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pmid:33777111

Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis.

Wanchen Ning · Aneesha Acharya · Zhengyang Sun · Anthony Chukwunonso Ogbuehi · Cong Li · Shiting Hua · Qianhua Ou · Muhui Zeng · Xiangqiong Liu · Yupei Deng · Rainer Haak · Dirk Ziebolz · Gerhard Schmalz · George Pelekos · Yang Wang · Xianda Hu

Frontiers in genetics · 2021 doi:10.3389/fgene.2021.648329

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Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis.
doi
10.3389/fgene.2021.648329
pmid
33777111
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[0]
Wanchen Ning
[1]
Aneesha Acharya
[2]
Zhengyang Sun
[3]
Anthony Chukwunonso Ogbuehi
[4]
Cong Li
[5]
Shiting Hua
[6]
Qianhua Ou
[7]
Muhui Zeng
[8]
Xiangqiong Liu
[9]
Yupei Deng
[10]
Rainer Haak
[11]
Dirk Ziebolz
[12]
Gerhard Schmalz
[13]
George Pelekos
[14]
Yang Wang
[15]
Xianda Hu
journal
Frontiers in genetics
year
2021
abstract
BACKGROUND: Periodontitis is a chronic immuno-inflammatory disease characterized by inflammatory destruction of tooth-supporting tissues. Its pathogenesis involves a dysregulated local host immune response that is ineffective in combating microbial challenges. An integrated investigation of genes involved in mediating immune response suppression in periodontitis, based on multiple studies, can reveal genes pivotal to periodontitis pathogenesis. Here, we aimed to apply a deep learning (DL)-based autoencoder (AE) for predicting immunosuppression genes involved in periodontitis by integrating multiples omics datasets. METHODS: Two periodontitis-related GEO transcriptomic datasets (GSE16134 and GSE10334) and immunosuppression genes identified from DisGeNET and HisgAtlas were included. Immunosuppression genes related to periodontitis in GSE16134 were used as input to build an AE, to identify the top disease-representative immunosuppression gene features. Using K-means clustering and ANOVA, immune subtype labels were assigned to disease samples and a support vector machine (SVM) classifier was constructed. This classifier was applied to a validation set (Immunosuppression genes related to periodontitis in GSE10334) for predicting sample labels, evaluating the accuracy of the AE. In addition, differentially expressed genes (DEGs), signaling pathways, and transcription factors (TFs) involved in immunosuppression and periodontitis were determined with an array of bioinformatics analysis. Shared DEGs common to DEGs differentiating periodontitis from controls and those differentiating the immune subtypes were considered as the key immunosuppression genes in periodontitis. RESULTS: We produced representative molecular features and identified two immune subtypes in periodontitis using an AE. Two subtypes were also predicted in the validation set with the SVM classifier. Three "master" immunosuppression genes, PECAM1, FCGR3A, and FOS were identified as candidates pivotal to immunosuppressive mechanisms in periodontitis. Six transcription factors, NFKB1, FOS, JUN, HIF1A, STAT5B, and STAT4, were identified as central to the TFs-DEGs interaction network. The two immune subtypes were distinct in terms of their regulating pathways. CONCLUSION: This study applied a DL-based AE for the first time to identify immune subtypes of periodontitis and pivotal immunosuppression genes that discriminated periodontitis from the healthy. Key signaling pathways and TF-target DEGs that putatively mediate immune suppression in periodontitis were identified. PECAM1, FCGR3A, and FOS emerged as high-value biomarkers and candidate therapeutic targets for periodontitis.
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[305]
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[306]
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[307]
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[308]
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[309]
GSM404314
sample_count
310
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Bacterial Correlates of Gingival Gene Expression
resolution_checked_at
2026-11-01T15:39:54Z
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downloaded
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Summary of periodontitis related GEO datasets used in this study.
