSE10334
[1]
247
[2]
77
[3]
2
[4]
79
[5]
>1
[6]
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[4]
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The 12 overlapping genes between 48 feature selection-obtained crosstalk genes and periodontitis-related genes in the DisGeNET database. Among the 12 genes, 6 genes, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3, were associated with chronic periodontitis.
structure object · 5 fields
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PMC8032519
section_index
24
section_title
3.10. The Identification of Core Crosstalk Genes
row_count
29
column_count
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table object · 8 fields
label
Table 9
caption
The 12 overlapping genes between 48 feature selection-obtained crosstalk genes and periodontitis-related genes in the DisGeNET database. Among the 12 genes, 6 genes, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3, were associated with chronic periodontitis.
rows array · 29 items
[0] array · 4 items
[0]
Gene symbol
[1]
Gene ID
[2]
Disease ID
[3]
Disease name
[1] array · 4 items
[0]
C3
[1]
718
[2]
C0031099
[3]
Periodontitis
[2] array · 4 items
[0]
C4A
[1]
720
[2]
C0266929
[3]
Chronic periodontitis
[3] array · 4 items
[0]
C4B
[1]
721
[2]
C0266929
[3]
Chronic periodontitis
[4] array · 4 items
[0]
CXCL12
[1]
6387
[2]
C0266929
[3]
Chronic periodontitis
[5] array · 4 items
[0]
FCGR3A
[1]
2214
[2]
C0266929
[3]
Chronic periodontitis
[6] array · 4 items
[0]
FCGR3A
[1]
2214
[2]
C0031099
[3]
Periodontitis
[7] array · 4 items
[0]
FCGR3A
[1]
2214
[2]
C0031106
[3]
Periodontitis, juvenile
[8] array · 4 items
[0]
FCGR3A
[1]
2214
[2]
C0399447
[3]
Early-onset periodontitis
[9] array · 4 items
[0]
FCGR3A
[1]
2214
[2]
C0031030
[3]
Periapical periodontitis
[10] array · 4 items
[0]
FCGR3B
[1]
2215
[2]
C0399447
[3]
Early-onset periodontitis
[11] array · 4 items
[0]
FCGR3B
[1]
2215
[2]
C0031106
[3]
Periodontitis, juvenile
[12] array · 4 items
[0]
HSPB1
[1]
3315
[2]
C0031030
[3]
Periapical periodontitis
[13] array · 4 items
[0]
IL1B
[1]
3553
[2]
C1719494
[3]
Periodontitis, localized aggressive
[14] array · 4 items
[0]
IL1B
[1]
3553
[2]
C1719495
[3]
Aggressive periodontitis, generalized
[15] array · 4 items
[0]
IL1B
[1]
3553
[2]
C0399447
[3]
Early-onset periodontitis
[16] array · 4 items
[0]
IL1B
[1]
3553
[2]
C0001342
[3]
Acute periodontitis
[17] array · 4 items
[0]
IL1B
[1]
3553
[2]
C0031106
[3]
Periodontitis, juvenile
[18] array · 4 items
[0]
IL1B
[1]
3553
[2]
C0031030
[3]
Periapical periodontitis
[19] array · 4 items
[0]
IL1B
[1]
3553
[2]
C4025886
[3]
Severe periodontitis
[20] array · 4 items
[0]
IL1B
[1]
3553
[2]
C0031099
[3]
Periodontitis
[21] array · 4 items
[0]
IL1B
[1]
3553
[2]
C0266929
[3]
Chronic periodontitis
[22] array · 4 items
[0]
MME
[1]
4311
[2]
C0031099
[3]
Periodontitis
[23] array · 4 items
[0]
MMP3
[1]
4314
[2]
C0031106
[3]
Periodontitis, juvenile
[24] array · 4 items
[0]
MMP3
[1]
4314
[2]
C0001342
[3]
Acute periodontitis
[25] array · 4 items
[0]
MMP3
[1]
4314
[2]
C0266929
[3]
Chronic periodontitis
[26] array · 4 items
[0]
MMP3
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4314
[2]
C0031099
[3]
Periodontitis
[27] array · 4 items
[0]
PLAT
[1]
5327
[2]
C1719495
[3]
Aggressive periodontitis, generalized
[28] array · 4 items
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VEGFA
[1]
7422
[2]
C0031099
[3]
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locator
section[24]/table-wrap[1]#tab9
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Differential gene expression analysis of periodontitis-related datasets was carried out using the Linear Models for Microarray (limma) package [12] in the R project (version 3.0.1, http://www.r-project.org/) [13].
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The data used to support the findings of this study are available from the corresponding author upon request.
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Differential gene expression analysis of periodontitis-related datasets was carried out using the Linear Models for Microarray (limma) package [12] in the R project (version 3.0.1, http://www.r-project.org/) [13].
