Methods for controlling cross-hybridization in analysis of nucleic acid sequences

Abstract

Methods, reagents and kits are disclosed for selecting target-specific oligonucleotide probes, which may be used in analyzing a target nucleic acid sequence. In one aspect the present invention is directed to selecting a set of target-specific oligonucleotide probes. A cross-hybridization oligonucleotide probe is identified based on a candidate target-specific oligonucleotide probe for the target nucleic acid sequence. The cross-hybridization oligonucleotide probe measures the extent of occurrence of a cross-hybridization event having a predetermined probability. Cross-hybridization results are determined employing the cross-hybridization oligonucleotide probe and the target-specific oligonucleotide probe. The target-specific oligonucleotide probe is selected or rejected for the set based on the cross-hybridization results.

1 . A method for producing an array comprising: 
 receiving sequence for one or more target nucleic acids;    determining one or more probes for each of said one or more target nucleic acids; outputting results of said determining step; and    fabricating an array from said outputted results.    
     
     
         2 . A method for producing an array comprising: 
 receiving information for one or more target nucleic acids;    determining one or more candidate probe sequences for each of said one or more target nucleic acids;    outputting results of said determining to provide for selecting or rejecting one or more candidate probe sequences; and    fabricating an array comprising a selected probe sequence.    
     
     
         3 . The method according to  claim 2 , wherein said method comprises communicating said outputted results with another computer.  
     
     
         4 . The method according to  claim 2 , wherein said information for said one or more target nucleic acids comprises sequence information.  
     
     
         5 . The method according to  claim 2 , wherein each of said candidate probes is evaluated for at least one parameter predictive of hybridization.  
     
     
         6 . The method according to  claim 2 , wherein said array comprises nucleic acids synthesized or spotted on a support.  
     
     
         7 . A system comprising: 
 an input means for receiving information on one or more target nucleic acids; a probe identification element for determining one or more candidate probes for each of said one or more target nucleic acids;    an output element for outputting results of said determining to provide for selecting or rejecting one or more candidate probe sequences; and    means for fabricating an array comprising selected probes.    
     
     
         8 . The system according to  claim 7 , wherein said output element communicates with another computer.  
     
     
         9 . The system according to  claim 7 , wherein said information for said one or more target nucleic acids comprises sequence information.  
     
     
         10 . The system according to  claim 9 , wherein each of said candidate probes is evaluated for at least one parameter predictive of hybridization.  
     
     
         11 . The system according to  claim 7 , wherein said array comprises nucleic acids synthesized or spotted on a support.  
     
     
         12 . A method for providing custom probe arrays, comprising the acts of: 
 receiving a user selection of one or more probe set identifiers that each identify a plurality of potential probes;    determining verified probe sets of verified probes corresponding to the probe set identifiers;    generating a custom probe array design based, at least in part, upon the verified probe sets; and    providing to the user one or more probe arrays based on the probe array design.    
     
     
         13 . A method for providing custom probe arrays, comprising the acts of: 
 receiving a user selection of one or more probe set identifiers that identify one or more potential probes;    determining verified probe sets of verified probes corresponding to the probe set identifiers;    generating a custom probe array design based, at least in part, upon the verified probe sets;    enabling for display to the user a representation of one or more aspects of the custom probe array design via one or more graphical user interfaces enabled to receive a user selection specifying acceptance, modification, or rejection of the custom probe array design; and providing to the user one or more probe arrays based on the probe array design and responsive to the user specification of acceptance or modification.    
     
     
         14 . The method of  claim 13 , wherein: the user selection is received over the Internet.  
     
     
         15 . The method of  claim 13 , wherein: the probe set identifiers comprise sequence information.  
     
     
         16 . The method of  claim 13 , wherein: the verified probe sets are determined based, at least in part, on any one or any combination of frequency, length, or position of probe sequence repeats; probe sequence length, thermodynamic properties, energetic parameters, or uniqueness; or one or more characteristics of target molecules specified by the user for use with the probe array.  
     
     
         17 . The method of  claim 13 , wherein: the graphical user interface is provided over a network.  
     
     
         18 . The method of  claim 13 , wherein: the probe arrays include synthesized or spotted probe arrays.  
     
     
         19 . A system for providing custom probe arrays, comprising: 
 an input manager constructed and arranged to receive a user selection of one or more probe set identifiers that identify one or more potential probes;    a gene or EST verifier constructed and arranged to determine one or more verified probe sets of verified probes corresponding to the probe set identifiers;    a probe array generator constructed and arranged to generate a custom probe array design based, at least in part, upon the verified probe sets;    and a user data processor constructed and arranged to enable for display a representation of one or more aspects of the custom probe array design via one or more graphical user interfaces that are further enabled to receive a user selection specifying acceptance, modification, or rejection of the custom probe array design, and further is constructed and arranged to provide to the user one or more probe arrays based on a user selection specifying acceptance or modification of the probe array design.    
     
     
         20 . The system of  claim 19 , wherein: the user selection is received over the Internet.  
     
     
         21 . The system of  claim 19 , wherein: the probe set identifiers comprise sequence information.  
     
     
         22 . The system of  claim 19 , wherein: the verified probe sets are determined based, at least in part, on any one or any combination of frequency, length, or position of probe sequence repeats; probe sequence length, thermodynamic properties, energetic parameters, or uniqueness; or one or more characteristics of target molecules specified by the user for use with the probe array.  
     
     
         23 . The system of  claim 19 , wherein: the graphical user interface is provided over a network.  
     
     
         24 . The system of  claim 19 , wherein: the probe arrays include synthesized or spotted probe arrays.