Affymetrix Patent Grants

Multiplex targeted amplification using flap nuclease

Granted: November 21, 2023
Patent Number: 11821030
Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5? or 3? flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are…

Methods for identifying DNA copy number changes using hidden markov model based estimations

Granted: May 23, 2023
Patent Number: 11657900
Methods for estimating genomic copy number and loss of heterozygosity using Hidden Markov Model based estimation are disclosed.

Array-based methods for analysing mixed samples using differently labelled allele-specific probes

Granted: March 14, 2023
Patent Number: 11603557
This disclosure provides methods and systems useful in array-based analysis of mixed nucleic acid populations, including for multiplex genotyping of a mixed nucleic acid sample and for detecting differences in copy number of a target polynucleotide and/or a target chromosome (e.g., microdeletions, duplications and aneuploidies). The disclosure also provides methods and systems useful in the diagnosis of genetic abnormalities in a mixed nucleic acid population taken non-invasively from an…

Viterbi decoder for microarray signal processing

Granted: February 28, 2023
Patent Number: 11594300
A system and method for region-based calling utilizes a probability distribution of a phi-transformed logarithmic ratio to determine a set of possible transition paths through markers and marker states, constructs a local evidence matrix for each of the markers and generates a total per-marker value for each segment in a discrete region.

Enzymatic methods for genotyping on arrays

Granted: February 7, 2023
Patent Number: 11572582
The invention relates to methods for enzymatic, genotyping of polymorphisms on solid supports. In some aspects, the methods include ligation of allele or base specific 5? interrogation probes to an array probe. The array probe is labeled by ligation of the interrogation probe. Ligation is dependent on the identity of the base immediately adjacent to the end of the array probe. In other aspects array bound probes are labeled by template dependent extension.

Methods for genotyping

Granted: April 19, 2022
Patent Number: 11306351
The present invention provides for methods for discriminating between alleles at polymorphic positions in a genome. In general, the methods employ allele-specific extension of oligonucleotides that are complementary to one of the alleles at the 3? end of the oligonucleotide. The allele-specific oligonucleotides are resistant to proofreading activity from a polymerase and may be extended in an allele-specific manner by a DNA polymerase with a functional 3? to 5? exonuclease activity. The…

Systems and methods for SNP characterization and identifying off target variants

Granted: April 12, 2022
Patent Number: 11302417
Methods for processing data using information gained from examining biological materials identifies and characterized probes for Single Nucleotide Polymorphisms and identifies Off Target Variants.

Multiplex amplification methods

Granted: March 1, 2022
Patent Number: 11261485
Compositions and methods for amplifying selected polynucleotides, including DNA and RNA, particularly in multiplex amplification reactions using common primers amplification. Generally, methods of the invention employ multiple steps such as template-specific hybridization, a linear amplification, partial degradation of nucleic acid, and ligation. At the end of the process the sequences of selected polynucleotides are flanked by the common sequences which can be used for exponential…

Nucleic acid analysis by joining barcoded polynucleotide probes

Granted: September 14, 2021
Patent Number: 11118216
Disclosed are compositions, methods and kits for determining the presence, absence, amount, copy number, or other characteristics of one or more polynucleotide sequences in two or more samples and use thereof in genotyping, evaluation of copy number variation, expression analysis, determination of splice variants and fusion genes, and other genetic analyses.

Methods, systems and apparatuses for testing and calibrating fluorescent scanners

Granted: May 18, 2021
Patent Number: 11009462
Disclosed are calibration apparatuses for fluorescent microscopy instruments and methods of making and using them. Specifically, disclosed are calibration apparatuses with a fluorescent layer, such as photoresist, deposited on a substrate, with an optional layer of a reflective material, such as chrome. Illumination of the fluorescent and/or reflective layers, and detection and analysis of the resulting emissions allows evaluation of the instrument with respect to both reflective and…

Methods and devices for reading microarrays

Granted: April 13, 2021
Patent Number: 10977478
In one embodiment of the invention, a method to image a probe array is described that includes focusing on a plurality of fiducials on a surface of an array. The method utilizes obtaining the best z position of the fiducials and using a surface fitting algorithm to produce a surface fit profile. One or more surface non-flatness parameters can be adjusted to improve the flatness image of the array surface to be imaged.

