Methods and systems for uniform enrichment of genomic regions
First Claim
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1. A method for uniform enrichment of a population of nucleic acid molecules in a sample, comprising:
- a) providing a sample of nucleic acid molecules comprising a plurality of target nucleic acid sequences,b) hybridizing the sample to nucleic acid probes complementary to the target nucleic acid sequences under hybridization conditions, wherein at least one of the target nucleic acid sequences exhibits enrichment bias for a complementary probe, and wherein the frequency of individual nucleic acid probe sequences is increased for a target nucleic acid sequence having below-average enrichment and decreased for a target nucleic acid sequence having above-average enrichment such that the nucleic acid probes provide uniform hybridization among said plurality of target nucleic acid sequences, andc) separating non-hybridized nucleic acid sequences from hybridized target nucleic acid sequences, thereby uniformly enriching a population of nucleic acid molecules in a sample.
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Abstract
The present invention provides methods and compositions for the enrichment of target nucleic acids in a microarray system. In particular, the present invention provides methods and compositions for uniform enrichment of target nucleic acid molecules in a microarray format. The present invention also provides for intentionally non-uniform enrichment among target nucleic acid molecules.
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Citations
27 Claims
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1. A method for uniform enrichment of a population of nucleic acid molecules in a sample, comprising:
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a) providing a sample of nucleic acid molecules comprising a plurality of target nucleic acid sequences, b) hybridizing the sample to nucleic acid probes complementary to the target nucleic acid sequences under hybridization conditions, wherein at least one of the target nucleic acid sequences exhibits enrichment bias for a complementary probe, and wherein the frequency of individual nucleic acid probe sequences is increased for a target nucleic acid sequence having below-average enrichment and decreased for a target nucleic acid sequence having above-average enrichment such that the nucleic acid probes provide uniform hybridization among said plurality of target nucleic acid sequences, and c) separating non-hybridized nucleic acid sequences from hybridized target nucleic acid sequences, thereby uniformly enriching a population of nucleic acid molecules in a sample. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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- 13. A process for uniform enrichment of a population of nucleic acid sequences in a sample, said process comprising hybridizing a plurality of immobilized hybridization probes to a plurality of corresponding target nucleic acid sequences within a population of nucleic acid molecules and separating non-hybridized nucleic acid sequences from hybridized target nucleic acid sequences, wherein at least one of the target nucleic acid sequences exhibits enrichment bias for a complementary probe, and wherein the frequency of individual hybridization probes is increased for target nucleic acid sequences having below-average enrichment and decreased for target nucleic acid sequences having above-average enrichment such that the nucleic acid probes provide uniform hybridization among said plurality of target nucleic acid sequences.
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18. A method for uniform enrichment of a population of nucleic acid molecules in a sample, comprising:
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a) providing a sample of nucleic acid molecules comprising a plurality of target nucleic acid sequences, b) hybridizing the sample to a support comprising immobilized nucleic acid probes under conditions to support hybridization between the immobilized nucleic acid probes and the plurality of target nucleic acid sequences, wherein said immobilized nucleic acid probes are complementary to said plurality of target nucleic acid sequences, wherein the density of said immobilized nucleic acid probes to optimally produce uniform read depth is predicted using an empirically-fit, linear regression model fitting read depth to the density of immobilized nucleic acid probes, and wherein the immobilized nucleic acid probes provide uniform hybridization among said plurality of target nucleic acid sequences, and c) separating non-hybridized nucleic acid sequences from hybridized target nucleic acid sequences, thereby uniformly enriching a population of nucleic acid molecules in a sample. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26, 27)
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Specification