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组学数据的综合分析:一种贝叶斯混合模型,用于评估 ChIP-chip 和 ChIP-seq 测量的一致性。

Integrative analyses for omics data: a Bayesian mixture model to assess the concordance of ChIP-chip and ChIP-seq measurements.

机构信息

Department of Statistics, TU Dortmund University, Dortmund, Germany.

出版信息

J Toxicol Environ Health A. 2012;75(8-10):461-70. doi: 10.1080/15287394.2012.674914.

Abstract

The analysis of different variations in genomics, transcriptomics, epigenomics, and proteomics has increased considerably in recent years. This is especially due to the success of microarray and, more recently, sequencing technology. Apart from understanding mechanisms of disease pathogenesis on a molecular basis, for example in cancer research, the challenge of analyzing such different data types in an integrated way has become increasingly important also for the validation of new sequencing technologies with maximum resolution. For this purpose, a methodological framework for their comparison with microarray techniques in the context of smallest sample sizes, which result from the high costs of experiments, is proposed in this contribution. Based on an adaptation of the externally centered correlation coefficient ( Schäfer et al. 2009 ), it is demonstrated how a Bayesian mixture model can be applied to compare and classify measurements of histone acetylation that stem from chromatin immunoprecipitation combined with either microarray (ChIP-chip) or sequencing techniques (ChIP-seq) for the identification of DNA fragments. Here, the murine hematopoietic cell line 32D, which was transduced with the oncogene BCR-ABL, the hallmark of chronic myeloid leukemia, was characterized. Cells were compared to mock-transduced cells as control. Activation or inhibition of other genes by histone modifications induced by the oncogene is considered critical in such a context for the understanding of the disease.

摘要

近年来,基因组学、转录组学、表观基因组学和蛋白质组学的不同变体分析有了显著的增加。这主要归因于微阵列技术的成功,以及最近测序技术的成功。除了在分子基础上理解疾病发病机制,例如在癌症研究中,分析这些不同类型数据的综合方法的挑战也变得越来越重要,这对于以最大分辨率验证新测序技术也很重要。为此,在本研究中提出了一种方法框架,用于在最小样本量的情况下,将其与微阵列技术进行比较,这是由于实验成本高而导致的。基于对外中心化相关系数( Schäfer 等人,2009)的改编,本文展示了如何应用贝叶斯混合模型来比较和分类来自染色质免疫沉淀与微阵列(ChIP-chip)或测序技术(ChIP-seq)结合的组蛋白乙酰化测量,以鉴定 DNA 片段。在本研究中,使用了转导了致癌基因 BCR-ABL 的造血细胞系 32D 作为模型,该基因是慢性髓细胞白血病的标志性基因。将细胞与作为对照的 mock 转导细胞进行比较。在这种情况下,考虑到组蛋白修饰对致癌基因诱导的其他基因的激活或抑制对疾病的理解是至关重要的。

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