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Genotyping and annotation of Affymetrix SNP arrays

机译:Affymetrix SNP阵列的基因分型和注释

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In this paper we develop a new method for genotyping Affymetrix single nucleotide polymorphism (SNP) array. The method is based on (i) using multiple arrays at the same time to determine the genotypes and (ii) a model that relates intensities of individual SNPs to each other. The latter point allows us to annotate SNPs that have poor performance, either because of poor experimental conditions or because for one of the alleles the probes do not behave in a dose–response manner. Generally, our methodagrees well with a method developed by Affymetrix. When both methods make a call they agree in 99.25% (using standard settings) of the cases, using a sample of 113 Affymetrix 10k SNP arrays. In the majority of cases where the two methods disagree, our method makes a genotype call, whereas the method by Affymetrix makes a no call, i.e. the genotype of the SNP is not determined. By visualization it is indicated that our method is likely to be correct in majority of these cases. In addition, we demonstrate that our method produces more SNPs that are in concordance with Hardy–Weinberg equilibrium than the method by Affymetrix. Finally, we have validated our method on HapMap data and shown that the performance of our method is comparable to other methods.
机译:在本文中,我们开发了一种用于对Affymetrix单核苷酸多态性(SNP)阵列进行基因分型的新方法。该方法基于(i)同时使用多个阵列来确定基因型,以及(ii)将各个SNP的强度相互关联的模型。后一点使我们可以注释性能较差的SNP,这可能是由于实验条件差或因为对于一个等位基因而言,探针的行为都不是剂量反应的。通常,我们的方法与Affymetrix开发的方法非常吻合。当使用这两种方法进行呼叫时,使用113个Affymetrix 10k SNP阵列的样本,它们在99.25%(使用标准设置)的情况下表示同意。在大多数情况下,这两种方法不一致,我们的方法进行基因型调用,而Affymetrix的方法进行否定调用,即未确定SNP的基因型。通过可视化表明,在大多数情况下,我们的方法可能是正确的。此外,我们证明,与Affymetrix方法相比,我们的方法可产生更多与Hardy-Weinberg平衡一致的SNP。最后,我们在HapMap数据上验证了我们的方法,并表明该方法的性能可与其他方法媲美。

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