The present disclosure provides compositions, apparatuses and methods for detecting target analytes using amplification-free probe complexes. In some embodiments, the amplification- free probe complexes can be used for detecting analytes on a cellular sample or inside a cellular sample.
C12Q 1/6816 - Hybridisation assays characterised by the detection means
2.
METHOD FOR IMPROVING NUCLEIC ACID SEQUENCING QUALITY BY ELIMINATING NUCLEIC ACIDS WITH DEAMINATED BASES FROM LIBRARY AND METHOD FOR SEQUENCING IN WHICH COMPLEXES OF PRIMERS, POLYMERASES AND LABELLED PROBES ARE BOUND TO CONCATEMERS
The present disclosure provides methods for reducing sequencing errors comprising one or any combination of: (i) removing deaminated bases in any nucleic acid molecule throughout a library preparation workflow which includes immobilised splints which bind to the library, the use of a compaction oligonucleotide, optionally with an intervening sequence, formation of closed circular nucleic acids, creating gaps using glycosylase and lyase activities at positions with deaminated bases. The library may be sequenced using pairwise sequencing, e.g. with dark sequencing and/or sequencing using a multivalent labelled probe for the formation of an avidity molecule and soluble primer and polymerase. Method for sequencing concatemers in which the concatermers are contacted with polymerases, soluble primers and a multivalent labelled molecule which forms a complex with the polymerase. Detecting polymerase position and nucleobase bound to the polymerase in the complex. These methods generate higher quality base calls during downstream sequencing workflows.
Disclosed herein are sequencing systems and sequencing methods for training neural networks and for utilizing the trained neural networks for sequencing analysis after acquiring flow cell images using the sequencing systems. The sequencing systems disclosed herein can include Field-Programmable Gate Array (FPGAs), artificial intelligence (AI) chips, or a combination thereof.
Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.
The present disclosure provides compositions and methods that employ the compositions for conducting pairwise sequencing and for generating concatemer template molecules for pairwise sequencing. The concatemers can be generated using a rolling circle amplification reaction which is conducted either on-support, or conducted in-solution and then distributed onto a support. The rolling circle amplification reaction generates concatemers containing tandem copies of a sequence of interest and at least one universal adaptor sequence. An increase in the number of tandem copies in a given concatemer increases the number of sites along the concatemer for hybridizing to multiple sequencing primers which serve as multiple initiation sites for polymerase-catalyzed sequencing reactions. When the sequencing reaction employs detectably labeled nucleotides and/or detectably labeled multivalent molecules (e.g., having nucleotide units), the signals emitted by the nucleotides or nucleotide units that participate in the parallel sequencing reactions along the concatemer yields an increased signal intensity for each concatemer.
Aspects of the present disclosure relate to a method for predicting quality of base calling in sequencing. A plurality of predictors may be selected and a corresponding value for each of the plurality of predictors may be determined from one or more flow cell images. A quality score may be determined from a look-up table based on the corresponding value for each of the plurality of predictors, wherein the look-up table comprises a plurality of dimensions corresponding to the plurality of predictors and is generated based on a training data set.
G06V 10/98 - Detection or correction of errors, e.g. by rescanning the pattern or by human interventionEvaluation of the quality of the acquired patterns
G06F 1/03 - Digital function generators working, at least partly, by table look-up
G06V 10/70 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
7.
TARGET PROBE COMPLEXES AND ANALYTE DETECTION COMPLEXES FOR IN SITU DETECTING AND IDENTIFYING TARGET ANALYTES
The present disclosure provides compositions and methods for detecting a plurality target analytes, including nucleic acids and proteins, in a cellular sample by conducting sequencing inside the cellular sample.
Systems, methods, and computer storage media for image registration in primary analysis are provided. In some embodiments, coordinates of polonies in a reference coordinate system are determined, wherein the polonies are obtained from flow cell images in one or more reference cycles. One or more template images in the reference coordinate system are generated by registering the polonies to the one or more template images using the coordinates thereof. A flow cell image in a cycle is obtained. A plurality of transformations of the flow cell image is then determined based on the one or more template images, each of the plurality of transformations corresponding to a subtile of the flow cell image and configured to register the subtile of the flow cell image to the one or more template images.
Fluorescence imaging systems designs, flow cell devices, and methods of are described herein that enable imaging of three or more axially displaced surfaces without using any optical compensators. The optical systems and flow cell devices herein provides higher throughput analysis for genomics and other imaging applications at a lower cost.
Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the sample plane to capture a series of images (e.g., of different fields-of-view), and improved imaging system duty cycle, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications.
Provided herein are engineered variants of archaeal, prokaryotic, and eukaryotic polymerases that exhibit enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, and improved uracil-tolerance, in polymerase-catalyzed nucleotide extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases, forming binding complexes and forming ternary complexes, and uses for conducting nucleic acid sequencing reactions.
The present disclosure provides compositions comprising read-capping nucleotide analogs, and methods using the read-capping nucleotide analogs for sequencing. The read-capping nucleotide analogs can be incorporated at the terminal 3' end of a sequencing read product when sequencing a first region of a template molecule is completed to generate a first capped sequencing read product. The first capped sequencing read products are not removed from the template molecules prior to sequencing a second region of the template molecules. Removal of the first capped sequencing read product from the template molecule is obviated because the incorporated read-capping nucleotide analog blocks binding and incorporation of nucleotide reagents used to sequence a second region of the nucleic acid template molecule. Using the read-capping nucleotide analogs, without the need to remove the sequencing read products, reduces damage to the template molecules and preserves intact template molecules after numerous sequencing cycles.
Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; Diagnostic reagents for scientific or research use; diagnostic reagents for clinical or medical laboratory use; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents for laboratory use; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific use, namely, nucleic acid sequencers, imaging devices and analyzers Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices and analyzers Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
15.
