Abstract: Copy or antisense RNA is synthesized in a way that preserves the relative amounts of particular RNA molecules in a population. RNA is reverse transcribed to form first strand cDNA. Second strand cDNA is made by enzyme-catalyzed DNA synthesis using exogenous primers, preferably random primers. Double-stranded cDNA formed from the first and second strands is then used as a template for in vitro transcription to form copy or antisense RNA. The transcription is driven by a promoter sequence which was introduced into the cDNA by the primers used for reverse transcription.

Abstract: Methods for testing oligonucleotide arrays are disclosed including methods for testing the efficiency of nucleotide coupling; methods for testing amounts of deprotected oligonucleotides; methods for determining amounts of depurinated oligonucleotides; and methods of detecting the presence of cleavable structural features, such as double-stranded nucleic acids

Abstract: The invention provides an affinity filter for the binding of phage-displayed proteins to dissolved target molecules. The phage-displayed proteins are contacted with immobilized target in the presence and absence of dissolved target; the behavior of the phage-displayed proteins as a function of concentration of dissolved target permits approximation of the affinity of the phage-displayed protein for target. The invention also provides a method to screen large numbers of compounds for their ability to compete with a compound known to bind a phage-displayed protein.

Abstract: Computer-aided techniques for analyzing biological sequences like nucleic acids are provided. The computer system may analyze hybridization intensities indicating hybridization affinity between nucleic acid probes and a sample nucleic acid sequence in order to call bases in the sample sequence. Multiple base calls may be combined to form a single base call. Additionally, the computer system may analyze hybridization intensities in order to monitor gene expression or the change in gene expression as compared to a baseline.

Abstract: This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample.

Abstract: The proportional amplification of nucleic acids can increase the amount of nucleic acids while preserving the relative abundance of the individual nucleic acid species, or portions thereof, in the original sample. A proportionally amplified nucleic acid preparation may be analyzed in a gene expression monitoring system, preferably involving a nucleic acid probe array.

Abstract: A method is described for determining the genotype of one or more individuals at a biallelic marker. The method employs amplification of a region of genomic DNA using color tagged, allele-specific primers and hybridization of the products to an array of allele-specific probes. The genotype is identified from the pattern of hybridization.

Abstract: The invention provides an affinity filter for the binding of phage-displayed proteins to dissolved target molecules. The phage-displayed proteins are contacted with immobilized target in the presence and absence of dissolved target; the behavior of the phage-displayed proteins as a function of concentration of dissolved target permits approximation of the affinity of the phage-displayed protein for target. The invention also provides a method to screen large numbers of compounds for their ability to compete with a compound known to bind a phage-displayed protein.

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.

Abstract: Computer-aided techniques for analyzing biological sequences like nucleic acids are provided. The computer system may analyze hybridization intensities indicating hybridization affinity between nucleic acid probes and a sample nucleic acid sequence in order to call bases in the sample sequence. Multiple base calls may be combined to form a single base call. Additionally, the computer system may analyze hybridization intensities in order to monitor gene expression or the change in gene expression as compared to a baseline.

Abstract: Novel means and methods for analyzing hybridization data derived from hybridization assays between a target nucleic acid and differently sequenced polynucleotide probes involve selecting probe sets that define reference sequences for sequence signatures and deriving useful data about the nature of the target nucleic acid molecule based on its hybridization to the probes. The methods are useful for determining whether the target contains a nucleic acid or polypeptide sequence signature, whether the target encodes a member of a gene family, or whether the target is derived from one of any number of genes.

Abstract: The proportional amplification of nucleic acids can increase the amount of nucleic acids while preserving the relative abundance of the individual nucleic acid species, or portions thereof, in the original sample. A proportionally amplified nucleic acid preparation may be analyzed in a gene expression monitoring system, preferably involving a nucleic acid probe array.

Abstract: Methods for testing oligonucleotide arrays are disclosed including methods for testing the efficiency of nucleotide coupling; methods for testing amounts of deprotected oligonucleotides; methods for determining amounts of depurinated oligonucleotides; and methods of detecting the presence of cleavable structural features, such as double-stranded nucleic acids.

Abstract: The generation of selective inhibitors for specific protein kinases would provide new tools for analyzing signal transduction pathways and possibly new therapeutic agents. We have invented an approach to the development of selective protein kinase inhibitors based on the unexpected binding mode of 2,6,9-trisubstituted purines to the ATP binding site of human CDK2. The most potent inhibitor, purvalanol B (IC50=6 nM), binds with a 30-fold greater affinity than the known CDK2 inhibitor, flavopiridol. The cellular effects of this class of compounds were examined and compared to those of flavopiridol by monitoring changes in mRNA expression levels for all genes in treated cells of Saccharomyces cerevisiae using high-density oligonucleotide probe arrays.

Abstract: This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample.

Abstract: The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase.

Abstract: Libraries of unimolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.

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.

Abstract: The even length proportional amplification of nucleic acids can increase the amount of nucleic acids while preserving the relative abundance of the individual nucleic acid species, or portions thereof, in the original sample. An even length proportionally amplified nucleic acid preparation may be analyzed in a gene expression monitoring system, preferably involving a nucleic acid probe array.

Abstract: Computer-aided techniques for analyzing biological sequences like nucleic acids are provided. The computer system may analyze hybridization intensities indicating hybridization affinity between nucleic acid probes and a sample nucleic acid sequence in order to call bases in the sample sequence. Multiple base calls may be combined to form a single base call. Additionally, the computer system may analyze hybridization intensities in order to monitor gene expression or the change in gene expression as compared to a baseline.