Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering.

Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering.
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DOI:
10.1038/s41598-017-17735-x
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发表时间:
2018-01-15
期刊:
影响因子:
4.6
通讯作者:
Poland GA
Poland GA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Voigt EA;Grill DE;Zimmermann MT;Simon WL;Ovsyannikova IG;Kennedy RB;Poland GA

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流感疫苗接种后的PBMC转录组包含有关影响疫苗应答的因素的有价值的信息。然而,从这些复杂的数据集中提取有意义的知识往往是困难的,需要先进的数据挖掘算法。我们研究了使用数据驱动的加权基因相关网络分析(WGCNA)基因聚类方法,以确定2010-2011年季节性三价流感疫苗接种前后从138名健康老年人(年龄50-74岁)收集的PBMC转录组数据集中的疫苗应答相关基因。WGCNA根据观察到的受试者之间的基因表达模式将14,197个基因数据集分为15个基因簇。八个簇强烈富集了参与特定免疫细胞类型和过程的基因,包括B细胞、T细胞、单核细胞、血小板、NK细胞、细胞毒性T细胞和抗病毒信号传导。基因簇成员的检查确定了对季节性流感疫苗接种的细胞和体液应答的特征,以及预先存在的细胞免疫。这项研究的结果说明了这种实验上可用的分析方法的实用性,并突出了以前与流感疫苗应答相关的基因(例如,CAMK 4,CD 19),具有先前在疫苗应答中未鉴定的功能的基因(例如,SPON 2、MATK、CST 7)和先前未表征的基因(例如CORO 1C、C8 orf 83),由于它们的表达模式而可能与流感疫苗诱导的免疫相关。
PBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-driven Weighted Gene Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine response-related genes in PBMC transcriptomic datasets collected from 138 healthy older adults (ages 50–74) before and after 2010–2011 seasonal trivalent influenza vaccination. WGCNA separated the 14,197 gene dataset into 15 gene clusters based on observed gene expression patterns across subjects. Eight clusters were strongly enriched for genes involved in specific immune cell types and processes, including B cells, T cells, monocytes, platelets, NK cells, cytotoxic T cells, and antiviral signaling. Examination of gene cluster membership identified signatures of cellular and humoral responses to seasonal influenza vaccination, as well as pre-existing cellular immunity. The results of this study illustrate the utility of this publically available analysis methodology and highlight genes previously associated with influenza vaccine responses (e.g., CAMK4, CD19), genes with functions not previously identified in vaccine responses (e.g., SPON2, MATK, CST7), and previously uncharacterized genes (e.g. CORO1C, C8orf83) likely related to influenza vaccine-induced immunity due to their expression patterns.
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