REITERATIVE SHORT READ SEQUENCING INSIDE A CELLULAR SAMPLE
The present disclosure provides methods for conducting in situ multiplex and multi-omics detection and identification using coded padlocks probes. The methods comprise simultaneous use of RNA-specific padlock probes and polypeptide-specific padlock probes to detect both RNA and polypeptides in a cellular sample. Both types of probes include a barcode that unique identifies the RNA or polypeptide that that padlock probe detects. Both types of probes also include a batch-specific sequencing primer binding site to enable sequencing a desired subset of concatemer template molecules. Use of the batch-specific sequencing primers reduces overcrowding signals and images, to produces optical images that are intense and resolvable. By conducting multiple rounds of sequencing on the same cellular sample using different batch-specific sequencing primers enables multiplex and multi-omics sequencing to reveal numerous target RNAs and their encoded polypeptides.
Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
The present disclosure provides solid-state optical test targets useful for evaluating the performance of an optical imaging system. The solid-state optical test targets comprise at least a first substrate made from a flat transparent material. In some embodiments, the solid-state optical test targets further comprise an opaque coating that forms a micropattern. The first substrate is positioned in direct contact with the micropattern. The optical test targets described herein lack a flow cell and lack a liquid, and are therefore solid-state apparatus. Since the solid-state optical test targets lack a flow cell and liquid, the thickness of the first substrate is adjusted to simulate the presence of a hypothetic flow cell which could be located for example below the first substrate. The adjusted thickness of the first substrate can simulate the collective effects of the first substrate and the hypothetical flow cell containing a fluid/liquid. The disclosure also provides flow cells comprising pluralities of fluorescent beads for use as fiducials, and methods of using same in high throughput sequencing applications.
G01N 21/27 - ColourSpectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the fields-of-view, improved imaging system duty cycle and a more compact system, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications at a lower cost.
The present disclosure provides nucleotide conjugates each configured to include a core attached to multiple nucleotide-arms, where the nucleotide-arms are modular and comprise (i) a core attachment moiety, (ii) a spacer, (iii) a linker, and (iv) a nucleotide unit. The nucleotide unit of each nucleotide-arm can bind a polymerase which is complexed with a nucleic acid template and nucleic acid primer. The nucleotide unit can bind the 3′ end of the primer at a position that is opposite a complementary nucleotide in the template strand. Under suitable conditions, the nucleotide unit of the nucleotide conjugates binds the primer strand but does not undergo polymerase-catalyzed incorporation. The binding event can be detected, and the specific base of the nucleotide unit can be identified. The nucleotide conjugates described herein are useful for nucleic acid sequencing methods, particularly for massively parallel sequencing methods employed for next gen sequencing platforms.
Nucleic acid hybridization buffer formulations and uses thereof are described that yield improvements in hybridization specificity, rate, and efficiency. The buffer formulation composition includes a target nucleic acid; at least one organic solvent having a dielectric constant in the range of no greater than 115; and a pH buffer system, wherein the target nucleic acid is attached to the surface via hybridization to a surface bound nucleic acid tethered to the surface, and wherein the hybridization of the target nucleic acid and surface bound nucleic acid has a high stringency and annealing rate.
The present disclosure provides compositions and methods for generating a plurality of nucleic acid concatemers immobilized to a support by conducting on-support circularization and ligation reactions using a plurality of linear library molecules and a plurality of immobilized splint capture primers. The present disclosure provides methods for seeding and optionally re-seeding the support to increase the density of immobilized nucleic acid concatemers that can be sequenced. In some embodiments, the immobilized concatemers can be used for conducting downstream sequencing workflows including batch sequencing and reiterative sequencing workflows. The present disclosure also provides methods for interrupting an ongoing sequencing run to re-seed the support to generate additional concatemers that can be sequenced.
The present disclosure provides flow cell devices, systems, and methods for facilitating and performing DNA sequencing analysis with reduced system complexity and cost, significant cost of goods saving, and reduced contamination level. The sequencing systems described herein permit processing of multiple flow cells simultaneously, such that sequencing and imaging steps, or multiple sequencing methods, can be performed in parallel using a single sequencing system.
G01N 35/02 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
23.
HIGH PERFORMANCE FLUORESCENCE IMAGING MODULE FOR GENOMIC TESTING ASSAY
Nucleic acid hybridization buffer formulations and uses thereof are described that yield improvements in hybridization specificity, rate, and efficiency. The buffer formulation composition includes a target nucleic acid; at least one polar, aprotic, organic solvent, and a pH buffer system, wherein the target nucleic acid is attached to the surface via hybridization to a surface bound nucleic acid tethered to the surface, and wherein the hybridization of the target nucleic acid and surface bound nucleic acid has a high stringency and annealing rate.
The present disclosure provides compositions comprising enzyme-based reagents, and methods using the enzyme-based reagents, for nucleic acid sequencing. The enzyme-based reagents efficiently remove sequencing read products from a first sequenced region of a template molecule, thereby reducing residual signals in a second sequenced region on the same template molecule.
Fluorescence imaging systems designs, flow cell devices, and methods of are described herein that enable imaging of three or more axially displaced surfaces without using any optical compensators. The optical systems and flow cell devices herein provides higher throughput analysis for genomics and other imaging applications at a lower cost.