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PMC7994531
section_index
4
section_title
Pre-processing of the Dataset
row_count
3
column_count
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table object · 8 fields
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TABLE 1
caption
Summary of periodontitis related GEO datasets used in this study.
rows array · 3 items
[0] array · 5 items
[0]
Data
[1]
GPL (General public license)
[2]
Gene
[3]
Sample control
[4]
Sample case
[1] array · 5 items
[0]
GSE16134
[1]
GPL570
[2]
24441
[3]
69
[4]
241
[2] array · 5 items
[0]
GSE10334
[1]
GPL570
[2]
24441
[3]
64
[4]
183
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section[4]/table-wrap[1]#T1
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Classifier performance outcomes of SVM.
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PMC7994531
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17
section_title
SVM Model and Its Validation
row_count
6
column_count
4
table object · 8 fields
label
TABLE 2
caption
Classifier performance outcomes of SVM.
rows array · 6 items
[0] array · 1 item
[0]
GSE16134
[1] array · 4 items
[0]
[1]
Test
[2]
Predict
[3]
Accuracy (%)
[2] array · 1 item
[0]
[3] array · 4 items
[0]
Cluster 1
[1]
27
[2]
21
[3]
[4] array · 4 items
[0]
Cluster 2
[1]
70
[2]
69
[3]
[5] array · 4 items
[0]
Total
[1]
97
[2]
90
[3]
92.78%
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section[17]/table-wrap[1]#T2
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Outcome of differential gene expression analysis for datasets GSE16134 and GSE10334.
structure object · 5 fields
pmcid
PMC7994531
section_index
18
section_title
DEGs Involved in Immunosuppression and Periodontitis
row_count
3
column_count
6
table object · 8 fields
label
TABLE 3
caption
Outcome of differential gene expression analysis for datasets GSE16134 and GSE10334.
rows array · 3 items
[0] array · 6 items
[0]
Data (Disease vs. Normal)
[1]
DEG (Up)
[2]
DEG (Down)
[3]
Total
[4]
Log FC Abs
[5]
P value
[1] array · 6 items
[0]
GSE16134
[1]
188
[2]
48
[3]
236
[4]
>1
[5]
<0.05
[2] array · 6 items
[0]
GSE10334
[1]
152
[2]
42
[3]
194
[4]
>1
[5]
<0.05
locator
section[18]/table-wrap[1]#T3
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section[18]/table-wrap[2]#T4
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null
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Differential expression analysis applied to disease samples based on identified subtypes.
structure object · 5 fields
pmcid
PMC7994531
section_index
18
section_title
DEGs Involved in Immunosuppression and Periodontitis
row_count
3
column_count
6
table object · 8 fields
label
TABLE 4
caption
Differential expression analysis applied to disease samples based on identified subtypes.
rows array · 3 items
[0] array · 6 items
[0]
Data (Subtype1 vs. Subtype 2)
[1]
DEG (Up)
[2]
DEG (Down)
[3]
Total
[4]
Log FC Abs
[5]
P value
[1] array · 6 items
[0]
GSE16134
[1]
134
[2]
85
[3]
219
[4]
>0.05
[5]
<0.05
[2] array · 6 items
[0]
GSE10334
[1]
145
[2]
95
[3]
240
[4]
>0.05
[5]
<0.05
locator
section[18]/table-wrap[2]#T4
[7] object · 16 fields
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read_table
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section[18]/table-wrap[3]#T5
version
null
note
AUC values of the three most significant genes.
structure object · 5 fields
pmcid
PMC7994531
section_index
18
section_title
DEGs Involved in Immunosuppression and Periodontitis
row_count
4
column_count
4
table object · 8 fields
label
TABLE 5
caption
AUC values of the three most significant genes.
rows array · 4 items
[0] array · 4 items
[0]
Gene
[1]
GSE10334_ROC_AUC (%)
[2]
GSE16134_ROC_AUC (%)
[3]
Mean (%)
[1] array · 4 items
[0]
PECAM1
[1]
87.09
[2]
90.45
[3]
88.77
[2] array · 4 items
[0]
FCGR3A
[1]
77.66
[2]
80.95
[3]
79.31
[3] array · 4 items
[0]
FOS
[1]
71.06
[2]
72.37
[3]
71.72
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note
The topological characteristics of the top 30 nodes in the TF-target interaction network.