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33869630", "kind": "science-record", "revision": 8, "content_hash": "sha256:3d54383d18d4f50e88e30481b18657025c79b56fe452213832a735c915f3590c", "created_at": "2026-11-01T15:41:32Z", "updated_at": "2026-11-01T22:46:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Shared Molecular Mechanisms between Alzheimer's Disease and Periodontitis Revealed by Transcriptomic Analysis.", "doi": "10.1155/2021/6633563", "pmid": "33869630", "authors": ["Jieqi Jin", "Mengkai Guang", "Anthony Chukwunonso Ogbuehi", "Simin Li", "Kai Zhang", "Yihong Ma", "Aneesha Acharya", "Bihan Guo", "Zongwu Peng", "Xiangqiong Liu", "Yupei Deng", "Zhaobi Fang", "Xiongjie Zhu", "Shiting Hua", "Cong Li", "Rainer Haak", "Dirk Ziebolz", "Gerhard Schmalz", "Lei Liu", "Baohua Xu", "Xiaofeng Huang"], "journal": "BioMed research international", "year": 2021, "abstract": "OBJECTIVE: To investigate the genetic crosstalk mechanisms that link periodontitis and Alzheimer's disease (AD).\nBACKGROUND: Periodontitis, a common oral infectious disease, is associated with Alzheimer's disease (AD) and considered a putative contributory factor to its progression. However, a comprehensive investigation of potential shared genetic mechanisms between these diseases has not yet been reported.\nMETHODS: Gene expression datasets related to periodontitis were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed to identify differentially expressed genes (DEGs). Genes associated with AD were downloaded from the DisGeNET database. Overlapping genes among the DEGs in periodontitis and the AD-related genes were defined as crosstalk genes between periodontitis and AD. The Boruta algorithm was applied to perform feature selection from these crosstalk genes, and representative crosstalk genes were thus obtained. In addition, a support vector machine (SVM) model was constructed by using the scikit-learn algorithm in Python. Next, the crosstalk gene-TF network and crosstalk gene-DEP (differentially expressed pathway) network were each constructed. As a final step, shared genes among the crosstalk genes and periodontitis-related genes in DisGeNET were identified and denoted as the core crosstalk genes.\nRESULTS: Four datasets (GSE23586, GSE16134, GSE10334, and GSE79705) pertaining to periodontitis were included in the analysis. A total of 48 representative crosstalk genes were identified by using the Boruta algorithm. Three TFs (FOS, MEF2C, and USF2) and several pathways (i.e., JAK-STAT, MAPK, NF-kappa B, and natural killer cell-mediated cytotoxicity) were identified as regulators of these crosstalk genes. Among these 48 crosstalk genes and the chronic periodontitis-related genes in DisGeNET, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 were shared and identified as the most pivotal candidate links between periodontitis and AD.\nCONCLUSIONS: Exploration of available transcriptomic datasets revealed C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 as the top candidate molecular linkage genes between periodontitis and AD.", "claims": [{"id": "claim-method", "statement": "Differential gene expression analysis of periodontitis-related datasets was carried out using the Linear Models for Microarray (limma) package [12] in the R project (version 3.0.1, http://www.r-project.org/) [13].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33869630", "locator": "sections[5] \"2.3. Differential Gene Expression Analysis\" paragraph 2", "quote": "Differential gene expression analysis of periodontitis-related datasets was carried out using the Linear Models for Microarray (limma) package [12] in the R project (version 3.0.1, http://www.r-project.org/) [13]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33869630", "locator": "sections[27] \"Data Availability\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:33869630"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33869630", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/6633563", "sha256": "sha256:32f3d96d095d16c687890ec073b57e97cfa5c022bfc6da9b63d99963bb0f9ee7", "bytes": 