Methods for evaluating oligonucleotide probe sequences
First Claim
1. A method for predicting the potential of an oligonucleotide to hybridize to a target nucleotide sequence, said method comprising:
- (a) identifying a predetermined number of unique oligonucleotides within a nucleotide sequence that is hybridizable with said target nucleotide sequence, said oligonucleotides being chosen to sample the entire length of said nucleotide sequence, (b) determining and evaluating for each of said oligonucleotides at least one parameter that is independently predictive of the ability of each of said oligonucleotides to hybridize to said target nucleotide sequence, (c) identifying a subset of oligonucleotides within said predetermined number of unique oligonucleotides based on an examination of said parameter, and (d) identifying oligonucleotides in said subset that are clustered along a region of said nucleotide sequence that is hybridizable to said target nucleotide sequence.
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Abstract
Methods are disclosed for predicting the potential of an oligonucleotide to hybridize to a target nucleotide sequence. A predetermined number of unique oligonucleotides is identified. The unique oligonucleotides are chosen to sample the entire length of a nucleotide sequence that is hybridizable with the target nucleotide sequence. At least one parameter that is independently predictive of the ability of each of the oligonucleotides of the set to hybridize to the target nucleotide sequence is determined and evaluated for each of the above oligonucleotides. A subset of oligonucleotides within the predetermined number of unique oligonucleotides is identified based on the evaluation of the parameter. Oligonucleotides in the subset are identified that are clustered along a region of the nucleotide sequence that is hybridizable to the target nucleotide sequence. The method may be carried out with the aid of a computer.
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Citations
101 Claims
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1. A method for predicting the potential of an oligonucleotide to hybridize to a target nucleotide sequence, said method comprising:
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(a) identifying a predetermined number of unique oligonucleotides within a nucleotide sequence that is hybridizable with said target nucleotide sequence, said oligonucleotides being chosen to sample the entire length of said nucleotide sequence, (b) determining and evaluating for each of said oligonucleotides at least one parameter that is independently predictive of the ability of each of said oligonucleotides to hybridize to said target nucleotide sequence, (c) identifying a subset of oligonucleotides within said predetermined number of unique oligonucleotides based on an examination of said parameter, and (d) identifying oligonucleotides in said subset that are clustered along a region of said nucleotide sequence that is hybridizable to said target nucleotide sequence. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
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41. A method for predicting the potential of an oligonucleotide to hybridize to a complementary target nucleotide sequence, said method comprising:
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(a) identifying a set of overlapping oligonucleotides from a nucleotide sequence that is complementary to said target nucleotide sequence, (b) determining and evaluating for each of said oligonucleotides at least two parameters that are independently predictive of the ability of each of said oligonucleotides to hybridize to said target nucleotide sequence wherein said parameters are poorly correlated with respect to one another, (c) identifying a subset of oligonucleotides within said set of oligonucleotides based on an examination of said parameters, and (d) identifying oligonucleotides in said subset that are clustered along a region of said complementary nucleotide sequence. - View Dependent Claims (42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 81, 93, 94, 96)
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78. A method for predicting the potential of an oligonucleotide to hybridize to a complementary target nucleotide sequence, said method comprising:
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(a) obtaining, from a nucleotide sequence complementary to said target nucleotide sequence, a set of overlapping oligonucleotides of identical length N and spaced one nucleotide apart, said set comprising L−
N+1 oligonucleotides,(b) determining and evaluating for each of said oligonucleotides the parameters;
(i) the predicted melt temperature of the duplex of said oligonucleotide and said target nucleotide sequence corrected for salt concentration and (ii) predicted free energy of the most stable intramolecular structure of the oligonucleotide at the temperature of hybridization of each of said oligonucleotides with said target nucleotide sequence,(c) identifying a subset of oligonucleotides within said set of oligonucleotides based on an examination of said parameters by establishing cut-off values for each of said parameters, (d) ranking oligonucleotides in said subset that are clustered along a region of said complementary nucleotide sequence based on the size of said clusters of oligonucleotides, and (e) selecting a subset of said clustered oligonucleotides. - View Dependent Claims (79, 80, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 95, 97)
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98. A computer based method for predicting the potential of an oligonucleotide to hybridize to a target nucleotide sequence, said method comprising:
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(a) identifying under computer control a predetermined number of unique oligonucleotides within a nucleotide sequence that is hybridizable with said target nucleotide sequence, said oligonucleotides being chosen to sample the entire length of said nucleotide sequence, (b) under computer control, determining and evaluating for each of said oligonucleotides a value for at least one parameter that is independently predictive of the ability of each of said oligonucleotides to hybridize to said target nucleotide sequence and storing said parameter values, (c) identifying under computer control, from said stored parameter values, a subset of oligonucleotides within said predetermined number of unique oligonucleotides based on an examination of said parameter, and (d) identifying under computer control oligonucleotides in said subset that are clustered along a region of said nucleotide sequence that is hybridizable to said target nucleotide sequence. - View Dependent Claims (99)
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100. A computer system for conducting a method for predicting the potential of an oligonucleotide to hybridize to a target nucleotide sequence, said system comprising:
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(a) input means for introducing a target nucleotide sequence into said computer system, (b) means for determining a number of unique oligonucleotide sequences that are within a nucleotide sequence that is hybridizable with said target nucleotide sequence, said oligonucleotide sequences being chosen to sample the entire length of said nucleotide sequence, (c) memory means for storing said oligonucleotide sequences, (d) means for controlling said computer system to carry out a determination and evaluation for each of said oligonucleotide sequences a value for at least one parameter that is independently predictive of the ability of each of said oligonucleotide sequences to hybridize to said target nucleotide sequence, (e) means for storing said parameter values, (f) means for controlling said computer to carry out an identification from said stored parameter values a subset of oligonucleotide sequences within said number of unique oligonucleotide sequences based on an examination of said parameter, (g) means for storing said subset of oligonucleotides, (h) means for controlling said computer to carry out an identification of oligonucleotide sequences in said subset that are clustered along a region of said nucleotide sequence that is hybridizable to said target nucleotide sequence. (i) means for storing said oligonucleotide sequences in said subset, and (j) means for outputting data relating to said oligonucleotide sequences in said subset. - View Dependent Claims (101)
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Specification