Flow cell devices, cartridges, and systems are described that provide reduced manufacturing complexity, lowered consumable costs, and flexible system throughput for nucleic acid sequencing and other chemical or biological analysis applications. The flow cell device can include a capillary flow cell device or a microfluidic flow cell device.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for clinical or medical laboratory use; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents for laboratory use; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific use, namely, nucleic acid sequencers, imaging devices and analyzers Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices and analyzers Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for clinical or medical laboratory use, other than for medical or veterinary purposes; reagents and reagent kits, other than for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents for laboratory use, other than for medical or veterinary purposes; reagent kits and reagent beads, other than for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use; diagnostic reagents for clinical or medical laboratory use, for medical or veterinary purposes; reagents and reagent kits, for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for clinical laboratory research use; clinical diagnostic reagents for laboratory use, for medical or veterinary purposes; reagent kits and reagent beads, for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific use, namely, nucleic acid sequencers, imaging devices for nucleic acids and biological molecules and analyzers in the nature of scientific laboratory research instruments for DNA analysis Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices for biomolecules and analyzers in the nature of flow-based analyzers providing cell and particle analysis, detection, or counting Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for clinical or medical laboratory use, other than for medical or veterinary purposes; reagents and reagent kits, other than for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents for laboratory use, other than for medical or veterinary purposes; reagent kits and reagent beads, other than for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of conducting high accuracy nucleic acid sequencing for medical, scientific and clinical research Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use; diagnostic reagents for clinical or medical laboratory use, for medical or veterinary purposes; reagents and reagent kits, for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for clinical laboratory research use; clinical diagnostic reagents for laboratory use, for medical or veterinary purposes; reagent kits and reagent beads, for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of conducting high accuracy nucleic acid sequencing for medical use and clinical medical use Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific use, namely, nucleic acid sequencers, imaging devices for nucleic acids and biological molecules and analyzers in the nature of scientific laboratory research instruments for DNA analysis Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices for biomolecules and analyzers in the nature of flow-based analyzers providing cell and particle analysis, detection, or counting; medical apparatus and instruments for conducting high accuracy nucleic acid sequencing Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
30.
ENGINEERED POLYMERASES WITH REDUCED SEQUENCE-SPECIFIC ERRORS
Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents, other than for medical or veterinary purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents, other than for medical or veterinary purposes; reagent beads with attached biomolecules and reagents kits comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for scientific and research use Medical diagnostic reagents; Diagnostic reagents for medical or veterinary purposes; Reagent beads with attached biomolecules and reagent kits for medical use comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents for medical use comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use Computer hardware, downloadable and recorded computer software and associated downloadable data files for computer systems for us in collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; diagnostic apparatus, not for medical purposes, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Medical diagnostic instruments for medical use, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents, other than for medical or veterinary purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents, other than for medical or veterinary purposes; reagent beads with attached biomolecules and reagents kits comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for scientific and research use Medical diagnostic reagents; Diagnostic reagents for medical or veterinary purposes; Reagent beads with attached biomolecules and reagent kits for medical use comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents for medical use comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use Computer hardware, downloadable and recorded computer software and associated downloadable data files for computer systems for us in collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; diagnostic apparatus, not for medical purposes, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Medical diagnostic instruments for medical use, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents, other than for medical or veterinary purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents, other than for medical or veterinary purposes; reagent beads with attached biomolecules and reagents kits comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for scientific and research use Medical diagnostic reagents; Diagnostic reagents for medical or veterinary purposes; Reagent beads with attached biomolecules and reagent kits for medical use comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents for medical use comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use Computer hardware, downloadable and recorded computer software and associated downloadable data files for computer systems for us in collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; diagnostic apparatus, not for medical purposes, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Medical diagnostic instruments for medical use, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
The present disclosure describes illumination methods and systems for illumination as well as methods and systems for autofocusing the systems. The systems can be used for, for example, microscopy and sequencing platforms. The methods and systems of the present disclosure can provide fast and accurate autofocusing, which can reduce error and improve system throughput.
The present disclosure describes illumination methods and systems for illumination and sequencing applications that can be utilized for, for example, microscopy and sequencing platforms. The methods and systems of the present disclosure can provide wide area, flat illumination, which can reduce error and improve system throughputs.
The present disclosure provides compositions comprising enzyme-based reagents, and methods using the enzyme-based reagents, for nucleic acid sequencing. The enzyme-based reagents efficiently remove sequencing read products from a first sequenced region of a template molecule, thereby reducing residual signals in a second sequenced region on the same template molecule.
The present disclosure provides a compound of Formula (I), (II), or (III):
The present disclosure provides a compound of Formula (I), (II), or (III):
The present disclosure provides a compound of Formula (I), (II), or (III):
an ionic derivative thereof, an isomer thereof, or a salt thereof. The present disclosure also provides conjugates of the compounds, and methods of using the compounds and the conjugates. The disclosure also provides the use of the compounds and conjugates in methods of sequencing nucleic acids.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C09B 23/06 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain containing an odd number of CH groups three CH groups, e.g. carbocyanines
C09B 23/10 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain containing an even number of CH groups
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
The present disclosure provides flow cell devices, systems, and methods for facilitating and performing DNA sequencing analysis with reduced system complexity and cost, significant COGS saving and reduced contamination level. The flow cell devices and systems can comprise: a support comprising one or more substrates; one or more channels defined by the one or more substrates and configured to allow fluids to flow therethrough; an inlet in fluidic connection with the one or more channels, the inlet comprising an open landing area in one substrate; and an outlet.
Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.
Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the fields-of-view, improved imaging system duty cycle and a more compact system, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications at a lower cost.
Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the fields-of-view, improved imaging system duty cycle and a more compact system, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications at a lower cost.
The present disclosure provides compositions comprising nucleic acid double-stranded splint adaptors, including kits, and methods that employ the double-stranded splint adaptors. The double-stranded splint adaptors (200) can be used in a one-pot, multi-enzyme reaction to introduce one or more new adaptor sequences into a library molecule. The double-stranded splint adaptor (200) comprises a first splint strand (long splint strand (300)) and a second splint strand (short splint strand (400)), where the first and second splint strands are hybridized together to form the double-stranded splint adaptor (200) having a double-stranded region and two flanking single-stranded regions. The second splint strand (400) carries the new adaptor sequence(s) to be introduced, such as for example a universal binding sequence, an index sequence and/or a random sequence.