52512, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/6633563", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8032519", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33869630:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7ff6bd27d0a24a54442c534b130a2e4ea2584737d9a7147e407e290031715016", "bytes": 891, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#tab1", "version": null, "note": "Details of the included periodontitis-related GEO datasets.", "structure": {"pmcid": "PMC8032519", "section_index": 15, "section_title": "3.1. Included Periodontitis-Related Datasets", "row_count": 5, "column_count": 7}, "table": {"label": "Table 1", "caption": "Details of the included periodontitis-related GEO datasets.", "rows": [["Included four datasets", "Type of periodontitis", "Experimental platform", "Number of examined genes", "Number of inflamed gingival tissue samples", "Number of healthy control samples", "Number of total samples"], ["GSE23586", "3 patients with severe chronic periodontitis", "GPL570", "23,518", "3", "3", "6"], ["GSE16134", "120 patients (65 with chronic periodontitis and 55 with aggressive periodontitis)", "GPL570", "24,441", "241", "69", "310"], ["GSE10334", "63 with chronic periodontitis and 27 with aggressive periodontitis", "GPL570", "24,441", "183", "64", "247"], ["GSE79705", "Generalized aggressive periodontitis (GAgP): n = 4; chronic periodontitis (CP): n = 4", "GPL18734", "19,305", "8", "4", "12"]], "row_count": 5, "column_count": 7, "numeric_cells": 28, "header_rows": 1, "locator": "section[15]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:33869630:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:66cff32966325f77aa78b70a74a71a6615044a7d8d2860189fdc4d62f722999e", "bytes": 698, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#tab2", "version": null, "note": "The number of up/downregulated DEGs identified in the four periodontitis-related datasets GSE23586, GSE16134, GSE10334, and GSE79705 at thresholds set for defining DEGs.", "structure": {"pmcid": "PMC8032519", "section_index": 16, "section_title": "3.2. Identification of Periodontitis-Related DEGs and Their Functions", "row_count": 5, "column_count": 7}, "table": {"label": "Table 2", "caption": "The number of up/downregulated DEGs identified in the four periodontitis-related datasets GSE23586, GSE16134, GSE10334, and GSE79705 at thresholds set for defining DEGs.", "rows": [["Data", "Number of upregulated DEGs", "Number of downregulated DEGs", "Number of total DEGs", "∣log2 FC∣", "p value", "Expression scale (if the data normalization was performed)"], ["GSE23586", "7", "69", "76", ">1", "<0.05", "True"], ["GSE16134", "188", "48", "236", ">1", "<0.05", "False"], ["GSE10334", "152", "42", "194", ">1", "<0.05", "False"], ["GSE79705", "219", "291", "510", ">0", "<0.05", "True"]], "row_count": 5, "column_count": 7, "numeric_cells": 24, "header_rows": 1, "locator": "section[16]/table-wrap[1]#tab2"}}, {"id": "asset:table:pmid:33869630:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b9e4f0fbb2e2599ebb446288d05388f7ef411fe20feb546f479bb72506456492", "bytes": 2841, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#tab3", "version": null, "note": "Topological characteristics of the top 30 nodes in the periodontitis-related PPI network, ranked in descending order of degree.", "structure": {"pmcid": "PMC8032519", "section_index": 17, "section_title": "3.3. The Hub Genes Identified by the Periodontitis-Related PPI Network", "row_count": 31, "column_count": 8}, "table": {"label": "Table 3", "caption": "Topological characteristics of the top 30 nodes in the periodontitis-related PPI network, ranked in descending order of degree.", "rows": [["Node", "Label", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Clustering coefficient", "Topological