Title: Modeling background intensity in DNA microarrays
Authors: Kroll, K. M ×
Barkema, G. T
Carlon, Enrico #
Issue Date: Jun-2008
Publisher: Amer physical soc
Series Title: Physical review e vol:77 issue:6 pages:1-8
Article number: 061915
Abstract: 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 nonspecific binding. We present 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 estimator 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 that we propose 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.
ISSN: 1539-3755
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Theoretical Physics Section
× corresponding author
# (joint) last author

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