Embodiments of the present disclosure relate to nucleotide with acetal 3′-OH blocking groups. Also provided herein are methods of using fully functionalized nucleotides containing the 3′ acetal blocking group for sequencing applications.
The present disclosure relates to a nanoparticle including a first layer including a first polymer and a first plurality of accessory oligonucleotides, a second layer including a second polymer and a single template site for bonding a template polynucleotide, and a third layer including a third polymer and a second plurality of accessory oligonucleotides. Also described herein is a method of making said nanoparticle, including “dip-coating,” e.g., successively dipping a surface with wettable nanodomains in different polymer solutions. Further described herein is a method of making the nanoparticles by forming them in nanowells and subsequently releasing them from the nanowells. Also described herein is a method of attaching the nanoparticle to a substrate and amplifying the template polynucleotide using a polymerase.
Genome-wide association studies may allow for detection of variants that are statistically significantly associated with disease risk. However, inferring which are the genes underlying these variant associations may be difficult. The presently disclosed approaches utilize machine learning techniques to predict genes from genome-wide association study summary statistics that substantially improves causal gene identification in terms of both precision and recall compared to other techniques.
G16H 50/20 - TIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicales; TIC spécialement adaptées à la détection, au suivi ou à la modélisation d’épidémies ou de pandémies pour le diagnostic assisté par ordinateur, p.ex. basé sur des systèmes experts médicaux
4.
PHOTO-SWITCHABLE CHEMISTRY FOR REVERSIBLE HYDROGELS AND REUSABLE FLOW CELLS
322H end group for dual functionality and/or pH responsiveness. For nucleic acid sequencing, amplification primers are grafted to photochemically-reversible hydrogels or nanogel particles reversibly bound to surfaces within a flow cell. After sequencing is complete, the photochemically-reversible hydrogel or nanogel particles is/are removable from the flow cell surfaces by irradiation, enabling the flow cell to be reusable.
Genome-wide association studies may allow for detection of variants that are statistically significantly associated with disease risk. However, inferring which are the genes underlying these variant associations may be difficult. The presently disclosed approaches utilize machine learning techniques to predict genes from genome-wide association study summary statistics that substantially improves causal gene identification in terms of both precision and recall compared to other techniques.
Provided herein is a method of using transposition to improve methods of sequencing RNA molecules. Provided herein is a method of tagging nucleic acid duplexes, such as DNA:RNA duplexes or DNA:DNA duplexes. The method includes the steps of providing a transposase and a transposon composition, providing one or more nucleic acid duplexes immobilized on a support, and contacting the transposase and transposon composition with the one or more nucleic acid duplexes under conditions wherein the one or more nucleic acid duplexes and transposon composition undergo a transposition reaction to produce one or more tagged nucleic acid duplexes, wherein the transposon composition comprises a double stranded nucleic acid molecule comprising a transferred strand and a non-transferred strand.
The disclosure relates to methods, compositions, and kits for improving seeding efficiency of flow cells with polynucleotides, and applications thereof, including for sequencing.
In some examples, novel nanogel particles are described having dual functionality, temperature responsiveness and pH responsiveness. For nucleic acid sequencing, amplification primers are grafted to nanogel particles to form primer-grafted nanogel particles, and the primer-grafted nanogel particles are captured onto surfaces within a flow cell. Within flow cells such as used in SBS nucleic acid sequencing, each primer-grafted nanogel particle functions as a nano-well in the flow cell, thus eliminating the need for nano-wells in some examples.
C08F 220/18 - Esters des alcools ou des phénols monohydriques des phénols ou des alcools contenant plusieurs atomes de carbone avec l'acide acrylique ou l'acide méthacrylique
C08F 220/60 - Amides contenant de l'azote en plus de l'azote de la fonction carbonamide
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p.ex. pour test de réaction en chaîne par polymérase [PCR]
An example of a flow cell includes a base support, a reversibly swellable resin positioned over the base support, and a depression defined in the reversibly swellable resin. The reversibly swellable resin includes at least one hydrophilic monomer selected from the group consisting of a poly(ethylene glycol) based monomer, poly(propylene glycol) based monomer, and combinations thereof. The depression has a first opening dimension when the reversibly swellable resin is in a non-swelled stated and has a second opening dimension, that is smaller than the first opening dimension, when the reversibly swellable resin is in a swelled state.
The present disclosure relates to a nanoparticle including a first layer including a first polymer and a first plurality of accessory oligonucleotides, a second layer including a second polymer and a single template site for bonding a template polynucleotide, and a third layer including a third polymer and a second plurality of accessory oligonucleotides. Also described herein is a method of making said nanoparticle, including "dip-coating," e.g., successively dipping a surface with wettable nanodomains in different polymer solutions. Further described herein is a method of making the nanoparticles by forming them in nanowells and subsequently releasing them from the nanowells. Also described herein is a method of attaching the nanoparticle to a substrate and amplifying the template polynucleotide using a polymerase.
Polynucleotide sequencing methods include incubating unlabeled nucleotides with a cluster of template polynucleotide strands having the same sequence when the identity of the previously added labeled nucleotide is being detected. The detection step provides time for the addition of the unlabeled nucleotides to be incorporated into the copy strands in which the previously added labeled nucleotide did not get incorporated. Thus, at the end of the detection step, all or most of the copy strands will be in phase and ready to incorporate the appropriate labeled nucleotide in the subsequence incorporate step.
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
C12Q 1/25 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des enzymes qui ne peuvent pas être classées dans les groupes
An example of a flow cell includes a base support, a reversibly swellable resin positioned over the base support, and a depression defined in the reversibly swellable resin. The reversibly swellable resin includes at least one hydrophilic monomer selected from the group consisting of a poly(ethylene glycol) based monomer, poly(propylene glycol) based monomer, and combinations thereof. The depression has a first opening dimension when the reversibly swellable resin is in a non-swelled stated and has a second opening dimension, that is smaller than the first opening dimension, when the reversibly swellable resin is in a swelled state.