coefficient"], ["MYC", "DEG_down", "1027", "2.432727", "0.177217", "0.411061", "0.001896", "0.002805"], ["HSPB1", "DEG_down", "433", "2.638061", "0.059908", "0.379066", "0.00278", "0.005213"], ["SMAD3", "DEG_up", "396", "2.667636", "0.052167", "0.374864", "0.004283", "0.005425"], ["UBC", "", "395", "2.112", "0.241673", "0.473485", "0.004524", "0.007004"], ["TRIM27", "DEG_up", "334", "2.864727", "0.046792", "0.349073", "0.000791", "0.006306"], ["VIM", "DEG_up", "320", "2.705212", "0.037607", "0.369657", "0.005251", "0.007619"], ["YWHAH", "DEG_up", "282", "2.838788", "0.034115", "0.352263", "0.001868", "0.00865"], ["DDB1", "DEG_down", "276", "2.76497", "0.029677", "0.361668", "0.003531", "0.008012"], ["RPS3", "DEG_down", "275", "2.844848", "0.015036", "0.351513", "0.019323", "0.014779"], ["KAT5", "DEG_down", "245", "2.717697", "0.028224", "0.367959", "0.00716", "0.007732"], ["SMARCA4", "DEG_down", "242", "2.715758", "0.021646", "0.368221", "0.010116", "0.008636"], ["RPL13", "DEG_down", "234", "2.755152", "0.015773", "0.362956", "0.024541", "0.011238"], ["PLCG1", "DEG_down", "227", "2.885091", "0.030011", "0.34661", "0.002144", "0.009614"], ["FOS", "DEG_up", "226", "2.880727", "0.024538", "0.347135", "0.003265", "0.009974"], ["AP2M1", "DEG_down", "214", "2.850182", "0.025582", "0.350855", "0.007635", "0.010848"], ["SF3B3", "DEG_down", "203", "2.765576", "0.015188", "0.361588", "0.014583", "0.010661"], ["TP53RK", "DEG_up", "200", "2.871394", "0.013972", "0.348263", "0.01608", "0.012798"], ["MMS19", "DEG_down", "195", "2.806909", "0.022335", "0.356264", "0.004705", "0.008763"], ["RPS7", "DEG_down", "193", "2.88303", "0.008126", "0.346857", "0.028335", "0.016367"], ["MEPCE", "DEG_down", "189", "2.905212", "0.0145", "0.344209", "0.005066", "0.012337"], ["TUBB4B", "DEG_down", "173", "2.880364", "0.008167", "0.347178", "0.007595", "0.019412"], ["CDH1", "DEG_down", "171", "2.888485", "0.016186", "0.346202", "0.005848", "0.011775"], ["EZR", "DEG_down", "170", "2.906667", "0.016295", "0.344037", "0.004107", "0.01554"], ["DDX41", "DEG_down", "168", "2.950061", "0.009545", "0.338976", "0.007057", "0.017509"], ["NUDC", "DEG_up", "160", "2.943758", "0.016886", "0.339702", "0.00283", "0.013954"], ["SF3A2", "DEG_down", "156", "2.949818", "0.009075", "0.339004", "0.009926", "0.01593"], ["RPL27", "DEG_down", "147", "2.912727", "0.003949", "0.343321", "0.043985", "0.020057"], ["NIFK", "DEG_up", "145", "3.107879", "0.011111", "0.321763", "0.010345", "0.016053"], ["SRPRB", "DEG_up", "143", "2.945333", "0.017545", "0.33952", "0.001674", "0.015983"], ["ATP1A1", "DEG_up", "140", "2.816606", "0.011269", "0.355037", "0.009147", "0.013032"]], "row_count": 31, "column_count": 8, "numeric_cells": 186, "header_rows": 1, "locator": "section[17]/table-wrap[1]#tab3"}}, {"id": "asset:table:pmid:33869630:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:17c8ac080cae5dbddf379b733d7f88ff625c92d67f6188271c5769b68cb82d3c", "bytes": 5152, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#tab4", "version": null, "note": "The 51 crosstalk genes that were upregulated and 41 crosstalk genes which were downregulated in periodontitis.", "structure": {"pmcid": "PMC8032519", "section_index": 18, "section_title": "3.4. Crosstalk Genes Bridging Alzheimer's Disease and Periodontitis", "row_count": 4, "column_count": 2}, "table": {"label": "Table 4", "caption": "The 51 crosstalk genes that were upregulated and 41 crosstalk genes which were downregulated in periodontitis.", "rows": [["Regulation pattern in periodontitis", "Crosstalk genes linking periodontitis and Alzheimer's disease"], ["Upregulated", "AMIGO1 (adhesion molecule with Ig-like domain 1; gene ID: 57463)ARG2 (arginase 2; gene ID: 384)BDKRB2 (bradykinin receptor B2; gene ID: 624)BRI3 (brain protein I3; gene ID: 25798)C1D (C1D nuclear receptor corepressor; gene ID: 10438)C3 (complement C3; gene ID: 718)C4A (complement C4A (Rodgers blood group); gene ID: 720)C4B (complement C4B; gene ID: 721)C4B_2 (complement component 4B (Chido blood group), copy 2; gene ID: 100293534)CASP7 (caspase 7; gene ID: 840)CD177 (CD177 molecule; gene ID: 57126)CD38 (CD38 molecule; gene ID: 952)CHCHD10 (coiled-coil-helix-coiled-coil-helix