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一种新的选择信息性 SNPs 的方法及其在遗传关联研究中的应用。

A novel method to select informative SNPs and their application in genetic association studies.

机构信息

College of Information Science and Engineering, Hunan University, Changsha, Hunan 410082, China.

出版信息

IEEE/ACM Trans Comput Biol Bioinform. 2012 Sep-Oct;9(5):1529-34. doi: 10.1109/TCBB.2012.70.

Abstract

The association studies between complex diseases and single nucleotide polymorphisms (SNPs) or haplotypes have recently received great attention. However, these studies are limited by the cost of genotyping all SNPs. Therefore, it is essential to find a small subset of tag SNPs representing the rest of the SNPs. The presence of linkage disequilibrium between tag SNPs and the disease variant (genotyped or not), may allow fine mapping study. In this paper, we combine a nearest-means classifier (NMC) and ant colony algorithm to select tags. Results show that our method (ACO/NMC) can get a similar prediction accuracy with method BPSO/SVM and is better than BPSO/STAMPA for small data sets. For large data sets, although the prediction accuracy of our method is lower than BPSO/SVM, ACO/NMC can reach a high accuracy (>99 percent) in a relatively short time. when the number of tags increases, the time complexity of NMC is nearly linear growth. To find out that the ability of tags to locate disease locus, we simulate a case-control study and use two-locus haplotype analysis to quantitatively assess the power. The result showed that 20 percent of all SNPs selected by NMC have about 10 percent higher power than random tags, on average.

摘要

近年来,复杂疾病与单核苷酸多态性(SNPs)或单倍型的关联研究受到了广泛关注。然而,这些研究受到全基因组 SNP 分型成本的限制。因此,找到一小部分能够代表其余 SNP 的代表性标签 SNP 至关重要。标签 SNP 与疾病变异(无论是否进行了基因分型)之间存在连锁不平衡,可能允许进行精细的图谱研究。在本文中,我们结合最近均值分类器(NMC)和蚁群算法来选择标签。结果表明,我们的方法(ACO/NMC)可以与 BPSO/SVM 方法获得相似的预测准确性,并且对于小数据集,优于 BPSO/STAMPA。对于大数据集,尽管我们的方法的预测准确性低于 BPSO/SVM,但 ACO/NMC 可以在相对较短的时间内达到很高的准确性(>99%)。随着标签数量的增加,NMC 的时间复杂度几乎呈线性增长。为了了解标签定位疾病基因座的能力,我们模拟了病例对照研究,并使用双位点单倍型分析来定量评估功效。结果表明,NMC 选择的所有 SNP 的 20%平均比随机标签具有约 10%更高的功效。

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