Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine.
Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine.
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DOI：
10.1038/gene.2010.37
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发表时间：
2010-12
影响因子：
5
通讯作者：
McKinney, B. A.
中科院分区：
文献类型：
--
作者：
Davis, N. A.;Crowe, J. E., Jr.;Pajewski, N. M.;McKinney, B. A.
关键词：
抗体对疫苗接种反应的变化可能涉及许多遗传变异的微小贡献，例如在基因网络和通路中相互作用的单核苷酸多态性（SNP）。为了积累分布在整个相互作用网络中的与表型相关的遗传信息，我们开发了一种网络特征向量中心性算法（SNPrank），该算法对弱主效应、基因与基因相互作用以及通过中心效应产生的小高阶相互作用敏感。与 Google PageRank 类似，我们将该算法解释为随机 SNP 冲浪者 (RSS) 的模拟，该冲浪者通过动态概率马尔可夫链在网络中积累信息位。 RSS 的转移矩阵基于数据驱动的遗传关联相互作用网络 (GAIN)，其节点是按主效应强度加权的 SNP，以及按基因-基因相互作用强度加权的边。我们将 SNPrank 应用于人类对天花疫苗免疫反应的候选基因关联研究的 GAIN 分析。 SNPrank 通过对抗体反应的网络相互作用效应暗示类视黄醇 X 受体 α (RXRA) 基因中的 SNP。这种维生素 A 和 D 信号传导介质之前曾被认为与人类免疫反应有关，尽管在标准分析中它会被忽略，因为它的重要性在其网络中心性背景之外并不显着。这项工作表明 SNPrank 是一种识别遗传关联数据中网络效应的强大方法，并揭示了与抗体反应之间潜在的维生素调节网络关联。
The variation in antibody response to vaccination likely involves small contributions of numerous genetic variants, such as single-nucleotide polymorphisms (SNPs), which interact in gene networks and pathways. To accumulate the bits of genetic information relevant to the phenotype that are distributed throughout the interaction network, we develop a network eigenvector centrality algorithm (SNPrank) that is sensitive to the weak main effects, gene–gene interactions and small higher-order interactions through hub effects. Analogous to Google PageRank, we interpret the algorithm as the simulation of a random SNP surfer (RSS) that accumulates bits of information in the network through a dynamic probabilistic Markov chain. The transition matrix for the RSS is based on a data-driven genetic association interaction network (GAIN), the nodes of which are SNPs weighted by the main-effect strength and edges weighted by the gene–gene interaction strength. We apply SNPrank to a GAIN analysis of a candidate-gene association study on human immune response to smallpox vaccine. SNPrank implicates a SNP in the retinoid X receptor α (RXRA) gene through a network interaction effect on antibody response. This vitamin A- and D-signaling mediator has been previously implicated in human immune responses, although it would be neglected in a standard analysis because its significance is unremarkable outside the context of its network centrality. This work suggests SNPrank to be a powerful method for identifying network effects in genetic association data and reveals a potential vitamin regulation network association with antibody response.
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影响因子：
5.3
作者：
Ovsyannikova IG;Dhiman N;Haralambieva IH;Vierkant RA;O'Byrne MM;Jacobson RM;Poland GA
通讯作者：
Poland GA
影响因子：
6.4
作者：
Reif, David M.;McKinney, Brett A.;Crowe, James E., Jr.
通讯作者：
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影响因子：
120.7
作者：
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通讯作者：
Edwards, KM
DOI：
10.1073/pnas.0605938103
发表时间：
2006-11-21
影响因子：
11.1
作者：
Oldham, Michael C.;Horvath, Steve;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
4.5
作者：
McKinney BA;Crowe JE;Guo J;Tian D
通讯作者：
Tian D