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pmid:40612110

Bioinformatics-based screening and validation of PANoptosis-related biomarkers in periodontitis.

Qing Sun · JinYue Hu · RuYue Wang · ShuiXiang Guo · GeGe Zhang · Ao Lu · Xue Yang · LiNa Wang

Frontiers in cell and developmental biology · 2025 doi:10.3389/fcell.2025.1619002

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title
Bioinformatics-based screening and validation of PANoptosis-related biomarkers in periodontitis.
doi
10.3389/fcell.2025.1619002
pmid
40612110
authors array · 8 items
[0]
Qing Sun
[1]
JinYue Hu
[2]
RuYue Wang
[3]
ShuiXiang Guo
[4]
GeGe Zhang
[5]
Ao Lu
[6]
Xue Yang
[7]
LiNa Wang
journal
Frontiers in cell and developmental biology
year
2025
abstract
Background: Periodontitis is the most prevalent chronic inflammatory disease affecting the periodontal tissues. PANoptosis, a recently characterized form of programmed cell death, has been implicated in various pathological processes; however, its mechanistic role in periodontitis remains unclear. This study integrates multi-omics data and machine learning approaches to systematically identify and validate key PANoptosis-related biomarkers in periodontitis. Methods: Periodontitis-related microarray datasets (GSE16134 and GSE10334) were obtained from the GEO database, and PANoptosis-related genes were retrieved from GeneCards. Differential gene expression analysis was performed using the GSE16134 dataset, followed by weighted gene co-expression network analysis (WGCNA) to identify relevant gene modules. The intersection of differentially expressed genes and WGCNA modules was used to define differentially expressed PANoptosis-related genes (PRGs). Protein-protein interaction (PPI) networks of these PRGs were constructed using the STRING database and visualized with Cytoscape. Subnetworks were identified using the MCODE plugin. Key genes were selected based on integration with rank-sum test results. Functional enrichment analysis was performed for these key genes. Machine learning algorithms were then applied to screen for potential biomarkers. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and box plots. The relationship between selected biomarkers and immune cell infiltration was explored using the CIBERSORT algorithm. Finally, RT-qPCR was conducted to validate biomarker expression in clinical gingival tissue samples. Results: Through comprehensive bioinformatics analysis and literature review, ZBP1 was identified as a PANoptosis-related biomarker in periodontitis. RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05). Conclusion: This study provides bioinformatic evidence linking PANoptosis to periodontitis. ZBP1 was identified as a key PANoptosis-related biomarker, suggesting that periodontitis may involve activation of the ZBP1-mediated PANoptosome complex.
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The diagnostic potential of the identified potential biomarkers was further evaluated by constructing receiver operating characteristic (ROC) curves using the “pROC” package in R. The area under the curve (AUC) was calculated to quantify diagnostic accuracy.
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The diagnostic potential of the identified potential biomarkers was further evaluated by constructing receiver operating characteristic (ROC) curves using the “pROC” package in R. The area under the curve (AUC) was calculated to quantify diagnostic accuracy.
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Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/https://www.genecards.org.
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Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/https://www.genecards.org.
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RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).
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RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).
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RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).
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RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).
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sample_count
310
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null
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null
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570
taxon
Homo sapiens
title
Bacterial Correlates of Gingival Gene Expression
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
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[0]
asset:data:geo:GSE10334 not downloaded
[1]
asset:data:geo:GSE10334 licence not read
[2]
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[3]
asset:data:geo:GSE16134 licence not read
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state
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[0] object · 10 fields
id
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network_analysis
specific
ppi_network
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dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
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evidence object · 3 fields
score
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quote
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network_analysis
specific
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Network / pathway analysis
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[0]
pathway_enrich
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GO enrichment
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null
specific
null
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receiver operating characteristic (ROC) curve analysis with area under the curve (AUC)
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missing_operations array · 0 items
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evidence object · 3 fields
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quote
The diagnostic potential of the identified potential biomarkers was further evaluated by constructing receiver operating characteristic (ROC) curves using the “pROC” package in R. The area under the curve (AUC) was calculated to quantify diagnostic accuracy.
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[0] object · 8 fields
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target-published-estimate
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null
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The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
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
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[0]
meta_analysis
[1]
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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
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[2]
pathway_enrich
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
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true
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[0]
GSE16134
[1]
GSE10334
resolved_accessions array · 2 items
[0]
GSE16134
[1]
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statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/https://www.genecards.org.
basis
The paper names GSE16134, GSE10334 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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[2]
pathway_enrich
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source:pmid:40612110
[1]
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[0]
run_analysis
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[0]
data:geo:GSE10334
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review object · 5 fields
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partial
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kind
extraction_review
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MiniMax-M3.1-Flash
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minimax
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minimax
read_at
2026-11-01T19:55:59Z
independence
single_reader
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method
verbatim
availability
verbatim
