Bayesian Random Segmentation Models to Identify Shared Copy Number Aberrations for Array CGH Data.

Bayesian Random Segmentation Models to Identify Shared Copy Number Aberrations for Array CGH Data.
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贝叶斯随机分割模型以识别数组CGH数据的共享拷贝数畸变。

DOI:
10.1198/jasa.2010.ap09250
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发表时间:
2010-12
影响因子:
3.7
通讯作者:
Morris JS
Morris JS
中科院分区:
数学1区
文献类型:
--
作者:
Baladandayuthapani V;Ji Y;Talluri R;Nieto-Barajas LE;Morris JS

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基于阵列的比较基因组杂交(aCGH)是一种高分辨率、高通量的研究癌症遗传基础的技术。所得数据由作为基因组DNA位置的函数的对数荧光比率组成,并提供相对DNA拷贝数变异的细胞遗传学表示。对这些数据的分析通常涉及估计每个位置处的潜在拷贝数状态,并分割具有相似拷贝数状态的DNA区域。大多数当前方法通过一次对单个样品/阵列建模来进行,并且因此不能跨多个样品借用强度来推断拷贝数畸变的共享区域。我们提出了一种分层贝叶斯随机分割方法,用于对aCGH数据进行建模,该方法利用来自共同人群的跨阵列信息来产生共享拷贝数变化的片段。这些变化表征了潜在人群,并使我们能够比较不同人群的aCGH谱,以评估基因组的哪些区域具有差异性改变。我们的方法,被称为BDSAgh(贝叶斯检测的共享像差在aCGH),是基于一个统一的贝叶斯分层模型,使我们能够获得的概率的变更状态以及差分变更的概率,对应于本地的错误发现率。我们评估我们的方法通过模拟和应用程序使用肺癌aCGH数据集的操作特性。
Array-based comparative genomic hybridization (aCGH) is a high-resolution high-throughput technique for studying the genetic basis of cancer. The resulting data consists of log fluorescence ratios as a function of the genomic DNA location and provides a cytogenetic representation of the relative DNA copy number variation. Analysis of such data typically involves estimation of the underlying copy number state at each location and segmenting regions of DNA with similar copy number states. Most current methods proceed by modeling a single sample/array at a time, and thus fail to borrow strength across multiple samples to infer shared regions of copy number aberrations. We propose a hierarchical Bayesian random segmentation approach for modeling aCGH data that utilizes information across arrays from a common population to yield segments of shared copy number changes. These changes characterize the underlying population and allow us to compare different population aCGH profiles to assess which regions of the genome have differential alterations. Our method, referred to as BDSAcgh (Bayesian Detection of Shared Aberrations in aCGH), is based on a unified Bayesian hierarchical model that allows us to obtain probabilities of alteration states as well as probabilities of differential alteration that correspond to local false discovery rates. We evaluate the operating characteristics of our method via simulations and an application using a lung cancer aCGH data set.
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