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Query Large Scale Microarray Compendium Datasets Using a Model-Based Bayesian Approach with Variable Selection

机译:使用具有变量选择的基于模型的贝叶斯方法查询大规模微阵列纲要数据集

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摘要

In microarray gene expression data analysis, it is often of interest to identify genes that share similar expression profiles with a particular gene such as a key regulatory protein. Multiple studies have been conducted using various correlation measures to identify co-expressed genes. While working well for small datasets, the heterogeneity introduced from increased sample size inevitably reduces the sensitivity and specificity of these approaches. This is because most co-expression relationships do not extend to all experimental conditions. With the rapid increase in the size of microarray datasets, identifying functionally related genes from large and diverse microarray gene expression datasets is a key challenge. We develop a model-based gene expression query algorithm built under the Bayesian model selection framework. It is capable of detecting co-expression profiles under a subset of samples/experimental conditions. In addition, it allows linearly transformed expression patterns to be recognized and is robust against sporadic outliers in the data. Both features are critically important for increasing the power of identifying co-expressed genes in large scale gene expression datasets. Our simulation studies suggest that this method outperforms existing correlation coefficients or mutual information-based query tools. When we apply this new method to the Escherichia coli microarray compendium data, it identifies a majority of known regulons as well as novel potential target genes of numerous key transcription factors.
机译:在微阵列基因表达数据分析中,经常需要识别与特定基因(例如关键调节蛋白)共享相似表达谱的基因。已经使用各种相关方法进行了多项研究,以鉴定共表达的基因。虽然适用于小型数据集,但由于样本量增加而引入的异质性不可避免地降低了这些方法的敏感性和特异性。这是因为大多数共表达关系并未扩展到所有实验条件。随着微阵列数据集大小的迅速增加,从大型多样的微阵列基因表达数据集中识别功能相关基因是一个关键的挑战。我们开发了一种基于贝叶斯模型选择框架的基于模型的基因表达查询算法。它能够检测子集的样品/实验条件下的共表达谱。另外,它允许识别线性变换的表达模式,并且对于数据中的零星异常值具有鲁棒性。这两个功能对于提高在大规模基因表达数据集中鉴定共表达基因的能力至关重要。我们的仿真研究表明,该方法优于现有的相关系数或基于互信息的查询工具。当我们将此新方法应用于大肠杆菌微阵列纲要数据时,它可以识别大多数已知的调节子以及众多关键转录因子的新型潜在靶基因。

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