The present disclosure provides compositions and methods that employ the compositions for conducting pairwise sequencing and for generating concatemer template molecules for pairwise sequencing. The concatemers can be generated using a rolling circle amplification reaction which is conducted either on-support, or conducted in-solution and then distributed onto a support. The rolling circle amplification reaction generates concatemers containing tandem copies of a sequence of interest and at least one universal adaptor sequence. An increase in the number of tandem copies in a given concatemer increases the number of sites along the concatemer for hybridizing to multiple sequencing primers which serve as multiple initiation sites for polymerase-catalyzed sequencing reactions. When the sequencing reaction employs detectably labeled nucleotides and/or detectably labeled multivalent molecules (e.g., having nucleotide units), the signals emitted by the nucleotides or nucleotide units that participate in the parallel sequencing reactions along the concatemer yields an increased signal intensity for each concatemer.
The present disclosure provides a compound of Formula (I), (II), or (III): an ionic derivative thereof, an isomer thereof, or a salt thereof. The present disclosure also provides conjugates of the compounds, and methods of using the compounds and the conjugates. The disclosure also provides the use of the compounds and conjugates in methods of sequencing nucleic acids.
C09B 23/08 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain containing an odd number of CH groups more than three CH groups, e.g. polycarbocyanines
C09B 23/06 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain containing an odd number of CH groups three CH groups, e.g. carbocyanines
G01N 33/533 - Production of labelled immunochemicals with fluorescent label
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
C09B 23/01 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain
45.
FLOW CELL DEVICES AND OPTICAL SYSTEMS FOR NUCLEIC ACID SEQUENCING
Fluorescence imaging systems designs, flow cell devices, and methods of are described herein that enable imaging of three or more axially displaced surfaces without using any optical compensators. The optical systems and flow cell devices herein provides higher throughput analysis for genomics and other imaging applications at a lower cost.
Described herein are systems, apparatus, methods, and/or computer program product embodiments, and/or combinations and sub-combinations thereof which enables automated determination of index sequence(s) during DNA sequencing data analysis. As a particular application of such, embodiments of methods, systems, and media for automatically determining index sequences are disclosed herein so that sequencing results from multiple samples can be sorted and separated accurately for downstream analysis, such as secondary analysis.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for clinical
or medical laboratory use, other than for medical or veterinary purposes; reagents and reagent kits, other than for medical or
veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and
buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules,
samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and
expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic
reagents for laboratory use, other than for medical or veterinary purposes; reagent kits and reagent beads, other than for medical
or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and
modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes; all of the foregoing
for use in connection with genetic, genomic and multi-omic sequencing and/or research, and none of the foregoing for use in the
fields of diabetes management, diabetes analyte testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing,
and/or ketone monitoring Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules,
comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels,
and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally
occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and
analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence
variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use;
diagnostic reagents for clinical or medical laboratory use, for medical or veterinary purposes; reagents and reagent kits, for
medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels,
and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules,
samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and
expression for clinical laboratory research use; clinical diagnostic reagents for laboratory use, for medical or veterinary purposes;
reagent kits and reagent beads, for medical or veterinary purposes, with attached biomolecules, comprised primarily of
oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for
clinical diagnostic laboratory purposes; all of the foregoing for use in connection with genetic, genomic and multi-omic sequencing
and/or research, and none of the foregoing for use in the fields of diabetes management, diabetes analyte testing, diabetes
monitoring, glucose testing, glucose monitoring, ketone testing, and/or ketone monitoring Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable
data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects,
laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic
purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for
use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific
use, namely, nucleic acid sequencers, imaging devices for nucleic acids and biological molecules and analyzers in the nature of
scientific laboratory research instruments for DNA analysis; all of the foregoing for use in connection with genetic, genomic and
multi-omic sequencing and/or research, and none of the foregoing for use in the fields of diabetes management, diabetes analyte
testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing, and/or ketone monitoring Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices for biomolecules and analyzers
in the nature of flow-based analyzers providing cell and particle analysis, detection, or counting; all of the foregoing for use in
connection with genetic, genomic and multi-omic sequencing and/or research, and none of the foregoing for use in the fields of
diabetes management, diabetes analyte testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing, and/or
ketone monitoring Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related
thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing
and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing,
analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all
the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online nondownloadable computer software for data collection, management, and analysis of genetic information for use in the fields of
diagnostic and clinical research and for clinical diagnostic purposes; all of the foregoing for use in connection with genetic,
genomic and multi-omic sequencing and/or research, and none of the foregoing for use in the fields of diabetes management,
diabetes analyte testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing, and/or ketone monitoring
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for clinical or medical laboratory use, other than for medical or veterinary purposes; reagents and reagent kits, other than for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents for laboratory use, other than for medical or veterinary purposes; reagent kits and reagent beads, other than for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use; diagnostic reagents for clinical or medical laboratory use, for medical or veterinary purposes; reagents and reagent kits, for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for clinical laboratory research use; clinical diagnostic reagents for laboratory use, for medical or veterinary purposes; reagent kits and reagent beads, for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific use, namely, nucleic acid sequencers, imaging devices for nucleic acids and biological molecules and analyzers in the nature of scientific laboratory research instruments for DNA analysis Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices for biomolecules and analyzers in the nature of flow-based analyzers providing cell and particle analysis, detection, or counting Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for clinical or medical laboratory use, other than for medical or veterinary purposes; reagents and reagent kits, other than for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic reagents for laboratory use, other than for medical or veterinary purposes; reagent kits and reagent beads, other than for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use; diagnostic reagents for clinical or medical laboratory use, for medical or veterinary purposes; reagents and reagent kits, for medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for clinical laboratory research use; clinical diagnostic reagents for laboratory use, for medical or veterinary purposes; reagent kits and reagent beads, for medical or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific use, namely, nucleic acid sequencers, imaging devices for nucleic acids and biological molecules and analyzers in the nature of scientific laboratory research instruments for DNA analysis Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices for biomolecules and analyzers in the nature of flow-based analyzers providing cell and particle analysis, detection, or counting Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online non-downloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for clinical
