Agilent Technologies, Inc.

Zohar H Yakhini

Nicholas Michael Sampas

Paul K Wolber

Glenda Choate Delenstarr

Cynthia Y Enderwick

Joel Myerson

Jeffrey Robert Sampson

Amir Ben-Dor

Peter G Webb

Anna M Tsalenko

Bo U Curry

Daniel H Lange

Herbert F Cattell

Robert Lloyd Kincaid

Leslie Anne Leonard

Paul S Meltzer

Edward R Dougherty

Yidong Chen

Scott D Connell

Michael L Bittner

Ron Shamir

Ashani Weeraratna

Peter Tsang

Yuan Jiang

Doron Lipson

Nick Sampas

Jeff Trent

Systems and methods for displaying gene- and/or protein-related data with respect to chromosome maps at locations identifying relevant positioning of the genes with which the gene- and/or protein related data are associated. Multiple experiments may be plotted onto the display adjacent one or more chromosome maps. Automatic extraction of genomic location, based on accession numbers or other unique identifiers and cross connection with expression data is provided. Statistical assessments of correlations between expression and genome localization may be performed. Zooming capabilities, thumbnail/fullview toggling, browsability and linked data may be included as features of the visualization systems described.

Visualizing expression data on chromosomal graphic schemes

Methods and systems for identifying and selecting nucleic acid probes for detecting a target with a nucleic acid probe array or comparative genome hybridization microarray, comprising selecting a plurality of potential target sequences, generating a plurality of candidate probes from the target sequences, filtering the plurality of candidate probes by analyzing candidate probes for selected probe properties in silico. Microarrays comprising probes selected by the methods of the invention are particularly useful for comparative genome hybridization and location analysis.

Probe design methods and microarrays for comparative genomic hybridization and location analysis

Methods and reagents are disclosed which provide for more sensitive, more accurate and higher through-put analyses of target nucleic acid sequences. The methods and reagents of the present invention may be generically applied to generally any target nucleic acid sequence and do not require a priori information about the presence, location or identity of mutations in the target nucleic acid sequence. The reagents of the invention are mixtures of oligonucleotide precursors having a high level of coverage and mass number complexity, and also having tags analyzable by mass spectrometry which are covalently linked to the precursors through cleavable bonds. A method is also disclosed for analyzing a target nucleic acid sequence employing the mixtures of oligonucleotide precursors having tags analyzable by mass spectrometry covalently linked to the oligonucleotide precursors through cleavable bonds, and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis. The enzymatic assay may be a polymerase extension assay or a ligation-based assay. The kits for carrying out the methods of the invention are also disclosed.

Method and reagents for analyzing the nucleotide sequence of nucleic acids

The present invention provides a system and methods for assaying nucleic acid molecules with reduced levels of background signal and enhanced specificity and sensitivity. In particular, the present invention provides a system and methods for detecting, sorting, tracking and characterizing nucleic acid molecules using hybridization assays with reduced levels of undesirable cross hybridization and reduced levels of intramolecular secondary structure.

Use of unstructured nucleic acids in assaying nucleic acid molecules

A method for evaluating an orientation of a molecular array having features arranged in a pattern. An image of the molecular array is obtained by scanning the molecular array to determine data signals emanating from discrete positions on a surface of the molecular array. An actual result of a function on pixels of the image which pixels lie in a second pattern, is calculated. This actual result is compared with an expected result which would be obtained if the second pattern had a predetermined orientation on the array. Array orientation can then be evaluated based on the result.

Method and system for extracting data from surface array deposited features

The overexpression of certain marker genes including Wnt5a has been found useful in the identification of more aggressive forms of malignant melanoma. Therefore, the overexpression of these genes in tumor samples of malignant melanoma may be useful in the diagnosis, profiling, and treatment of patients suffering from this disease. Inhibitors of Wnt5a activity may be useful in the treatment of aggressive forms of malignant melanoma. Inhibition of Wnt5a activity may be effected by any method including anti-sense therapy, gene therapy, and pharmaceutical intervention.

Classifying cancers

A method and system for extracting data signals from a scanned image resulting from optical, radiometric, or other types of analysis of a molecular array. The positions of corner features are first located. Then, an initial feature coordinate grid is determined from the positions of the corner features. A refined feature coordinate grid is then calculated based on the positions of strong features, and is used to identify the positions of weak features and the positions of the local background regions surrounding all features. Finally, signal intensity values are extracted from the features and their respective local background regions in the scanned image, and background-subtracted signal intensity values, background-subtracted and normalized signal intensity ratios, and variability information and confidence intervals are determined based on the extracted values.

A method and system for applying arbitrary similarity metrics to data entities in order to partition the entities into subsets of related entities. The method and system iteratively construct successive subsets, during construction of each subset adding candidate entities, not yet assigned to a subset, with high affinities toward the subset and removing entities previously assigned to the subset for which the affinities toward the subset have decreased. The method and system efficiently partition data with a high probability of finding an optimal or near-optimal partitioning.

Method and system for partitioning data into subsets of related data

A computational method and system for predicting the hybridization potential for two polymers. A probe/target interaction matrix is prepared to contain indications of all possible probe/target subunit interaction stabilities. The probe/target interaction matrix is analyzed to create a list of possible single-fragment hybridizations. A graph is then generated with vertices representing fragments, and edges representing possible loops in one or both of the probe and target sequences that allow the pair of fragments interconnected by the edge to coexist within a multi-fragment cross-hybridization. Finally, the graph is analyzed to construct a list of all possible single-fragment and multi-fragment cross-hybridizations possible between the probe molecule and the target molecule. The different hybridizations are scored and sorted by score.

Computational method and system for predicting fragmented hybridization and for identifying potential cross-hybridization

Methods and reagents are disclosed which satisfy the need for more sensitive, more accurate and higher through-put analyses of target nucleic acid sequences. The methods and reagents may be generically applied to generally any target nucleic acid sequence and do not require a priori information about the presence, location or identity of mutations in the target nucleic acid sequence. The reagents of the invention are mixtures of natural and mass-modified oligonucleotide precursors having a high level of coverage and mass number complexity. A method is also disclosed for analyzing a target nucleic acid sequence employing the mixtures of natural and mass-modified oligonucleotide precursors and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis, generally via MALDI-TOF. The enzymatic assay may be a polymerase extension assay or a ligase assay. The kits for carrying out the methods of the invention are also disclosed.

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Ya'acov, Israel

Zohar H Yakhini