Exploiting genomics in the search for new drugs
First Claim
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1. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is down-regulated in response to both compound 52 and flavopiridol.
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Abstract
The cellular effects of potentially therapeutic compounds are characterized in mammalian cells and yeast. In the latter case the effects can be characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays.
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Citations
79 Claims
- 1. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is down-regulated in response to both compound 52 and flavopiridol.
- 2. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is up-regulated in response to both compound 52 and flavopiridol.
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3. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is down-regulated in response to compound 52 but not to flavopiridol.
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4. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is up-regulated in response to compound 52 but not to flavopiridol.
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5. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is down-regulated in response to flavopiridol but not to compound 52.
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6. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is up-regulated in response to flavopiridol but not to compound 52.
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11. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is down-regulated in cdc28-4 mutants.
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12. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is down-regulated or up-regulated in response to both compound 52 and flavopiridol.
- 13. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is up-regulated or down-regulated in cdc28-4 mutants.
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15. A set of at least two probes, wherein each of said probes comprises a segment of the nucleotide sequence of a gene which is up-regulated in cdc28-4 mutants.
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53. A method of comparing the specificity of drugs, comprising:
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contacting a first drug with a first population of cells and a second drug with a second population of said cells;
preparing a transcription indicator from each of the first and the second populations of cells, wherein a transcription indicator is selected from the group consisting of cellular RNA, cellular mRNA, cRNA and cDNA;
preparing a transcription indicator from a third population of said cells which is not contacted with a drug;
hybridizing the transcription indicators to oligonucleotide arrays to form a pattern of hybridization for each of said populations of cells;
comparing each of the first and the second populations'"'"' patterns of hybridization to the third population'"'"'s pattern of hybridization to identify changes induced by the first and the second drugs;
comparing changes induced by the first and second drugs, wherein a drug which effects more changes is less specific than a drug which effects fewer changes. - View Dependent Claims (54, 55, 56, 57, 58, 59, 60, 61, 62)
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63. A method of comparing the effects of a drug to the effects of a mutation, comprising:
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contacting a drug with a first population of cells;
preparing a transcription indicator from the first population of cells, wherein a transcription indicator is selected from the group consisting of cellular RNA, cellular mRNA, cRNA and cDNA;
preparing a transcription indicator from a second population of cells which population is not contacted with a drug, wherein the second population of cells carry a mutation in a gene of interest relative to the first population of cells;
preparing a transcription indicator from a third population of cells which is not contacted with a drug and which does not carry the mutation;
hybridizing the transcription indicators to oligonucleotide arrays;
to form a pattern of hybridization for each of said populations of cells;
comparing each of the first and the second populations'"'"' patterns of hybridization to the third population'"'"'s pattern of hybridization to identify changes caused by the drug and the mutation;
comparing the changes caused by the drug to those caused by the mutation;
wherein a drug and a mutation which affect hybridization to one or more common oligonucleotides identifies the gene of interest as a candidate target of the drug;
wherein a drug which affects hybridization to both common oligonucleotides and unique oligonucleotides identifies the drug as affecting targets other than the gene. - View Dependent Claims (64, 65, 66, 67, 68, 69, 70, 71)
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72. A method of comparing the specificity of drugs, comprising:
comparing changes in expression induced by a first drug to those induced by a second drug, wherein a drug which effects more changes is less specific than a drug which effects fewer changes, wherein the changes are determined the process of;
contacting the first drug with a first population of cells and the second drug with a second population of said cells;
preparing a transcription indicator from each of the first and the second populations of cells, wherein a transcription indicator is selected from the group consisting of cellular RNA, cellular mRNA, cRNA and cDNA;
preparing a transcription indicator from a third population of said cells which is not contacted with a drug;
hybridizing the transcription indicators to oligonucleotide arrays to form a pattern of hybridization for each of said populations of cells; and
comparing a first and a second populations'"'"' patterns of hybridization to a third population'"'"'s pattern of hybridization to identify changes induced by the first and the second drugs. - View Dependent Claims (73, 74)
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75. A method of comparing the effects of a drug to the effects of a mutation, comprising:
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comparing changes in expression caused by a drug to those caused by a mutation, wherein the changes in expression are determined by the process of;
contacting the drug with a first population of cells;
preparing a transcription indicator from the first population of cells, wherein a transcription indicator is selected from the group consisting of cellular RNA, cellular mRNA, cRNA and cDNA;
preparing a transcription indicator from a second population of cells which population is not contacted with a drug, wherein the second population of cells carry the mutation in a gene of interest relative to the first population of cells;
preparing a transcription indicator from a third population of cells which is not contacted with a drug and which does not carry the mutation;
hybridizing the transcription indicators to oligonucleotide arrays to form a pattern of hybridization for each of said populations of cells;
comparing each of the first and the second populations'"'"' patterns of hybridization to the third population'"'"'s pattern of hybridization to identify changes caused by the drug and the mutation;
wherein a drug and a mutation which affect hybridization to one or more common oligonucleotides identifies the gene of interest as a candidate target of the drug;
wherein a drug which affects hybridization to both common oligonucleotides and unique oligonucleotides identifies the drug as affecting targets other than the gene. - View Dependent Claims (76, 77, 78, 79)
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Specification