or medical laboratory use, other than for medical or veterinary purposes; reagents and reagent kits, other than for medical or
veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and
buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules,
samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and
expression for scientific research use, for diagnostic scientific use, and for clinical laboratory research use; clinical diagnostic
reagents for laboratory use, other than for medical or veterinary purposes; reagent kits and reagent beads, other than for medical
or veterinary purposes, with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and
modified nucleotides, polypeptides, buffers, labels, and substrates, for clinical diagnostic laboratory purposes; all of the foregoing
for use in connection with genetic, genomic and multi-omic sequencing and/or research, and none of the foregoing for use in the
fields of diabetes management, diabetes analyte testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing,
and/or ketone monitoring Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules,
comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels,
and substrates, for clinical medical diagnostic purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally
occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and
analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence
variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use;
diagnostic reagents for clinical or medical laboratory use, for medical or veterinary purposes; reagents and reagent kits, for
medical or veterinary purposes, comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels,
and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules,
samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and
expression for clinical laboratory research use; clinical diagnostic reagents for laboratory use, for medical or veterinary purposes;
reagent kits and reagent beads, for medical or veterinary purposes, with attached biomolecules, comprised primarily of
oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for
clinical diagnostic laboratory purposes; all of the foregoing for use in connection with genetic, genomic and multi-omic sequencing
and/or research, and none of the foregoing for use in the fields of diabetes management, diabetes analyte testing, diabetes
monitoring, glucose testing, glucose monitoring, ketone testing, and/or ketone monitoring Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable
data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects,
laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic
purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for
use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; clinical diagnostic instruments for scientific
use, namely, nucleic acid sequencers, imaging devices for nucleic acids and biological molecules and analyzers in the nature of
scientific laboratory research instruments for DNA analysis; all of the foregoing for use in connection with genetic, genomic and
multi-omic sequencing and/or research, and none of the foregoing for use in the fields of diabetes management, diabetes analyte
testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing, and/or ketone monitoring Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, imaging devices for biomolecules and analyzers
in the nature of flow-based analyzers providing cell and particle analysis, detection, or counting; all of the foregoing for use in
connection with genetic, genomic and multi-omic sequencing and/or research, and none of the foregoing for use in the fields of
diabetes management, diabetes analyte testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing, and/or
ketone monitoring Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related
thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing
and sequencing nucleic acids from human beings; providing online non-downloadable computer software for collecting, storing,
analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all
the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; providing online nondownloadable computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; all of the foregoing for use in connection with genetic, genomic and multi-omic sequencing and/or research, and none of the foregoing for use in the fields of diabetes management, diabetes analyte testing, diabetes monitoring, glucose testing, glucose monitoring, ketone testing, and/or ketone monitoring
51.
MULTIVALENT BINDING COMPOSITIONS WITH REACTIVE GROUPS
The present disclosure provides nucleotide conjugates each configured to include a core attached to multiple nucleotide-arms, where the nucleotide-arms are modular and comprise (i) a core attachment moiety, (ii) a spacer, (iii) a linker, and (iv) a nucleotide unit. The nucleotide unit of each nucleotide-arm can bind a polymerase which is complexed with a nucleic acid template and nucleic acid primer. The nucleotide unit can bind the 3′ end of the primer at a position that is opposite a complementary nucleotide in the template strand. Under suitable conditions, the nucleotide unit of the nucleotide conjugates binds the primer strand but does not undergo polymerase-catalyzed incorporation. The binding event can be detected, and the specific base of the nucleotide unit can be identified. The nucleotide conjugates described herein are useful for nucleic acid sequencing methods, particularly for massively parallel sequencing methods employed for next gen sequencing platforms.
Disclosed herein are system, apparatus, method, and/or computer program product embodiments, and/or combinations and sub-combinations thereof which enables 3D base calling using flow cell images of samples such as in situ cells or tissue to ensure accurate base calling and sequencing analysis of 3D samples. Embodiments of the methods, systems, and media for 3D base calling of flow cell images includes image intensity, location, size, and/or of clusters or polonies to be relied on for accurate base calling.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12N 15/62 - DNA sequences coding for fusion proteins
G06T 7/66 - Analysis of geometric attributes of image moments or centre of gravity
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G01N 15/0227 - Investigating particle size or size distribution by optical means using imagingInvestigating particle size or size distribution by optical means using holography
53.
INCREASING SEQUENCING THROUGHPUT IN NEXT GENERATION SEQUENCING OF THREE-DIMENSIONAL SAMPLES
Described herein are aspects for sequencing three-dimensional samples using flow cell images. An aspect begins by obtaining a plurality of subsets of flow cell images of a sample in a plurality of sequencing cycles from a subset of channels. The aspect then generates base calls for the sample based on the subsets of flow cell images.
G06T 7/90 - Determination of colour characteristics
G06V 10/75 - Organisation of the matching processes, e.g. simultaneous or sequential comparisons of image or video featuresCoarse-fine approaches, e.g. multi-scale approachesImage or video pattern matchingProximity measures in feature spaces using context analysisSelection of dictionaries
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
Described herein are aspects for color correction of flow cell images acquired from different channels for making accurate base calling during DNA sequencing. An aspect begins by receiving a plurality of flow cell images and determining coordinates of polonies in the flow cell images in a reference coordinate system. The image intensity of the polonies is then determined. Channel cross-talk parameters are determined based in the image intensity of the polonies. Using the channel cross-talk parameters, the processor generates color-corrected flow cell images.
The present disclosure provides compositions comprising nucleic acid double-stranded splint adaptors, including kits, and methods that employ the double-stranded splint adaptors. The double-stranded splint adaptors (200) can be used in a one-pot, multi-enzyme reaction to introduce one or more new adaptor sequences into a library molecule. The double-stranded splint adaptor (200) comprises a first splint strand (long splint strand (300)) and a second splint strand (short splint strand (400)), where the first and second splint strands are hybridized together to form the double-stranded splint adaptor (200) having a double-stranded region and two flanking single-stranded regions. The second splint strand (400) carries the new adaptor sequence(s) to be introduced, such as for example a universal binding sequence, an index sequence and/or a random sequence.
