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Non-linear analysis of GeneChip arrays

机译:GeneChip阵列的非线性分析

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摘要

The application of microarray hybridization theory to Affymetrix GeneChip data has been a recent focus for data analysts. It has been shown that the hyperbolic Langmuir isotherm captures the shape of the signal response to concentration of Affymetrix GeneChips. We demonstrate that existing linear fit methods for extracting gene expression measures are not well adapted for the effect of saturation resulting from surface adsorption processes. In contrast to the most popular methods, we fit background and concentration parameters within a single global fitting routine instead of estimating the background before obtaining gene expression measures. We describe a non-linear multi-chip model of the perfect match signal that effectively allows for the separation of specific and non-specific components of the microarray signal and avoids saturation bias in the high-intensity range. Multimodel inference, incorporated within the fitting routine, allows a quantitative selection of the model that best describes the observed data. The performance of this method is evaluated on publicly available datasets, and comparisons to popular algorithms are presented.
机译:微阵列杂交理论在Affymetrix GeneChip数据中的应用一直是数据分析师关注的焦点。已经显示,双曲线的朗缪尔等温线捕获了对Affymetrix GeneChips浓度的信号响应的形状。我们证明,现有的用于提取基因表达量的线性拟合方法不能很好地适应表面吸附过程引起的饱和效应。与最流行的方法相反,我们在单个全局拟合例程中拟合背景和浓度参数,而不是在获得基因表达量之前估算背景。我们描述了一个完美匹配信号的非线性多芯片模型,该模型可以有效地分离微阵列信号的特定和非特定成分,并避免高强度范围内的饱和偏差。拟合例程中包含的多模型推断功能可以定量选择最能描述观测数据的模型。该方法的性能在可公开获得的数据集上进行了评估,并与流行算法进行了比较。

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