Systems and methods for probe design to detect the presence of simple and complex indels
Granted: January 14, 2020
Patent Number:
10535420
Methods and systems for the determination of a collection of relevant single nucleotide polymorphisms (SNP) probe compatible insertion/deletion probes across a genome to determine probes that can detect a variety of insertions and deletions.
Analysis of data obtained from microarrays
Granted: December 24, 2019
Patent Number:
10515447
Disclosed are methods and software for biological data analysis. Specifically, provided are methods, computer programs and systems for analyzing data in the form of various intensity measurements obtained from an oligonucleotides microarray experiment. Such data may be microarray data obtained from an experiment conducted to determine copy number of a human genetic sample. The data are corrected by application of one or more covariate adjusters which may be applied simultaneously and…
Methods, systems and apparatuses for testing and calibrating fluorescent scanners
Granted: September 24, 2019
Patent Number:
10422750
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 of analysis of methylation
Granted: September 10, 2019
Patent Number:
10407717
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…
Locus specific amplification using array probes
Granted: June 25, 2019
Patent Number:
10329600
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.
Polyfluoreno[4,5-cde]oxepine conjugates and their use in methods of analyte detection
Granted: June 11, 2019
Patent Number:
10316136
The invention provides for polyfluoreno[4,5-cde]oxepine conjugates and their use in methods of analyte detection.
Methods and devices for reading microarrays
Granted: May 28, 2019
Patent Number:
10303922
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.
Methods and computer software for detecting splice variants
Granted: April 30, 2019
Patent Number:
10275568
Methods and software products for analysis of alternative splicing are disclosed. In general the methods involve normalizing probe set or exon intensity to an expression level measurement of the gene. The methods may be used to identify tissue-specific alternative splicing events.
Methods for identifying DNA copy number changes using hidden markov model based estimations
Granted: March 12, 2019
Patent Number:
10229244
Methods for estimating genomic copy number and loss of heterozygosity using Hidden Markov Model based estimation are disclosed.
Silane mixtures
Granted: February 26, 2019
Patent Number:
10213762
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…
Methods for genotyping selected polymorphism
Granted: December 18, 2018
Patent Number:
10155976
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…
Multiplex targeted amplification using flap nuclease
Granted: November 6, 2018
Patent Number:
10119162
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
Granted: October 23, 2018
Patent Number:
10108777
Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to…
Methods and devices for reading microarrays
Granted: July 10, 2018
Patent Number:
10019620
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: May 29, 2018
Patent Number:
9982293
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…
Methods, systems and apparatuses for testing and calibrating fluorescent scanners
Granted: April 3, 2018
Patent Number:
9933365
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…
Array-based translocation and rearrangement assays
Granted: April 3, 2018
Patent Number:
9932636
Methods for detecting genomic rearrangements are provided. In one embodiment, methods are provided for the use of paired end tags from restriction fragments to detect genomic rearrangements. Sequences from the ends of the fragments are brought together to form ditags and the ditags are detected. Combinations of ditags are detected by an on-chip sequencing strategy that is described herein, using inosine for de novo sequencing of short segments of DNA. In another aspect, translocations…
Polyfluoreno[4,5-cde]oxepine polymers and conjugates thereof
Granted: February 20, 2018
Patent Number:
9896538
The invention provides for polyfluoreno[4,5-cde]oxepine conjugates and their use in methods of analyte detection.
Complexity management of genomic DNA
Granted: December 19, 2017
Patent Number:
9845490
The presently claimed invention provides for novel methods and kits for analyzing a collection of target sequences in a nucleic acid sample. A sample is amplified under conditions that enrich for a subset of fragments that includes a collection of target sequences. The invention further provides for analysis of the above sample by hybridization to an array, which may be specifically designed to interrogate the collection of target sequences for particular characteristics, such as, for…
Enzymatic methods for genotyping on arrays
Granted: December 19, 2017
Patent Number:
9845494
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 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.
