The present disclosure provides systems and methods for preparing a DNA library from a sample comprising shelf-stable lyophilized microspheres comprising DNA library preparation reagents providing a streamlined workflow for DNA library preparation. The present disclosure also provides a smart consumable container for collecting and transporting the sample.
Systems for sequencing biopolymers and methods of manufacturing the systems are disclosed. In one example, such a system may include an application specific integrated circuit (ASIC) layer, a post array layer beneath the AISC layer, and a nanopore layer above the ASIC layer. The ASIC layer is formed by building active circuitry on a front side of a semiconductor wafer and polishing a back side of the semiconductor wafer. The post array layer is formed by etching a front side of a support substrate and the post array layer provides mechanical support to the ASIC layer. The nanopore layer contains membrane and nanopores. The membrane inhibits passage of water-soluble molecules and the nanopores permit passage of water-soluble molecules. In some embodiments, the system may have short through-substrate vias extending through the ASIC layer. In some embodiments, wafer bonding processes may be used when fabricating the system.
In some examples, a nucleoside triphosphate analogue may include a sugar, a nucleobase coupled to the sugar, a triphosphate group coupled to the sugar, a heteroatom coupled to an alpha phosphate of the triphosphate group, and a first substituent coupled to the heteroatom. The heteroatom may be selected from the group consisting of oxygen, nitrogen, and carbon. The first substituent may include at least one of an alkyl chain or a polymer.
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
4.
A CIRCUIT DESIGN TO APPLY DIFFERENT VOLTAGES IN A NANOPORE ARRAY
In one aspect, the disclosed technology relates to systems and methods for sequencing polynucleotides. In one embodiment, the disclosed system for sequencing polynucleotides includes: a plurality of sequencing cells, each of the plurality of sequencing cells comprising a nanopore for sensing a polynucleotide; a plurality of electronic circuits, each of the plurality of electronic circuits associated with one of the plurality of sequencing cells; and at least one voltage source operably connected to at least one shift register, the output terminals of the at least one shift register operably connected to the plurality of electronic circuits.
An apparatus includes a fluidic circuit, a bypass fluidic circuit, a first set of fluid wells, a second set of fluid wells, a first valve, and a second valve. The first valve operatively associated with the first set of fluid wells such that the first selectively fluidly connects any one of the first set of fluid wells to a first valve outlet. The second valve operatively associated with the fluidic circuit, the bypass fluidic circuit, the first valve outlet, and the second set of fluid wells such that the second valve selectively fluidly connects any one of the second set of fluid wells and the first valve outlet to the fluidic circuit or the first valve outlet to the bypass fluidic circuit.
A cell culture plate according to one embodiment of the present invention is a cell culture plate which is formed by side walls and a bottom surface, includes a space containing a culture medium, has an open top, and is formed to be vertically stacked. The bottom surface includes a well area in which a plurality of wells are formed and a peripheral area formed around the well area, and the cell culture plate includes a culture medium flow hole formed through the bottom surface to allow a culture medium to flow in the peripheral area; a magnetic bead which is provided to open/close the culture medium flow hole by moving up and down due to a magnetic force, and formed of a material responding to magnetic force; and a bead holding space which forms a space allowing the movement of the magnetic bead and prevents the magnetic bead from being separated.
A method for extending a depth of field of a nucleic acid sequencer may comprise optimization steps which are repeated one or more times, in which a result of passing light through an objective lens and a mask is compared with an ideal result, and any discrepancy is used to update the mask. Such a mask may be incorporated into a nucleic acid sequencer which adds fluorescent tags to nucleic acid sites and then detect light emitted from the fluorescent tags, thereby extending the sequencer's depth of field.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
8.
ALPHA-MODIFIED NUCLEOSIDE TRIPHOSPHATES AND METHOD FOR THEIR SYNTHESIS
A nucleoside triphosphate analogue including a sugar, a nucleobase coupled to the sugar, a triphosphate group coupled to the sugar, a heteroatom coupled to an alpha phosphate of the triphosphate group, and a first substituent coupled to the heteroatom. The heteroatom may be selected from the group consisting of oxygen, nitrogen, and carbon. The first substituent may include at least one of an alkyl chain or a polymer. The nucleoside triphosphate analogue may have the formula (I).
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Described herein are methods and systems for determining a sequence of a nucleic acid template by removing mutations found in a mutated sequence read. In some embodiments, methods and systems include steps of aligning unmutated sequence reads of a nucleic acid template to mutated sequence reads, and determining a most probable sequence of the nucleic acid template and a per-base accuracy score correlated with the probability that the base matches with the nucleic acid template, thereby determining the sequence of the nucleic acid template.
Automated methods conducted in a sequencing flowcell, and kits for reusing a flowcell, are provided herein. In some examples, an automated method conducted in a sequencing flowcell may include, at a surface of the sequencing flowcell coupled to a first moiety, using a reagent to decouple a first complex from the first moiety. In some examples, the first complex may include a second moiety which couples to the first moiety and a polynucleotide coupled to the second moiety. In some examples, the method may further include using a nuclease to polynucleotides in the sequencing flowcell. The method may include, after using the reagent and after using the nuclease, coupling a second complex to the first moiety. The second complex may include a third moiety which couples with the first moiety and an oligonucleotide coupled to the third moiety.
An example of a kit includes a flow cell assembly. The flow cell assembly includes a reaction chamber, a temperature controlled flow channel in selective fluid communication with an inlet of the reaction chamber, and a filter positioned in the temperature controlled flow channel. The reaction chamber includes depressions separated by interstitial regions and capture primers attached within each of the depressions. The filter is i) to block concentrated biological sample-polymer complexes generated in the temperature controlled flow channel at a first temperature, and ii) to allow passage of concentrated biological sample and polymer released from the complexes in the temperature controlled flow channel at a second temperature.
A method and system for polynucleotide sequencing and sequence assembly using a k-mer graph approach is disclosed. The methods may include receiving a sample comprising a nucleic acid sequence, fragmenting the sample into a plurality of shorter sequences, and aligning the shorter sequences to a reference genome to identify a k-mer sequence. The systems may include a processor, a memory, and a storage device configured to store the reference genome and the sample. The processor may be configured to execute the steps of the method, including aligning shorter sequences to a reference genome.