domain containing 10; gene ID: 400916)COX8A (cytochrome c oxidase subunit 8A; gene ID: 1351)CSF3 (colony-stimulating factor 3; gene ID: 1440)CTGF (cellular communication network factor 2; gene ID: 1490)CTSS (cathepsin S; gene ID: 1520)CXCL1 (C-X-C motif chemokine ligand 1; gene ID: 2919)CXCL12 (C-X-C motif chemokine ligand 12; gene ID: 6387)CXCL8 (C-X-C motif chemokine ligand 8; gene ID: 3576)CXCR4 (C-X-C motif chemokine receptor 4; gene ID: 7842)ENPP2 (ectonucleotide pyrophosphatase/phosphodiesterase 2; gene ID: 5168)FCGR3A (Fc fragment of IgG receptor IIIa; gene ID: 2214)FCGR3B (Fc fragment of IgG receptor IIIb; gene ID: 2215)FHL2 (four and a half LIM domains 2; gene ID: 2274)FOS (Fos proto-oncogene, AP-1 transcription factor subunit; gene ID: 2353)FOXO1 (forkhead box O1; gene ID: 2308)GSTK1 (glutathione S-transferase kappa 1; gene ID: 373156)GSTO1 (glutathione S-transferase omega 1; gene ID: 9446)HCLS1 (hematopoietic cell-specific Lyn substrate 1; gene ID: 3059)IGFBP7 (insulin-like growth factor binding protein 7; gene ID: 3490)IL1B (interleukin-1 beta; gene ID: 3553)LYZ (lysozyme; gene ID: 4069)MAK16 (MAK16 homolog; gene ID: 84549)MEF2C (myocyte-specific enhancer factor 2C; gene ID: 4208)MME (membrane metalloendopeptidase; gene ID: 4311)MMP1 (matrix metallopeptidase 1; gene ID: 4312)MMP3 (matrix metallopeptidase 3; gene ID: 4314)MS4A1 (membrane-spanning 4-domains A1; gene ID: 931)MSRA (methionine sulfoxide reductase A; gene ID: 4482)MZB1 (marginal zone B and B1 cell-specific protein; gene ID: 51237)NDUFB8 (NADH:ubiquinone oxidoreductase subunit B8; gene ID: 4714)PECAM1 (platelet endothelial cell adhesion molecule 1; gene ID: 5175)PLAT (plasminogen activator, tissue type; gene ID: 5327)PSENEN (presenilin enhancer, gamma-secretase subunit; gene ID: 55851)SEL1L (SEL1L adaptor subunit of ERAD E3 ubiquitin ligase; gene ID: 6400)SERPINI1 (serpin family I member 1; gene ID: 5274)ST6GAL1 (ST6 beta-galactoside alpha-2,6-sialyltransferase 1; gene ID: 6480)VCAN (versican; gene ID: 1462)VIM (vimentin; gene ID: 7431)WARS2 (tryptophanyl tRNA synthetase 2, mitochondrial; gene ID: 10352)"], [""], ["Downregulated", "ABCA12 (ATP binding cassette subfamily A member 12; gene ID: 26154)ACE (angiotensin I converting enzyme; gene ID: 1636)ADRB1 (adrenoceptor beta 1; gene ID: 153)BCL2L2 (BCL2-like 2; gene ID: 599)BRSK1 (BR serine/threonine kinase 1; gene ID: 84446)CALML5 (calmodulin-like 5; gene ID: 51806)CALR (calreticulin; gene ID: 811)CD36 (CD36 molecule; gene ID: 948)CDH1 (cadherin 1; gene ID: 999)CDK5R1 (cyclin-dependent kinase 5 regulatory subunit 1; gene ID: 8851)CTDSP2 (CTD small phosphatase 2; gene ID: 10106)DNM1 (dynamin 1; gene ID: 1759)DSG1 (desmoglein 1; gene ID: 1828)FLG (filaggrin; gene ID: 2312)GJA1 (gap junction protein alpha 1; gene ID: 2697)GRHL3 (grainyhead-like transcription factor 3; gene ID: 57822)GRIN3B (glutamate ionotropic receptor NMDA type subunit 3B; gene ID: 116444)HM13 (histocompatibility minor 13; gene ID: 81502)HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase; gene ID: 3156)HSPB1 (heat shock protein family B (small) member 1; gene ID: 3315)KAT5 (lysine acetyltransferase 5; gene ID: 10524)MAP3K12 (mitogen-activated protein kinase kinase kinase 12; gene ID: 7786)MED12 (mediator complex subunit 12; gene ID: 9968)MFN2 (mitofusin 2; gene ID: 9927)MYC (MYC proto-oncogene, bHLH transcription factor; gene ID: 4609)NEFL (neurofilament light; gene ID: 4747)NES (exportin 1; gene ID: 7514)NGF (nerve growth factor; gene ID: 4803)NOS3 (nitric oxide synthase 3; gene ID: 4846)NPTXR (neuronal pentraxin receptor; gene ID: 23467)PLXNA3 (plexin A3; gene ID: 55558)PPIL2 (peptidylprolyl isomerase-like 2; gene ID: 23759)PTGS1 (prostaglandin-endoperoxide synthase 1; gene ID: 5742)RPL13 (ribosomal protein L13; gene ID: 6137)SCIMP (SLP adaptor and CSK interacting membrane protein; gene ID: 388325)SPPL2B (signal peptide peptidase-like 2B; gene ID: 56928)TIAF1 (TGFB1-induced antiapoptotic factor 1; gene ID: 9220)TP73 (tumor protein P73; gene ID: 7161)TYRP1 (tyrosinase-related