The present disclosure provides compositions and related methods, e.g., for preparing immobilized nucleic acid nanostructures using compaction oligonucleotides. In some embodiments, rolling circle amplification reaction can be conducted with compaction oligonucleotides on-support or in-solution to generate concatemer molecules having multiple copies of a polynucleotide unit arranged in tandem. Each polynucleotide unit comprises a sequence-of-interest and at least one universal adaptor sequence that binds one end of a compaction oligonucleotide. The 5′ and 3′ regions of the compaction oligonucleotide can hybridize to the concatemer to pull together distal portions of the concatemer causing compaction of the concatemer to form a nanostructure. Nanostructures having tighter size and shape compared to concatemers generated in the absence of the compaction oligonucleotides. The compact and stable characteristics of the nucleic acid nanostructures improves sequencing accuracy by increasing signal intensity and they retain their shape and size during multiple sequencing cycles.
e.g.e.g., for preparing immobilized nucleic acid nanostructures using compaction oligonucleotides. In some embodiments, rolling circle amplification reaction can be conducted with compaction oligonucleotides on-support or in-solution to generate concatemer molecules having multiple copies of a polynucleotide unit arranged in tandem. Each polynucleotide unit comprises a sequence-of-interest and at least one universal adaptor sequence that binds one end of a compaction oligonucleotide. The 5' and 3' regions of the compaction oligonucleotide can hybridize to the concatemer to pull together distal portions of the concatemer causing compaction of the concatemer to form a nanostructure. Nanostructures having tighter size and shape compared to concatemers generated in the absence of the compaction oligonucleotides. The compact and stable characteristics of the nucleic acid nanostructures improves sequencing accuracy by increasing signal intensity and they retain their shape and size during multiple sequencing cycles.
The present disclosure provides compositions, apparatuses and methods for capturing on a support nucleic acids from cellular samples, preparing library molecules on the support, amplifying the library molecules on the support to generate nucleic acid template molecules, and analyzing the immobilized nucleic acid template molecules including detecting and/or sequencing the immobilized nucleic acid template molecules. The immobilized nucleic acid template molecules correspond to the nucleic acids from the cellular samples. The immobilized nucleic acid template molecules are spatially located on the support at positions that correspond to the spatial location of the nucleic acids from the cellular sample.
The present disclosure provides compositions, apparatuses and methods for capturing on a support nucleic acids from cellular samples, preparing library molecules on the support, amplifying the library molecules on the support to generate nucleic acid template molecules, and analyzing the immobilized nucleic acid template molecules including detecting and/or sequencing the immobilized nucleic acid template molecules. The immobilized nucleic acid template molecules correspond to the nucleic acids from the cellular samples. The immobilized nucleic acid template molecules are spatially located on the support at positions that correspond to the spatial location of the nucleic acids from the cellular sample.
The present disclosure provides compositions comprising nucleic acid double-stranded splint adaptors, including kits, and methods that employ the double-stranded splint adaptors, e.g., PCR-free workflows. The double-stranded splint adaptors (200) can be used in a one-pot, multi-enzyme reaction to introduce one or more new adaptor sequences into a library molecule. The double-stranded splint adaptor (200) comprises a first splint strand (long splint strand (300)) and a second splint strand (short splint strand (400)), where the first and second splint strands are hybridized together to form the double-stranded splint adaptor (200) having a double-stranded region and two flanking single-stranded regions. The second splint strand (400) carries the new adaptor sequence(s) to be introduced, such as for example a universal binding sequence and/or an index sequence.
The present disclosure provides compositions comprising nucleic acid double-stranded splint adaptors, including kits, and methods that employ the double-stranded splint adaptors, e.g., PCR-free workflows. The double-stranded splint adaptors (200) can be used in a one-pot, multi-enzyme reaction to introduce one or more new adaptor sequences into a library molecule. The double-stranded splint adaptor (200) comprises a first splint strand (long splint strand (300)) and a second splint strand (short splint strand (400)), where the first and second splint strands are hybridized together to form the double-stranded splint adaptor (200) having a double-stranded region and two flanking single-stranded regions. The second splint strand (400) carries the new adaptor sequence(s) to be introduced, such as for example a universal binding sequence and/or an index sequence.
The disclosure relates to methods for obtaining nucleic acid sequence information by constructing a nucleic acid library and reconstructing longer nucleic acid sequences by assembling a series of shorter nucleic acid sequences.
Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3' modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.
Systems, methods, and computer storage media for for image registration in primary analysis are provided. In some embodiments, coordinates of polonies in a reference coordinate system are determined, wherein the polonies are obtained from flow cell images in one or more reference cycles. One or more template images in the reference coordinate system are generated by registering the polonies to the one or more template images using the coordinates thereof. A flow cell image in a cycle is obtained. A plurality of transformations of the flow cell image is then determined based on the one or more template images, each of the plurality of transformations corresponding to a subtile of the flow cell image and configured to register the subtile of the flow cell image to the one or more template images.
Provided herein are system, apparatus, method, and/or computer program product embodiments, and/or combinations and sub-combinations thereof which enables adapter trimming and/or adapter determination during sequencing data analysis. Based on a plurality of match scores, one or more sequence alignments are selected. Each of the plurality of match scores may be based on a first number of matched bases and a second number of total bases. First and second consensus positions are generated from the one or more sequencing alignments. A trimming position is determined based on the first and second consensus positions and a first and second consensus match score.
The present disclosure provides compositions comprising reagents employed in a nucleic acid library preparation workflow for removing deaminated bases, and methods for using the reagents. The compositions and methods described herein reduce base call errors, such as C:G to T:A transitions, in nucleic acid sequencing workflows.
The disclosure relates to methods for obtaining nucleic acid sequence information by constructing a nucleic acid library and reconstructing longer nucleic acid sequences by assembling a series of shorter nucleic acid sequences.
The present disclosure provides compositions comprising reagents employed in a nucleic acid library preparation workflow for removing deaminated bases, and methods for using the reagents. The compositions and methods described herein reduce base call errors, such as C:G to T:A transitions, in nucleic acid sequencing workflows.
