Liu Yao-Zhong, Maney Pooja, Puri Jyoti, Zhou Yu, Baddoo Melody, Strong Michael, Wang Yu-Ping, Flemington Erik, Deng Hong-Wen
Center of Genomics and Bioinformatics, Dept. of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States.
Dept. of Periodontics, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
Gene. 2016 May 1;581(2):152-60. doi: 10.1016/j.gene.2016.01.036. Epub 2016 Jan 23.
Monocytes are an important cell type in chronic periodontitis (CP) by interacting with oral bacteria and mediating host immune response. The aim of this study was to reveal new functional genes and pathways for CP at monocyte transcriptomic level.
We performed an RNA-sequencing (RNA-seq) study of peripheral blood monocytes (PBMs) in 5 non-smoking moderate to severe CP (case) individuals vs. 5 controls. We took advantage of a microarray study of periodontitis to support our findings. We also performed pathway-based analysis on the identified differentially expressed (DEx) transcripts/isoforms using DAVID (Database for Annotation, Visualization and Integrated Discovery).
Through differential expression analyses at both whole gene (or whole non-coding RNA) and isoform levels, we identified 380 DEx transcripts and 5955 DEx isoforms with a PPEE (posterior probability of equal expression) of <0.05. Pervasive up-regulation of transcripts at isoform level in CP vs. control individuals was observed, suggesting a more functionally active monocyte transcriptome for CP. By comparing with the microarray dataset, we identified several CP-associated novel genes (e.g., FACR and CUX1) that have functions to interact with invading microorganisms or enhance TNF production on lipopolysaccharide stimulation. DAVID analysis of both the RNA-seq and the microarray datasets leads to converging evidence supporting "endocytosis", "cytokine production" and "apoptosis" as significant biological processes in CP.
As the first RNA-seq study of PBMs for CP, this study provided novel findings at both gene (e.g., FCAR and CUX1) and biological process level. The findings will contribute to better understanding of CP disease mechanisms.
单核细胞通过与口腔细菌相互作用并介导宿主免疫反应，是慢性牙周炎（CP）中的一种重要细胞类型。本研究的目的是在单核细胞转录组水平揭示CP新的功能基因和通路。
我们对5名非吸烟的中度至重度CP（病例）个体与5名对照者的外周血单核细胞（PBM）进行了RNA测序（RNA-seq）研究。我们利用一项牙周炎的微阵列研究来支持我们的发现。我们还使用DAVID（注释、可视化和综合发现数据库）对鉴定出的差异表达（DEx）转录本/异构体进行了基于通路的分析。
通过在全基因（或全非编码RNA）和异构体水平的差异表达分析，我们鉴定出380个DEx转录本和5955个DEx异构体，其等效表达后验概率（PPEE）<0.05。在CP个体与对照个体中，观察到异构体水平转录本的普遍上调，表明CP的单核细胞转录组功能更活跃。通过与微阵列数据集比较，我们鉴定出几个与CP相关的新基因（如FACR和CUX1），它们具有与入侵微生物相互作用或在脂多糖刺激下增强TNF产生的功能。对RNA-seq和微阵列数据集的DAVID分析得出了一致的证据，支持“内吞作用”、“细胞因子产生”和“凋亡”是CP中的重要生物学过程。
作为首次对CP的PBM进行的RNA-seq研究，本研究在基因（如FCAR和CUX1）和生物学过程水平均提供了新的发现。这些发现将有助于更好地理解CP疾病机制。