protein 1; gene ID: 7306)USF2 (upstream transcription factor 2, C-Fos interacting; gene ID: 7392)VEGFA (vascular endothelial growth factor A; gene ID: 7422)"]], "row_count": 4, "column_count": 2, "numeric_cells": 2, "header_rows": 1, "locator": "section[18]/table-wrap[1]#tab4"}}, {"id": "asset:table:pmid:33869630:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:699dcaca7aea84f98b3863785d4eb056eebf920dbc3103f234b87a17a6b695c4", "bytes": 2844, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[2]#tab5", "version": null, "note": "Topological characteristics of the top 30 nodes in the crosstalk gene-related PPI network, ranked in descending order of degree.", "structure": {"pmcid": "PMC8032519", "section_index": 18, "section_title": "3.4. Crosstalk Genes Bridging Alzheimer's Disease and Periodontitis", "row_count": 31, "column_count": 8}, "table": {"label": "Table 5", "caption": "Topological characteristics of the top 30 nodes in the crosstalk gene-related PPI network, ranked in descending order of degree.", "rows": [["Node", "Label", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Clustering coefficient", "Topological coefficient"], ["MYC", "DEG_AD_down", "1027", "2.127525", "0.466698", "0.47003", "5.03E − 04", "0.001842"], ["HSPB1", "DEG_AD_down", "433", "2.36959", "0.184598", "0.422014", "0.001636", "0.003351"], ["VIM", "DEG_AD_up", "320", "2.663301", "0.116611", "0.375474", "0.001763", "0.005783"], ["KAT5", "DEG_AD_down", "245", "2.566359", "0.089476", "0.389657", "0.003011", "0.005621"], ["RPL13", "DEG_AD_down", "234", "2.589729", "0.089708", "0.386141", "0.001394", "0.005672"], ["FOS", "DEG_AD_up", "226", "2.883151", "0.083642", "0.346843", "1.97E − 04", "0.017606"], ["CDH1", "DEG_AD_down", "171", "2.93191", "0.058428", "0.341075", "0", "0.025911"], ["TP73", "DEG_AD_down", "137", "2.61483", "0.046781", "0.382434", "0.006333", "0.009173"], ["FHL2", "DEG_AD_up", "136", "2.641085", "0.057192", "0.378632", "0.004031", "0.00889"], ["CALR", "DEG_AD_down", "135", "2.812464", "0.046142", "0.35556", "0.002764", "0.010949"], ["GSTK1", "DEG_AD_up", "111", "2.988459", "0.035152", "0.334621", "0", "0.026289"], ["MME", "DEG_AD_up", "104", "2.836988", "0.040386", "0.352487", "0.001307", "0.011694"], ["MED12", "DEG_AD_down", "91", "2.695615", "0.030682", "0.370973", "0.006105", "0.012517"], ["CASP7", "DEG_AD_up", "90", "2.901039", "0.027131", "0.344704", "0.005243", "0.015603"], ["DNM1", "DEG_AD_down", "84", "2.960185", "0.029086", "0.337817", "0.001147", "0.023716"], ["FOXO1", "DEG_AD_up", "67", "2.977784", "0.017403", "0.33582", "0.004071", "0.026586"], ["CXCR4", "DEG_AD_up", "65", "2.998557", "0.020851", "0.333494", "0.003846", "0.028808"], ["NOS3", "DEG_AD_down", "62", "2.963647", "0.018786", "0.337422", "0.002644", "0.027957"], ["NDUFB8", "DEG_AD_up", "56", "3.042412", "0.02136", "0.328687", "0", "0.027447"], ["UBC", "Other gene", "53", "2.084824", "0.149265", "0.479657", "0.015965", "0.027336"], ["NES", "DEG_AD_down", "53", "2.920946", "0.017012", "0.342355", "0.007983", "0.022954"], ["CDK5R1", "DEG_AD_down", "50", "3.0176", "0.0133", "0.331389", "0.002449", "0.037222"], ["NEFL", "DEG_AD_down", "49", "2.913445", "0.014886", "0.343236", "0.008503", "0.024673"], ["C3", "DEG_AD_up", "43", "3.043278", "0.01705", "0.328593", "0", "0.042101"], ["SEL1L", "DEG_AD_up", "42", "3.036065", "0.013066", "0.329374", "0", "0.045635"], ["DSG1", "DEG_AD_down", "41", "3.046163", "0.00857", "0.328282", "0", "0.068464"], ["GJA1", "DEG_AD_down", "41", "3.035199", "0.015703", "0.329468", "0", "0.04037"], ["MEF2C", "DEG_AD_up", "41", "3.039238", "0.008676", "0.32903", "0", "0.068892"], ["LYZ", "DEG_AD_up", "40", "3.042123", "0.008578", "0.328718", "0", "0.065086"], ["GSTO1", "DEG_AD_up", "38", "2.820254", "0.010905", "0.354578", "0.019915", "0.030356"]], "row_count": 31, "column_count": 8, "numeric_cells": 183, "header_rows": 1, "locator": "section[18]/table-wrap[2]#tab5"}}, {"id": "asset:table:pmid:33869630:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e5016c42dafee984b459ade3ec4011b61633300aa9be2d437be4c041eb70b170", "bytes": 810, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[20]/table-wrap[1]#tab6", "version": null, "note": "Classification performance of the 48 feature selection-obtained crosstalk genes in the four periodontitis-related datasets.", "structure": {"pmcid": "PMC8032519", "section_index": 20, "section_title": "3.6. 