Nucleic Acids Research Advance Access originally published online on December 14, 2006
Nucleic Acids Research 2007 35(3):e18; doi:10.1093/nar/gkl1064
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Nucleic Acids Research, 2007, Vol. 35, No. 3 e18
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Free energy of DNA duplex formation on short oligonucleotide microarrays
1 Department of Biostatistics and Applied Mathematics, The University of Texas M. D. Anderson Cancer Center 1515 Holcombe Boulevard, Unit 237, Houston, TX 77030, USA 2 Program in Biomathematics and Biostatistics, The University of Texas Graduate School of Biomedical Sciences at Houston 6767 Bertner Avenue, Houston, TX 77225, USA 3 Genomic Institute of Novartis Research Foundation, 10675 John Jay Hopkins Dr San Diego, CA 92121, USA 4 Department of Statistics and Actuarial Sciences, University of Central Florida Orlando, FL 32816, USA
*To whom correspondence should be addressed. Tel: +1 713 5634298; Fax: +1 713 5634243; Email: lzhangli{at}mdanderson.org
Received August 7, 2006. Revised November 15, 2006. Accepted November 20, 2006.
DNA/DNA duplex formation is the basic mechanism that is used in genome tiling arrays and SNP arrays manufactured by Affymetrix. However, detailed knowledge of the physical process is still lacking. In this study, we show a free energy analysis of DNA/DNA duplex formation these arrays based on the positional-dependent nearest-neighbor (PDNN) model, which was developed previously for describing DNA/RNA duplex formation on expression microarrays. Our results showed that the two ends of a probe contribute less to the stability of the duplexes and that there is a microarray surface effect on binding affinities. We also showed that free energy cost of a single mismatch depends on the bases adjacent to the mismatch site and obtained a comprehensive table of the cost of a single mismatch under all possible combination of adjacent bases. The mismatch costs were found to be correlated with those determined in aqueous solution. We further demonstrate that the DNA copy number estimated from the SNP array correlates negatively with the target length; this is presumably caused by inefficient PCR amplification for long fragments. These results provide important insights into the molecular mechanisms of microarray technology and have implications for microarray design and the interpretation of observed data.
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