Abstract
BackgroundOne important preprocessing step in the analysis of microarray data is background subtraction. In high-density oligonucleotide arrays this is recognized as a crucial step for the global performance of the data analysis from raw intensities to expression values.ResultsWe propose here an algorithm for background estimation based on a model in which the cost function is quadratic in a set of fitting parameters such that minimization can be performed through linear algebra. The model incorporates two effects: 1) Correlated intensities between neighboring features in the chip and 2) sequence-dependent affinities for non-specific hybridization fitted by an extended nearest-neighbor model.ConclusionThe algorithm has been tested on 360 GeneChips from publicly available data of recent expression experiments. The algorithm is fast and accurate. Strong correlations between the fitted values for different experiments as well as between the free-energy parameters and their counterparts in aqueous solution indicate that the model captures a significant part of the underlying physical chemistry.
Highlights
One important preprocessing step in the analysis of microarray data is background subtraction
In this paper we present an algorithm for the calculation of the background level for Affymetrix expression arrays, known as GeneChips
In this paper we present an algorithm for background estimation which combines information from the sequence composition and physical neighbors on the chip
Summary
One important preprocessing step in the analysis of microarray data is background subtraction. In high-density oligonucleotide arrays this is recognized as a crucial step for the global performance of the data analysis from raw intensities to expression values. The analysis of microarray data has attracted continuous interest over the past years in the Bioinformatics community The problem consists in obtaining the gene expression level from the experimental measurements, which are the emitted fluorescence intensities from different sites in the array. Where ISP(c) is the specific signal due to the hybridization of the surface-bound probe sequence with a complementary target sequence. This quantity depends on the concentration c of the complementary strand in solution (target). It arises due to spurious effects such as incomplete hybridization where probe sequences bind to only partially complementary targets or due to other optical effects
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