A fluidic device holder configured to orient a fluidic device. The device holder includes a support structure configured to receive a fluidic device. The support structure includes a base surface that faces in a direction along the Z-axis and is configured to have the fluidic device positioned thereon. The device holder also includes a plurality of reference surfaces facing in respective directions along an XY-plane. The device holder also includes an alignment assembly having an actuator and a movable locator arm that is operatively coupled to the actuator. The locator arm has an engagement end. The actuator moves the locator arm between retracted and biased positions to move the engagement end away from and toward the reference surfaces. The locator arm is configured to hold the fluidic device against the reference surfaces when the locator arm is in the biased position.
Substrates comprising dual functional polymer layered surfaces and the preparation thereof by using UV nano-imprinting processes are disclosed. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.
G03F 7/00 - Production par voie photomécanique, p. ex. photolithographique, de surfaces texturées, p. ex. surfaces impriméesMatériaux à cet effet, p. ex. comportant des photoréservesAppareillages spécialement adaptés à cet effet
G03F 7/16 - Procédés de couchageAppareillages à cet effet
4.
CONTROLLED POLYNUCLEOTIDE TRANSLOCATION IN NANOPORE SEQUENCING
Provided herein are methods for modification-based controlled polynucleotide translocation in nanopores for sequencing, modified nucleotides, and kits and systems for performing the disclosed methods. In some embodiments, modifications can be used to control polynucleotide translocation by modifying nucleotides on a strand of polynucleotide to carry a modification, where the modifications can arrest or slow translocation when encountering the nanopore. In some embodiments, application of a voltage can move one nucleotide and its attached modification through the nanopore at a time.
An microreactor array is provided that includes a plurality of microreactors in a substrate. The plurality of microreactors is in fluid communication with a common fluid delivery channel. Each of the microreactors includes an electrode configured to generate one or more gaseous bubbles that can block reagent access to selected microreactors. A method for selective reactions in a microreactor array is also provide.
Methods, systems, and apparatus, including computer programs for improving the accuracy of a variant call by accounting for indications of correlated error events. In one aspect, a method may include actions of accessing a pileup of sequence reads aligned to a first region of a reference genome, obtaining information describing one or more characteristics of each of the plurality of reads of the pileup, providing one or more inputs to a probability model describing the one or more characteristics of the plurality of reads of the pileup, wherein the probability model is configured to determine a score, for each hypothesis of one or more hypotheses selected based on the one or more inputs, that indicates whether each hypothesis is true, obtaining output information for each of the one or more hypotheses, and determining, based on the obtained output information, a likelihood that a true variant exists at the first position.
G16B 20/20 - Détection d’allèles ou de variantes, p. ex. détection de polymorphisme d’un seul nucléotide
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
G06N 7/01 - Modèles graphiques probabilistes, p. ex. réseaux probabilistes
G16B 30/10 - