Affymetrix, Inc.

Glaxo Group Limited

Other

Affymetric, Inc.

Robert J Lipshutz

Mark S Chee

Stephen P A Fodor

Ronald J Sapolsky

Thomas R Gingeras

Xiaohua C Huang

Earl A Hubbell

Richard P Rava

Maureen T Cronin

Edward L Sheldon

Peter E Lobban

MacDonald S Morris

Rolfe C Anderson

Stephen P Fodor

Charles Garrett Miyada

Michael Graham Walker

Ghassan Ghandour

Macdonald S Morris

David J Lockhart

Willem P Stemmer

Shoulian Dong

Martin J Goldberg

James L Winkler

Keith W Jones

Michael H Shapero

August Estabrook

Luis Jevons

Willem Pc Stemmer

Derek H Bernhart

Chunwei Wang

Nila Shah

Kaliyur Narasimhan

Bellon Laurent

Xiaohua X Huang

Lawrence Greenfield

John Efcavitch

A method, device and system for hybridizing a target oligonucleotide to at least one array comprising a plurality of mixing beads are provided. A target solution is mixed by agitating the mixing beads while the target oligonucleotides are hybridizing to the complementary probes on the array. In another embodiment, a permeable barrier contains the mixing beads, thereby preventing them from contacting the array surface.

Hybridization device, methods, and system using mixing beads

The present invention generally provides a rapid efficient method for analyzing polymorphic or biallelic markers, and arrays for carrying out these analyses. In general, the methods of the present invention employ arrays of oligonucleotide probes that are complementary to target nucleic acids which correspond to the marker sequences of an individual. The probes are typically arranged in detection blocks, each block being capable of discriminating the three genotypes for a given marker, i.e., the heterozygote or either of the two homozygotes. The method allows for rapid, automatable analysis of genetic linkage to even complex polygenic traits.

Polymorphism detection

The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the 'capturing' and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Capturing sequences adjacent to type-IIs restriction sites for genomic library mapping

The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the biotransformation genes, such as cytochromes P450. For example, one such array comprises four probe sets. A first probe set comprises a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a reference sequence from a biotransformation gene, the segment including at least one interrogation position complementary to a corresponding nucleotide in the reference sequence. Second, third and fourth probe sets each comprise a corresponding probe for each probe in the first probe set. The probes in the second, third and fourth probe sets are identical to a sequence comprising the corresponding probe from the first probe set or a subsequence of at least three nucleotides thereof that includes the at least one interrogation position, except that the at least one interrogation position is occupied by a different nucleotide in each of the four corresponding probes from the four probe sets.

Arrays of nucleic acid probes for analyzing biotransformation genes

Capturing sequences adjacent to type-IIS restriction sites for genomic library mapping

The invention provides methods of comparing a target nucleic acid with a reference nucleic acid using nucleic acid arrays.

Method of comparing a target nucleic acid and a reference nucleic acid

The present invention provides for novel methods of sample preparation and analysis involving reproducibly reducing the complexity of a nucleic sample. The invention further provides for analysis of the above sample by hybridization to an array which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism. The invention further provides for novel methods of using a computer system to model enzymatic reactions in order to determine experimental conditions before conducting actual experiments.

Complexity management and analysis of genomic DNA

The invention provides chips of immobilized probes, and methods employing the chips, for comparing a reference polynucleotide sequence of known sequence with a target sequence showing substantial similarity with the reference sequence, but differing in the presence of e.g., mutations.

Arrays of nucleic acid probes on biological chips

A computer system for analyzing nucleic acid sequences is provided. The computer system is used to calculate probabilities for determining unknown bases by analyzing the fluorescence intensities of hybridized nucleic acid probes on biological chips. Additionally, information from multiple experiments is utilized to improve the accuracy of calling unknown bases.

Computer-aided probability base calling for arrays of nucleic acid probes on chips

The present invention generally provides a rapid efficient method for analyzing polymorphic or biallelic markers, and arrays for carrying out these analyses. In general, the methods of the present invention employ arrays of oligonucleotide probes that are complementary to target nucleic acids which correspond to the marker sequences of an individual. The probes are typically arranged in detection blocks, each block being capable of discriminating the three genotypes for a given marker, e.g., the heterozygote or either of the two homozygotes. The method allows for rapid, automatable analysis of genetic linkage to even complex polygenic traits.

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Identifying a base in a nucleic acid

The present invention provides a miniaturized integrated nucleic acid diagnostic device and system. The or more sample acquisition and preparation operations, in combination with one or more sample analysis operations. For example, the device can integrate several or all of the operations involved in sample acquisition and storage, sample preparation and sample analysis, within a single integrated unit. The device is useful in a variety of applications, and most notably, nucleic acid based diagnostic applications and de novo sequencing applications.

Integrated nucleic acid diagnostic device

This invention provides nucleic acid affinity matrices that bear a large number of different nucleic acid affinity ligands allowing the simultaneous selection and removal of a large number of preselected nucleic acids from the sample. Methods of producing such affinity matrices are also provided. In general the methods involve the steps of a) providing a nucleic acid amplification template array comprising a surface to which are attached at least 50 oligonucleotides having different nucleic acid sequences, and wherein each different oligonucleotide is localized in a predetermined region of said surface, the density of said oligonucleotides is greater than about 60 different oligonucleotides per 1 cm , and all of said different oligonucleotides have an identical terminal 3&prime; nucleic acid sequence and an identical terminal 5&prime; nucleic acid sequence. b) amplifying said multiplicity of oligonucleotides to provide a pool of amplified nucleic acids; and c) attaching the pool of nucleic acids to a solid support.

Nucleic acid affinity columns

A computer system for analyzing nucleic acid sequences is provided. The computer system is used to perform multiple methods for determining unknown bases by analyzing the fluorescence intensities of hybridized nucleic acid probes. The results of individual experiments are improved by processing nucleic acid sequences together. Comparative analysis of multiple experiments is also provided by displaying reference sequences in one area and sample sequences in another area on a display device.

Computer-aided visualization and analysis system for sequence evaluation

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Palo Alto, CA, United States of America

Robert J Lipshutz