标题： Affymetrix基因芯片中背景强度的建模 显示英文标题

标题： Modelling background intensity in Affymetrix Genechips

摘要： DNA微阵列是可以原则上检测和定量复杂生物混合物中特定核酸序列存在的装置。 测量过程包括检测微阵列表面上多个探针序列嫁接点的荧光信号。 数据分析的问题之一是信号中包含由于非特异性结合引起的噪声背景成分。 本文提出了一种用于Affymetrix基因芯片背景估计的物理模型。 该模型结合了两种不同的方法。 第一种方法基于序列组成，特别是其序列依赖性杂交亲和力。 第二种方法基于芯片上特定点物理邻近位置强度的相关性。 这两种效应被纳入一个包含24个自由参数的背景函数中，这些参数通过训练数据集的最小化来固定。 在所有分析的数据中，通过最小化获得的序列特异性参数与溶液中RNA/DNA杂交的实验测定堆叠自由能显示出强烈的关联。 此外，与实验背景数据总体一致，并且我们证明了本文提出的基于物理学的模型在平均情况下比纯粹统计学的方法在背景计算方面表现更好。 因此，该模型为Affymetrix基因芯片中的背景扣除方案提供了一个有趣的替代方法。 显示英文摘要

摘要： DNA microarrays are devices that are able, in principle, to detect and quantify the presence of specific nucleic acid sequences in complex biological mixtures. The measurement consists in detecting fluorescence signals from several spots on the microarray surface onto which different probe sequences are grafted. One of the problems of the data analysis is that the signal contains a noisy background component due to non-specific binding. This paper presents a physical model for background estimation in Affymetrix Genechips. It combines two different approaches. The first is based on the sequence composition, specifically its sequence dependent hybridization affinity. The second is based on the strong correlation of intensities from locations which are the physical neighbors of a specific spot on the chip. Both effects are incorporated in a background functional which contains 24 free parameters, fixed by minimization on a training data set. In all data analyzed the sequence specific parameters, obtained by minimization, are found to strongly correlate with empirically determined stacking free energies for RNA/DNA hybridization in solution. Moreover, there is an overall agreement with experimental background data and we show that the physics-based model proposed in this paper performs on average better than purely statistical approaches for background calculations. The model thus provides an interesting alternative method for background subtraction schemes in Affymetrix Genechips.