Abstract: Methods, biomarkers, and expression signatures are disclosed for assessing the regulation status of Wnt/?-catenin signaling pathway in a cell sample or subject. More specifically, several aspects of the invention provide a set of genes which can be used as biomarkers and gene signatures for evaluating Wnt/?-catenin pathway deregulation status in a sample; classifying a cell sample as having a deregulated or regulated Wnt/?-catenin signaling pathway; determining whether an agent modulates the Wnt/?-catenin signaling pathway in sample; predicting response of a subject to an agent that modulates the Wnt/?-catenin signaling pathway; assigning treatment to a subject; and evaluating the pharmacodynamic effects of therapies designed to regulate Wnt/?-catenin pathway signaling.

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: The present invention relates to sets of genetic markers whose expression is correlated with prognosis of breast cancer in individuals having breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate individuals having a good prognosis, e.g., no reoccurrence or metastasis within five years of initial diagnosis, and individuals having a poor prognosis, e.g., reoccurrence or metastasis within five years of initial diagnosis. The invention relates to methods of prognosis using these markers. The invention also relates to microarrays containing probes to these markers, and to kits containing ready-to-use microarrays and computer software for data analysis using the prognostic and statistical methods disclosed herein.

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: 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: 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 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: 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 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 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 provides methods of classifying and treating patients based on prognosis. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the diagnostic, prognostic and statistical methods disclosed herein.

Abstract: The present invention provides methods and computer programs for detecting variations in measurements of a biological variable, e.g., variations in cell viability, under different conditions, e.g., with or without treatment of a drug, under the treatments of different drugs, or under different environmental conditions. The methods and programs of the invention determine a metric of difference between measurements under different condition, and make use of predetermined errors of the measurements, e.g., errors determined from an error model, to estimate the errors in the metric of difference. Such an approach provides a more accurate estimate of the errors of measurements, which, in turn, provides a more accurate estimate of the error of the difference metric.

Abstract: The present invention relates to genetic markers whose expression is correlated with progression of CML. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate chronic phase individuals from those in blast crisis. 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 of determining whether an agent is more like a partial agonist of a target molecule than a full agonist of the same target molecule. In another aspect, the present invention provides methods to select a candidate compound that may reduce blood plasma glucose concentration in a mammal. Populations of genes are provided that are useful in the practice of the present invention.

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: 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: The invention provides methods for characterizing the condition or status of a tissue or organ in a multicellular organism, e.g., an animal, by combining a plurality of clinical measures are combined into a composite clinical score (CCS) and using such a CCS to represent the condition or status of the tissue or organ. The invention provides methods for predicting the condition or status of a tissue or organ in a multicellular organism, e.g., an animal, based on measurements of a set of cellular constituent markers, e.g., measured expression levels of a set of marker genes. The invention also provides methods for selecting the set of marker genes whose expression levels can be used in determining the CCS.

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 one aspect, the present invention provides methods for determining whether an agent (e.g., candidate drug) possesses a biological activity. In another aspect, the present invention provides populations of nucleic acid molecules useful in the practice of the present invention as probes for measuring the level of expression of populations of genes.

Abstract: The present invention provides methods for utilizing the changes of hybridization levels in time during approach to equilibrium duplex formation for identifying specific hybridization to polynucleotide probes. In the invention, the changes of hybridization levels at one or more polynucleotide probes by a sample comprising a plurality of nucleic acid molecules having different sequences are monitored during their progress towards equilibrium and the continuing increase of hybridization signals beyond cross-hybridization is used as an indication of specific binding. The invention also provides methods of comparing specificities of different polynucleotides probes. The invention further provides methods for ranking and selecting polynucleotide probes that are specific to particular nucleic acids and methods for enhancing the detection of nucleic acids. The invention further provides methods for determining the orientation of nucleotide sequences.

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 provides methods of classifying and treating patients based on prognosis. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the diagnostic, prognostic and statistical methods disclosed herein.