Song Chi, Min Xiaoyi, Zhang Heping
Ohio State University.
Georgia State University.
Ann Appl Stat. 2016 Dec;10(4):2102-2129. doi: 10.1214/16-AOAS966. Epub 2017 Jan 5.
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.
染色体拷贝数变异(CNV)是基因组区域与其正常拷贝数状态的偏差,这可能与许多人类疾病相关。当前的遗传学研究通常收集数百到数千个样本,以研究CNV与疾病之间的关联。可以通过检测基于阵列强度测量序列的均值变化点来识别CNV。尽管多个样本很重要,但大多数现有的CNV识别方法都是基于单样本的。仅提出了少数几种使用扫描统计量的多样本方法,这些方法计算量很大,并且是针对常见或罕见变化点检测设计的。在本文中,我们提出了一种新颖的多样本方法,通过自适应地组合筛选和排序算法(SaRa)的扫描统计量,该方法计算效率高,能够检测常见和罕见变化点。我们证明,渐近地,该方法几乎可以确定地找到真正的变化点,并从理论上表明,当关注共享变化点时,多样本方法优于单样本方法。此外,我们报告了广泛的模拟研究,以检验我们提出的方法的性能。最后,使用我们提出的方法以及两种竞争方法,我们试图在原发性开角型青光眼基因与环境研究的数据中检测CNV,并得出结论,我们的方法更快,所需信息更少,而我们检测CNV的能力相当或更好。