structure object · 5 fields
pmcid
PMC7994531
section_index
20
section_title
Identification of Hub Transcription Factors That Targeted DEGs
row_count
31
column_count
8
table object · 8 fields
label
TABLE 6
caption
The topological characteristics of the top 30 nodes in the TF-target interaction network.
rows array · 31 items
[0] array · 8 items
[0]
Name
[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]
AR
[1]
TF&DEG_Up
[2]
87
[3]
1.6327
[4]
0.4063
[5]
0.6125
[6]
0.0270
[7]
0.0351
[2] array · 8 items
[0]
NFKB1
[1]
TF&DEG_Down
[2]
62
[3]
1.7143
[4]
0.2926
[5]
0.5833
[6]
0.0518
[7]
0.0457
[3] array · 8 items
[0]
MYC
[1]
TF&DEG_Down
[2]
56
[3]
1.7398
[4]
0.2342
[5]
0.5748
[6]
0.0610
[7]
0.0497
[4] array · 8 items
[0]
JUN
[1]
TF&DEG_Down
[2]
49
[3]
1.8163
[4]
0.1276
[5]
0.5506
[6]
0.0859
[7]
0.0541
[5] array · 8 items
[0]
TP53
[1]
TF&DEG_Down
[2]
41
[3]
2.0816
[4]
0.0906
[5]
0.4804
[6]
0.0634
[7]
0.0603
[6] array · 8 items
[0]
FOS
[1]
TF&DEG_Down
[2]
40
[3]
1.8776
[4]
0.0975
[5]
0.5326
[6]
0.1077
[7]
0.0670
[7] array · 8 items
[0]
HIF1A
[1]
TF&DEG_Up
[2]
17
[3]
2.0051
[4]
0.0433
[5]
0.4987
[6]
0.1985
[7]
0.1076
[8] array · 8 items
[0]
STAT5B
[1]
TF&DEG_Up
[2]
16
[3]
2.5408
[4]
0.0063
[5]
0.3936
[6]
0.0917
[7]
0.1517
[9] array · 8 items
[0]
FOXO3
[1]
TF&DEG_Down
[2]
15
[3]
2.3418
[4]
0.0175
[5]
0.4270
[6]
0.2000
[7]
0.1202
[10] array · 8 items
[0]
STAT4
[1]
TF&DEG_Up
[2]
15
[3]
2.0459
[4]
0.0329
[5]
0.4888
[6]
0.2190
[7]
0.1298
[11] array · 8 items
[0]
CTNNB1
[1]
TF&DEG_Down
[2]
14
[3]
2.1837
[4]
0.0514
[5]
0.4579
[6]
0.1648
[7]
0.1186
[12] array · 8 items
[0]
BAX
[1]
TF&DEG_Down
[2]
13
[3]
2.2857
[4]
0.0264
[5]
0.4375
[6]
0.1795
[7]
0.1348
[13] array · 8 items
[0]
KLF4
[1]
TF&DEG_Down
[2]
13
[3]
1.9949
[4]
0.0268
[5]
0.5013
[6]
0.2821
[7]
0.1560
[14] array · 8 items
[0]
IRF2
[1]
TF&DEG_Down
[2]
13
[3]
2.5918
[4]
0.0283
[5]
0.3858
[6]
0.0385
[7]
0.1110
[15] array · 8 items
[0]
ESR2
[1]
TF&DEG_Up
[2]
11
[3]
2.2092
[4]
0.0060
[5]
0.4527
[6]
0.3455
[7]
0.1706
[16] array · 8 items
[0]
NFKB2
[1]
TF&DEG_Down
[2]
10
[3]
2.3827
[4]
0.0182
[5]
0.4197
[6]
0.2889
[7]
0.1806
[17] array · 8 items
[0]
PLAU
[1]
TF&DEG_Down
[2]
10
[3]
2.4694
[4]
0.0140
[5]
0.4050
[6]
0.1556
[7]
0.1538
[18] array · 8 items
[0]
EGFR
[1]
DEG_Up
[2]
9
[3]
2.1327
[4]
0.0037
[5]
0.4689
[6]
0.4167
[7]
0.2059
[19] array · 8 items
[0]
VDR
[1]
TF&DEG_Down
[2]
9
[3]
2.4388
[4]
0.0030
[5]
0.4100
[6]
0.2500
[7]
0.1993
[20] array · 8 items
[0]
RARB
[1]
TF&DEG_Up
[2]
8
[3]
2.2245
[4]
0.0083
[5]
0.4495
[6]
0.3571
[7]
0.2083
[21] array · 8 items
[0]
BCL2L1
[1]
DEG_Down
[2]
7
[3]
2.1531
[4]
0.0021
[5]
0.4645
[6]
0.6190
[7]
0.2706
[22] array · 8 items
[0]
SIM2
[1]
TF&DEG_Up
[2]
7
[3]
2.2245
[4]
0.0045
[5]
0.4495
[6]
0.2857
[7]
0.2351
[23] array · 8 items