Aptamer detection techniques are described that may include aptamer modification to facilitate incorporation of adapter sequences. In an embodiment, a 3' end of an aptamer may be modified by deprotection and subsequent ligation to the deprotected 3' end or extension of the deprotected 3' end. The modifications at the 3' end of the adaptor may include adaptor sequences used for library preparation of a sequencing library.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
09 - Scientific and electric apparatus and instruments
42 - Scientific, technological and industrial services, research and design
Goods & Services
Biological preparations, other than for medical purposes; Agents, reagents, assays, enzymes, nucleotides, buffers, chemical preparations, and biological preparations for scientific and research use; Diagnostic reagents and preparations, other than for medical use; Agents, reagents, assays, enzymes, nucleotides, buffers, chemical preparations, and biological preparations for scientific and research use, including in the fields of genotyping, medical research, dental research, clinical research, metagenomics, biotechnology, drug development research, disease treatment research, pharmaceutical research, medical laboratory research, life sciences, biology, microbiology, dermatology, genetic testing, nucleic acid sequencing, and genetics, oncology, prenatal, diseases, in vitro diagnostic research, infectious diseases, reproductive health, neonatal intensive care, and personalized medicine, not for medical purposes; Kits containing nucleotides, reagents, enzymes, enzyme substrates, agents, assays, buffers, chemical preparations, or biological preparations for use thereof for non-medical purposes; Kits comprising of nucleotides, reagents, enzymes, enzyme substrates, agents, assays, buffers, chemical preparations, or biological preparations for scientific and research use, including in the fields of genotyping, medical research, dental research, clinical research, metagenomics, biotechnology, drug development research, disease treatment research, pharmaceutical research, medical laboratory research, life sciences, biology, microbiology, dermatology, genetic testing, nucleic acid sequencing, and genetics, oncology, prenatal, diseases, in vitro diagnostic research, infectious diseases, reproductive health, neonatal intensive care, and personalized medicine, not for medical purposes Agents, reagents, assays, enzymes, nucleotides, buffers, chemical preparations, and biological preparations for medical and dental use; Diagnostic reagents and preparations for medical and dental use; Clinical diagnostic reagents; Biological preparations for medical use; Goods for the treatment of illness and disease being biological and chemical preparations for medical and dental purposes; Bacterial preparations for medical use; Biological tissue cultures for medical and dental use; Blood for medical purposes; Kits comprised of nucleotides, reagents, enzymes, agents, assays, buffers, chemical preparations, or biological preparations for medical purposes; Kits comprised of nucleotides, reagents, enzymes, agents, assays, buffers, chemical preparations, or biological preparations for medical genetic testing and medical diagnostic purposes; Agents, reagents, assays, enzymes, nucleotides, buffers, chemical preparations, and biological preparations for medical and dental use, including in the fields of medical diagnostics, clinical diagnostics, dental diagnostics, laboratory medicine, genetic testing, nucleic acid sequencing, genetics, dermatology, oncology, prenatal, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, and drug development; Kits comprised of enzyme substrates for medical genetic testing and medical diagnostic purposes Laboratory devices for detecting genetic sequences; diagnostic apparatus for the detection of pathogens for laboratory or research use; scientific apparatus and instruments for use in genetic analysis; apparatus for dna and rna testing for research purposes; apparatus and instruments for testing gases, liquids, or solids; dna chips; data processing apparatus but not in the nature of devices used to calculate and report website traffic statistics; computers; computer hardware but not in the nature of devices used to calculate and report website traffic statistics; computer networking hardware but not in the nature of devices used to calculate and report website traffic statistics; computer hardware and software for use in the fields of nucleic acid sequencing, genotyping, medical diagnostics, clinical diagnostics, medical research, diagnostic research, clinical research, drug development, drug development research, medical laboratory research, life sciences, biology, microbiology, biotechnology, metagenomics, genetic testing and genetics; scientific and research apparatus and instruments including nucleic acid sequencers, arrays, scanners, electronic imaging devices and analyzers, testing sample collection equipment, sample quality control instruments, sequencing reagent cartridges and trays, test sample preparation equipment, and laboratory equipment for laboratory use including in the fields of nucleic acid sequencing, genotyping, medical diagnostics, clinical diagnostics, medical research, diagnostics, clinical research, drug development, pharmaceuticals, medical laboratory research, life sciences, biology, microbiology, biotechnology, metagenomics, genetic testing, and genetics; micro-processors; data processors but not in the nature of devices used to calculate and report website traffic statistics; computer network hubs and servers but not in the nature of devices used to calculate and report website traffic statistics; next-generation sequencing (ngs) bioinformatics data processor; cards with integrated circuits; computer chips; encoded electronic chip cards containing programming used for dna sequencing; computer application software for mobile phones, handheld computers, tablet computers, and computers, namely, software to receive and store dna and genetic records, and to authorize medical and research personnel to use records; downloadable electronic publications in the fields of nucleic acid sequencing, genotyping, diagnostics, diagnostic research, medical diagnostics, clinical diagnostics, laboratory medicine, clinical research, drug development, pharmaceuticals, laboratory research, scientific research, medical research, life sciences, biology, microbiology and metagenomics, biotechnology, genetic testing, and genetics; downloadable electronic reports in the fields of nucleic acid sequencing, genotyping, diagnostics, diagnostic research, medical diagnostics, clinical diagnostics, laboratory medicine, clinical research, drug development, pharmaceuticals, laboratory research, scientific research, medical research, life sciences, biology, microbiology and metagenomics, biotechnology, genetic testing, and genetics. Scientific, biological, and medical research; Services for scientific and research purposes, namely, genetic analysis and reporting services; Medical research; Providing on-line non-downloadable computer software for research and analysis of medical and biomedical data; Providing on-line non-downloadable computer search engine software; Providing online non-downloadable computer software for the custom design and ordering of medical, medical diagnostic, medical treatment and medical research goods, assays, agents, enzymes, nucleotides, nucleic acids, buffers, chemical preparations, biological preparations, reagents, instruments and apparatus; Software as a service (SaaS) services featuring software for collecting, storing, analyzing, sharing, and reporting biological, genetic, clinical, medical, and diagnostic information, and for sample tracking and managing projects, laboratory workflow and data; Platform as a service (PaaS) services featuring computer software platforms for collecting, storing, analyzing, sharing, and reporting biological, genetic, clinical, medical, and diagnostic information, and for sample tracking and managing projects, laboratory workflow and data; Software as a service (SaaS) services and platform as a service (PaaS), featuring hosting software for use by others for use in the custom design and ordering of medical , medical diagnostic, medical treatment and medical research goods, assays, agents, enzymes, nucleotides, nucleic acids, buffers, chemical preparations, biological preparations, reagents, instruments and apparatus, in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, nucleic acid sequencing, genetics, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Software as a service (SaaS) services and platform as a service (PaaS) for use with diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, genetics, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Software as a service (SaaS) services and platform as a service (PaaS) services for collecting, storing, analyzing, sharing and reporting biological, genetic, clinical, medical, and diagnostic information, and for sample tracking and managing projects, laboratory workflow and data; Hosting an online network service, namely, a community web site that enables users to store, analyze and share data in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, nucleic acid sequencing, genetics, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Nucleic acid sequencing and analysis services for scientific and research purposes; Genome sequencing and analysis services for scientific and research purposes; Genetic analysis and reporting services for scientific and research purposes; Installation and maintenance of computer software, databases, and database applications for others; Installation and maintenance of computer software and database applications for others for use in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, genetics, nucleic acid sequencing, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Clinical diagnostic and consultation services in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, genetics, nucleic acid sequencing, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Scientific and technological services and research relating thereto; Scientific laboratory services; Medical laboratory services; Computer services, namely, data recovery services; Computer services, namely, cloud hosting provider services and onsite provider services for storing, analyzing and sharing information in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, nucleic acid sequencing, genetics, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Providing an online network service that enables users to store, access, manage, analyze and share data for use in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, genetics, nucleic acid sequencing, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Design and development of automated laboratory apparatus, laboratory equipment, and computer systems for others; Providing consulting services for others relating to data management and information technology infrastructure development; Proof of concept services for others, namely, scientific and technical consulting and research services relating to experiment design, library preparation, library preparation quality control, sample tracking, sample quality control, and preparation of customized protocols and user guides; Design and preparation of computer databases for others for collecting, storing, analyzing, and reporting biological information; Computer diagnostic services in analyzing and sequencing nucleic acids and other biological molecules and materials; Development of automated laboratory equipment and systems, and computer hardware for collecting, storing, analyzing, sharing and reporting biological, genetic, clinical, medical, and diagnostic and treatment information, and for sample tracking and managing projects, laboratory workflow and data to the order and specification of others; Technical support services, namely, troubleshooting of computer software problems; Technical support services, namely, infrastructure management services for monitoring, administration and management of cloud computing IT and application systems in the fields of diagnostics, clinical diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, nucleic acid sequencing, genetics, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Testing, analysis, and evaluation of the knowledge, skills and abilities of others in the fields of medical diagnostics, clinical diagnostics, companion diagnostics, medical research, medical treatment, dental diagnostics, dental research, diagnostics, clinical research, drug development, disease treatment, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, life sciences, biology, microbiology, biotechnology, metagenomics, genetic testing, nucleic acid sequencing, and genetics to determine conformity with certification standards; Updating of computer software for others; Cloud computing featuring software for analyzing and sequencing nucleic acids and other biological molecules, for use in the fields of nucleic acid sequencing, genotyping, genetic testing, and genetics; Biological material analysis services; Database design and development; DNA analysis services for the identification and treatment of illness and disease; Providing temporary use of on-line non-downloadable data compression and decompression software; Providing temporary use of on-line non-downloadable computer software for compressing and decompressing data and files; Providing temporary use of on-line non-downloadable computer software for encrypting data and files; Providing temporary use of on-line non-downloadable computer software for maximizing data and file storage; Providing temporary use of on-line non-downloadable computer software for use in file compression, file decompression, archiving, and computer file management; Providing temporary use of on-line non-downloadable computer software for accessing and decompressing archives stored in files, and then viewing and downloading one or more decompressed individual files stored inside the original compressed files archive; Providing temporary use of on-line non-downloadable computer software for creating a compressed file archive containing one or more user-selected individual files; Providing temporary use of on-line non-downloadable computer software for copying, deleting, comparing, managing, organizing, compressing, decompressing, restoring, repairing, creating, storing, synchronizing, securing and archiving of data and files; Software as a service (SaaS) services featuring non-downloadable software for use in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, nucleic acid sequencing, genetics, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Providing temporary use of on-line non-downloadable computer software for compressing and decompressing genomic data files; Providing temporary use of on-line non-downloadable computer software for analysis of sequencing data in the fields of nucleic acid sequencing, genotyping, genetic testing, and genetics; Providing temporary use of on-line non-downloadable computer software for analyzing next-generation sequencing (NGS) data; Providing temporary use of on-line non-downloadable computer software for analyzing next-generation sequencing (NGS) data in the fields of diagnostics, companion diagnostics, medical diagnostics, medical treatment, medical research, clinical diagnostics, clinical research, dental diagnostics, dental research, medical laboratory research, laboratory medicine, genetic testing, nucleic acid sequencing, genetics, genotyping, life sciences, dermatology, oncology, prenatal screening and testing, diseases, in vitro diagnostics, infectious diseases, reproductive health, neonatal intensive care, personalized medicine, microbiology, biology, biotechnology, metagenomics, pharmaceuticals, dietary supplements, dietary supplement development, fungicide development, herbicide development, drug development and disease treatment; Providing temporary use of on-line non-downloadable computer software for capturing, storing, accessing, displaying, sharing, compressing, migrating, and managing digital files; Providing temporary use of on-line non-downloadable computer software for processing, visualizing, storing, sharing, and manipulating genetic data and next-generation sequencing (NGS) data; Providing temporary use of on-line non-downloadable computer software that enables users to store, access, manage, analyze and share data; Providing scientific analysis services in the field of genetics and next-generation sequencing (NGS); Providing scientific analysis services of genomic data; computer services, namely, cloud hosting provider services for storing, analyzing and sharing information; Providing temporary use of on-line non-downloadable computer software for use with genomic data; Providing temporary use of on-line cloud based software for providing security and privacy; Software as a service (SaaS) services and Platform as a service (PaaS) services for enabling multi-omics analysis; Software as a service (SaaS) services and Platform as a service (PaaS) services for use in the field of data science; Computer services, namely, providing on-line non-downloadable software for creating and sharing interactive graphical user interfaces in the nature of dashboard visualizations; Software as a service (SaaS) services, featuring software for a user interface designed to enable access to application and server infrastructure performance management with a dashboard for software application and computing infrastructure performance metrics and events for aggregation, manipulation, graphing and reporting; Software as a service (SaaS) services featuring software for enabling user interaction with genomics data via a graphical user interface; Software as a service (SaaS) services featuring software for providing users the opportunity to interactively explore integrated genomic data and associated clinical data; Platform as a service (PaaS) featuring computer software platforms for providing decentralized computing services in the nature of securing and protecting electronic data and automating workflows; Providing temporary use of on-line non-downloadable graphical, command line, menu driven, form based, and natural language user interface software; Providing temporary use of on-line non-downloadable software for user interfaces, dashboards, and command lines; Application service provider (ASP) featuring software for providing access to multiple databases that contain aggregated results of genotyping and genetic, genomic, molecular, and biomarker data; Providing scientific analysis and informational reports services based upon results of genetic, genomic, molecular, and biomarker data; Software as a service (SaaS) services featuring software for research and analysis of medical and biomedical data; Application service provider featuring application programming interface (API) software for others to build and market genetic, genomic, molecular, and biomarker data; Platform as a service (PaaS) featuring computer software platforms to gather, compile, analyze, authenticate, validate, control, protect, exchange, and modify genetic, genomic, molecular, and biomarker data; Providing browser-based online non-downloadable computer software for use in management of genetic, genomic, molecular, and biomarker data; Platform as a service (PaaS) featuring computer software platforms for the collection, use, or exchange of genetic, genomic, molecular, and biomarker data; Providing a website featuring information on DNA data; Providing software as a service (SaaS) services featuring software for employing genetic algorithms and deep learning techniques; Providing temporary use of on-line non- downloadable software for reporting and analyzing data; Application service provider featuring application programming interface (API) software for reporting and analyzing data; Development of proprietary bioinformatic analysis software pipelines and computer systems for collecting, storing, characterizing, sorting, viewing, and delivering genetic information; Providing scientific research data in the field of genomics, including custom, proprietary bioinformatic analysis of data generated by NGS technology or unanalyzed biological data; Providing temporary use of on-line non-downloadable computer software for use in laboratory information management; Providing temporary use of on-line non-downloadable software for laboratory workflow process automation, open database modeling, and integrating multiple data sources; Providing temporary use of on-line non-downloadable computer software for storage, organization, processing, retrieval and output of sampling and testing information; Computer services, namely, cloud hosting provider services in the fields of laboratory information management, laboratory information management systems and laboratory information technology; Providing temporary use of on-line non-downloadable software for use in proprietary bioinformatic analysis software pipelines and computer systems; Providing temporary use of on-line non- downloadable software for building and customizing workflows; Providing temporary use of on-line non-downloadable software for use in aggregating and querying large data sets; Providing temporary use of on-line non-downloadable software that utilizes AI (artificial intelligence) or ML (machine learning) algorithms; Providing temporary use of on-line non-downloadable cloud-based software that combines genomic knowledge and AI based optimization with a genomic database; Providing temporary use of on-line non-downloadable computer software using artificial intelligence algorithms and machine learning to support platforms that contain genetic and genomic information; Providing on- line non-downloadable software incorporating artificial intelligence and machine learning models for collecting, analyzing, assessing, interpreting and predicting genetic and genomic data or information; Providing online non-downloadable software for retrieval and correlation of genetic or genomic data; Software as a service (SaaS) services featuring software for analyzing and visualizing genetic or genomic data; Providing online non-downloadable software for use in genetic sequencer integration; Providing online non-downloadable software for use in genetic sequencer integration and for use in integrating third-party software into a single workflow; Providing online non-downloadable software for use in an integrated data science environment; Providing online non-downloadable software to analyze, manage, aggregate, mine, and explore genetic or genomic data; Providing online non-downloadable software in the nature of a modular, secure data platform for scalable multi-omics data management, analysis, and exploration; providing non-downloadable cloud-based data management and analysis software platform that enables researchers to manage, analyze, and interpret large volumes of multi-omics data in a secure, scalable, and adaptable environment; Providing online non-downloadable software for use in streamlining genomics workflow; Providing online non-downloadable software that provides users with scalable data analysis; Providing online non-downloadable software that supports highly automated workflows and custom solutions for optimized high-throughput studies; Providing online non-downloadable data aggregation and data science software; Providing online non-downloadable omics software used for exploring large genomic data sets and discovering insights related to said data sets; Providing online non-downloadable software that provides data residency, single sign-on, audit logs, and access control capabilities; Scientific and technological services and research and design relating thereto; Medical research services.
Well assemblies enabling optical access therein and related systems and methods are disclosed. In accordance with an implementation, an apparatus includes a body, dry reagent, and a cover. The body defines a well and has an opening, an aperture, and a field of view (FOV) enabling optical access from the aperture to the well. The dry reagent is contained within the well. The cover is coupled to the body and covering the opening.
In an example method, a grafting solution is applied to a patterned substrate using a liquid-phase thin-film deposition technique. The patterned substrate includes a lane surrounded by, or a plurality of depressions separated by interstitial regions; and a polymer in the lane or in each of the plurality of depressions. The polymer is functionalized with a first click reaction moiety. The grafting solution includes a solvent; a polymer matrix material dissolved in the solvent; and primers of a primer set dissolved in the solvent, each of the primers being terminated with a second click reaction moiety. The applied grafting solution is dried. During drying, a solid polymer matrix is formed and at least some of the primers attach to the polymer i) via the first and second click reaction moieties and ii) in at least a portion of the lane or in at least some of the plurality of depressions.
An example of a flow cell includes a substrate; a first primer set attached to a first region on the substrate, the first primer set including an un-cleavable first primer and a cleavable second primer; and a second primer set attached to a second region on the substrate, the second primer set including a cleavable first primer and an un-cleavable second primer.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
Presented are methods and compositions for using immobilized transposase and a transposon end for generating an immobilized library of 5′-tagged double-stranded target DNA on a surface. The methods are useful for generating 5′- and 3′-tagged DNA fragments for use in a variety of processes, including massively parallel DNA sequencing.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C40B 40/08 - Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
C40B 50/14 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
C40B 50/18 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support using a particular method of attachment to the solid support
Automated methods conducted in a sequencing flowcell, and kits for reusing a flowcell, are provided herein. In some examples, an automated method conducted in a sequencing flowcell may include, at a surface of the sequencing flowcell coupled to a first moiety, using a reagent to decouple a first complex from the first moiety. In some examples, the first complex may include a second moiety which couples to the first moiety and a polynucleotide coupled to the second moiety. In some examples, the method may further include using a nuclease to polynucleotides in the sequencing flowcell. The method may include, after using the reagent and after using the nuclease, coupling a second complex to the first moiety. The second complex may include a third moiety which couples with the first moiety and an oligonucleotide coupled to the third moiety.
The technology relates in part to estimating fetal fraction in non-invasive prenatal testing using one or more fragmentomics parameters. In some aspects, the technology relates to estimating fetal fraction according to nucleic acid fragment lengths and sequence motif frequencies.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
In an example method, a grafting solution is applied to a patterned substrate using a liquid-phase thin-film deposition technique. The patterned substrate includes a lane surrounded by, or a plurality of depressions separated by interstitial regions; and a polymer in the lane or in each of the plurality of depressions. The polymer is functionalized with a first click reaction moiety. The grafting solution includes a solvent; a polymer matrix material dissolved in the solvent; and primers of a primer set dissolved in the solvent, each of the primers being terminated with a second click reaction moiety. The applied grafting solution is dried. During drying, a solid polymer matrix is formed and at least some of the primers attach to the polymer i) via the first and second click reaction moieties and ii) in at least a portion of the lane or in at least some of the plurality of depressions.
In accordance with embodiments herein a method for capturing cells of interest in a digital microfluidic system is provided, comprising utilizing a droplet actuator to transport a sample droplet to a microwell device. The microwell device includes a substrate having a plurality of microwells that open onto a droplet operations surface of the microwell device. The sample droplet includes cells of interest that enter the microwells. The method introduces capture beads to the microwells, and the capture elements are immobilized on the capture beads. The method utilizes the droplet actuator to transport a cell lysis reagent droplet to the microwell device. Portions of the cell lysis reagent droplet enter the microwells and, during an incubation period, cause the cells of interest to release analyte that is captured by the capture elements on the capture beads.
Presented herein are techniques for identifying and/or validating sequence variants in genomic sequence data. The techniques include generating an error rate reflective of sequence errors present in the genomic sequence data. The error rate may be used to validate potential sequence variants. The error rate may be based on errors identified during consensus sequence confirmation for sequence reads associated with individual unique molecular identifiers.
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
Two-phase flushing systems and methods. An example method includes moving a valve to a first position to fluidly connect a first reagent reservoir containing a first reagent to a flow cell and flowing the first reagent from the first reagent reservoir to the flow cell to perform a biochemical reaction. The method includes moving the valve to a second position to fluidly connect a gas to the flow cell and flowing gas into the flow cell to expel at least a portion of the first reagent from the biochemical reaction from the flow cell. The method includes moving the valve to a third position to fluidly connect a buffer reagent reservoir containing a buffer reagent to the flow cell and flowing the buffer reagent into the flow cell.
Described herein are heterocyclic azide-containing monomer units, copolymers comprising such heterocyclic azide-containing monomer units, substrate-bound copolymers, and oligonucleotide-bound copolymers, methods for making such copolymers and reacting them with a substrate and/or oligonucleotide, and methods of using such copolymers for immobilization of oligonucleotides to a substrate, for example for use in DNA sequencing or other diagnostic applications.
A mixture of clustered and unclustered magnetic beads are generated from magnetic beads i) functionalized with a first primer of a primer set and ii) contained in a suspension. Each clustered bead includes a first amplicon attached to the first primer and a 5'-tagged second amplicon hybridized to the first amplicon. A 5'-tag of the second amplicon is a binding pair first member. Coated non-magnetic beads (including a binding pair second member coating, and having a diameter that is at least ten times larger than each magnetic bead) are introduced into the suspension. The clustered magnetic beads bind to at least some of coated non-magnetic beads to form bead-on-bead complexes. The unclustered magnetic beads remain free in the suspension, and are separated from the suspension. The 5'-tagged second amplicon is dehybridized from the first amplicon to generate single stranded clustered magnetic beads, which are then separated from the suspension.
This disclosure describes methods, non-transitory-computer readable media, and systems that can identify and apply a temperature weight to a pathogenicity prediction for an amino-acid variant at a particular protein position to calibrate and improve an accuracy of such a prediction. For example, in some cases, a variant pathogenicity machine-learning model generates an initial pathogenicity score for a protein or a target amino acid at a particular protein position based on an amino-acid sequence of the protein. The disclosed system further identifies a temperature weight that estimates a degree of certainty for pathogenicity scores output by the variant pathogenicity machine-learning model. To generate such a weight, the disclosed system can use a new triangle attention neural network as a temperature prediction machine-learning model. Based on the temperature weight and the initial pathogenicity score, the disclosed system generates a calibrated pathogenicity score for the target amino acid at the particular protein position.
Devices for sequencing biopolymers, methods of manufacturing the devices, and methods of using the devices are disclosed. In one example, such a device has a nanopore and a horizontal nanochannel. In some embodiments, the horizontal nanochannel may take a tortuous path. In some embodiments, such a device includes gas or air bubble generators or pressure pulse generators to block or unblock the horizontal nanochannel.
Embodiments provided herein relate to methods and compositions for next generation sequencing. Some embodiments include the preparation of a template library from a target nucleic acid using one-sided transposition, sequencing the template library, and capturing the contiguity information.
Embodiments of the present disclosure relates to various bisulfite-free chemical methods for detecting methylation of cytosine in the DNA sample. These methods convert methylated and hydroxymethylated cytosine in the nucleic acid sequence to a modified or pseudo thymine or a uracil moiety which then can be detected in sequencing.
In an example of a method for making a flow cell, a sacrificial layer is deposited over a substrate including depressions separated by interstitial regions. The sacrificial layer is dry etched from the depressions, and the sacrificial layer remains on the interstitial regions. A functionalized layer is deposited over the depressions and over the sacrificial layer. The sacrificial layer is removed from the interstitial regions, which also removes the functionalized layer that overlies the interstitial regions.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
C23C 14/18 - Metallic material, boron or silicon on other inorganic substrates
Genomic library preparation using Cas-gRNA RNPs, and targeted epigenetic assays, are provided herein. Some compositions include, from a first species, substantially only single-stranded polynucleotides; from a second species, substantially only double-stranded polynucleotides; and amplification primers ligated to ends of the second double-stranded polynucleotides and substantially not ligated to any ends of the first double-stranded polynucleotides. Some compositions include first and second molecules of a target polynucleotide having a sequence, the first molecule having a first end at a first subsequence, the second molecule having a first end at a second subsequence, wherein the first subsequence only partially overlaps with the second subsequence. Some examples provide a composition that includes a target polynucleotide and a first fusion protein including a Cas-gRNA RNP coupled to a transposase having an amplification adapter coupled thereto. The Cas-gRNA RNP may be hybridized to a subsequence in the target polynucleotide.
This disclosure describes methods, non-transitory-computer readable media, and systems that can identify and apply a temperature weight to a pathogenicity prediction for an amino-acid variant at a particular protein position to calibrate and improve an accuracy of such a prediction. For example, in some cases, a variant pathogenicity machine-learning model generates an initial pathogenicity score for a protein or a target amino acid at a particular protein position based on an amino-acid sequence of the protein. The disclosed system further identifies a temperature weight that estimates a degree of certainty for pathogenicity scores output by the variant pathogenicity machine-learning model. To generate such a weight, the disclosed system can use a new triangle attention neural network as a temperature prediction machine-learning model. Based on the temperature weight and the initial pathogenicity score, the disclosed system generates a calibrated pathogenicity score for the target amino acid at the particular protein position.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
38.
CONCURRENT SEQUENCING OF FORWARD AND REVERSE COMPLEMENT STRANDS ON CONCATENATED POLYNUCLEOTIDES FOR METHYLATION DETECTION
Some embodiments relate to methods and compositions for preparing combinatorially indexed beads. Some embodiments include sequential addition of different indexes to polynucleotides attached to beads. In some embodiments, indexes are added by chemical ligation, polymerase extension, ligation of partially double-stranded adaptors, or short splint ligation.
Aptamer detection techniques with dynamic range compression are described that permit removal of a portion of more abundant aptamers in an aptamer-based assay. In an embodiment, a mixture of tagged probes and dummy probes can be used such that the dummy probes bind abundant aptamers and in turn are not captured or amplified for detection in downstream steps. Other techniques are also contemplated, including targeted removal of or cleavage of probes that bind to excess aptamers.
Reagent cartridges and related systems and methods are disclosed. In accordance with an implementation, an apparatus includes a first flexible container, a second flexible container, and a coupling. The first flexible container has an end and defines a first interior containing reagent. The second flexible container has an end and defines a second interior. The first flexible container is positioned within the second interior. The coupling has a first portion coupled to the end of the first flexible container and a second portion coupled to the end of the second flexible container. The coupling has a reagent port fluidly coupled to the first interior of the first flexible container and a pressure port fluidly coupled to the second interior of the second flexible container.
The determination of pharmacogenomics gene star alleles using high-throughput targeted genotyping includes obtaining input genetic sequence variation data from a high-throughput genotyping platform based on a pharmacogenomic genotyping of a sample, applying a Bayesian graphical model to determine a plurality of different star allele calls corresponding to the sample, and providing a respective quality score for each star allele call of the plurality of different star allele calls. For instance, the application of the Bayesian graphical model uses multi-solution integer programming to explore a model space of the Bayesian graphical model in a first phase that includes structural variant candidate identification and a second phase that includes star allele candidate identification based on the structural variant candidate identification, to determine the plurality of different star allele calls.
Array-based targeted copy number detection, for instance detection on contaminated and/or variable concentration samples, includes obtaining a collection of intensity signals from assays of a set of input samples, performing a cross-sample calibration on the intensity signals based on reference sample(s), which calibration includes constructing a reference signal distribution based on intensity signals of the reference sample(s) and for one or more input samples calibrating a set of intensity signals corresponding to the input sample based on the reference signal distribution, determining, for the one or more input samples, and from a respective one or more calibrated sets of intensity signals corresponding to the one or more input samples, a respective at least one aggregated calibrated signal from targeted genomic region(s) to produce a collection of aggregated calibrated signals, and detecting variant(s) in the targeted genomic region(s) based on the collection of aggregated calibrated signals.
The determination of pharmacogenomics gene star alleles using high-throughput targeted genotyping includes obtaining input genetic sequence variation data from a high-throughput genotyping platform based on a pharmacogenomic genotyping of a sample, applying a Bayesian graphical model to determine a plurality of different star allele calls corresponding to the sample, and providing a respective quality score for each star allele call of the plurality of different star allele calls. For instance, the application of the Bayesian graphical model uses multi-solution integer programming to explore a model space of the Bayesian graphical model in a first phase that includes structural variant candidate identification and a second phase that includes star allele candidate identification based on the structural variant candidate identification, to determine the plurality of different star allele calls.
The assembly includes a docking console and a manifold. The docking console includes a cartridge support surface having a first end and a second end. The manifold has one or more wells defined therein. The docking console further includes a manifold retention bracket to releasably hold the manifold against a fluid cartridge supported on the cartridge support surface at an interface position such that the one or more wells are in fluid communication with the fluid cartridge and a biased seal bar to press the fluid cartridge against the manifold held by the manifold retention bracket. A hydrophilic porous frit disposed within at least one of the wells and is to permit liquid to flow through the outlet aperture but prevent gas from passing through the outlet aperture.
The invention provides systems and methods for making sequencing libraries that are useful for quantitatively analyzing nucleic acids in a sample. Sample nucleic acids are randomly cleaved at, and PCR handled are attached to, a random cut site. The nucleic acid is amplified into a sequencing library in which a sequencing primer generates a sequence read from adjacent the random cut site. The sequence reads can be mapped to a reference, but they will also include a unique identifier sequence that comes from within the nucleic acid molecule being analyzed, i.e., an intrinsic molecular identifier (IMI). The IMI is unique for each molecule and can thus be used to deduplicate sequence reads originating from the same molecule.
In an example of a method for making a flow cell, a sacrificial layer is deposited over a substrate including depressions separated by interstitial regions. The sacrificial layer is dry etched from the depressions, and the sacrificial layer remains on the interstitial regions. A functionalized layer is deposited over the depressions and over the sacrificial layer. The sacrificial layer is removed from the interstitial regions, which also removes the functionalized layer that overlies the interstitial regions.
Array-based targeted copy number detection, for instance detection on contaminated and/or variable concentration samples, includes obtaining a collection of intensity signals from assays of a set of input samples, performing a cross-sample calibration on the intensity signals based on reference sample(s), which calibration includes constructing a reference signal distribution based on intensity signals of the reference sample(s) and for one or more input samples calibrating a set of intensity signals corresponding to the input sample based on the reference signal distribution, determining, for the one or more input samples, and from a respective one or more calibrated sets of intensity signals corresponding to the one or more input samples, a respective at least one aggregated calibrated signal from targeted genomic region(s) to produce a collection of aggregated calibrated signals, and detecting variant(s) in the targeted genomic region(s) based on the collection of aggregated calibrated signals.
Polypeptide nanopores synthetically functionalized with positively charged species, and methods of making and using the same, are provided herein. In some examples, a polypeptide nanopore includes a first side, a second side, a channel extending through the first and second sides, and a mutated amino acid residue. The mutated amino acid residue may be synthetically functionalized with a positively charged species that inhibits translocation of cations through the channel.
G01N 33/487 - Physical analysis of biological material of liquid biological material
B82B 1/00 - Nanostructures formed by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
B82B 3/00 - Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
The present disclosure is directed to decoupling library capture (template seeding) from cluster generation to optimise both processes. This is achieved by introducing orthogonality between the seeding and clustering primer.
The present invention provides systems, apparatuses, and methods to detect the presence of fetal cells when mixed with a population of maternal cells in a sample and to test fetal abnormalities, e.g. aneuploidy. The present invention involves labeling regions of genomic DNA in each cell in said mixed sample with different labels wherein each label is specific to each cell and quantifying the labeled regions of genomic DNA from each cell in the mixed sample. More particularly the invention involves quantifying labeled DNA polymorphisms from each cell in the mixed sample.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
The present invention includes methods and computer programs for use in the detection preeclampsia and/or determining an increased risk for preeclampsia in a pregnant female, the methods including identifying in a biosample obtained from the pregnant female cell-free DNA signals, including concentration, fetal fraction, and fragment size distribution. These methods provide for the identification of patients at risk of preeclampsia in the first trimester of pregnancy.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16H 50/00 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
53.
OLIGO-MODIFIED NUCLEOTIDE ANALOGUES FOR NUCLEIC ACID PREPARATION
Nucleic acid techniques are disclosed. Embodiments include modified nucleotides with oligonucleotide adapters that are coupled via cleavable linkers. Incorporation of the modified nucleotide at a 3′ end of a nucleic acid permits end-adapterization via ligation of a free 5′ end of the oligonucleotide adapter to a 3′ reactive group of the modified nucleotide and cleavage at the cleavable linker to liberate a free 3′ end.
Disclosed herein include methods, compositions, reaction mixtures, kits and systems for identification of methylated cytosines in nucleic acids using a bisulfite-free, one-step chemoenzymatic modification of methylated cytosines.
An array includes a support including a plurality of discrete wells, a gel material positioned in each of the plurality of discrete wells, and a quality control tracer grafted to the gel material in each of the plurality of discrete wells. The quality control tracer comprises (a) a cleavable nucleotide sequence comprising a cleavage site and (b) a detectable label; and in some aspects, is a cleavable nucleotide sequence with a detectable label and a non-reactive nucleotide sequence or a primer nucleotide sequence.
Embodiments of the present disclosure relate to nucleotides with 3′ allyl blocking groups. Also provided herein are methods of sequencing using nucleotides with 3′ allyl blocking groups described herein, and sequencing kits.
The disclosed embodiments concern methods, systems and computer program products for determining sequences of interest using unique molecular indexes (UMIs) that are uniquely associable with individual polynucleotide fragments, including sequences with low allele frequencies or long sequence length. In some implementations, the UMIs include variable-length nonrandom UMIs (vNRUMIs). Methods and systems for making and using sequencing adapters comprising vNRUMIs are also provided.
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
58.
SUBSTITUTED COUMARIN DYES AND USES AS FLUORESCENT LABELS
The present application relates to substituted coumarin derivatives and their uses as fluorescent labels. These compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 407/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
This disclosure describes embodiments of methods, systems, and non-transitory computer readable media that accurately estimates the crosstalk from an adjacent cluster of oligonucleotides onto a target cluster of oligonucleotides and removes or reduces the crosstalk emitted by the adjacent cluster of oligonucleotides from the target cluster of oligonucleotides. For instance, the disclosed systems can detect the intensity values for a target cluster and the adjacent cluster. Based on the intensity values of the adjacent cluster, the disclosed systems can determine an inter-cluster-interference metric that estimates the crosstalk emitted from the adjacent cluster. The disclosed systems can remove the inter-cluster-interference metric from the intensity value of the target cluster and generate modified intensity values for the target cluster.
This disclosure describes embodiments of methods, systems, and non-transitory computer readable media that accurately estimates the crosstalk from an adjacent cluster of oligonucleotides onto a target cluster of oligonucleotides and removes or reduces the crosstalk emitted by the adjacent cluster of oligonucleotides from the target cluster of oligonucleotides. For instance, the disclosed systems can detect the intensity values for a target cluster and the adjacent cluster. Based on the intensity values of the adjacent cluster, the disclosed systems can determine an inter-cluster-interference metric that estimates the crosstalk emitted from the adjacent cluster. The disclosed systems can remove the inter-cluster-interference metric from the intensity value of the target cluster and generate modified intensity values for the target cluster.
Improved copy number variant (CNV) calling in a genomic sequence, and potential recovery, includes (i) obtaining genetic sequence variant data that includes records indicating structural variant(s) (SVs) and records indicating CNV(s) in the genomic sequence, (ii) determining, based on an initial CNV indicated in the genetic sequence variant data and on initial SV(s) indicated in the genetic sequence variant data, an SV-informed CNV call as an updated version of the initial CNV, where the determining uses information from the initial SV(s) to determine a start breakpoint position and an end breakpoint position for the SV-informed CNV call, at least one of the start breakpoint position and end breakpoint position being updated, informed by the initial SV(s), in comparison to a corresponding start breakpoint position and/or end breakpoint position of the initial CNV, and (ii) writing the determined SV-informed CNV call as record(s) in a genetic sequence variant data file.
METHODS OF MODIFYING METHYLCYTOSINE OR DERIVATIVE THEREOF USING A PHOTOREDOX REACTION, AND METHODS OF USING THE SAME TO DETECT THE METHYLCYTOSINE OR DERIVATIVE THEREOF IN A POLYNUCLEOTIDE
Disclosed herein are methods of using photoredox reactions to modify 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), 5-formlcytosine (5-fC), or 5-carboxylcytosine (5-caC) in a polynucleotide. In some examples, a photoredox reaction is used to install a functional group at the 5-position of the 5-caC, wherein the installed functional group further reacts with the 5-caC to form a product having at least two rings. In other examples, a photoredox reaction is used to install a functional group at the 5-methyl group of the 5-mC, wherein the installed functional group further reacts with the 5-mC to form a product having at least two rings. In other examples, a photoredox reaction is used to oxidize the 5-mC or 5-hmC to 5-fC; and a functional group at the 5-position of the 5-fC, wherein the installed functional group further reacts with the 5-fC to form a product having at least two rings.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Systems and methods for identifying conditions in a sample obtain a set of sample sequence reads from the sample. For each respective read, or respective sample contig derived from a respective subset of the set, a corresponding sequence comparison between the respective read or contig and each reference sequence in a set of reference sequences is performed. There is calculated, from these sequence comparisons, a respective probability that the respective read or contig corresponds to a particular reference sequence in the set of reference sequences thereby computing a plurality of probabilities. The presence or an absence of each of the conditions in the sample is identified based at least in part on these probabilities. One condition is identification of a species present in the sample, and the percentage of the genome of this species identified in the reads is provided.
The present disclosure is related to methods and materials for depleting unwanted RNA species from a nucleic acid sample. In particular, the present disclosure describes how to remove unwanted rRNA, tRNA, mRNA or other RNA species that could interfere with the analysis, manipulation and study of target RNA molecules in a sample.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
Systems, methods, and apparatuses are described herein. For instance, a detection apparatus may comprise memory and at least one processor. The detection apparatus may be configured to obtain an image comprising at least one feature and a plurality of fiducials. The plurality of fiducials may be arranged in a pattern. The detection apparatus may be configured to determine a plurality of sub-regions of the image. Each sub-region comprises a subset of the fiducials comprised in the image. The detection apparatus may be configured to perform a geometric transform on each sub-region to generate a respective local transform associated with each sub-region. The detection apparatus may be configured to register respective locations of the fiducials comprised in the image based on the respective local transform associated with each sub-region. A size of each sub-region may be selected such that each sub-region is substantially invariant to stage jitter.
Systems and methods for identifying a host of an AMR marker from one or more samples are provided, which include obtaining short-read sequence data derived from one or more samples; identifying one or more AMR markers from the short-read sequence data to obtain short-read metrics, the short-read metrics comprising quantitative metrics such as RPKM, median depth, read count, or others of any one or more of the AMR markers identified in the short-reads; obtaining one or more reference sequence data; identifying one or more AMR markers from the reference sequence data to obtain reference metrics, the reference metrics comprising quantitative metrics such as RPKM, median depth, read count, or others of any one or more of the AMR markers identified in the reference sequence; identifying a host of the one or more AMR markers in the sample when average ratios between the short-read metrics and the reference metrics are below a threshold ratio.
Systems, methods, and apparatuses are described herein. For instance, a detection apparatus may comprise memory and at least one processor. The detection apparatus may be configured to obtain an image comprising at least one feature and a plurality of fiducials. The plurality of fiducials may be arranged in a pattern. The detection apparatus may be configured to determine a plurality of sub-regions of the image. Each sub-region comprises a subset of the fiducials comprised in the image. The detection apparatus may be configured to perform a geometric transform on each sub-region to generate a respective local transform associated with each sub-region. The detection apparatus may be configured to register respective locations of the fiducials comprised in the image based on the respective local transform associated with each sub-region. A size of each sub-region may be selected such that each sub-region is substantially invariant to stage jitter.
Improved copy number variant (CNV) calling in a genomic sequence, and potential recovery, includes (i) obtaining genetic sequence variant data that includes records indicating structural variant(s) (SVs) and records indicating CNV(s) in the genomic sequence, (ii) determining, based on an initial CNV indicated in the genetic sequence variant data and on initial SV(s) indicated in the genetic sequence variant data, an SV-informed CNV call as an updated version of the initial CNV, where the determining uses information from the initial SV(s) to determine a start breakpoint position and an end breakpoint position for the SV-informed CNV call, at least one of the start breakpoint position and end breakpoint position being updated, informed by the initial SV(s), in comparison to a corresponding start breakpoint position and/or end breakpoint position of the initial CNV, and (ii) writing the determined SV-informed CNV call as record(s) in a genetic sequence variant data file.
Techniques are described for processing a text document or passage to derive a suitable set of phrases from the document or passage. These phrases may in turn be related to codes or other labels useful to a reviewer, such as insurance, diagnostic, or clinical codes, genes related to identified phenotypes, and so forth. In certain embodiments, one or more tries generated based on respective ontologies may be used to process and parse the input text passage or document to derive candidate phrases. To improve performance, a limited number of skips may be allowed. The candidate phrases and corresponding intervals may, in one implementation, be used to populate a graph having nodes and edges and from which a set of phrases may be determined that provides maximal coverage of the text passage or document and having limited (or no) overlaps.
Systems and methods for identifying a host of an AMR marker from one or more samples are provided, which include obtaining short-read sequence data derived from one or more samples; identifying one or more AMR markers from the short-read sequence data to obtain short-read metrics, the short-read metrics comprising quantitative metrics such as RPKM, median depth, read count, or others of any one or more of the AMR markers identified in the short-reads; obtaining one or more reference sequence data; identifying one or more AMR markers from the reference sequence data to obtain reference metrics, the reference metrics comprising quantitative metrics such as RPKM, median depth, read count, or others of any one or more of the AMR markers identified in the reference sequence; identifying a host of the one or more AMR markers in the sample when average ratios between the short-read metrics and the reference metrics are below a threshold ratio.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
72.
PALLADIUM CATALYST COMPOSITIONS AND METHODS FOR SEQUENCING BY SYNTHESIS
The present application relates to palladium catalyst composition and uses in sequencing by synthesis. In particular, the Pd catalyst composition comprises one or more macrocycles (e.g., cyclodextrin or analogs thereof) as additives for improving thermal or oxidative stability of the active Pd(0) species.
Embodiments of the present invention relate to analyzing components of a cell. In some embodiments, the present invention relate to analyzing components of a single cell. In some embodiments, the methods and compositions relate to sequencing nucleic acids. In some embodiments, the methods and compositions relate to identifying and/or quantitating nucleic acid, proteins, organelles, and/or cellular metabolites.
A composition for amplifying a polynucleotide is provided that includes a substrate comprising a first region and a second region. A first plurality of capture primers is coupled to the first region of the substrate. A second plurality of capture primers is coupled to the second region of the substrate. The capture primers of the second plurality of capture primers are longer than the capture primers of the first plurality of capture primers. A first plurality of orthogonal capture primers are coupled to the first region of the substrate. A second plurality of orthogonal capture primers are coupled to the second region of the substrate. The orthogonal capture primers of the second plurality of orthogonal capture primers are shorter than the orthogonal capture primers of the first plurality of orthogonal capture primers.
We propose a neural network-implemented method for base calling analytes. The method includes accessing a sequence of per-cycle image patches for a series of sequencing cycles, where pixels in the image patches contain intensity data for associated analytes, and applying three-dimensional (3D) convolutions on the image patches on a sliding convolution window basis such that, in a convolution window, a 3D convolution filter convolves over a plurality of the image patches and produces at least one output feature. The method further includes beginning with output features produced by the 3D convolutions as starting input, applying further convolutions and producing final output features and processing the final output features through an output layer and producing base calls for one or more of the associated analytes to be base called at each of the sequencing cycles.
G06V 10/75 - Image or video pattern matching; Proximity measures in feature spaces using context analysis; Selection of dictionaries
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
76.
Deep Learning-Based Pathogenicity Classifier for Promoter Single Nucleotide Variants (pSNVs)
We disclose computational models that alleviate the effects of human ascertainment biases in curated pathogenic non-coding variant databases by generating pathogenicity scores for variants occurring in the promoter regions (referred to herein as promoter single nucleotide variants (pSNVs)). We train deep learning networks (referred to herein as pathogenicity classifiers) using a semi-supervised approach to discriminate between a set of labeled benign variants and an unlabeled set of variants that were matched to remove biases.
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G06N 3/044 - Recurrent networks, e.g. Hopfield networks
Embodiments of the present disclosure relate to nucleotide and nucleoside molecules with 3′ vinyl or isonitrile containing blocking groups and/or tetrazine or strained unsaturated ring containing cleavable linkers. Additionally, the present disclosure provides methods of using the nucleoside/nucleotide in oligonucleotide synthesis, and methods of sequencing using the nucleotide described herein.
The present application relates to compositions and methods for sequencing by synthesis. A blocking group of a nucleotide may be removed by a transition metal catalyst, the transition metal catalyst activated by a non-reducing ligand and a reducing agent.
B01J 31/14 - Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides of aluminium or boron
Described herein are methods of removing false positive uracils due to the deamination of unmethylated cytosines in assays using engineered cytosine deaminases to deaminate methylated cytosines, the methods utilizing enzymes that discriminate against uracil residues, such as for example, uracil-intolerant polymerases, uracil DNA glycosylase (UDG), and/or USER™ (Uracil-Specific Excision Reagent) enzyme, to remove false positive uracil residues from cytidine deaminase mediated methylation sequencing assays.
This application relates to methods of denaturing double-stranded DNA (dsDNA). In some examples, the methods utilize dried sodium hydroxide. In some examples, the method includes loading dsDNA into a first portion of a cartridge, wherein the second portion of the cartridge contains sodium hydroxide in a dry form; and mixing the dsDNA with the sodium hydroxide, thereby denaturing the dsDNA.
The technology disclosed corrects inter-cluster intensity profile variation for improved base calling on a cluster-by-cluster basis. The technology disclosed accesses current intensity data and historic intensity data of a target cluster, where the current intensity data is for a current sequencing cycle and the historic intensity data is for one or more preceding sequencing cycles. A first accumulated intensity correction parameter is determined by accumulating distribution intensities measured for the target cluster at the current and preceding sequencing cycles. A second accumulated intensity correction parameter is determined by accumulating intensity errors measured for the target cluster at the current and preceding sequencing cycles. Based on the first and second accumulated intensity correction parameters, next intensity data for a next sequencing cycle is corrected to generate corrected next intensity data, which is used to base call the target cluster at the next sequencing cycle.
G06F 18/2411 - Classification techniques relating to the classification model, e.g. parametric or non-parametric approaches based on the proximity to a decision surface, e.g. support vector machines
G06F 18/2135 - Feature extraction, e.g. by transforming the feature space; Summarisation; Mappings, e.g. subspace methods based on approximation criteria, e.g. principal component analysis
Embodiments of the present disclosure relate to nucleotides with 3' allyl blocking groups. Also provided herein are methods of sequencing using nucleotides with 3' allyl blocking groups described herein, and sequencing kits.
C40B 50/14 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
84.
SPATIAL TRANSCRIPTOMICS LIBRARY PREPARATION MATERIALS AND METHODS
The present disclosure relates, in general, to methods for improving preparation of a spatial transcriptomics RNA, library, for example a mRNA library, by improving capture of RNA transcript information from a tissue sample in situ. The spatial transcriptomics library from a tissue sample is useful to determine a genetic profile and help diagnose a person who has or is at risk of having a disease, such as cancer, genetic disease, autoimmune disease, and other indications, and improve treatment of the subject.
The present application relates to palladium compositions, methods for sequencing by synthesis using nucleotides with 3′ blocking groups, and sequencing kits, where one or more palladium scavengers were used to improve sequencing metrics such phasing and prephasing values.
Examples of flow cells include substrates. Embodiments of the present disclosure also relate to methods of fabricating flow cell substrates. Some example workflows exploit light blocking properties of an imprint layer such that the process does not include etch steps. Such processes may be used to create substrates compatible with simultaneous paired-end sequencing methods.
G03F 7/11 - Photosensitive materials - characterised by structural details, e.g. supports, auxiliary layers having cover layers or intermediate layers, e.g. subbing layers
B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
G03F 7/038 - Macromolecular compounds which are rendered insoluble or differentially wettable
87.
AMPLIFICATION TECHNIQUES FOR NUCLEIC ACID CHARACTERIZATION
Nucleic acid amplification techniques are disclosed. Embodiments include generating concatenated nucleic acids using rolling circle amplification of templates, e.g., starting from a cDNA of a full-length mRNA or from synthetic templates, and sequencing and/or detecting the concatenated nucleic acids. In some embodiments, the technology disclosed includes amplification reactions that include CRISPR-Cas interactions that generate primers as a result of the CRISPR-Cas interactions, whereby primers are in turn used as part of detectable amplification reactions. The disclosed amplification techniques may use synthetic oligonucleotides or primers.
The invention relates to methods for indexing samples during the sequencing of polynucleotide templates, resulting in the attachment of tags specific to the source of each nucleic acid sample such that after a sequencing run, both the source and sequence of each polynucleotide can be determined. Thus, the present invention pertains to analysis of complex genomes (e.g., human genomes), as well as multiplexing less complex genomes, such as those of bacteria, viruses, mitochondria, and the like.
The present disclosure relates, in general, to materials and methods for improving RNA capture in situ from tissue samples and improved methods for synthesizing cDNA from the captured RNA.
Biological samples on multiple surfaces of a support structure may be imaged using a machine comprising a lens, a flow cell and a controller. Such a machine may capture light emitted from nucleic acids disposed on first and second surfaces of the flow cell when the lens is, respectively, at first and second distances from the flow cell. In such a machine, the lens may be immersed in a first fluid, and the first and second surfaces of the flow cell may be separated by a second fluid. Additionally, in such a machine, differences between marginal and axial light rays in the field of view of the lens may be substantially equal when the lens is at the first and second distances from the flow cell.
The technology disclosed is directed to context-dependent base calling. The technology disclosed describes a system including memory storing k-mer-specific centroids for k-mers. The k-mer-specific centroids are learned by training a base calling pipeline to represent base calls of an already base called sequence in k-mer-specific time series, transform the k-mer-specific time series into predicted k-mer-specific centroids, merge the predicted k-mer-specific centroids on a sequencing cycle-by-sequencing cycle basis to generate predicted per-sequencing cycle intensity values, determine a training loss (e.g., a transformation loss) based on comparing the predicted per-sequencing cycle intensity values against known intensity values of the base calls, update the predicted k-mer-specific centroids based on the determined training loss, and store the updated centroids as the k-mer-specific centroids. The system also includes runtime logic that uses the k-mer-specific centroids to base call bases in a yet-to-be base called sequence in dependence upon k-mer context.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
92.
METHODS OF SEQUENCING USING 3' BLOCKED NUCLEOTIDES
Embodiments of the present disclosure relate to nucleotide and nucleoside molecules with acetal or allyl 3′ blocking groups. Also provided herein are methods to prepare such nucleotide and nucleoside molecules, and the uses of fully functionalized nucleotides containing the 3′ blocking groups for sequencing applications.
In an example method, a positive photoresist is deposited over a substrate that includes depressions separated by interstitial regions. The positive photoresist is exposed to ultraviolet light at an angle that is non-perpendicular, non-parallel, and offset from a surface plane of the depressions such that a first portion of the positive photoresist in each depression remains soluble and a second portion of the positive photoresist in each depression is rendered insoluble. The soluble portions of the positive photoresist are removed, which exposes a first substrate portion in each depression. A first functionalized layer is deposited over the first substrate portion in each depression. The insoluble portions of the positive photoresist are removed, which exposes a second substrate portion in each depression. The second functionalized layer is selectively deposited over the second substrate portion in each depression.
G03F 7/039 - Macromolecular compounds which are photodegradable, e.g. positive electron resists
G03F 7/038 - Macromolecular compounds which are rendered insoluble or differentially wettable
G03F 7/11 - Photosensitive materials - characterised by structural details, e.g. supports, auxiliary layers having cover layers or intermediate layers, e.g. subbing layers
Methods for on-flow cell selective capture and enrichment of clustered beads, general capture strategies on bead mobility on flow cell surfaces, sorting clustered and unclustered beads, and flow cell reusability for bead immobilization onto flow cells.
An example of a flow cell includes a substrate; a plurality of reactive regions spatially separated from one another across the substrate; and a plurality of independently removable coatings respectively positioned over each of the plurality of reactive regions. Each of the plurality of reactive regions includes a polymeric hydrogel layer; and a reactive entity attached to the polymeric hydrogel layer.
Flow cell assemblies and related systems and methods are disclosed. An apparatus includes a flow cell assembly having a body, a first laminate, a second laminate, and a flow cell. The body carries a flow cell inlet gasket, a flow cell outlet gasket, and an outlet gasket. The body includes a fluidic aperture. The first laminate is coupled to the body and forms a first fluidic channel between the flow cell outlet gasket and the fluidic aperture. The second laminate is coupled to the body and forms a second fluidic channel between the fluidic aperture and the outlet gasket. The flow cell is supported by the body and includes a channel having a flow cell inlet and a flow cell outlet. The flow cell inlet is fluidly coupled to the flow cell inlet gasket and the flow cell outlet is fluidly coupled to the flow cell outlet gasket.
A method for modifying an interstitial surface separating recesses from one another can include flowing a first fluid over the interstitial surface and into the recesses, such that the interstitial surface is substantially coated with the first fluid and the recesses are substantially filled with the first fluid; and while the first fluid remains within the recesses, replacing the first fluid coating the interstitial surface with a second fluid comprising a reagent.
Multivalent assemblies for target hybridization are described. The multivalent assemblies include oligonucleotide sets that hybridize to a target nucleic acid to permit capture of the target nucleic acid. In an embodiment, the multivalent assemblies are heteromultivalent such that the oligonucleotide sets include different oligonucleotides that bind to different regions of the target nucleic acid.
The present application relates to compositions and methods for sequencing by synthesis. A blocking group of a nucleotide may be removed by a transition metal catalyst, the transition metal catalyst activated by a non-reducing ligand and a reducing agent.
Systems, methods, and apparatus are described herein for aggregating genome data into bins with summary data at various levels. As described herein, a computing device may be configured to receive genome data associated with a genome. The computing device may be configured to generate an aggregate file using the received genome data. The aggregate file may include a plurality of bins at a plurality of depths. The computing device may be configured to determine summary data for respective reads associated with one or more respective portions of the genome covered by respective bins of the plurality of bins. The computing device may be configured to store the summary data for the respective reads in respective bins of the plurality of bins. The computing device may be configured to display a portion of the summary data in response to a selection of a genomic region by a user.
