Combinatorial array for nucleic acid analysis
First Claim
1. A method for analyzing data from hybridization of a sample to an array of oligonucleotide probes, wherein the sample comprises a plurality of nucleotide sequences, each nucleotide sequence corresponding to a particular gene, wherein some or all of the oligonucleotide probes are assigned to invertible subblocks such that each gene which hybridizes to an oligonucleotide probe assigned to a particular subblock does not hybridize to the oligonucleotide probes in the other subblocks, and which method comprises a step of separately analyzing the data for the oligonucleotide probes in each subblock.
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Abstract
This invention relates to an array, including a universal micro-array, for the analysis of nucleic acids, such as DNA. The devices and methods of the invention can be used for identifying gene expression patterns in any organism. More specifically, all possible oligonucleotides (n-mers) necessary for the identification of gene expression patterns are synthesized. According to the invention, n is large enough to give the specificity to uniquely identify the expression pattern of each gene in an organism of interest, and is small enough that the method and device can be easily and efficiently practiced and made. The invention provides a method of analyzing molecules, such as polynucleotides (e.g., DNA), by measuring the signal of an optically-detectable (e.g., fluorescent, ultraviolet, radioactive or color change) reporter associated with the molecules. In a polynucleotide analysis device according to the invention, levels of gene expression are correlated to a signal from an optically-detectable (e.g. fluorescent) reporter associated with a hybridized polynucleotide. The invention includes an algorithm and method to interpret data derived from a micro-array or other device, including techniques to decode or deconvolve potentially ambiguous signals into unambiguous or reliable gene expression data.
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Citations
105 Claims
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1. A method for analyzing data from hybridization of a sample to an array of oligonucleotide probes,
wherein the sample comprises a plurality of nucleotide sequences, each nucleotide sequence corresponding to a particular gene, wherein some or all of the oligonucleotide probes are assigned to invertible subblocks such that each gene which hybridizes to an oligonucleotide probe assigned to a particular subblock does not hybridize to the oligonucleotide probes in the other subblocks, and which method comprises a step of separately analyzing the data for the oligonucleotide probes in each subblock.
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48. A method for assigning all or some of a plurality of oligonucleotide probes to subblocks suitable for analyzing data from hybridization of a sample to an array of the oligonucleotide probes,
wherein the sample comprises a plurality of nucleotide sequences, each nucleotide sequence corresponding to a particular gene, which method comprises steps of: -
(a) associating a gene ga with a gene list for a subblock, wherein the gene ga is not already associated with a gene list for a subblock; and
(b) assigning an oligonucleotide probe ox to the subblock, wherein the oligonucleotide probe ox hybridizes to the gene ga, wherein the steps are repeated for each subblock until each gene is associated with a gene list for a subblock. - View Dependent Claims (49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63)
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64. A method for selecting a particular sequence length n for an array comprising a plurality (N0) of oligonucleotide probes having the particular sequence length n, which method comprises:
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(a) identifying a sequence length n providing an average probe degeneracy <
d(n)>
suitable for analyzing nucleic acid expression using the array; and
(b) selecting the identified sequence length n, wherein the average probe degeneracy <
d(n)>
indicates the number of different nucleic acids that hybridize, on average, to a particular oligonucleotide probe. - View Dependent Claims (65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 102, 103, 104, 105)
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101. A method according to claim 101 wherein the steps (c)-(d) are repeated for not more than two iterations.
Specification