[0]
ABL1
[1]
TF&DEG_Down
[2]
6
[3]
2.2959
[4]
0.0029
[5]
0.4356
[6]
0.3333
[7]
0.2561
[24] array · 8 items
[0]
TGFB1
[1]
DEG_Down
[2]
6
[3]
2.0816
[4]
0.0005
[5]
0.4804
[6]
0.8667
[7]
0.3209
[25] array · 8 items
[0]
PRL
[1]
DEG_Up
[2]
6
[3]
2.4286
[4]
0.0014
[5]
0.4118
[6]
0.4000
[7]
0.2434
[26] array · 8 items
[0]
CD40LG
[1]
DEG_Up
[2]
6
[3]
2.4694
[4]
0.0031
[5]
0.4050
[6]
0.4000
[7]
0.2508
[27] array · 8 items
[0]
IFNG
[1]
DEG_Up
[2]
6
[3]
2.5918
[4]
0.0013
[5]
0.3858
[6]
0.3333
[7]
0.2405
[28] array · 8 items
[0]
MMP2
[1]
DEG_Up
[2]
6
[3]
2.4031
[4]
0.0003
[5]
0.4161
[6]
0.8000
[7]
0.2670
[29] array · 8 items
[0]
DUSP1
[1]
DEG_Down
[2]
5
[3]
2.2245
[4]
0.0022
[5]
0.4495
[6]
0.4000
[7]
0.3270
[30] array · 8 items
[0]
MAPK1
[1]
DEG_Down
[2]
5
[3]
2.3061
[4]
0.0009
[5]
0.4336
[6]
0.5000
[7]
0.3090
locator
section[20]/table-wrap[1]#T6
gaps array · 4 items
[0]
asset:data:geo:GSE10334 not downloaded
[1]
asset:data:geo:GSE10334 licence not read
[2]
asset:data:geo:GSE16134 not downloaded
[3]
asset:data:geo:GSE16134 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
group_comparison
specific
anova
label
Group comparison
dsl_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.7
band
medium
quote
ANOVA
[1] object · 10 fields
id
method-2
family
machine_learning
specific
support_vector_machine
label
Machine learning
dsl_operations array · 3 items
[0]
train_classifier
[1]
cross_validate
[2]
roc_auc
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
support vector machine
[2] object · 10 fields
id
method-3
family
clustering
specific
kmeans
label
Clustering
dsl_operations array · 1 item
[0]
kmeans_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
K-means
[3] object · 10 fields
id
method-4
family
null
specific
null
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Receiver operating characteristic (ROC) curve analysis using area under the curve (AUC)
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
A receiver operating characteristic (ROC) curve was plotted for the model using the “pROC” (Robin et al., 2011) and the “ggplot2” packages in R5.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
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group_comparison_anova
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basis
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capability object · 4 fields
tier
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capability:computational_analysis
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basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
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[0]
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statements array · 1 item
[0]
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.
