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Piecewise-constant and low-rank approximation for identification of recurrent copy number variations

机译:分段常数和低秩近似,用于识别重复拷贝数变异

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Motivation: The post-genome era sees urgent need for more novel approaches to extracting useful information from the huge amount of genetic data. The identification of recurrent copy number variations (CNVs) from array-based comparative genomic hybridization (aCGH) data can help understand complex diseases, such as cancer. Most of the previous computational methods focused on single-sample analysis or statistical testing based on the results of single-sample analysis. Finding recurrent CNVs from multi-sample data remains a challenging topic worth further study. Results: We present a general and robust method to identify recurrent CNVs from multi-sample aCGH profiles. We express the raw dataset as a matrix and demonstrate that recurrent CNVs will form a low-rank matrix. Hence, we formulate the problem as a matrix recovering problem, where we aim to find a piecewise-constant and low-rank approximation (PLA) to the input matrix. We propose a convex formulation for matrix recovery and an efficient algorithm to globally solve the problem. We demonstrate the advantages of PLA compared with alternative methods using synthesized datasets and two breast cancer datasets. The experimental results show that PLA can successfully reconstruct the recurrent CNV patterns from raw data and achieve better performance compared with alternative methods under a wide range of scenarios
机译:动机:后基因组时代迫切需要更新颖的方法来从大量的遗传数据中提取有用的信息。从基于阵列的比较基因组杂交(aCGH)数据中识别出复发拷贝数变异(CNV),可以帮助理解诸如癌症的复杂疾病。以前的大多数计算方法都集中在基于单样本分析结果的单样本分析或统计测试上。从多样本数据中发现复发性CNV仍然是一个具有挑战性的话题,值得进一步研究。结果:我们提出了一种通用且鲁棒的方法,可从多样本aCGH概况中识别出复发性CNV。我们将原始数据集表示为矩阵,并证明递归CNV将形成低秩矩阵。因此,我们将该问题公式化为矩阵恢复问题,我们的目标是找到输入矩阵的分段常数和低秩逼近(PLA)。我们提出了一种用于矩阵恢复的凸公式,以及一种可以整体解决该问题的有效算法。与使用合成数据集和两个乳腺癌数据集的替代方法相比,我们证明了PLA的优势。实验结果表明,在多种情况下,PLA可以从原始数据成功重建循环CNV模式,并与其他方法相比具有更好的性能。

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