Modeling of DNA microarray data by using physical properties of hybridization
- G. A. Held*,
- G. Grinstein, and
- Y. Tu
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Communicated by Charles H. Bennett, IBM Thomas J. Watson Research Center, Yorktown Heights, NY, April 25, 2003 (received for review January 31, 2003)
Abstract
A method of analyzing DNA microarray data based on the physical modeling of hybridization is presented. We demonstrate, in experimental data, a correlation between observed hybridization intensity and calculated free energy of hybridization. Then, combining hybridization rate equations, calculated free energies of hybridization, and microarray data for known target concentrations, we construct an algorithm to compute transcript concentration levels from microarray data. We also develop a method for eliminating outlying data points identified by our algorithm. We test the efficacy of these methods by comparing our results with an existing statistical algorithm, as well as by performing a cross-validation test on our model.
Footnotes
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↵ * To whom correspondence should be addressed at: IBM Thomas J. Watson Research Center, P.O. Box 218, Yorktown Heights, NY 10598. E-mail: gaheld{at}us.ibm.com.
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Abbreviations: PM, perfect match; MM, mismatch.
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Note. After submission of this article, we became aware of concurrent research (19) that addresses similar questions to our work, albeit through different methods.
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↵ † We have defined ΔG as the negative of the free energy of hybridization; thus, increasingΔG implies a stronger tendency to hybridize. Our ΔG is equal to –ΔG 0 in the notation of ref. 11.
- Copyright © 2003, The National Academy of Sciences
