Abstract: The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

Abstract: The invention provides methods for evaluating the representation of expected nucleic acid molecules in a test population of nucleic acid molecules. The methods each comprise the steps of: (a) hybridizing a population of sample nucleic acid molecules obtained from a test population of nucleic acid molecules to a substrate comprising a population of target nucleic acid molecules, wherein (i) each target nucleic acid molecule comprises a predetermined sequence corresponding to an expected nucleic acid molecule, and (ii) each target nucleic acid molecule is localized to a defined area of the substrate; and (b) evaluating the representation of expected nucleic acid molecules in the test population of nucleic acid molecules by analyzing the pattern of hybridization of the sample population of nucleic acid molecules to the target nucleic acid molecules.

Abstract: Non-contiguous regions of interest as well as contiguous regions of interest are similarly processed. After an isotope peak detector has identified isotope peaks on LC/MS images, a microaligner microaligns bounding areas of identified isotope peaks and redefines the bounding areas to help subsequent scoring process. Forms of isotope peaks influence formation of a peak association matrix and a mass/charge association map which creates association in the mass/charge dimension. A correlation scorer produces reproducibility scores as well as quality scores to help aid scientists to discover biological features of interest.

Abstract: The present invention provides methods for identifying a modulator of glucocorticoid receptor activity. In one embodiment, the methods include the steps of (a) contacting neuron-like cells, in vitro, with a chemical agent; (b) measuring the expression of a member, or group of members, of a group of genes (as defined herein) in the neuron-like cells contacted with the chemical agent; and (c) determining whether the chemical agent significantly alters the expression of the member, or group of members, of the group of genes, thereby determining whether the chemical agent is likely to be a modulator of glucocorticoid receptor activity. In another embodiment, an in vivo method for identifying a modulator of glucocorticoid receptor activity is provided.

Abstract: In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5? end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5?end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8.

Abstract: The present invention provides methods for selectively amplifying a target population of nucleic acid molecules in a population of RNA template molecules (e.g., all mRNA molecules expressed in a cell type except for the most highly expressed mRNA species). The invention also provides a method of generating a population of oligonucleotide primers for transcriptome profiling of total RNA from a subject of interest.

Abstract: The present invention provides devices, systems and methods for RNA isolation from biological samples containing white blood cells, such as whole blood. The devices have a device body that includes a first chamber having a first membrane that selectively binds white blood cells, a second chamber having a second membrane that reversibly binds RNA and a plurality of ports that are removably attached to a reagent pack and waste receptacle via a valving system controlled by a control unit.

Abstract: The present invention relates to methods and compositions for assessing the quality of microarrays. In particular, the invention relates to the use of quality control probes that are synthesized on the microarray monomer by monomer in a step-by-step synthesis. By assessing the degree of signal from the quality control probes and determining their deviation from expected signal intensities, the quality of microarray synthesis can be ascertained. The invention further relates to a method of detecting defects occurring during storage or processing of the microarray. The invention further relates to a method of using a computer to identify microarrays that have had a defect or defects during synthesis, storage, or processing.

Abstract: The present invention relates to the identification and use of single nucleotide polymorphisms and haplotypes in the Niemann Pick C1-Like 1 (NPC1L1) gene. In particular, methods are provided for correlating NPC1L1 polymorphisms and haplo-types with the responsiveness of a pharmaceutically active compound administered to a human subject. The invention further relates to a method for estimating the responsiveness of a pharmaceutically active compound administered to a human subject which method comprises determining at least one polymorphism in the NPC1L1 gene. The methods are based on determining polymorphisms in the NPC1L1 gene and correlating the responsiveness of a pharmaceutically active compound in the human by reference to one or more polymorphism in NPC1L1.

Abstract: A method for fluorophore bias removal in microarray experiments in which the fluorophores used in microarray experiment pairs are reversed. Further, a method for calculating the individual errors associated with each measurement made in nominally repeated microarray experiments. This error measurement is optionally coupled with rank based methods in order to determine a probability that a cellular constituent is up or down regulated in response to a perturbation. Finally, a method for determining the confidence in the weighted average of the expression level of a cellular constituent in nominally repeated microarray experiments.

Abstract: In differential and non-differential analyses, composite images derived from replicates of liquid-chromatography/mass-spectrometry processes can provide scientists with a better signal-to-noise ratio in discovering biological features of interest. Certain distinct peaks in composite images point to distinct biological features but some distinct peaks in composite images may also point to biological features that have common chemical species ancestry. A peak reassembly process is used to indicate whether two adjacent peaks should point to a biological feature using complementation analysis and collision analysis.