basis
The paper names GSE16134, GSE10334 in Gene Expression Omnibus (GEO) database of NCBI and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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review object · 5 fields
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MiniMax-M3.1-Flash
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minimax
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single_reader
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verbatim
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GEO GSE10334
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agent:corpus-assay-engine
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33777111", "kind": "science-record", "revision": 7, "content_hash": "sha256:3636ceb97112e52693f5884dc80c5e7e8fd711e6be010540400c9fc4018fbf46", "created_at": "2026-11-01T15:41:30Z", "updated_at": "2026-11-01T22:03:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis.", "doi": "10.3389/fgene.2021.648329", "pmid": "33777111", "authors": ["Wanchen Ning", "Aneesha Acharya", "Zhengyang Sun", "Anthony Chukwunonso Ogbuehi", "Cong Li", "Shiting Hua", "Qianhua Ou", "Muhui Zeng", "Xiangqiong Liu", "Yupei Deng", "Rainer Haak", "Dirk Ziebolz", "Gerhard Schmalz", "George Pelekos", "Yang Wang", "Xianda Hu"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "BACKGROUND: Periodontitis is a chronic immuno-inflammatory disease characterized by inflammatory destruction of tooth-supporting tissues. Its pathogenesis involves a dysregulated local host immune response that is ineffective in combating microbial challenges. An integrated investigation of genes involved in mediating immune response suppression in periodontitis, based on multiple studies, can reveal genes pivotal to periodontitis pathogenesis. Here, we aimed to apply a deep learning (DL)-based autoencoder (AE) for predicting immunosuppression genes involved in periodontitis by integrating multiples omics datasets.\nMETHODS: Two periodontitis-related GEO transcriptomic datasets (GSE16134 and GSE10334) and immunosuppression genes identified from DisGeNET and HisgAtlas were included. Immunosuppression genes related to periodontitis in GSE16134 were used as input to build an AE, to identify the top disease-representative immunosuppression gene features. Using K-means clustering and ANOVA, immune subtype labels were assigned to disease samples and a support vector machine (SVM) classifier was constructed. This classifier was applied to a validation set (Immunosuppression genes related to periodontitis in GSE10334) for predicting sample labels, evaluating the accuracy of the AE. In addition, differentially expressed genes (DEGs), signaling pathways, and transcription factors (TFs) involved in immunosuppression and periodontitis were determined with an array of bioinformatics analysis. Shared DEGs common to DEGs differentiating periodontitis from controls and those differentiating the immune subtypes were considered as the key immunosuppression genes in periodontitis.\nRESULTS: We produced representative molecular features and identified two immune subtypes in periodontitis using an AE. Two subtypes were also predicted in the validation set with the SVM classifier. Three \"master\" immunosuppression genes, PECAM1, FCGR3A, and FOS were identified as candidates pivotal to immunosuppressive mechanisms in periodontitis. Six transcription factors, NFKB1, FOS, JUN, HIF1A, STAT5B, and STAT4, were identified as central to the TFs-DEGs interaction network. The two immune subtypes were distinct in terms of their regulating pathways.\nCONCLUSION: This study applied a DL-based AE for the first time to identify immune subtypes of periodontitis and pivotal immunosuppression genes that discriminated periodontitis from the healthy. Key signaling pathways and TF-target DEGs that putatively mediate immune suppression in periodontitis were identified. PECAM1, FCGR3A, and FOS emerged as high-value biomarkers and candidate therapeutic targets for periodontitis.", "claims": [{"id": "claim-method", "statement": "A receiver operating characteristic (ROC) curve was plotted for the model using the “pROC” (Robin et al., 2011) and the “ggplot2” packages in R5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777111", "locator": "sections[10] \"Evaluation of the SVM Classifier\" paragraph 2", "quote": "A receiver operating characteristic (ROC) curve was plotted for the model using the “pROC” (Robin et al., 2011) and the “ggplot2” packages in R5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33777111", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:33777111"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE10334"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE10334"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33777111", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.648329", "sha256": 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