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The Identification of Transcription Factors Regulating the Crosstalk Genes", "row_count": 33, "column_count": 8}, "table": {"label": "Table 7", "caption": "Topological characteristics of the top 30 nodes in the TF-crosstalk gene target network, ranking in descending order.", "rows": [["Node", "Label", "Degree", "Average shortest path length", "Betweenness centrality", "Closeness centrality", "Clustering coefficient", "Topological coefficient"], ["FOS", "DEG_up&TF", "89", "2.178295", "0.206101", "0.459075", "0.020429", "0.03825"], ["VEGFA", "DEG_down", "77", "2.211886", "0.197219", "0.452103", "0.010936", "0.038456"], ["MEF2C", "DEG_up&TF", "76", "2.328165", "0.159945", "0.429523", "0.004211", "0.044258"], ["CDH1", "DEG_down", "69", "2.540052", "0.159392", "0.393693", "0", "0.086634"], ["CXCR4", "DEG_up", "47", "2.596899", "0.075105", "0.385075", "9.25E − 04", "0.083836"], ["MME", "DEG_up", "44", "2.664083", "0.04365", "0.375364", "0", "0.131313"], ["C4A", "DEG_up", "38", "2.661499", "0.029742", "0.375728", "0.01138", "0.118617"], ["VIM", "DEG_up", "38", "2.521964", "0.060293", "0.396516", "0.012802", "0.065789"], ["CSF3", "DEG_up", "36", "2.550388", "0.031734", "0.392097", "0.019048", "0.075137"], ["C4B", "DEG_up", "34", "2.679587", "0.018887", "0.373192", "0.012478", "0.122037"], ["VCAN", "DEG_up", "34", "2.726098", "0.030567", "0.366825", "0", "0.143717"], ["IL1B", "DEG_up", "33", "2.741602", "0.05746", "0.36475", "0", "0.134602"], ["BRSK1", "DEG_down", "30", "2.741602", "0.030404", "0.36475", "0", "0.153788"], ["SERPINI1", "DEG_up", "29", "2.793282", "0.019014", "0.358002", "0", "0.127586"], ["USF2", "DEG_down&TF", "27", "2.591731", "0.027575", "0.385842", "0.045584", "0.081607"], ["GRHL3", "DEG_down", "27", "2.775194", "0.027067", "0.360335", "0", "0.150732"], ["HSPB1", "DEG_down", "26", "2.780362", "0.017981", "0.359665", "0", "0.155678"], ["MMP3", "DEG_up", "26", "2.607235", "0.024377", "0.383548", "0.036923", "0.074984"], ["CTGF", "DEG_up", "25", "2.788114", "0.020669", "0.358665", "0", "0.161905"], ["HMGCR", "DEG_down", "25", "2.767442", "0.041119", "0.361345", "0", "0.16"], ["GATA2", "TF", "24", "2.095607", "0.052687", "0.477189", "0.018116", "0.104678"], ["PLAT", "DEG_up", "24", "2.762274", "0.028075", "0.362021", "0", "0.173148"], ["ETS1", "TF", "22", "2.273902", "0.03767", "0.439773", "0.012987", "0.092022"], ["NPTXR", "DEG_down", "22", "2.826873", "0.020478", "0.353748", "0", "0.154545"], ["AR", "TF", "21", "2.24031", "0.040698", "0.446367", "0.02381", "0.105465"], ["YBX1", "TF", "21", "2.315245", "0.037801", "0.43192", "0.004762", "0.098928"], ["BCL2L2", "DEG_down", "21", "2.813953", "0.018179", "0.355372", "0", "0.144048"], ["FCGR3A", "DEG_up", "21", "2.81137", "0.020521", "0.355699", "0", "0.192799"], ["ABCA12", "DEG_down", "20", "2.79845", "0.010961", "0.357341", "0", "0.2"], ["SP1", "TF", "20", "2.191214", "0.037362", "0.456368", "0.026316", "0.109167"], ["CDK5R1", "DEG_down", "20", "2.824289", "0.017878", "0.354071", "0", "0.156098"], ["FLG", "DEG_down", "20", "2.653747", "0.012281", "0.376826", "0.042105", "0.093043"]], "row_count": 33, "column_count": 8, "numeric_cells": 193, "header_rows": 1, "locator": "section[22]/table-wrap[1]#tab7"}}, {"id": "asset:table:pmid:33869630:8", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5ba33ebc1750e52ebc7e3c3df317805e28dad3ece3be060b12f09b3348fd83ec", "bytes": 501, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[23]/table-wrap[1]#tab8", "version": null, "note": "The number of crosstalk gene-related DEPs within the four periodontitis-related datasets.", "structure": {"pmcid": "PMC8032519", "section_index": 