Abstract: In one aspect, the present invention provides methods for amplifying a microRNA molecule to produce DNA molecules. The methods each include the steps of: (a) using primer extension to make a DNA molecule that is complementary to a target microRNA molecule; and (b) using a universal forward primer and a reverse primer to amplify the DNA molecule to produce amplified DNA molecules. In some embodiments of the method, at least one of the forward primer and the reverse primer comprise at least one locked nucleic acid molecule.

Abstract: The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.

Abstract: In one aspect, the present invention provides methods for storing a composition useful for synthesizing nucleic acid molecules. The methods of this aspect of the invention include the steps of: (a) freezing multiple aliquots of a liquid composition comprising from 1000 units/mL to 5000 units/mL of a reverse transcriptase, or from 10,000 units/mL to 50,000 units/mL of an RNA polymerase, wherein the multiple aliquots of the liquid composition are disposed within multiple receptacles defined by a container body; and (b) a step selected from the group consisting of (1) storing the frozen aliquots at a temperature below ?15° C., and (2) drying the frozen aliquots to produce dried aliquots of the composition, wherein each dried aliquot of the composition comprises an amount of water that is less than 0.1% by weight of the dried aliquot, and storing the dried aliquots at a temperature below ?15° C.

Abstract: In one aspect, the present invention provides methods for determining whether a gene mediates the response of a living cell to an agent. In another aspect, the present invention provides methods to identify a mammalian subject responsive to a KSP inhibitor.

Abstract: In one aspect the present invention provides methods of synthesizing a preparation of nucleic acid molecules, the methods comprising the steps of: (a) utilizing an RNA template to enzymatically synthesize a first DNA molecule that is complementary to at least 50 contiguous bases of the RNA template; (b) utilizing the first DNA molecule as a template to enzymatically synthesize a second DNA molecule, thereby forming a double-stranded DNA molecule wherein the first DNA molecule is hybridized to the second DNA molecule; (c) utilizing the first or second DNA molecule of the double-stranded DNA molecule as a template to enzymatically synthesize a first RNA molecule that is complementary to either the first DNA molecule or to the second DNA molecule; and (d) utilizing the first RNA molecule as a template to enzymatically synthesize a third DNA molecule that is complementary to the first RNA molecule.

Abstract: The present invention provides methods for analyzing measurement errors in measured signals obtained in an experiment, e.g., measured intensity signals obtained in a microarray gene expression experiment. In particular, the invention provides a method for transforming measured signals into a domain in which the measurement errors in the transformed signals are normalized by errors as determined from an error model. The methods of the invention are particularly useful for analyzing measurement errors in signals in which at least portion of the error is dependent on the magnitudes of the signals. Such transformed signals permit analysis of data using traditional statistical methods, e.g., ANOVA and regression analysis. Magnitude-independent errors can also be used for comparing level of measurement errors in signals of different magnitudes.

Abstract: The present invention provides prognostic methods for conditions such as cancer, for example, breast cancer, comprising classifying an individual by a plurality of phenotypic, genotypic or clinical characteristics of the condition into a plurality of patient subsets, and analyzing the pattern of expression of prognosis-informative genes identified for that subset in a sample from the individual. The present invention also provides methods for constructing such patient subsets and of identifying prognosis-informative genesets for such subsets. The invention further provides methods of assigning a therapeutic regimen to an individual, microarrays useful for performing prognosis, kits comprising these microarrays, and computer systems and programs for implementing the methods of the invention.

Abstract: The present invention provides methods for selectively amplifying a target population of nucleic acid molecules (e.g., all mRNA molecules expressed in a cell type except for the most highly expressed mRNA species). The present invention also provides populations of oligonucleotides including the nucleic acid sequences set forth in SEQ ID NOS:1-933. These oligonucleotides can be used, for example, to prime the synthesis of cDNA molecules complementary to mRNA molecules isolated from mammalian blood without priming the synthesis of cDNA molecules complementary to globin mRNA, or ribosomal RNA molecules.

Abstract: The present invention provides methods for purifying nucleic acid molecules, wherein each method includes the steps of: (a) synthesizing nucleic acid molecules in a reaction mixture; (b) contacting the nucleic acid molecules with a proteinase for a period of time sufficient to degrade protein in the reaction mixture; (c) applying the nucleic acid molecules treated in accordance with step (b) to a size-limiting filter so that at least some of the nucleic acid molecules are trapped on the filter; and (d) washing the filter with a phosphate buffer having a pH in the range of from about 5.7 to about 8.5.