In an example of a method, a deoxyribonucleic acid sample is exposed to tagmentation in the presence of a tagmentation buffer including a divalent cation cofactor and a transposase enzyme to generate a tagmented DNA fragment complex. A chelator mixture is added to the tagmented DNA fragment complex. The chelator mixture includes a chelator of the divalent cation cofactor at a weight ratio that is at least 1:1 with the divalent cation cofactor; and has a pH ranging from 8 to 9. The tagmented DNA fragment complex is incubated in the chelator mixture at a temperature of at least 55°C for at least about 60 seconds, so that the transposase enzyme dissociates from a tagmented DNA fragment of the tagmented DNA fragment complex.
Methods of Preparing Directional Tagmentation Sequencing Libraries Using Transposon-Based Technology with Unique Molecular Identifiers for Error Correction
Materials and methods for preparing nucleic acid libraries for next-generation sequencing are described herein. A variety of approaches are described relating to the use of unique molecular identifiers with transposon-based technology in the preparation of sequencing libraries. Also described herein are sequencing materials and methods for identifying and correcting amplification and sequencing errors.
An example nanoimprint lithography (NIL) resin composition includes a total of three monomers, wherein two of the three monomers are selected from the group consisting of two different epoxy substituted silsesquioxane monomers; two different epoxy substituted cyclosiloxane monomers; and two different non-organosilicon epoxy monomers. A third of the three monomers is a fluorinated monomer that is present in an amount ranging from about from 0.5 mass % to about 4 mass %, based on a total solids content of the NIL resin composition. The NIL resin also includes a photoinitiator and a solvent.
C09D 163/00 - Compositions de revêtement à base de résines époxy; Compositions de revêtement à base de dérivés des résines époxy
C08G 59/36 - Composés époxydés contenant au moins trois groupes époxyde en mélange avec des composés mono-époxydés
C08G 59/32 - Composés époxydés contenant au moins trois groupes époxyde
C08G 59/68 - Macromolécules obtenues par polymérisation à partir de composés contenant plusieurs groupes époxyde par molécule en utilisant des agents de durcissement ou des catalyseurs qui réagissent avec les groupes époxyde caractérisées par les catalyseurs utilisés
C09D 7/63 - Adjuvants non macromoléculaires organiques
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
16.
MULTIBAND SCANNING AND FIBER BUNDLE TO ENABLE REDUCED LIGHT SOURCE INTENSITY AND IMPROVED IMAGING QUALITY
Some implementations of the disclosure describe an imaging system comprising: a camera including multiple image sensors that are spaced apart, each of the image sensors to capture an image of a respective sample location of multiple sample locations of a sample; and a fiber bundle comprising multiple fiber cores, each of the fiber cores to emit a light beam that is projected on a respective one of the sample locations.
G02B 6/04 - OPTIQUE ÉLÉMENTS, SYSTÈMES OU APPAREILS OPTIQUES - Détails de structure de dispositions comprenant des guides de lumière et d'autres éléments optiques, p.ex. des moyens de couplage formés par des faisceaux de fibres
An example nanoimprint lithography (NIL) resin composition includes a total of three monomers, wherein two of the three monomers are selected from the group consisting of two different epoxy substituted silsesquioxane monomers; two different epoxy substituted cyclosiloxane monomers; and two different non-organosilicon epoxy monomers. A third of the three monomers is a fluorinated monomer that is present in an amount ranging from about from 0.5 mass% to about 4 mass%, based on a total solids content of the NIL resin composition. The NIL resin also includes a photoinitiator and a solvent.
An example of a sequencing nanoparticle includes a core of a negatively chargeable, hydrophobic polymer. Alternating layers of a positively charged acrylamide hydrogel and the negatively charged polymer are positioned on the core, wherein the positively charged acrylamide hydrogel forms an outer layer of the sequencing nanoparticle. A negatively charged primer set is attached to the outer layer.
An example of a sequencing nanoparticle includes a core of a negatively chargeable, hydrophobic polymer. Alternating layers of a positively charged acrylamide hydrogel and the negatively charged polymer are positioned on the core, wherein the positively charged acrylamide hydrogel forms an outer layer of the sequencing nanoparticle. A negatively charged primer set is attached to the outer layer.
A co-polymer includes a plurality of a first monomer including a terminal functional group that is to attach to at least two different primers; a plurality of a second monomer including a second functional group that is different from the terminal functional group, and that is selected from the group consisting of a phenyl group, methoxy propyl, glycosyl, vinyl pyrrolidone, and an imidazole group; and a plurality of a third monomer that is different from the first and second monomers. This co-polymer may be used in a flow cell, and may enhance the clustering efficiency and kinetics.
Disclosed herein is a method for enriching a sequencing library comprising double-stranded nucleic acid fragments comprising preparing a library of double-stranded fragments having one or more adaptors at ends of the double-stranded fragment; denaturing the double-stranded fragments to form single-stranded fragments; and hybridizing an extension primer that binds to a target sequence of at least one insert in the library of double-stranded fragments and that does not bind to non-target sequences. In an embodiment, the adaptor is a hairpin adaptor, and extension from the extension primer using a polymerase with 5′ to 3′ exonuclease activity removes all or part of a sequence of the hairpin adaptor that is at least partially complementary to the amplification primer sequence. Each fragment may comprise an insert comprising double-stranded nucleic acid and a hairpin adaptor at the 5′ end of one or both strands of the double-stranded fragments. Hairpin adaptors may comprise an amplification primer sequence and a sequence at least partially complementary to the amplification primer sequence.
The present application relates to dyes containing fused tetracyclic bis-boron containing heterocycle and their uses as fluorescent labels. These dyes may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.
In an example method, a series of time-based clustering images is generated for a plurality of library fragments from a genome sample. Each time-based clustering image in the series is sequentially generated. To generate each time-based clustering image in the series: i) a respective sample is introduced to a flow cell, the respective sample including contiguity preserved library fragments of the plurality of library fragments, wherein the contiguity preserved library fragments are attached to a solid support or are attached to each other; ii) the contiguity preserved library fragments are released from the solid support or from each other; iii) the contiguity preserved library fragments are amplified to generate a plurality of respective template strands; iv) the respective template strands are stained; and v) the respective template strands are imaged.
