EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units.
EPIBLASTER-fast exhaustive two-locus epistasis detection strategy using graphical processing units.
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DOI：
10.1038/ejhg.2010.196
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发表时间：
2011-04-01
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影响因子：
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通讯作者：
Muller-Myhsok, Bertram
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文献类型：
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作者：
Kam-Thong, Tony;Czamara, Darina;Muller-Myhsok, Bertram
基因座间上位性相互作用的检测被认为可以更深入地了解人类疾病背后复杂的生物学和生化途径。研究两个基因座之间的相互作用是传统的和完善的单基因座分析的自然进展。然而，迄今为止，所涉及的计算所需的额外成本和持续时间阻碍了研究人员对上位性进行全基因组分析。在本文中，我们提出了一种方法，使这样的分析进行得非常迅速。该方法被称为EPIBLASTER，适用于病例对照研究，由两个步骤组成，其中计算所有可能的SNP对的对照和病例之间Pearson相关系数的差异，作为显着相互作用的指示，从而避免进一步分析。对于被视为潜在显著的相互作用子集，使用逻辑回归的似然比检验进行第二阶段分析，以获得个体效应和相互作用项的估计系数的P值。该算法是利用商用图形处理单元的并行计算能力来实现的，以大大减少所涉及的计算时间。在当前的设置和示例数据集（211个病例，222个对照，299468个SNP;以及601个病例，825个对照，291095个SNP）中，该系数评估阶段可以在大约1天内完成。我们的方法允许详尽和快速检测显着的SNP对相互作用，而不施加显着的边际效应的单个位点参与对。
Detection of epistatic interaction between loci has been postulated to provide a more in-depth understanding of the complex biological and biochemical pathways underlying human diseases. Studying the interaction between two loci is the natural progression following traditional and well-established single locus analysis. However, the added costs and time duration required for the computation involved have thus far deterred researchers from pursuing a genome-wide analysis of epistasis. In this paper, we propose a method allowing such analysis to be conducted very rapidly. The method, dubbed EPIBLASTER, is applicable to case-control studies and consists of a two-step process in which the difference in Pearson's correlation coefficients is computed between controls and cases across all possible SNP pairs as an indication of significant interaction warranting further analysis. For the subset of interactions deemed potentially significant, a second-stage analysis is performed using the likelihood ratio test from the logistic regression to obtain the P-value for the estimated coefficients of the individual effects and the interaction term. The algorithm is implemented using the parallel computational capability of commercially available graphical processing units to greatly reduce the computation time involved. In the current setup and example data sets (211 cases, 222 controls, 299468 SNPs; and 601 cases, 825 controls, 291095 SNPs), this coefficient evaluation stage can be completed in roughly 1 day. Our method allows for exhaustive and rapid detection of significant SNP pair interactions without imposing significant marginal effects of the single loci involved in the pair.