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arXiv · 1001.0653

The effects of mismatches on hybridization in DNA microarrays: determination of nearest neighbor parameters

J. Hooyberghs·P. Van Hummelen·E. Carlon
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Abstract

Quantifying interactions in DNA microarrays is of central importance for a better understanding of their functioning. Hybridization thermodynamics for nucleic acid strands in aqueous solution can be described by the so-called nearest-neighbor model, which estimates the hybridization free energy of a given sequence as a sum of dinucleotide terms. Compared with its solution counterparts, hybridization in DNA microarrays may be hindered due to the presence of a solid surface and of a high density of DNA strands. We present here a study aimed at the determination of hybridization free energies in DNA microarrays. Experiments are performed on custom Agilent slides. The solution contains a single oligonucleotide. The microarray contains spots with a perfect matching complementary sequence and other spots with one or two mismatches: in total 1006 different probe spots, each replicated 15 times per microarray. The free energy parameters are directly fitted from microarray data. The experiments demonstrate a clear correlation between hybridization free energies in the microarray and in solution. The experiments are fully consistent with the Langmuir model at low intensities, but show a clear deviation at intermediate (non-saturating) intensities. These results provide new interesting insights for the quantification of molecular interactions in DNA microarrays.

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J. Hooyberghs, P. Van Hummelen, E. Carlon. 2010-01-05. The effects of mismatches on hybridization in DNA microarrays: determination of nearest neighbor parameters. https://doi.org/10.1093/nar%2Fgkp109

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