Amplification and analysis of selected targets on solid supports

Granted: February 16, 2021
Patent Number: 10920269
Methods are provided for multiplexed amplification of selected targets and analysis of the amplified targets. In preferred aspects the amplification and analysis take place on the same solid support and preferably in a localized area such as a bead or a feature of an array. Targets are circularized by hybridization to probes followed by ligation of the ends of the target to form a closed circle. The targets are then used as template for extension of an array bound probe resulting in…

Differential filtering of genetic data

Granted: December 22, 2020
Patent Number: 10872681
Computer software products, methods, and systems are described which provide functionality to a user conducting experiments designed to detect and/or identify genetic sequences and other characteristics of a genetic sample, such as, for instance, gene copy number and aberrations thereof. The presently described software allows the user to interact with a graphical user interface which depicts the genetic information obtained from the experiment. The presently disclosed methods and…

System, method, and computer software product for genotype determination using probe array data

Granted: November 10, 2020
Patent Number: 10832796
An embodiment of a method of analyzing data from processed images of biological probe arrays is described that comprises receiving a plurality of files comprising a plurality of intensity values associated with a probe on a biological probe array; normalizing the intensity values in each of the data files; determining an initial assignment for a plurality of genotypes using one or more of the intensity values from each file for each assignment; estimating a distribution of cluster…

Analysis of methylation using nucleic acid arrays

Granted: November 3, 2020
Patent Number: 10822659
Arrays for genome-wide analysis of methylation are disclosed. In a preferred aspect arrays comprising a plurality of probes complementary to a plurality of identified CpG islands in the human, mouse and rat genome are disclosed. The arrays may be used to detect methylation within CpG islands in samples from human, mouse and rat genomes.

Multiplex targeted amplification using flap nuclease

Granted: November 3, 2020
Patent Number: 10822649
Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5? or 3? flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are…

Methods of analysis of methylation

Granted: November 3, 2020
Patent Number: 10822642
Methods for determining the methylation status of a plurality of cytosines are disclosed. In some aspects genomic DNA target sequences containing CpGs are targeted for analysis by multiplex amplification using target specific probes that can be specifically degraded prior to amplification. The targets may be modified with bisulfite prior to amplification. In another aspect targets are cut with methylation sensitive or insensitive restriction enzymes and marked with a tag using the target…

Methods of determining the presence or absence of a plurality of target polynucleotides in a sample

Granted: May 12, 2020
Patent Number: 10648030
The disclosure provides a method of determining the presence or absence of a plurality of target polynucleotides in a sample including combining a sample that may comprise one or more of the plurality of target polynucleotides with a plurality of sets of complementary polynucleotides; incubating the polynucleotides under conditions that allow hybridization of complementary sequences; joining the first and second complementary polynucleotides to form one or more product polynucleotides;…

DNA ligation on RNA template

Granted: May 12, 2020
Patent Number: 10648021
Disclosed are methods and compositions for detection and amplification of nucleic acids, wherein two DNA strands hybridized to an RNA strand are ligated. In one aspect, the disclosed methods include removal of an energy source, such as ATP, upon charging a ligase to form an enzyme-AMP intermediate, and then adding substrate, which results in one complete round of RNA-templated DNA ligation. In another aspect, the ligation reaction is accomplished by use of a mixture of at least two…

Methods and devices for reading microarrays

Granted: March 10, 2020
Patent Number: 10586095
In one embodiment of the invention, a method to image a probe array is described that includes focusing on a plurality of fiducials on a surface of an array. The method utilizes obtaining the best z position of the fiducials and using a surface fitting algorithm to produce a surface fit profile. One or more surface non-flatness parameters can be adjusted to improve the flatness image of the array surface to be imaged.