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THE SCREENING AND RANKING ALGORITHM FOR CHANGE-POINTS DETECTION IN MULTIPLE SAMPLES

机译:多样本变化点检测的筛选与排序算法

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摘要

The chromosome copy number variation (CNV) is the deviation of genomic regions from their normal copy number states, which may associate with many human diseases. Current genetic studies usually collect hundreds to thousands of samples to study the association between CNV and diseases. CNVs can be called by detecting the change-points in mean for sequences of array-based intensity measurements. Although multiple samples are of interest, the majority of the available CNV calling methods are single sample based. Only a few multiple sample methods have been proposed using scan statistics that are computationally intensive and designed toward either common or rare change-points detection. In this paper, we propose a novel multiple sample method by adaptively combining the scan statistic of the screening and ranking algorithm (SaRa), which is computationally efficient and is able to detect both common and rare change-points. We prove that asymptotically this method can find the true change-points with almost certainty and show in theory that multiple sample methods are superior to single sample methods when shared change-points are of interest. Additionally, we report extensive simulation studies to examine the performance of our proposed method. Finally, using our proposed method as well as two competing approaches, we attempt to detect CNVs in the data from the Primary Open-Angle Glaucoma Genes and Environment study, and conclude that our method is faster and requires less information while our ability to detect the CNVs is comparable or better.
机译:染色体拷贝数变异(CNV)是基因组区域与正常拷贝数状态的偏离,这可能与许多人类疾病有关。当前的遗传研究通常收集数百至数千个样本,以研究CNV与疾病之间的关联。可以通过为基于阵列的强度测量序列检测平均值的变化点来调用CNV。尽管感兴趣的是多个样本,但是大多数可用的CNV调用方法都是基于单个样本的。已经提出了使用扫描统计量的少数几种样本方法,这些方法计算量大并且针对常见或罕见变化点检测而设计。在本文中,我们通过自适应地结合筛选和排名算法(SaRa)的扫描统计量,提出了一种新颖的多样本方法,该方法计算效率高,并且能够检测常见和稀有的变化点。我们证明渐近该方法可以几乎确定地找到真实的变化点,并在理论上证明当关注共享变化点时,多个样本方法要优于单个样本方法。此外,我们报告了广泛的仿真研究,以检验我们提出的方法的性能。最后,使用我们提出的方法和两种相互竞争的方法,我们尝试从原发性开角型青光眼基因和环境研究中检测数据中的CNV,并得出结论:我们的方法速度更快,所需信息更少,而我们能够检测出CNV相当或更好。

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  • 年(卷),期 -1(10),4
  • 年度 -1
  • 页码 2102–2129
  • 总页数 34
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