Analysis of methylation using nucleic acid arrays
Granted: November 28, 2017
Patent Number:
9828640
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 amplification methods
Granted: November 14, 2017
Patent Number:
9816134
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…
Differential filtering of genetic data
Granted: October 24, 2017
Patent Number:
9798855
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…
Methods and devices for reading microarrays
Granted: September 19, 2017
Patent Number:
9767342
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.
System, method, and computer software product for genotype determination using probe array data
Granted: September 12, 2017
Patent Number:
9760675
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…
Circulating miRNA biomaker signatures
Granted: July 18, 2017
Patent Number:
9708643
Methods for diagnosis and surveillance of complex multi-factorial disorders such as cancer by screening of easily accessible biomarkers are disclosed. Highly stable cell free Circulating Nucleic Acids (CNA) present as both RNA and DNA species have been discovered in the blood and plasma of humans. Correlations between tumor-associated genomic/epigenetic/transcriptional changes and alterations in CNA levels are strong predictors of the utility of this biomarker class as clinical…
Assays for affinity profiling of nucleic acid binding proteins
Granted: June 27, 2017
Patent Number:
9689867
Methods, compositions and kits are disclosed for assays to determine the binding affinity of DNA-binding proteins or RNA-binding proteins for their corresponding recognition site(s). In particular, assays are disclosed for measuring binding affinities when either the binding protein, or the recognition sequence of the recognition site, or cofactor proteins, contain one or more mutations. The disclosed assays can thus be utilized to measure the effect on transcription factor binding…
Multiplex capture of nucleic acids
Granted: May 30, 2017
Patent Number:
9663822
Methods of capturing two or more nucleic acids simultaneously from a single sample are provided. Different nucleic acids are captured through cooperative hybridization events on different subsets of particles or at different selected positions on a spatially addressable solid support. Methods of capturing one or more long nucleic acids and methods of capturing one or more nucleic acid for sequencing are also provided. Compositions, kits, and systems related to the methods are also…
Methods, systems and apparatuses for testing and calibrating fluorescent scanners
Granted: March 21, 2017
Patent Number:
9599561
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…
Silane mixtures
Granted: January 31, 2017
Patent Number:
9556360
Silanation compositions containing a mixture of two or more silanation reagents, where at least one silanation reagent includes a functional group capable of supporting polymer synthesis and at least one silanation reagent includes no functional group capable of supporting polymer synthesis are useful in modulating the active site density and hydrolytic stability of a surface. These compositions are particularly useful in silanating a surface prior to preparation of a polymer array and…
Multiplex targeted amplification using flap nuclease
Granted: December 27, 2016
Patent Number:
9528148
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…
Multiplex targeted amplification using flap nuclease
Granted: December 20, 2016
Patent Number:
9523122
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…
System, method, and product for imaging probe arrays with small feature sizes
Granted: September 13, 2016
Patent Number:
9445025
An embodiment of a method for resolving features on a probe array is described that, comprises acquiring a plurality of micro-shifted images of a region of a probe array; reconstructing an image of the probe array using the micro-shifted images; and deriving intensity values for one or more probe features disposed on the probe array from the reconstructed image.
Methods for genotyping selected polymorphism
Granted: July 12, 2016
Patent Number:
9388461
Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some…
Complexity management of genomic DNA
Granted: July 12, 2016
Patent Number:
9388460
The presently claimed invention provides for novel methods and kits for reducing the complexity of a nucleic acid sample by providing non-gel based methods for amplification of a subset of the sequences in a sample. In a preferred embodiment, amplification of a subset can be accomplished by digesting a sample with two or more restriction enzymes and ligating adaptors to the fragments so that only a subset of the fragments can be amplified. The invention further provides for analysis of…
Methods for genotyping
Granted: July 12, 2016
Patent Number:
9388459
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 proof reading 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…
Locus specific amplification using array probes
Granted: July 12, 2016
Patent Number:
9388457
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. In preferred aspects the analysis is a determination of sequence at one or more locations in the amplified target. The methods may be used for genotyping, sequencing and analysis of copy number.
Methods for synthesizing pools of probes
Granted: June 7, 2016
Patent Number:
9359640
Compositions, methods and kits are disclosed for synthesizing and amplifying pools of probes using precursor oligonucleotides. In some aspects the precursor is amplified and nicking enzymes are used to separate the full length probes from the amplification products. The methods enable the preparation of single stranded DNA probes of defined sequence and length that are suitable for use in target detection assays.
Method for detecting transcription factor-protein interactions
Granted: May 10, 2016
Patent Number:
9334537
A method is provided for identifying complexes between a transcription factor and another protein, the method comprising: isolating from a biological sample transcription factor complexes based on whether the transcription factor complexes comprise a particular type of transcription factor; and identifying which of a plurality of different proteins are present in the isolated transcription factor complexes.
Manufacturing and processing polymer arrays
Granted: March 22, 2016
Patent Number:
9290798
The invention provides methods to process multiple microarrays by providing a microarray plate and processing plates. In an embodiment of the invention, methods for assembling microarray plates by using wafers are described for high throughput microarray processing.
