Combinatorial affinity selection
First Claim
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1. A method for analyzing a nucleic acid sample, the method comprising:
- capturing a first set of nucleic acids and a second set of nucleic acids from a nucleic acid sample, wherein capturing comprises hybridizing the first set of nucleic acids with a first nucleic acid affinity matrix and hybridizing the second set of nucleic acids with the second nucleic acid affinity matrix, wherein the first nucleic acid affinity matrix comprises a first plurality of oligonucleotides attached to a first plurality of beads, wherein the second nucleic acid affinity matrix comprises a second plurality of oligonucleotides attached to a second plurality of beads, and wherein the first plurality of oligonucleotides is different than the second plurality of oligonucleotides and wherein at least ten different oligonucleotides are attached to each bead;
removing unhybridized nucleic acids from the first and second nucleic acid affinity matrices;
separating the first plurality of beads from the second plurality of beads;
separating the first set of nucleic acids from the first plurality of oligonucleotides and the second set of nucleic acids from the second plurality of oligonucleotides; and
analyzing the first and second sets of nucleic acids, wherein analyzing comprises sequencing the first and second sets of nucleic acids.
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Abstract
In one aspect of the invention, methods for analyzing nucleic acid sample are provided. In a preferred embodiment, nucleic acids are selected using affinity matrices prior hybridization with a microarray.
32 Citations
28 Claims
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1. A method for analyzing a nucleic acid sample, the method comprising:
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capturing a first set of nucleic acids and a second set of nucleic acids from a nucleic acid sample, wherein capturing comprises hybridizing the first set of nucleic acids with a first nucleic acid affinity matrix and hybridizing the second set of nucleic acids with the second nucleic acid affinity matrix, wherein the first nucleic acid affinity matrix comprises a first plurality of oligonucleotides attached to a first plurality of beads, wherein the second nucleic acid affinity matrix comprises a second plurality of oligonucleotides attached to a second plurality of beads, and wherein the first plurality of oligonucleotides is different than the second plurality of oligonucleotides and wherein at least ten different oligonucleotides are attached to each bead; removing unhybridized nucleic acids from the first and second nucleic acid affinity matrices; separating the first plurality of beads from the second plurality of beads; separating the first set of nucleic acids from the first plurality of oligonucleotides and the second set of nucleic acids from the second plurality of oligonucleotides; and analyzing the first and second sets of nucleic acids, wherein analyzing comprises sequencing the first and second sets of nucleic acids. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method for analyzing a nucleic acid sample, the method comprising:
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providing a mixture of unhybridized nucleic acids, a first plurality of beads having a first plurality of oligonucleotides attached thereto and with a first set of nucleic acids hybridized to the first plurality of oligonucleotides, and a second plurality of beads having a second plurality of oligonucleotides attached thereto and with a second set of nucleic acids hybridized to the second plurality of oligonucleotides, and wherein the first plurality of oligonucleotides is different from the second plurality of oligonucleotides and wherein at least ten different oligonucleotides are attached to each bead; removing unhybridized nucleic acids from the first and second plurality of beads; separating the first plurality of beads from the second plurality of beads; separating the first set of nucleic acids from the first plurality of oligonucleotides and the second set of nucleic acids from the second plurality of oligonucleotides; and analyzing the first and second sets of nucleic acids by sequencing. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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28. A method for analyzing a nucleic acid sample, the method comprising:
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providing a mixture of unhybridized nucleic acids, a first plurality of beads having a first plurality of oligonucleotides attached thereto and with a first set of nucleic acids hybridized to the first plurality of oligonucleotides, and a second plurality of beads having a second plurality of oligonucleotides attached thereto and with a second set of nucleic acids hybridized to the second plurality of oligonucleotides, and wherein the first plurality of oligonucleotides is different from the second plurality of oligonucleotides and wherein the first plurality of beads has magnetic properties and the second plurality of beads does not have magnetic properties; removing unhybridized nucleic acids from the first and second plurality of beads; separating the first plurality of beads from the second plurality of beads; separating the first set of nucleic acids from the first plurality of oligonucleotides and the second set of nucleic acids from the second plurality of oligonucleotides; and analyzing the first and second sets of nucleic acids by sequencing.
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Specification