The present disclosure includes methods, systems, and media for performing a phasing and prephasing correction in sequencing analysis, comprising: determining corrected image intensities of a plurality of polonies, Ipc(N), based on a cycle N-1 phasing coefficient, pN-1, a cycle N-1 prephasing coefficient, ppN-1, or both; obtaining base calls in the cycle N based on the corrected image intensities of the plurality of polonies in the cycle N, Ipc(N); selecting, by the processor, polonies from the plurality of polonies based on the base calls; determining a cycle N phasing coefficient, pN, a cycle N prephasing coefficient, ppN, or both; and updating image intensities of the plurality of polonies in cycle N, I(N), using updated and corrected image intensities, Ipc_n(N), wherein Ipc_n(N) is obtained based on the cycle N phasing coefficient, pN, the cycle N prephasing coefficient, ppN, or both.
Aspects of the present disclosure relate to a method for predicting quality of base calling in sequencing. A plurality of predictors may be selected and a corresponding value for each of the plurality of predictors may be determined from one or more flow cell images. A quality score may be determined from a look-up table based on the corresponding value for each of the plurality of predictors, wherein the look-up table comprises a plurality of dimensions corresponding to the plurality of predictors and is generated based on a training data set.
The present disclosure provides methods for conducting in situ multiplex and multi-omics detection and identification using coded padlocks probes. The methods comprise simultaneous use of RNA-specific padlock probes and polypeptide-specific padlock probes to detect both RNA and polypeptides in a cellular sample. Both types of probes include a barcode that unique identifies the RNA or polypeptide that that padlock probe detects. Both types of probes also include a batch-specific sequencing primer binding site to enable sequencing a desired subset of concatemer template molecules. Use of the batch-specific sequencing primers reduces overcrowding signals and images, to produces optical images that are intense and resolvable. By conducting multiple rounds of sequencing on the same cellular sample using different batch-specific sequencing primers enables multiplex and multi-omics sequencing to reveal numerous target RNAs and their encoded polypeptides.
in situin situ multiplex and multi-omics detection and identification using coded padlocks probes. The methods comprise simultaneous use of RNA-specific padlock probes and polypeptide-specific padlock probes to detect both RNA and polypeptides in a cellular sample. Both types of probes include a barcode that unique identifies the RNA or polypeptide that that padlock probe detects. Both types of probes also include a batch-specific sequencing primer binding site to enable sequencing a desired subset of concatemer template molecules. Use of the batch-specific sequencing primers reduces overcrowding signals and images, to produces optical images that are intense and resolvable. By conducting multiple rounds of sequencing on the same cellular sample using different batch-specific sequencing primers enables multiplex and multi-omics sequencing to reveal numerous target RNAs and their encoded polypeptides.
Image data analysis, and particularly identifying cluster or polony locations for performing base-calling in a digital image of a flow cell during DNA sequencing is described. A method may include generating a first plurality of flow cell images of a cellular sample immobilized on a support by conducting one or more cycles of sequencing reactions. The cellular sample may include a plurality of concatemer molecules therewithin. For the first plurality of flow cell image, pixel intensities, and a respective color purity of each of the pixel intensities may be determined. A base calling template may include base calling locations based on the pixel intensities and the respective color purity of the pixel intensities. The base calling template may be for registering a second plurality of flow cell images of the support in one or more subsequent cycles of the one or more cycles.
G06T 7/66 - Analysis of geometric attributes of image moments or centre of gravity
G06T 7/30 - Determination of transform parameters for the alignment of images, i.e. image registration
G06V 10/75 - Organisation of the matching processes, e.g. simultaneous or sequential comparisons of image or video featuresCoarse-fine approaches, e.g. multi-scale approachesImage or video pattern matchingProximity measures in feature spaces using context analysisSelection of dictionaries
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
84.
MULTIVALENT BINDING COMPOSITIONS WITH REACTIVE GROUPS
The present disclosure provides nucleotide conjugates each configured to include a core attached to multiple nucleotide-arms, where the nucleotide-arms are modular and comprise (i) a core attachment moiety, (ii) a spacer, (iii) a linker, and (iv) a nucleotide unit. The nucleotide unit of each nucleotide-arm can bind a polymerase which is complexed with a nucleic acid template and nucleic acid primer. The nucleotide unit can bind the 3' end of the primer at a position that is opposite a complementary nucleotide in the template strand. Under suitable conditions, the nucleotide unit of the nucleotide conjugates binds the primer strand but does not undergo polymerase-catalyzed incorporation. The binding event can be detected, and the specific base of the nucleotide unit can be identified. The nucleotide conjugates described herein are useful for nucleic acid sequencing methods, particularly for massively parallel sequencing methods employed for next gen sequencing platforms.
The present disclosure provides nucleotide conjugates each configured to include a core attached to multiple nucleotide-arms, where the nucleotide-arms are modular and comprise (i) a core attachment moiety, (ii) a spacer, (iii) a linker, and (iv) a nucleotide unit. The nucleotide unit of each nucleotide-arm can bind a polymerase which is complexed with a nucleic acid template and nucleic acid primer. The nucleotide unit can bind the 3' end of the primer at a position that is opposite a complementary nucleotide in the template strand. Under suitable conditions, the nucleotide unit of the nucleotide conjugates binds the primer strand but does not undergo polymerase-catalyzed incorporation. The binding event can be detected, and the specific base of the nucleotide unit can be identified. The nucleotide conjugates described herein are useful for nucleic acid sequencing methods, particularly for massively parallel sequencing methods employed for next gen sequencing platforms.
Multivalent binding compositions including a particle-nucleotide conjugate having a plurality of copies of a nucleotide attached to the particle are described. The multivalent binding compositions allow one to localize detectable signals to active regions of biochemical interaction, e.g., sites of protein-protein interaction, protein-nucleic acid interaction, nucleic acid hybridization, or enzymatic reaction, and can be used to identify sites of base incorporation in elongating nucleic acid chains during polymerase reactions and to provide improved base discrimination for sequencing and array based applications.
