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牙周炎的免疫景观揭示了浸润免疫细胞和分子网络的改变——这些改变聚集在一起,形成了一个用于牙周炎相关免疫分析和可视化的交互式网络工具。

Immune landscape of periodontitis unveils alterations of infiltrating immunocytes and molecular networks-aggregating into an interactive web-tool for periodontitis related immune analysis and visualization.

机构信息

Department of Orthodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14, Sect 3, Renmin South Rd, Chengdu, 610041, Sichuan, China.

Department of Bone Metabolism, Shandong Key Laboratory of Oral Tissue Regeneration, School/Hospital of Stomatology, Shandong University, Jinan, Shandong, China.

出版信息

J Transl Med. 2020 Nov 18;18(1):438. doi: 10.1186/s12967-020-02616-1.

Abstract

BACKGROUND

Immunity reaction plays an essential role in periodontitis progress and we aim to investigate the underlying regulatory network of immune reactions in periodontitis.

METHODS

CIBERSORT was used to estimate immunocyte fractions in different clinical statuses. Logistic regression was used to assess the immunocyte weight in periodontitis. Immune-related periodontitis subtypes were identified by the Nonnegative Matrix Factorization algorithm. Gene-set enrichment analysis and Gene-set variation analysis were conducted to analyze pathway activities. Immunocytes related gene modules were identified by Weighted gene co-expression network analysis.

RESULTS

Altered immunocytes in healthy versus periodontitis, aggressive versus chronic, male versus female and age were identified. Immunocytes enriched in periodontitis were calculated, and their correlation was also explored. Two distinct immune-related periodontitis subtypes were identified and one is characterized by B cell reactions and the other is IL-6 cytokine reactions. 463 statistically significant correlations between 22 immunocytes and pathways were revealed. Immunocytes and clinical phenotypes matched their gene modules, and their functions were annotated. Last, an easy-to-use and user-friendly interactive web-tool were developed for periodontitis related immune analysis and visualization ( https://118.24.100.193:3838/tool-PIA/ ).

CONCLUSIONS

This study systematically investigated periodontitis immune atlas and caught a glimpse of the underlying mechanism of periodontitis from gene-pathway-immunocyte networks, which can not only inspire researchers but also help them in periodontitis related immune researches.

摘要

背景

免疫反应在牙周炎的进展中起着至关重要的作用,我们旨在研究牙周炎中免疫反应的潜在调控网络。

方法

使用 CIBERSORT 估计不同临床状态下的免疫细胞分数。使用逻辑回归评估牙周炎中的免疫细胞权重。通过非负矩阵分解算法识别与免疫相关的牙周炎亚型。进行基因集富集分析和基因集变异分析以分析途径活性。通过加权基因共表达网络分析鉴定免疫细胞相关基因模块。

结果

鉴定了健康与牙周炎、侵袭性与慢性、男性与女性和年龄之间改变的免疫细胞。计算了富含牙周炎的免疫细胞,并探索了它们的相关性。确定了两种不同的与免疫相关的牙周炎亚型,一种以 B 细胞反应为特征,另一种以 IL-6 细胞因子反应为特征。揭示了 22 种免疫细胞与途径之间的 463 个具有统计学意义的相关性。免疫细胞与临床表型与其基因模块相匹配,并对其功能进行了注释。最后,开发了一个易于使用和用户友好的交互式网络工具,用于牙周炎相关免疫分析和可视化(https://118.24.100.193:3838/tool-PIA/)。

结论

本研究系统地研究了牙周炎免疫图谱,并从基因-途径-免疫细胞网络中窥见了牙周炎的潜在机制,这不仅可以启发研究人员,还有助于他们进行牙周炎相关的免疫研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db41/7672958/bec94e12c8bf/12967_2020_2616_Fig1_HTML.jpg

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