G06F 16/58 - Recherche caractérisée par l’utilisation de métadonnées, p.ex. de métadonnées ne provenant pas du contenu ou de métadonnées générées manuellement
G06V 10/26 - Segmentation de formes dans le champ d’image; Découpage ou fusion d’éléments d’image visant à établir la région de motif, p.ex. techniques de regroupement; Détection d’occlusion
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
B01L 7/00 - Appareils de chauffage ou de refroidissement; Dispositifs d'isolation thermique
Described herein is a polynucleotide for use as a sequencing template comprising multiple inserts. Also described herein are method of generating and using these polynucleotides and methods of use of such templates, including analysis of contiguity information. Further, sequencing templates comprising an insert sequence and a copy of the insert sequence can be used to correct for random errors generated during sequencing or amplification or to identify nucleobase damage or other mutation that leads to non-canonical base pairing in a double-stranded nucleic acid. Methods of performing methylation analysis are also described herein.
A co-polymer includes a plurality of a first monomer including a terminal functional group that is to attach to at least two different primers; a plurality of a second monomer including a second functional group that is different from the terminal functional group, and that is selected from the group consisting of a phenyl group, methoxy propyl, glycosyl, vinyl pyrrolidone, and an imidazole group; and a plurality of a third monomer that is different from the first and second monomers. This co-polymer may be used in a flow cell, and may enhance the clustering efficiency and kinetics.
A flow cell includes a support and a heteropolymer attached to the support. The heteropolymer includes an acrylamide monomer including an attachment group to react with a functional group attached to a primer, and a monomer including a stimuli-responsive functional group. The monomer including the stimuli-responsive functional group may be pH-responsive, temperature-responsive, saccharide-responsive, nucleophile-responsive, and/or salt-responsive.
The present disclosure relates to methods, compositions, and kits for treating target nucleic acids, including methods and compositions for fragmenting and tagging nucleic acid (e.g., DNA) using transposome complexes bound to a solid support.
Embodiments of the present disclosure relate to kits, compositions, and methods for nucleic acid sequencing, for example, two-channel nucleic acid sequencing by synthesis using blue and green light excitation. In particular, unlabeled nucleotides for incorporation may be used in conjunction with affinity reagents containing detectable labels excitable by blue and/or green lights, for specific binding to each type of nucleotides incorporated.
3'-blocked nucleotides, methods of deblocking the same, and methods of synthesizing polynucleotides using the same are provided herein. In some examples, a nucleotide is disposed within the aperture on the first side of a nanopore. The nucleotide may be coupled to a 3'-blocking group including a trigger. The trigger may be selectively activated using an initiator. The activated trigger may be used to remove the 3'-blocking group from the nucleotide.
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p.ex. pour test de réaction en chaîne par polymérase [PCR]
C07H 19/10 - Radicaux pyrimidine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques
C07H 19/20 - Radicaux purine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques
C07H 21/00 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to certain pharmacogenetic (PGX) genes. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to major histocompatibility complex (MHC) genes. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
The technology disclosed directly operates on sequencing data and derives its own feature filters. It processes a plurality of aligned reads that span a target base position. It combines elegant encoding of the reads with a lightweight analysis to produce good recall and precision using lightweight hardware. For instance, one million training examples of target base variant sites with 50 to 100 reads each can be trained on a single GPU card in less than 10 hours with good recall and precision. A single GPU card is desirable because it a computer with a single GPU is inexpensive, almost universally within reach for users looking at genetic data. It is readily available on could-based platforms.
G16B 40/00 - TIC spécialement adaptées aux biostatistiques; TIC spécialement adaptées à l’apprentissage automatique ou à l’exploration de données liées à la bio-informatique, p.ex. extraction de connaissances ou détection de motifs
G16B 20/00 - TIC spécialement adaptées à la génomique ou protéomique fonctionnelle, p. ex. corrélations génotype-phénotype
Provided is a method, including stretching a polynucleotide over a substrate including a plurality of equally spaced cleavage regions including a plurality of transposases, cleaving the polynucleotide with two or more of the plurality of transposases to form a plurality of polynucleotide fragments, and separating, within the plurality of polynucleotide fragments, a population of longer polynucleotide fragments from a population of shorter polynucleotide fragments. Also provided is a method including stretching a polynucleotide over a substrate including a plurality of equally spaced cleavage regions including a plurality of transposases, cleaving the polynucleotide with two or more of the plurality of transposases to form a plurality of polynucleotide fragments, and separating, within the plurality of polynucleotide fragments, a population of longer polynucleotide fragments from a population of shorter polynucleotide fragments.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to an American College of Medical Genetics (ACMG) panel of genes. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to certain challenging medically relevant genes (CMRG). Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to certain genes throughout the genome and expressed regions with low mappability. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
A transposome complex capable of producing size-controlled nucleic acid fragments is described herein. In some embodiments, the transposome complex includes multiple inactive transposomes with active transposomes on both ends of the multiple inactive transposomes. Applications, uses, and variations of the disclosed transposome complex include, but are not limited to, library preparation for a nucleic acid and tuning the length of the transposome complex to produce nucleic acid fragments of predetermined or desired lengths.
Reagent cartridges and related systems and methods for controlling reagent temperature are disclosed. In accordance with an implementation, an apparatus includes a system and a reagent cartridge. The system includes a reagent cartridge receptacle, a non-contact temperature controller, a processor operatively coupled to the temperature controller. The reagent cartridge is receivable within the reagent cartridge receptacle and includes a flow cell assembly, a plurality of reagent reservoirs, and a manifold assembly. The manifold assembly includes a common fluidic line and a plurality of reagent fluidic lines. Each of the plurality of reagent fluidic lines is adapted to be fluidically coupled to a corresponding reagent reservoir and selectively couplable to the common fluidic line. The processor is to cause the temperature controller to change a temperature of at least one of the common fluidic line or one or more of the reagent fluidic lines.
Presented herein are altered polymerase enzymes for improved incorporation of nucleotides and nucleotide analogues, in particular altered polymerases that maintain high fidelity under reduced incorporation times, as well as methods and kits using the same.
Embodiments of the present disclosure relate to compositions and kits for use in sequencing by synthesis to improve fluorescent signal intensity and reduce signal decay caused by short wavelength light source during the imaging events. Methods of sequencing using the compositions and kits described herein are also provided.
C07H 21/00 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques
C07H 21/04 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p.ex. acides nucléiques avec le désoxyribosyle comme radical saccharide
C12Q 1/6809 - Méthodes de détermination ou d’identification des acides nucléiques faisant intervenir la détection différentielle
C12Q 1/6816 - Tests d’hybridation caractérisés par les moyens de détection
42.
METHODS AND SYSTEMS FOR ENCAPSULATING LYOPHILISED MICROSPHERES
The present disclosure relates to a method, including providing one or more lyophilised microspheres in a mixing vessel at a first temperature and generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel, under conditions effective to encapsulate the one or more lyophilised microspheres with a coating formulation. In an example, the fluidized bed has a fluidization rate of between about 1 cubic meters per hour (m3/h) and about 30 m3/h. In another example, the fluidized bed has an environmental humidity of between about 10% and about 20%. In still another example, the coating formulation is applied at a spray rate of between about 1.5 grams per minute (g/min) and about 10 g/min. In yet another example, the coating formulation is applied at an atomizing rate of between about 0.5 bar and about 1.5 bar. In a further example, the fluidized bed is in a Wurster configuration, a top spray configuration, or a combination thereof. The present disclosure also relates to a system, including one or more lyophilised microspheres, a mixing vessel configured for holding the one or more lyophilised microspheres, a mixer for generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel at a location, and at least one spray nozzle configured to introduce a shell formulation into the mixing vessel at the location.
The present disclosure relates to a method, including providing one or more lyophilised microspheres in a mixing vessel at a first temperature and generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel, under conditions effective to encapsulate the one or more lyophilised microspheres with a coating formulation. In an example, the fluidized bed has a fluidization rate of between about 1 cubic meters per hour (m3/h) and about 30 m3/h. In another example, the fluidized bed has an environmental humidity of between about 10% and about 20%. In still another example, the coating formulation is applied at a spray rate of between about 1.5 grams per minute (g/min) and about 10 g/min. In yet another example, the coating formulation is applied at an atomizing rate of between about 0.5 bar and about 1.5 bar. In a further example, the fluidized bed is in a Wurster configuration, a top spray configuration, or a combination thereof. The present disclosure also relates to a system, including one or more lyophilised microspheres, a mixing vessel configured for holding the one or more lyophilised microspheres, a mixer for generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel at a location, and at least one spray nozzle configured to introduce a shell formulation into the mixing vessel at the location.
B01J 13/04 - Fabrication de microcapsules ou de microbilles par des procédés physiques, p.ex. séchage, pulvérisation
B01J 8/18 - Procédés chimiques ou physiques en général, conduits en présence de fluides et de particules solides; Appareillage pour de tels procédés les particules étant fluidisées
44.
DNA ORIGAMI STRUCTURE AND PROTEIN NANOPORE CONSTRUCT
The present application discloses a novel DNA origami structure and a nanopore construct associated with the DNA origami structure. The DNA origami structure includes a first hydrophilic section at a first end of the DNA origami structure, a stopper section adjacent the first hydrophilic section, a second hydrophilic section at a second end of the DNA origami structure, a hydrophobic section between the stopper section and the second hydrophilic section, and an open cavity running through the DNA origami structure from the first end to the second end. The stopper section is configured to lay against the membrane when the DNA origami structure is inserted through the membrane.
The present disclosure relates to methods, compositions, and kits for generating a library of tagged nucleic acid fragments without using PCR amplification, including methods and compositions for fragmenting and tagging nucleic acids (e.g., DNA) using transposome complexes immobilized on solid support.
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p.ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6837 - Couplage enzymatique ou biochimique d’acides nucléiques à une phase solide utilisant des réseaux de sondes ou des puces à sondes
C12Q 1/6853 - Réactions d’amplification d’acides nucléiques utilisant des amorces ou des matrices modifiées
C40B 40/06 - Bibliothèques comprenant des nucléotides ou des polynucléotides ou leurs dérivés
C40B 50/14 - Synthèse en phase solide, c. à d. dans laquelle au moins un bloc servant à créer la bibliothèque est lié à un support solide au cours de la création de la bibliothèque; Procédés particuliers de clivage à partir du support solide
There is set forth herein, in one example, an apparatus. The apparatus can comprise, for example: a first reaction site and a second reaction site associated to a common pixel, wherein the pixel comprises a pixel sensor.
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.
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.
The present disclosure is concerned with proteins, methods, compositions, and kits for mapping of methylation status of nucleic acids, including 5-methylcytosine and 5-hydroxymethyl cytosine (5hmC). In one embodiment, proteins are provided that selectively act on certain modified cytosines of target nucleic acids and converts them to thymidine or modified thymidine analogues. In another embodiment, proteins are provided that selectively act on certain modified cytosines of target nucleic acids and converts them to uracil or thymidine and selectively do not act on other certain modified cytosines of target nucleic acids. Also provided are compositions and kits that include one or more of the proteins and methods for using one or more of the proteins.
The application relates to DNA sequencing systems and methods. Systems and methods for determining the nucleotide sequence of a polynucleotide include attaching three different fluorescent dyes to three different nucleotides during incorporation. In particular, long Stokes shifted dyes may be used to determine the sequence of polynucleotides in a sequencing by synthesis system.
Embodiments of the present disclosure relate to compositions and methods for improving the intensity of the fluorescent signals during nucleic acid sequencing. In particular, at least one biotin-binding site of the labeled streptavidin is blocked to reduce fluorescent signal deflation.
The present application relates to chromenoquinoline dyes and their uses as fluorescent labels. For example, these dyes may be used to label nucleotides for nucleic acid sequencing.
C09B 57/00 - Autres colorants synthétiques de structure connue
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
G01N 33/50 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique
The present disclosure is generally directed to strategies for template capture and amplification during sequencing. In some examples, a solid support is used for template capture and amplification.
Barriers including molecules covalently bonded to amphiphilic molecules, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids includes one or more layers comprising a plurality of amphiphilic molecules; and a first layer comprising a plurality of molecules covalently bonded to amphiphilic molecules of the plurality of amphiphilic molecules.
B01D 67/00 - Procédés spécialement adaptés à la fabrication de membranes semi-perméables destinées aux procédés ou aux appareils de séparation
B01D 69/02 - Membranes semi-perméables destinées aux procédés ou aux appareils de séparation, caractérisées par leur forme, leur structure ou leurs propriétés; Procédés spécialement adaptés à leur fabrication caractérisées par leurs propriétés
Embodiments of the present disclosure relate to compositions and kits for use in sequencing by synthesis to improve fluorescent signal intensity and reduce signal decay caused by short wavelength light source during the imaging events. Methods of sequencing using the compositions and kits described herein are also provided.
Embodiments of the present disclosure relate to modified extension primers for use in generating clustered polynucleotides for sequencing by synthesis. In particular, the disclosure relates to methods of chemically linearizing clustered polynucleotides in preparation for sequencing by cleavage of one or more strands of double-stranded polynucleotides immobilized on a solid support by a periodate salt.
Devices including osmotically balanced barriers, and methods of making and using the same, are provided herein. A fluidic well may include a barrier having first and second sides. A first fluid within the fluidic well may contact the first side of the barrier, and may have a first composition including a first concentration of a salt. A second fluid within the fluidic well may contact the second side of the barrier and may have a second composition including a second concentration of the salt that is different than the first concentration. The difference between the first and second concentrations of the salt may generate a first osmotic pressure across the barrier. The second composition further may include a concentration of a compound other than the salt. The concentration of the compound may generate a second osmotic pressure across the barrier that opposes and substantially balances the first osmotic pressure.
G01N 33/487 - Analyse physique de matériau biologique de matériau biologique liquide
59.
COMPOSITIONS INCLUDING AQUEOUS AMINE BORANE COMPLEXES AND POLYNUCLEOTIDES, AND METHODS OF USING THE SAME TO DETECT METHYLCYTOSINE OR HYDROXYMETHYLCYTOSINE
Disclosed herein are aqueous compositions that include a pyridine complex and a polynucleotide. The compositions can be used to detect methylcytosine and/or hydroxymethylcytosine in the polynucleotide. In some examples, the compositions may be used as part of a TET-assisted borane sequencing workflow.
Methods of inserting a nanopore into a polymeric membrane are provided herein. The membrane may be destabilized using a chaotropic solvent. The nanopore may be inserted into the destabilized polymer membrane. The chaotropic solvent may be removed to stabilize the polymer membrane with the nanopore inserted therein.
Nanopore devices including barriers using diblock or triblock copolymers, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids is suspended by a barrier support defining an aperture. The barrier may include one or more layers suspended across the aperture and including molecules of a block copolymer. Each molecule of the block copolymer may include one or more hydrophilic blocks having an approximate length A and one or more hydrophobic blocks having an approximate length B. The hydrophilic blocks may form outer surfaces of the barrier and the hydrophobic blocks may be located within the barrier. The hydrophobic blocks may include a polymer selected from the group consisting of poly(dimethylsiloxane) (PDMS), polybutadiene (PBd), polyisoprene, polymyrcene, polychloroprene, hydrogenated polydiene, fluorinated polyethylene, polypeptide, and poly(isobutylene) (PIB).
Barriers including crosslinked amphiphilic molecules, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids includes at least one layer comprising a plurality of amphiphilic molecules. Amphiphilic molecules of the plurality of amphiphilic molecules are crosslinked to one another.
Nanopore devices including barriers using amphiphilic units, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids includes a first layer comprising a first plurality of amphiphilic units, a second layer comprising a second plurality of the amphiphilic units and contacting the first plurality of amphiphilic units. The amphiphilic units may be substantially the same size as one another. The amphiphilic units respectively may include hydrophobic blocks and hydrophilic blocks coupled to the hydrophobic blocks.
B01D 69/02 - Membranes semi-perméables destinées aux procédés ou aux appareils de séparation, caractérisées par leur forme, leur structure ou leurs propriétés; Procédés spécialement adaptés à leur fabrication caractérisées par leurs propriétés
B01D 71/82 - Matériaux macromoléculaires non prévus spécifiquement dans un seul des groupes caractérisés par la présence de groupes déterminés, p.ex. introduits par un post-traitement chimique
C08G 77/28 - Polysiloxanes contenant du silicium lié à des groupes organiques contenant des atomes autres que le carbone, l'hydrogène et l'oxygène groupes contenant du soufre
C08L 83/08 - Polysiloxanes contenant du silicium lié à des groupes organiques contenant des atomes, autres que le carbone, l'hydrogène et l'oxygène
C08G 81/00 - Composés macromoléculaires obtenus par l'interréaction de polymères en l'absence de monomères, p.ex. polymères séquencés
C09D 187/00 - Compositions de revêtement à base de composés macromoléculaires non spécifiés, obtenus autrement que par des réactions de polymérisation ne faisant intervenir que des liaisons non saturées carbone-carbone
64.
BARRIERS INCLUDING BIOLOGICAL NANOPORE FOR DNA SEQUENCING, THE BARRIERS BEING MADE OF CO-POLYMERS WITH END AND/OR MIDDLE GROUPS, AND METHODS OF MAKING THE SAME
Nanopore devices including barriers using polymers with end groups, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids is provided. The barrier may be suspended by a barrier support defining an aperture. The barrier may include one or more layers suspended across the aperture and including molecules of a block copolymer. Each molecule of the block copolymer may include one or more hydrophilic blocks having an approximate length A and one or more hydrophilic blocks having an approximate length B. The hydrophilic blocks may form outer surfaces of the barrier and the hydrophobic blocks being located within the barrier. End groups may be coupled to ends of the hydrophilic blocks that form outer surfaces of the barrier. The end groups may have a different hydrophilicity than the hydrophilic blocks.
B01D 69/02 - Membranes semi-perméables destinées aux procédés ou aux appareils de séparation, caractérisées par leur forme, leur structure ou leurs propriétés; Procédés spécialement adaptés à leur fabrication caractérisées par leurs propriétés
C08G 77/28 - Polysiloxanes contenant du silicium lié à des groupes organiques contenant des atomes autres que le carbone, l'hydrogène et l'oxygène groupes contenant du soufre
C08G 81/00 - Composés macromoléculaires obtenus par l'interréaction de polymères en l'absence de monomères, p.ex. polymères séquencés
C09D 187/00 - Compositions de revêtement à base de composés macromoléculaires non spécifiés, obtenus autrement que par des réactions de polymérisation ne faisant intervenir que des liaisons non saturées carbone-carbone
In an example method, an initial depression is defined in a first resin layer of a multi-layer stack including the first resin layer over a second resin layer or a base support. The first resin layer is resistant to silanization in an organic solvent, the second resin layer or the base support is reactive toward silanization in the organic solvent, and the first resin layer and the second resin layer or the base support are orthogonally etchable. A remaining portion of the first resin layer at the initial depression is anisotropically etched, using air or O2 plasma, through to expose a surface of the second resin layer or the base support and to form a depression. The multi-layer stack is exposed to a silane in the organic solvent to selectively silanizing the surface of the second resin layer or the base support at the depression.
G03F 7/00 - Production par voie photomécanique, p.ex. photolithographique, de surfaces texturées, p.ex. surfaces imprimées; Matériaux à cet effet, p.ex. comportant des photoréserves; Appareillages spécialement adaptés à cet effet
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
66.
SUBSTRATE WITH ORTHOGONALLY FUNCTIONAL NANODOMAINS
Embodiments of the present disclosure also relate to methods of fabricating flow cell substrates. Some exemplary workflows exploit orthogonal chemistries of substrate layers such that the process does not include polishing steps. Substrates prepared by the method described herein can include a first primer set and a second primer set compatible with simultaneous paired-end sequencing methods.
G03F 7/00 - Production par voie photomécanique, p.ex. photolithographique, de surfaces texturées, p.ex. surfaces imprimées; Matériaux à cet effet, p.ex. comportant des photoréserves; Appareillages spécialement adaptés à cet effet
67.
METHODS AND COMPOSITIONS FOR CLUSTER GENERATION BY BRIDGE AMPLIFICATION
The present disclosure is concerned with compositions and methods for reducing the steps used in the generation of monoclonal clusters by combining the enzymes used for linearization and removal of unused surface primers.
The invention relates to methods and kits for use in nucleic acid sequencing, in particular methods for use in concurrent sequencing, and in particular concurrent sequencing of tandem insert libraries.
A method of determining sequence information from two or more polynucleotide sequence portions, the method comprising: selecting one of a plurality of classifications based on first and second intensity data, wherein each classification represents one or more possible combinations of respective nucleobases of the two or more polynucleotide sequence portions, and wherein at least one classification represents more than one possible combination of respective nucleobases.
The invention relates to methods and associated products for preparing polynucleotide sequences for detection of modified cytosines and sequencing said polynucleotides to detect modified cytosines. The methods comprise treatment of the target polynucleotide with a conversion reagent that is configured to convert a modified cytosine to thymine or a nucleobase which is read as thymine/uracil, and/or configured to convert an unmodified cytosine to uracil or a nucleobase which is read as thymine/uracil. In particular embodiments, portions of both strands of the treated target are sequenced concurrently.
A method of base calling nucleobases of two or more polynucleotide sequence portions, wherein said polynucleotide sequence portions have been selectively processed such that an intensity of the signals obtained based upon the respective first nucleobase is greater than an intensity of the signals obtained based upon the respective second nucleobase.
Systems and methods of identifying nucleobases in a template polynucleotide are disclosed. In one embodiment, such a method may include providing a substrate comprising a plurality of double stranded template polynucleotides in a cluster. Each double stranded template polynucleotide may comprise a first strand and a second strand. The method may further include contacting the plurality of double stranded template polynucleotides with first primers which bind to the first strand and second primers which bind to the second strand. The method may further include extending the first primers and the second primers by contacting the cluster with labeled nucleobases to form first labeled primers and second labeled primers. The method may further include stimulating light emissions from the first and second labeled primers, wherein an amplitude of the signal generated by the first labeled primers is greater than an amplitude of the signal generated by the second labeled primers. The method may further include identifying the labeled nucleobases added to the first primers and the second primers based on the amplitude of the signal generated by the labeled nucleobases.
Systems and methods of identifying nucleobases in a template polynucleotide are disclosed. In one embodiment, such a method may include providing a substrate comprising a plurality of the template polynucleotides in a cluster. The method may further include generating light to stimulate fluorescent emissions from the cluster. The method may further include receiving a first signal emitted at a first intensity from a first plurality of nucleotide analogs hybridized to the plurality of template polynucleotides at a first site. The method may further include receiving a second signal emitted at a second intensity from a second plurality of nucleotide analogs hybridized to the plurality of template polynucleotides at a second site. The method may further include identifying the nucleobases hybridized at the first and second sites of the template polynucleotide based on a combination of the first and second signals.
An example of a flow cell includes a substrate having depressions separated by interstitial regions. First and second primers are immobilized within the depressions. First transposome complexes are immobilized within the depressions, and the first transposome complexes include a first amplification domain. Second transposome complexes are also immobilized within the depressions, and the second transposome complexes include a second amplification domain. Some of the first transposome complexes, or some of the second transposome complexes, or some of both of the first and second transposome complexes include a modification to reduce tagmentation efficiency.
A variety of different types of targeted transposome complexes are described herein that may be used to mediate sequence-specific targeted transposition of nucleic acids. Also described herein is a method of characterizing desired samples in a mixed pool of samples comprising both desired samples and unwanted samples comprising, to produce sequencing data from double-stranded nucleic acid, initially sequencing a library comprising a plurality of nucleic acid samples from a mixed pool, wherein each nucleic acid library comprises nucleic acids from a single sample and a unique sample barcode to distinguish the nucleic acids from the single sample from the nucleic acids from other samples in the library; analyzing the sequencing data and identifying unique sample barcodes associated with sequencing data from desired samples; performing a selection step on the library comprising enriching nucleic acid samples from desired samples and/or depleting nucleic acid samples from unwanted samples; and resequencing the nucleic acid library.
A functionalized nanostructure includes a metal nanostructure; an un-cleavable first primer and a cleavable second primer attached to a first region of the metal nanostructure through i) a first thiol linkage attached to a first polymer chain having a first polarity or ii) respective first thiol linkages attached to respective first polymer chains having the first polarity; and a cleavable first primer and an un-cleavable second primer attached to a second region of the metal nanostructure through i) a second thiol linkage attached to a second polymer chain having a second polarity different from the first polarity or ii) respective second thiol linkages attached to respective second polymer chains having the second polarity.
An example of a method includes providing a substrate with an exposed surface comprising a first chemical group, wherein the providing optionally comprises modifying the exposed surface of the substrate to incorporate the first chemical group; reacting the first chemical group with a first reactive group of a functionalized polymer molecule to form a functionalized polymer coating layer covalently bound to the exposed surface of the substrate; grafting a primer to the functionalized polymer coating layer by reacting the primer with a second reactive group of the functionalized polymer coating layer; and forming a water-soluble protective coating on the primer and the functionalized polymer coating layer. Examples of flow cells incorporating examples of the water-soluble protective coating are also disclosed herein.
An apparatus includes a chassis, a frame, a sample support member, an imaging assembly, an actuation assembly, and a vibration capture assembly. The frame is coupled with the chassis. The sample support member is supported by the frame. The actuation assembly is supported by the frame and is operable to drive movement of the imaging assembly relative to the sample support member. The vibration capture assembly is operable to selectively transition between a plurality of modes, including a damping mode and an isolation mode. In the damping mode, the vibration capture assembly is configured to resist movement of the frame relative to the chassis in response to operation of the actuation assembly. In the isolation mode, the vibration capture assembly is configured to prevent transmission of vibrational movement in the chassis to the frame.
This disclosure describes methods, non-transitory computer readable media, and systems that can use a machine-learning to determine factors or scores indicating an error level with which a given methylation assay detects methylation of cytosine bases. For instance, the disclosed systems use a machine-learning model to generate a bias score indicating a degree to which a given methylation assay errs in detecting cytosine methylation when specific sequence contexts surround such cytosines compared to other sequence contexts. The machine-learning model may take various forms of models, including a decision-tree model, a neural network, or a combination of a decision-tree model and a neural network. In some cases, the disclosed system combines or uses bias scores from multiple machine-learning models to generate a consensus bias score.
G16B 20/20 - Détection d’allèles ou de variantes, p. ex. détection de polymorphisme d’un seul nucléotide
G16B 40/00 - TIC spécialement adaptées aux biostatistiques; TIC spécialement adaptées à l’apprentissage automatique ou à l’exploration de données liées à la bio-informatique, p.ex. extraction de connaissances ou détection de motifs
85.
CYCLOOCTATETRAENE CONTAINING DYES AND COMPOSITIONS
Embodiments of the present disclosure relate to cyclooctatetraene containing dyes and their uses as fluorescent labels. Also provided are composition containing cyclooctatetraene. The dyes and compositions may be used in various biological applications, such as nucleic acid sequencing.
Embodiments of the present disclosure relate to cyclooctatetraene containing dyes and their uses as fluorescent labels. Also provided are composition containing cyclooctatetraene. The dyes and compositions may be used in various biological applications, such as nucleic acid sequencing.
A polynucleotide sequencing method comprises (i) removing a label and a blocking moiety from a blocked, labeled nucleotide incorporated into a copy polynucleotide strand that is complementary to at least a portion of a template polynucleotide strand; and (ii) washing the removed label and blocking moiety away from the copy strand with a wash solution comprising a first buffer comprising a scavenger compound. Removing the label and blocking moieties may comprise chemically removing the moieties. The first buffer may also comprise an antioxidant and may be used in a scanning buffer used during a nucleotide detection step.
Described herein are technologies for classifying a protein structure (such as technologies for classifying the pathogenicity of a protein structure related to a nucleotide variant). Such a classification is based on two-dimensional images taken from a three-dimensional image of the protein structure. With respect to some implementations, described herein are multi-view convolutional neural networks (CNNs) for classifying a protein structure based on inputs of two-dimensional images taken from a three-dimensional image of the protein structure. In some implementations, a computer-implemented method of determining pathogenicity of variants includes accessing a structural rendition of amino acids, capturing images of those parts of the structural rendition that contain a target amino acid from the amino acids, and, based on the images, determining pathogenicity of a nucleotide variant that mutates the target amino acid into an alternate amino acid.
G16H 50/20 - TIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicales; TIC spécialement adaptées à la détection, au suivi ou à la modélisation d’épidémies ou de pandémies pour le diagnostic assisté par ordinateur, p.ex. basé sur des systèmes experts médicaux
G16H 50/30 - TIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicales; TIC spécialement adaptées à la détection, au suivi ou à la modélisation d’épidémies ou de pandémies pour l’évaluation des risques pour la santé d’une personne
89.
METHODS OF DETECTING METHYLCYTOSINE AND HYDROXYMETHYLCYTOSINE BY SEQUENCING
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.
Polynucleotide sequencing methods for sequencing one or more polynucleotide templates that uses primers bound to a surface as sequencing primers. The surface primers may include at least a portion of a surface oligonucleotide used during cluster formation. The sequencing methods may be used for single stranded sequencing or double stranded sequencing. Double stranded sequencing methods may employ an enzyme that has nick-translation activity. A kit includes all the reagents needed for sequencing does not include sequencing primers. The kit may be used to accomplish the sequencing methods of the present disclosure.
Imaging systems and related methods are disclosed. In accordance with an implementation, a system includes a flow cell receptacle to receive a flow cell that receives a sample and an imaging system having a light source assembly, and an imaging device. The light source assembly to form a substantially collimated beam. The optical assembly including an asymmetric beam expander group that includes one or more asymmetric elements or anamorphic elements disposed along an optical axis. The optical assembly to receive the substantially collimated beam from the light source assembly, and transform the substantially collimated beam into a shaped sampling beam having an elongated cross section in a far field at or near a focal plane of the optical assembly to optically probe the sample. The imaging device to obtain image data associated with the sample in response to the optical probing of the sample with the sampling beam.
The technology disclosed relates to accessing a multiple sequence alignment that aligns a query residue sequence to a plurality of non-query residue sequences, applying a set of periodically-spaced masks to a first set of residues at a first set of positions in the multiple sequence alignment, and cropping a portion of the multiple sequence alignment that includes the set of periodically-spaced masks at the first set of positions, and a second set of residues at a second set of positions in the multiple sequence alignment to which the set of periodically-spaced masks is not applied. The first set of residues includes a residue-of-interest at a position-of-interest in the query residue sequence.
The technology disclosed relates to generating species-differentiable evolutionary profiles using a weighting logic. In particular, the technology disclosed relates to determining a weighted summary statistic for a given residue category at a given position in a multiple sequence alignment based on one or more weights of one or more sequences in the multiple sequence alignment that have a residue of the given residue category at the given position.
The technology disclosed relates to determining feasibility of using a reference genome of a non-target species for variant calling a sample of a target species. In particular, the technology disclosed relates to mapping sequenced reads of a sample of a target species to a reference genome of a non-target species to detect a first set of variants in the sequenced reads of the sample of the target species, and mapping the sequenced reads of the sample of the target species to a reference genome of a pseudo-target species to detect a second set of variants in the sequenced reads of the sample of the target species.
The technology disclosed relates to inter-model prediction score recalibration. In one implementation, the technology disclosed relates to a system including a first model that generates, based on evolutionary conservation summary statistics of amino acids in a target protein sequence, a first pathogenicity score-to-rank mapping for a set of variants in the target protein sequence; and a second model that generates, based on epistasis expressed by amino acid patterns spanning the target protein sequence and a plurality of non-target protein sequences aligned in multiple sequence alignment, a second pathogenicity score-to-rank mapping for the set of variants. The system also includes a reassignment logic that reassigns pathogenicity scores from the first set of pathogenicity scores to the set of variants based on the first and second score-to-rank mappings, and an output logic to generate a ranking of the set of variants based on the reassigned scores.
The present disclosure relates to a method including exposing a composition comprising a wax-microsphere matrix to a first melt-condition, wherein said wax-microsphere matrix comprises a wax component and a plurality of lyophilised microspheres, wherein said plurality of lyophilised microspheres comprise one or more reagent, whereby exposing said composition comprising said wax-microsphere matrix to said first melt-condition melts the wax component; exposing said composition to a first release-condition to rehydrate at least one lyophilised microsphere; and exposing said at least one rehydrated lyophilised microsphere to a separation-condition to separate said wax component from said at least one rehydrated lyophilised microsphere. Also disclosed are methods of preparing a wax-microsphere matrix and releasing one or more reagent from a wax-microsphere matrix as well as compositions. Also disclosed are cartridges with a reagent reservoir including the compositions described herein. Also disclosed are systems for controlling release of one or more reagent including the compositions described herein.
C12Q 1/6848 - Réactions d’amplification d’acides nucléiques caracterisées par les moyens d’empêcher la contamination ou d’augmenter la spécificité ou la sensibilité d’une réaction d’amplification
97.
DYNAMIC GRAPHICAL STATUS SUMMARIES FOR NUCELOTIDE SEQUENCING
This disclosure describes methods, non-transitory computer readable media, and systems that can query the status of various stages in an end-to-end sequencing process and generate a graphical status summary for the sequencing process that depicts icons indicating statuses of the various stages. For instance, the disclosed systems can generate a graphical status summary for a nucleotide sequencing taskset that includes icons depicting statuses of a sequencing run, a data transfer of base-call data to a device for variant analysis, and the variant analysis—each part of the same nucleotide sequencing taskset. By exchanging data with a sequencing device for read data and one or more servers for variant analysis, the disclosed system can quickly provide a graphical status summary of an end-to-end sequencing process marked by various tasks within a nucleotide sequencing taskset.
Embodiments of the present disclosure relates to periodate salt compositions for use in the chemical linearization of double-stranded polynucleotides in preparation for sequencing application, for example, sequencing-by-synthesis (SBS). Kits containing the periodate salt composition and methods of sequencing polynucleotides are also described.
An example of a flow cell includes a substrate having depressions separated by interstitial regions. First and second primers are immobilized within the depressions. First transposome complexes are immobilized within the depressions, and the first transposome complexes include a first amplification domain. Second transposome complexes are also immobilized within the depressions, and the second transposome complexes include a second amplification domain. Some of the first transposome complexes, or some of the second transposome complexes, or some of both of the first and second transposome complexes include a modification to reduce tagmentation efficiency.
This disclosure describes methods, non-transitory computer readable media, and systems that can facilitate execution of external workflows for diagnostic analysis of nucleotide sequencing data utilizing a container orchestration engine. For example, the disclosed systems can utilize a container orchestration engine to allow external systems (e.g., third-party systems) to generate and implement workflows for analyzing sequencing data. In executing individual workflow containers of a sequencing diagnostic workflow, the disclosed systems can isolate the workflow containers to prevent access to, or corruption of, other data while also orchestrating allocation of computing resources available at a genomic sequence processing device to execute the workflow containers.
G16B 50/30 - Entreposage de données; Architectures informatiques
H04L 67/1008 - Sélection du serveur pour la répartition de charge basée sur les paramètres des serveurs, p.ex. la mémoire disponible ou la charge de travail
brevets
