Abstract: Rapid, sensitive, reproducible high-throughput methods for detecting methylation patterns in samples of nucleic acid, especially in the promoter region of genes which are enriched with CpG islands, are provided. The methods include isolating complexes of methylated DNA and methylation binding protein, optionally amplifying the isolated methylated DNA, and detecting the methylated DNA or its amplification products in a multiplex and robust manner. By using the inventive methodology, methylated and unmethylated sequences present in the original sample of nucleic acid can be distinguished. By profiling and comparing the methylation status of genes in different samples, one can utilize the information for diagnosis and treatment of diseases or conditions associated with aberrant DNA hypermethylation or hypomethylation.

Abstract: Methods of detecting one or more nucleic acids from whole blood or plasma are provided. The nucleic acids are captured on a solid support and detected. Compositions, kits, and systems related to the methods are also described.

Abstract: Methods for detecting and optionally quantitating one or more target nucleic acids are provided, in which a surrogate nucleic acid is captured to each target nucleic acid, amplified, and detected. Compositions, kit, and systems related to the methods are also described.

Abstract: Methods of detecting nucleic acids, including methods of detecting two or more nucleic acids in multiplex branched-chain DNA assays, are provided. Nucleic acids captured on a solid support are detected, for example, through cooperative hybridization events that result in specific association of a label with the nucleic acids. Compositions, kits, and systems related to the methods are also described.

Abstract: Methods of detecting two or more nucleic acids in a multiplex branched-chain DNA assay are provided. Different nucleic acids are captured through cooperative hybridization events on different, identifiable subsets of particles or at different selected positions on a spatially addressable solid support. Compositions, kits, and systems related to the methods are also described.

Abstract: Methods of capturing two or more nucleic acids simultaneously from a single sample are provided. Different nucleic acids are captured through cooperative hybridization events on different subsets of particles or at different selected positions on a spatially addressable solid support. Compositions, kits, and systems related to the methods are also described.

Abstract: A method is provided for screening for agents that affect protein degradation rates, the method comprising: taking a library of cells, the cells expressing a fusion protein comprising a reporter protein and a protein encoded by a sequence from a cDNA library derived from a sample of cells, the sequence from the cDNA library varying within the cell library; contacting the library of cells with a plurality of agents which may affect protein degradation rates; for each agent, selecting cells in the library which express short-lived proteins based on whether the cells have different reporter signal intensities than other cells in the library, the difference being indicative of the selected cells expressing shorter lived fusion proteins than the fusion proteins expressed by the other cells in the library; and characterizing the fusion proteins expressed by the selected cells for each agent.

Abstract: Methods, arrays and kits are provided for rapidly and efficiently identifying and quantifying multiple different activated transcription factors in a biological sample at the same time. In one aspect, a method is provided for isolating DNA probes which bind to activated transcription factors, including the step of mixing a library of double stranded DNA probes with a sample containing activated transcription factors. The transcription factor probes that have bound to the activated transcription factors are isolated from the mixture via an agarose gel separation. The bound probes can be identified, for example, by using an array of hybridization probes.

Abstract: The present invention provides methods, compositions and kits for highly efficient, high throughput detection of mutation or nucleotide variation of an organism. By exploiting the molecular interactions between strands of nucleic acid and between nucleic acid and protein, assays have been developed to detect nucleotide variation, in particular, single nucleotide polymorphism (SNP) in various biological samples including human genomic DNA and virus. In preferred embodiments, immunoassays are developed to specifically capture a nucleic acid-protein complex formed between a 4-way nucleic acid structure called Holliday junction and a protein that specifically recognizes the Holliday junction. These assays can be used in a wide variety of applications such as diagnostics, genotyping, genetic profiling, mutation detection, disease prevention, therapeutic treatment, and screening for therapeutic targets or therapeutics.

Abstract: The present invention provides methods for determining the genotype of a nucleic acid at the site of a polymorphism. The methods achieve sensitivities great enough to detect the presence of any difference between the nucleic acids, even single nucleotide polymorphisms. In the methods, the nucleic acid is compared to a reference nucleic acid having a known genotype. The nucleic acids can be of any length, even less than 100 base pairs. In methods, one or more extra mismatches are introduced into the nucleic acids at or near the site of the polymorphism. The nucleic acids are contacted under conditions in which they are capable of forming a stable four-way complex that can be detected to indicate that the nucleic acids differ in genotype.

Abstract: The present invention provides sensitive methods for detecting the presence or absence of a difference between related nucleic acid sequences. In one aspect of the invention, a method is provided for detecting a difference in the sequence of two nucleic acid molecules. The method includes the steps of: contacting two nucleic acids under conditions that allow the formation of a four-way complex and branch migration; contacting the four-way complex with a tracer molecule and a detection molecule under conditions in which the detection molecule is capable of binding the tracer molecule or the four-way complex; and determining binding of the tracer molecule to the detection molecule before and after exposure to the four-way complex. Competition of the four-way complex with the tracer molecule for binding to the detection molecule indicates a difference between the two nucleic acids.

Abstract: Method and kits are provided for screening for transcription factor modulators efficiently. In one aspect, the method can be employed to profile multiple, different transcription factors activated in a sample in the presence of each of the transcription factor modulators. Comparison of the activated transcription factor profiles in the presence and absence of the modulator identifies the transcription factor modulator that modulates the activation of specific transcription factors.

Abstract: Methods, arrays and kits are provided for rapidly and efficiently identifying and quantifying multiple different activated transcription factors in a biological sample at the same time. In one embodiment, the method includes the step of mixing a library of different transcription factor probes with a sample containing activated transcription factors. The transcription factor probes that have bound to the activated transcription factors may be isolated from the complexes formed between the probes and the activated transcription factors. The bound probes can be identified, for example, by using an array of hybridization probes.