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5
usage object · 3 fields
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9631
completion_tokens
2018
cached_tokens
256
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extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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[1]
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[2]
review.human_critique
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absent
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not_run
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null
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[0]
execution.not_run
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entities array · 3 items
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pmid:40612110
type
paper
label
pmid:40612110
[1] object · 3 fields
id
source:pmid:40612110
type
manuscript
label
PMID 40612110 full text
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id
data:geo:GSE10334
type
dataset
label
GEO GSE10334
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
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pmid:40612110
type
paper
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pmid:40612110
[1] object · 3 fields
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source:pmid:40612110
type
manuscript
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PMID 40612110 full text
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id
data:geo:GSE10334
type
dataset
label
GEO GSE10334
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agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-40612110
type
extraction
used array · 1 item
[0]
source:pmid:40612110
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agent:minimax-reader
[2] object · 4 fields
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activity-resolve-GSE10334
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE10334
agent
agent:corpus-assay-engine
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agent:corpus-assay-engine
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agent:minimax-reader
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343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
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pmid:40612110
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sha256:7888a7df8cb48a97c1edaff4686b2a5aeb5781d713997ce0c03a8b9591a6e653
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[3]
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[4]
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[6]
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[7]
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[8]
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[0] object · 11 fields
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microarray
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[0]
eriodontitis. Methods: Periodontitis-related microarray datasets (GSE16134 and GSE10334) were obtain
order_basis
paper_text_order:545
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assay:1
[1] object · 11 fields
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data_generation
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99e1195c7d6f
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evidence array · 4 items
[0]
ored using the CIBERSORT algorithm. Finally, RT-qPCR was conducted to validate biomarker expressi
[1]
Noptosis-related biomarker in periodontitis. RT-qPCR validation demonstrated that ZBP1 expression
[2]
d using the CIBERSORT algorithm. Finally, RT-qPCR was conducted to validate biomarker expressi
[3]
tosis-related biomarker in periodontitis. RT-qPCR validation demonstrated that ZBP1 expression
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paper_text_order:1647
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assay:2
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40612110", "kind": "science-record", "revision": 3, "content_hash": "sha256:678cf483171d3aaa9fcfb51b62e62b3bac4f8fa474fdadfd1ed16f930efa5e85", "created_at": "2026-11-01T20:30:42Z", "updated_at": "2026-11-01T22:14:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics-based screening and validation of PANoptosis-related biomarkers in periodontitis.", "doi": "10.3389/fcell.2025.1619002", "pmid": "40612110", "authors": ["Qing Sun", "JinYue Hu", "RuYue Wang", "ShuiXiang Guo", "GeGe Zhang", "Ao Lu", "Xue Yang", "LiNa Wang"], "journal": "Frontiers in cell and developmental biology", "year": 2025, "abstract": "Background: Periodontitis is the most prevalent chronic inflammatory disease affecting the periodontal tissues. PANoptosis, a recently characterized form of programmed cell death, has been implicated in various pathological processes; however, its mechanistic role in periodontitis remains unclear. This study integrates multi-omics data and machine learning approaches to systematically identify and validate key PANoptosis-related biomarkers in periodontitis.\nMethods: Periodontitis-related microarray datasets (GSE16134 and GSE10334) were obtained from the GEO database, and PANoptosis-related genes were retrieved from GeneCards. Differential gene expression analysis was performed using the GSE16134 dataset, followed by weighted gene co-expression network analysis (WGCNA) to identify relevant gene modules. The intersection of differentially expressed genes and WGCNA modules was used to define differentially expressed PANoptosis-related genes (PRGs). Protein-protein interaction (PPI) networks of these PRGs were constructed using the STRING database and visualized with Cytoscape. Subnetworks were identified using the MCODE plugin. Key genes were selected based on integration with rank-sum test results. Functional enrichment analysis was performed for these key genes. Machine learning algorithms were then applied to screen for potential biomarkers. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and box plots. The relationship between selected biomarkers and immune cell infiltration was explored using the CIBERSORT algorithm. Finally, RT-qPCR was conducted to validate biomarker expression in clinical gingival tissue samples.\nResults: Through comprehensive bioinformatics analysis and literature review, ZBP1 was identified as a PANoptosis-related biomarker in periodontitis. RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).\nConclusion: This study provides bioinformatic evidence linking PANoptosis to periodontitis. ZBP1 was identified as a key PANoptosis-related biomarker, suggesting that periodontitis may involve activation of the ZBP1-mediated PANoptosome complex.", "claims": [{"id": "claim-method", "statement": "The diagnostic potential of the identified potential biomarkers was further evaluated by constructing receiver operating characteristic (ROC) curves using the “pROC” package in R. The area under the curve (AUC) was calculated to quantify diagnostic accuracy.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40612110", "locator": "sections[10] \"2.8 Validation of diagnostic ability of potential biomarkers\" paragraph 3", "quote": "The diagnostic potential of the identified potential biomarkers was further evaluated by constructing receiver operating characteristic (ROC) curves using the “pROC” package in R. The area under the curve (AUC) was calculated to quantify diagnostic accuracy."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/https://www.genecards.org.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40612110", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://www.ncbi.nlm.nih.gov/geo/https://www.genecards.org."}], "state": "complete"}, {"id": "claim-target-result", "statement": "RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05)."}, "evidence": [{"asset": "source:pmid:40612110", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "RT-qPCR validation demonstrated that ZBP1 expression was significantly elevated in periodontitis tissues compared to healthy periodontal tissues (P < 0.05).", "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:40612110"], "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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