Genome-wide characterization of transcriptional patterns in high and low antibody responders to rubella vaccination.
Genome-wide characterization of transcriptional patterns in high and low antibody responders to rubella vaccination.
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DOI：
10.1371/journal.pone.0062149
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Poland GA
中科院分区：
文献类型：
--
作者：
Haralambieva IH;Oberg AL;Ovsyannikova IG;Kennedy RB;Grill DE;Middha S;Bot BM;Wang VW;Smith DI;Jacobson RM;Poland GA
对当前风疹疫苗的免疫反应表现出显着的个体间差异。我们对风疹疫苗接种高抗体反应者和低抗体反应者的 PBMC 进行了 mRNA-Seq 分析，以描绘病毒刺激后的转录差异。广义线性模型用于评估受刺激样本与未受刺激样本的每个基因倍数变化 (FC) 或结果与刺激之间的相互作用。模型结果通过 FC 和 p 值进行评估。进行通路分析和独立基因组测试以评估基因组效应。在检测到的17,566个基因中，我们鉴定了1,080个在病毒刺激下高度显着差异表达的基因（p<1.00E−15，FDR<1.00E−14），包括各种免疫功能和炎症相关基因，涉及细胞信号传导、细胞调控和转录的基因以及功能未知的基因。通过免疫结果和刺激状态分析，确定了 27 个基因（p≤0.0006 和 FDR≤0.30）在高抗体反应者与低抗体反应者中对病毒刺激的反应不同，包括主要组织相容性复合体 (MHC) I 类基因（HLA-A、HLA-B 和 B2M，其中 p = 0.0001、p = 0.0005 和p = 0.0002），以及两个与先天免疫和炎症相关的基因（EMR3 和 MEFV，分别为 p = 1.46E−08 和 p = 0.0004）。通路和基因集分析还揭示了高反应者和低反应者之间抗原呈递和先天/炎症基因集以及通路的转录差异。使用 mRNA-Seq 全基因组转录分析，我们鉴定了抗原呈递和先天/炎症基因，可能有助于解释风疹疫苗诱导的免疫反应变化。这些信息可能为疫苗诱导的免疫提供新的科学见解，有助于合理的疫苗开发和免疫反应监测。
Immune responses to current rubella vaccines demonstrate significant inter-individual variability. We performed mRNA-Seq profiling on PBMCs from high and low antibody responders to rubella vaccination to delineate transcriptional differences upon viral stimulation. Generalized linear models were used to assess the per gene fold change (FC) for stimulated versus unstimulated samples or the interaction between outcome and stimulation. Model results were evaluated by both FC and p-value. Pathway analysis and self-contained gene set tests were performed for assessment of gene group effects. Of 17,566 detected genes, we identified 1,080 highly significant differentially expressed genes upon viral stimulation (p<1.00E−15, FDR<1.00E−14), including various immune function and inflammation-related genes, genes involved in cell signaling, cell regulation and transcription, and genes with unknown function. Analysis by immune outcome and stimulation status identified 27 genes (p≤0.0006 and FDR≤0.30) that responded differently to viral stimulation in high vs. low antibody responders, including major histocompatibility complex (MHC) class I genes (HLA-A, HLA-B and B2M with p = 0.0001, p = 0.0005 and p = 0.0002, respectively), and two genes related to innate immunity and inflammation (EMR3 and MEFV with p = 1.46E−08 and p = 0.0004, respectively). Pathway and gene set analysis also revealed transcriptional differences in antigen presentation and innate/inflammatory gene sets and pathways between high and low responders. Using mRNA-Seq genome-wide transcriptional profiling, we identified antigen presentation and innate/inflammatory genes that may assist in explaining rubella vaccine-induced immune response variations. Such information may provide new scientific insights into vaccine-induced immunity useful in rational vaccine development and immune response monitoring.
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影响因子：
3.2
作者：
Dhiman, Neelam;Haralambieva, Iana H.;Kennedy, Richard B.;Vierkant, Robert A.;O'Byrne, Megan M.;Ovsyannikova, Inna G.;Jacobson, Robert M.;Poland, Gregory A.
通讯作者：
Poland, Gregory A.
影响因子：
--
作者：
Dhiman, N.;Ovsyannikova, G.;Poland, G. A.
通讯作者：
Poland, G. A.
影响因子：
20.3
作者：
Boulland, Marie-Laure;Marquet, Jeanine;Castellano, Flavia
通讯作者：
Castellano, Flavia
影响因子：
5
作者：
FROME, EL;CHECKOWAY, H
通讯作者：
CHECKOWAY, H
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y