eQED: an efficient method for interpreting eQTL associations using protein networks.

eQED: an efficient method for interpreting eQTL associations using protein networks.
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DOI:
10.1038/msb.2008.4
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发表时间:
2008
影响因子:
9.9
通讯作者:
Ideker, Trey
Ideker, Trey
中科院分区:
生物学1区
文献类型:
--
作者:
Suthram, Silpa;Beyer, Andreas;Karp, Richard M.;Eldar, Yonina;Ideker, Trey

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表达数量性状位点(eqtl)分析是一项新兴技术,其中个体通过一组遗传标记进行基因分型,同时使用DNA微阵列进行表型分析。由于标记的间距和连锁不平衡,每个标记可能靠近许多基因,这使得很难精细地绘制这些基因中的哪些是导致下游表达变化的因果因素。为了解决这一挑战,我们提出了一种有效的方法来确定候选基因在位点上的优先级。这种方法被称为“eQTL电图”(eQED),通过将两个数据集建模为电流源和电阻的接线图,将eQTL与蛋白质相互作用网络集成在一起。eQED在酵母中恢复一组参考调节剂-靶标对的准确度达到79%,显著高于其他三种竞争方法。eQED还注释了368种蛋白质-蛋白质相互作用及其信息流的方向性,准确率约为75%。
Analysis of expression quantitative trait loci (eQTLs) is an emerging technique in which individuals are genotyped across a panel of genetic markers and, simultaneously, phenotyped using DNA microarrays. Because of the spacing of markers and linkage disequilibrium, each marker may be near many genes making it difficult to finely map which of these genes are the causal factors responsible for the observed changes in the downstream expression. To address this challenge, we present an efficient method for prioritizing candidate genes at a locus. This approach, called ‘eQTL electrical diagrams' (eQED), integrates eQTLs with protein interaction networks by modeling the two data sets as a wiring diagram of current sources and resistors. eQED achieved a 79% accuracy in recovering a reference set of regulator–target pairs in yeast, which is significantly higher than the performance of three competing methods. eQED also annotates 368 protein–protein interactions with their directionality of information flow with an accuracy of approximately 75%.
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