Quantitative analysis of hybridization patterns and intensities in oligonucleotide arrays

Abstract

Systems and methods for enhanced quantitative analysis of hybridization intensity measurements obtained from oligonucleotide probes and other probes exposed to target samples are provided by virtue of the present invention. One embodiment ameliorates the effects of high frequency noise superimposed on a hybridization intensity measurement signal measured over successive probe alignments to a target sample sequence. Detection of expressed genes and ESTs and quantitative measurement of expression level may be improved. Mutation detection and base calling may be improved.

What is claimed is:  
     
         1 . A method for analyzing a sample nucleic acid sequence, said method comprising: 
 providing a plurality of hybridization intensities, including hybridizing a plurality of probes to said sample nucleic acid sequence, said plurality of hybridization intensities collectively defining a hybridization spectrum of said sample nucleic acid sequence;    producing an indication of similarity by comparing said hybridization spectrum of said sample nucleic acid sequence to a reference hybridization spectrum, including applying a low-pass filter procedure to said hybridization spectrum; and    using the indication of similarity to indicate an expression of a gene specified by said sample nucleic acid sequence.    
     
     
         2 . A method for analyzing a sample nucleic acid sequence comprising the steps of: 
 providing a plurality of hybridization intensities of probes including exposing said probes to said sample nucleic acid sequence;    applying a non-linear low-pass filter to said plurality of hybridization intensities; and    comparing pairs of said relative hybridization intensities, wherein comparing pairs of said relative hybridization intensities determines an expression of a gene specified by said sample nucleic acid sequence.    
     
     
         3 . A method for analyzing a sample nucleic acid sequence, said method comprising: 
 providing a plurality of hybridization intensities, including hybridizing a plurality of probes to said sample nucleic acid sequence, said plurality of hybridization intensities collectively defining a hybridization spectrum of said sample nucleic acid sequence;    producing an indication of similarity, including applying a linear regression procedure to said hybridization spectrum and said reference hybridization spectrum, and comparing said hybridization spectrum of said sample nucleic acid sequence to a reference hybridization spectrum; and    using the indication of similarity to identify an expression of a gene specified by said sample nucleic acid sequence.