Abstract: The present invention is related generally to analysis of polynucleotides, particularly polynucleotides derived from genomic DNA. The invention provides methods, compositions and systems for such analysis. Encompassed by the invention are arrays of polynucleotides in which the polynucleotides have undergone multiple rounds of amplification in order to increase the strength of signals associated with single polynucleotide molecules.

Abstract: Combinatorial processing including stirring is described, including defining multiple regions of a substrate, processing the multiple regions of the substrate in a combinatorial manner, introducing a fluid into a first aperture at a first end of a body to dispense the fluid out of a second aperture at a second end of the body and into one of the multiple regions, and agitating the fluid using an impeller at a second end of the body to facilitate interaction of the fluid with a surface of the substrate.

Abstract: Provided herein is a method for gene expression profiling multiple myeloma patients into distinct subgroups via DNA hybridization and hierarchical clustering analysis of the hybridization data where the results may further be used to identify therapeutic gene targets. Also provided is a method for controlling bone loss in an individual via pharmacological inhibitors of DKK1 protein. In addition provided herein is a method for diagnosing multiple myeloma using a 15-gene model that classifies myeloma into groups 1-7.

Abstract: System and method for preparing a microarray for a disease association gene transcript test. Disease considerations for this unique test include a custom set of genetic sequences associated in peer-reviewed literature with various known diseases such as Addison's disease, anemia, asthma, atherosclerosis, autism, breast cancer, estrogen metabolism, Grave's disease, hormone replacement therapy, major histocompatibility complex (MHC) genes, longevity, lupus, multiple sclerosis, obesity, osteoarthritis, prostate cancer, and type 2 diabetes. The base dataset may be developed through clinical samples obtained by third-parties. Online access of real-time phenotype/genotype associative testing for physicians and patients may be promoted through an analysis of a customized microarray testing service.

Abstract: The present invention provides a universal peptide-binding scaffold. This scaffold is used to bind a target. The target can be a peptide or peptides of interest (for example, peptides associated with a disease state) or can represent the entire proteome. The target can be either protein fragments prepared by enzymatic digestion of the entire proteome or N- or C-terminal short sequences exposed by chemical denaturation of the entire proteome (unfolded proteins). The universal peptide-binding scaffold can be tailored to specifically bind a target using the methods described herein.

Abstract: Random arrays of single molecules are provided for carrying out large scale analyses, particularly of biomolecules, such as genomic DNA, cDNAs, proteins, and the like. In one aspect, arrays of the invention comprise concatemers of DNA fragments that are randomly disposed on a regular array of discrete spaced apart regions, such that substantially all such regions contain no more than a single concatemer. Preferably, such regions have areas substantially less than 1 ?m2 and have nearest neighbor distances that permit optical resolution of on the order of 109 single molecules per cm2. Many analytical chemistries can be applied to random arrays of the invention, including sequencing by hybridization chemistries, sequencing by synthesis chemistries, SNP detection chemistries, and the like, to greatly expand the scale and potential applications of such techniques.

Abstract: The present invention provides parallel methods for identifying the locations of insertion elements that are distributed at different sites in the genome among a collection of cells.

Abstract: The invention relates to a method of detecting the precise locations of methyl-cytosines in a given nucleic acid sequence. In particular, the invention features a method which includes sequencing a template nucleic acid that is attached to a hairpin nucleic acid or double-stranded nucleic acid anchor, which contain specifically-designed sites for nicking or other endonucleases. The template nucleic acid is then regenerated to single-stranded form via methods described herein, and then treated to convert either the methylated cytosines, or non-methylated cytosines, and the template nucleic acid is then re-sequenced The results of the first and second sequencing reactions are then compared.

Abstract: A technique is disclosed for performing sequencing of polymers such as DNA and RNA. A sample containing multiple sites to be sequenced is cyclically subjected to attachment of nucleotides, and imaging. A digital mask corresponding to sites of interest in the sample array is generated and image data for the sites is processed differently from image data not corresponding to sites of interest. The latter may be discarded during the sequencing operation. The use of the mask improves computational efficiency and reduces memory allocated for the image data during sequencing.

Abstract: The system includes a microfabricated electrochemical biosensor for detecting the presence and/or quantity of the target analyte in the sample reagent. The biosensor includes a substrate and at least two electrically conductive electrodes. Each of the electrical conductive electrodes consists of a single layer of an electrically conductive material. The electrodes can be fabricated on the substrate by integrated circuit technology.

Abstract: The present invention relates to binding surfaces for the immobilization of ligands, ligand surfaces and structured surface arrays which present a plurality of identical or different ligands. The invention further relates to a process for the production and the use of such surfaces and to specific binder molecules which can be used for the preparation thereof.

Abstract: Disclosed herein are methods for identifying, isolating and comparing proteins and other biomolecules differing between two complex biological samples using affinity chromatography and phage display techniques.

Abstract: The invention concerns a method for identifying a ligand capable of selectively modulating a functional cascade involving a target, and uses thereof for high-throughput screening of molecules of interest, in particular therapeutic (medicine). Said method comprises at least the following steps: a) identifying an antibody or an antibody fragment comprising at least one of the variable domains of an immunoglobulin chain, capable of binding to said target and modulating said functional cascade involving said target; b) screening from a bank of molecules, ligands modulating the bond between said target and the antibody or antibody fragment identified in a); and c) identifying among said modulating ligands obtained in b), those capable of modulating said functional cascade.

Abstract: A microarray disc characterized in that a substrate is provided with a pregroove and a thin film with an excellent adherence to a probe DNA or protein is disposed at least on the pregroove, and that a liquid drop containing the probe DNA or protein is arranged on a convex part or concave part of the pregroove so that the liquid drop expands in the tangential direction of the pregroove due to the surface tension of the liquid drop and/or in the instance of concave part, due to the restriction by the concave groove wall with any expansion in the direction perpendicular to the groove, and that in the above condition, the probe DNA or protein is immobilized on the substrate.

Abstract: Provided are compositions and methods for determining whether a tumor in a subject is sensitive or resistant to a chemotherapeutic agent. Further provided are methods and compositions for identifying a chemotherapeutic agent to which a subject's tumor is resistant or sensitive. Methods and compositions for selecting a chemotherapeutic agent for treating a subject with a tumor are also provided.

Abstract: This invention provides high unit density arrays of microparticles and methods of assembling such arrays. The microparticles in the arrays may be functionalized with chemical or biological entities specific to a given target analyte. The high unit density arrays of this invention are formed on chips which may be combined to form multichip arrays according to the methods described herein. The chips and/or multichip arrays of this invention are useful for chemical and biological assays.

Abstract: This invention provides methods for characterizing the amounts of nucleic acids, including plus/minus determinations, the use of different constructs, the use of a library and a reference library. Expression may also be compared in two or more samples using the methods of this invention. Also provided are heterophasic arrays comprising labeled positive copies of nucleic acids hybridized to the array and labeled negative copies of nucleic acids hybridized to the array, in which the labeled positive copies are separately quantifiable from the labeled negative copies.