Optimized probe selection method

Abstract

The present invention provides methods for optimizing oligonucleotide hybridization probes for use in basic and clinical research. Specifically, the invention involves hybridizing serially diluted genomic sample to the oligonucleotide probes on the array, such that a signal intensity is produced for each of the probes; computationally identifying optimized probes which exhibit signal intensities that correspond to the serial dilutions of genomic sample and are reproducibly strong relative to non-optimized probes.

1 . A method for optimizing oligonucleotide probes for use in a hybridization-based assay, the method comprising the steps of:
 a) providing a plurality of oligonucleotide probes on a hybridization array;   b) providing serial dilutions of a genomic sample, wherein the genomic sample is labeled;   c) hybridizing the labeled and serially diluted genomic sample to the probes on the array, such that a signal intensity is produced for each of the probes, wherein the hybridization step is performed at least one time;   d) computationally generating weighted regression data from the signal intensity produced for each of the probes;   e) entering the regression data into a database; and   f) querying the database to select optimized probes which exhibit signal intensities that correspond to the serial dilutions of genomic sample, are reproducible, and strong relative to non-optimized probes.   
     
     
         2 . The method of  claim 1  wherein the oligonucleotide probes are DNA or RNA. 
     
     
         3 . The method of  claim 1  wherein the hybridization-based assays are selected from the group consisting of microarray-based assays, bead-based assays, genotyping assays, and RNAi assays. 
     
     
         4 . The method of  claim 1  wherein the hybridization-based assays is a microarray-based assay, wherein the microarray is synthesized by maskless array synthesis.