Image data analysis, particularly identifying cluster locations for performing base-calling in a digital flow cell image during DNA sequencing, is described. Each nucleic acid template molecule immobilized on a support may include an insert sequence and a sample index sequence. The sample index sequence may include a k-mer sequence. A sequencing system may conduct k cycles of sequencing reactions of the k-mer sequence before conducting one or more cycles of the insert sequence sequencing reactions and generate a first plurality of flow cell images. Pixel intensities may be determined for pixels of the first plurality of flow cell images. A base calling template may be determined and include base calling locations based on the pixel intensities and respective color purities of the pixel intensities. The base calling template may register a second plurality of flow cell images of the support in one or more cycles subsequent to the k cycles.
G06T 7/66 - Analysis of geometric attributes of image moments or centre of gravity
G06T 7/30 - Determination of transform parameters for the alignment of images, i.e. image registration
G06V 10/75 - Organisation of the matching processes, e.g. simultaneous or sequential comparisons of image or video featuresCoarse-fine approaches, e.g. multi-scale approachesImage or video pattern matchingProximity measures in feature spaces using context analysisSelection of dictionaries
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
Methods and systems for detecting the presence of a target nucleic acid sequence in one or more samples of a plurality of samples are described. The methods may comprise the use of linear barcoded nucleic acid probes that, upon hybridization to a target nucleic acid sequence, may be ligated to circularize the probe molecule, amplified, and sequenced. The use of a probe-specific barcode integrated into the nucleic acid probe molecule, and sample-specific barcodes that may be incorporated into the nucleic acid probe molecule or added during the amplification step, enable large-scale multiplexed assay and sample processing.
The present disclosure provides compositions comprising nucleic acid single-stranded splint strands, including kits, and methods that employ the single-stranded splint strands. The single-stranded splint strands can hybridize to portions of linear library molecules to form circularized library-splint complexes having a nick, where the nick can be ligated to form covalently closed circular molecules which can be subjected to downstream amplification and sequencing workflows.
The present disclosure provides compositions comprising nucleic acid double-stranded splint adaptors, including kits, and methods that employ the double-stranded splint adaptors. The double-stranded splint adaptors (200) can be used in a one-pot, multi-enzyme reaction to introduce one or more new adaptor sequences into a library molecule. The double-stranded splint adaptor (200) comprises a first splint strand (long splint strand (300)) and a second splint strand (short splint strand (400)), where the first and second splint strands are hybridized together to form the double-stranded splint adaptor (200) having a double-stranded region and two flanking single-stranded regions. The second splint strand (400) carries the new adaptor sequence(s) to be introduced, such as for example a universal binding sequence and/or an index sequence.
The present disclosure provides compositions comprising nucleic acid single-stranded splint strands, including kits, and methods that employ the single-stranded splint strands. The single-stranded splint strands can hybridize to portions of linear library molecules to form circularized library-splint complexes having a nick, where the nick can be ligated to form covalently closed circular molecules which can be subjected to downstream amplification and sequencing workflows.
The present disclosure provides compositions comprising nucleic acid double-stranded splint adaptors, including kits, and methods that employ the double-stranded splint adaptors. The double-stranded splint adaptors (200) can be used in a one-pot, multi-enzyme reaction to introduce one or more new adaptor sequences into a library molecule. The double-stranded splint adaptor (200) comprises a first splint strand (long splint strand (300)) and a second splint strand (short splint strand (400)), where the first and second splint strands are hybridized together to form the double-stranded splint adaptor (200) having a double-stranded region and two flanking single-stranded regions. The second splint strand (400) carries the new adaptor sequence(s) to be introduced, such as for example a universal binding sequence and/or an index sequence.
Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3' modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.
Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.
Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.
Provided herein are engineered variants of archaeal polymerases that exhibit exonuclease-minus activity, enhanced thermostability, enhanced incorporation of 3′ modified nucleotides, improved uracil-tolerance and/or reduce sequence-specific errors in polymerase-catalyzed nucleotide binding and extension reactions relative to wild type polymerase enzymes. Also provided are uses of the engineered polymerases for forming complexed polymerases and forming binding complexes, and uses for conducting nucleic acid sequencing reactions.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Assays and reagents for use in genetic research; diagnostic reagents for scientific or research use; diagnostic reagents for medical laboratory use; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for scientific research use, for diagnostic scientific use, and for laboratory research use; diagnostic reagents for laboratory use; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for diagnostic laboratory purposes Medical diagnostic reagents; clinical medical diagnostic reagents; reagent kits and reagent beads with attached biomolecules, comprised primarily of oligonucleotides and other nucleic acids, natural and modified nucleotides, polypeptides, buffers, labels, and substrates, for use in diagnostic tests for medical purposes; reagents and reagent kits comprised primarily of nucleic acids, naturally occurring or modified nucleotides, enzymes, labels, and buffers, all for the purpose of preparing, detecting, sequencing, and analyzing nucleic acids and other biological molecules, samples of biological molecules, genes, genomes, nucleotide sequence variants and modifications, regulation, transcription, and expression for diagnostic medical use and for clinical medical use Computer systems, namely, computer hardware, downloadable and recorded computer software and associated downloadable electronic data files for collecting, storing, analyzing and reporting biological information, and for sample tracking and managing projects, laboratory workflow and data, all the foregoing for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; downloadable and recorded computer software for data collection, management, and analysis of genetic information for use in the fields of diagnostic and clinical research and for clinical diagnostic purposes; instruments for scientific use, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Clinical diagnostic instruments for medical use, namely, nucleic acid sequencers, genetic imaging devices and analyzers for genetic analysis Providing reagent sample diagnostic testing services for others for scientific research purposes and scientific research related thereto; clinical diagnostic services for scientific research purposes, namely, preparing, amplifying, labeling, detecting, analyzing and sequencing nucleic acids from human beings
