Methods for Improved Selection of Oligo-Probes for Array Design
Uses of high throughput genomic technologies, including microarray technologies, are growing exponentially. One major limitation of current array technology is the poor predictability of hybridization signal intensity in relation to target concentration. Hybridization signal intensity change in response to changes in target concentration is highly variable, making accurate determination of changes in gene expression and copy number difficult. Currently used methods for microarray design and oligo-probe selection do not account for all kinetic and other parameters which are important for target hybridization to immobilized oligo-probes.
The methods described in this invention employ additional kinetic and compositional parameters to identify preferred oligo-probes in an existing array, select new sets of oligo-probes based on target sequences and preferred parameters for solid support thermodynamics, and design new arrays incorporating these preferred oligo-probes. For oligo-probes selected according to this model, changes in hybridization intensity correlate more closely with changes in target concentration. Thus, microarrays designed according to this method should be suitable for accurate measurement of gene expression level.
Microarray technology has become an important tool in biomedical research. Common applications of this technology are gene expression profiling, SNP detection, and evaluation of gene copy number by comparative genomic hybridization.
Stage of Development
A provisional patent application has been filed with the USPTO. This technology is available for sponsored research and/or licensing under either exclusive or non-exclusive terms.
*Matveeva et al. (2003). Thermodynamic criteria for high hit rate antisense oligonucleotide design. Nucleic Acids Res;31(17):4989-94.
*Matveeva et al. (2003). Thermodynamic calculations and statistical correlations for oligo-probes design. Nucleic Acids Res;31(14):4211-7.
John Atkins, Alexander Tsodikov, Susan Freier, Morgan Giddings, Jacqueline Wyatt, Raymond Gesteland, Olga Matveeva
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