23, "section_title": "3.9. Signaling Pathways Enriched in the Crosstalk Genes", "row_count": 6, "column_count": 7}, "table": {"label": "Table 8", "caption": "The number of crosstalk gene-related DEPs within the four periodontitis-related datasets.", "rows": [["Data", "Sample", "DEP", "DEP", "DEP", "Log FC", "p value"], ["Up", "Down", "Total", "Abs"], ["GSE23586", "6", "1", "12", "13", ">1", "<0.05"], ["GSE16134", "310", "84", "2", "86", ">1", "<0.05"], ["GSE10334", "247", "77", "2", "79", ">1", "<0.05"], ["GSE79705", "12", "4", "4", "8", ">0", "<0.05"]], "row_count": 6, "column_count": 7, "numeric_cells": 28, "header_rows": 2, "locator": "section[23]/table-wrap[1]#tab8"}}, {"id": "asset:table:pmid:33869630:9", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:22ade746a93267f18ff982a361f8a4fff5b5ffd43fbd637c0158d7e77e6ccc44", "bytes": 1916, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[24]/table-wrap[1]#tab9", "version": null, "note": "The 12 overlapping genes between 48 feature selection-obtained crosstalk genes and periodontitis-related genes in the DisGeNET database. Among the 12 genes, 6 genes, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3, were associated with chronic periodontitis.", "structure": {"pmcid": "PMC8032519", "section_index": 24, "section_title": "3.10. The Identification of Core Crosstalk Genes", "row_count": 29, "column_count": 4}, "table": {"label": "Table 9", "caption": "The 12 overlapping genes between 48 feature selection-obtained crosstalk genes and periodontitis-related genes in the DisGeNET database. Among the 12 genes, 6 genes, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3, were associated with chronic periodontitis.", "rows": [["Gene symbol", "Gene ID", "Disease ID", "Disease name"], ["C3", "718", "C0031099", "Periodontitis"], ["C4A", "720", "C0266929", "Chronic periodontitis"], ["C4B", "721", "C0266929", "Chronic periodontitis"], ["CXCL12", "6387", "C0266929", "Chronic periodontitis"], ["FCGR3A", "2214", "C0266929", "Chronic periodontitis"], ["FCGR3A", "2214", "C0031099", "Periodontitis"], ["FCGR3A", "2214", "C0031106", "Periodontitis, juvenile"], ["FCGR3A", "2214", "C0399447", "Early-onset periodontitis"], ["FCGR3A", "2214", "C0031030", "Periapical periodontitis"], ["FCGR3B", "2215", "C0399447", "Early-onset periodontitis"], ["FCGR3B", "2215", "C0031106", "Periodontitis, juvenile"], ["HSPB1", "3315", "C0031030", "Periapical periodontitis"], ["IL1B", "3553", "C1719494", "Periodontitis, localized aggressive"], ["IL1B", "3553", "C1719495", "Aggressive periodontitis, generalized"], ["IL1B", "3553", "C0399447", "Early-onset periodontitis"], ["IL1B", "3553", "C0001342", "Acute periodontitis"], ["IL1B", "3553", "C0031106", "Periodontitis, juvenile"], ["IL1B", "3553", "C0031030", "Periapical periodontitis"], ["IL1B", "3553", "C4025886", "Severe periodontitis"], ["IL1B", "3553", "C0031099", "Periodontitis"], ["IL1B", "3553", "C0266929", "Chronic periodontitis"], ["MME", "4311", "C0031099", "Periodontitis"], ["MMP3", "4314", "C0031106", "Periodontitis, juvenile"], ["MMP3", "4314", "C0001342", "Acute periodontitis"], ["MMP3", "4314", "C0266929", "Chronic periodontitis"], ["MMP3", "4314", "C0031099", "Periodontitis"], ["PLAT", "5327", "C1719495", "Aggressive periodontitis, generalized"], ["VEGFA", "7422", "C0031099", "Periodontitis"]], "row_count": 29, "column_count": 4, "numeric_cells": 57, "header_rows": 1, "locator": "section[24]/table-wrap[1]#tab9"}}], "gaps": []}, "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": "Differential gene expression analysis of periodontitis-related datasets was carried out using the Linear Models for Microarray (limma) package [12] in the R project (version 3.0.1, http://www.r-project.org/) [13]."}}, {"id": "method-2", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "support vector machine"}}], "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "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. 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