Heavy-Tailed Noise Suppression and Derivative Wavelet Scalogram for Detecting DNA Copy Number Aberrations

Heavy-Tailed Noise Suppression and Derivative Wavelet Scalogram for Detecting DNA Copy Number Aberrations
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用于检测 DNA 拷贝数畸变的重尾噪声抑制和导数小波尺度图

DOI:
10.1109/tcbb.2017.2723884
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发表时间:
2017
期刊:
IEEE/ACM Transactions on Computational Biology and Bioinformatics
影响因子:
--
通讯作者:
Huang, Heng
Huang, Heng
中科院分区:
--
文献类型:
--
作者:
Nguyen, Nha;Vo, An;Sun, Haibin;Huang, Heng

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现有的阵列比较基因组杂交(array comparative genomic hybridization,阵列CGH)数据处理方法和评价模型大多假设阵列CGH数据中噪声的概率密度函数(probability density function,pdf)为高斯分布。然而,在实践中,这样的噪声分布是尖峰和重尾的。因此,高斯pdf不足以近似阵列CGH数据中的噪声,从而引入染色体畸变的错误检测,导致对疾病发病机制的误解。阵列CGH数据中更准确、更充分的噪声模型对于DNA拷贝数变异的检测是必要的,也是有益的。通过对不同平台上的真实的阵列计算全息数据的分析表明,广义高斯分布(GGD)能很好地拟合阵列计算全息数据中噪声的分布。基于我们的新噪声模型,我们提出了一种新的阵列计算全息处理方法结合平滑和分割方法的优点。该方法利用广义高斯二元收缩函数和单向导数小波尺度图,在广义高斯噪声中进行小波尺度图重构。在平滑阶段,利用新的广义高斯噪声模型,推导了平稳小波域的重尾噪声抑制算法。在分割步骤中,一维高斯导数小波尺度图被用来检测断点。实验中使用了真实的和模拟的阵列计算全息数据,并分别加入不同的噪声(如高斯噪声、GGD噪声和真实的噪声)。我们证明了我们的新方法优于其他国家的最先进的方法,在均方根误差和接收机工作特性曲线。
Most existing array comparative genomic hybridization (array CGH) data processing methods and evaluation models assumed that the probability density function (pdf) of noise in array CGH data is a Gaussian distribution. However, in practice, such noise distribution is peaky and heavy-tailed. Therefore, a Gaussian pdf is not adequate to approximate the noise in array CGH data and hence introduces wrong detections of chromosomal aberrations and leads misunderstanding on disease pathogenesis. A more accurate and sufficient model of noise in array CGH data is necessary and beneficial to the detection of DNA copy number variations. We analyze the real array CGH data from different platforms and show that the distribution of noise in array CGH data is fitted very well by generalized Gaussian distribution (GGD). Based on our new noise model, we propose a novel array CGH processing method combining the advantages of both the smoothing and segmentation approaches. The new method uses generalized Gaussian bivariate shrinkage function and one-directional derivative wavelet scalogram in generalized Gaussian noise. In the smoothing step, with the new generalized Gaussian noise model, we derive the heavy-tailed noise suppression algorithm in stationary wavelet domain. In the segmentation step, the 1D Gaussian derivative wavelet scalogram is employed to detect break points. Both real and simulated array CGH data with different noises (such as Gaussian noise, GGD noise, and real noise) are used in our experiments. We demonstrate that our new method outperforms other state-of-the-art methods, in terms of both root mean squared errors and receiver operating characteristic curves.
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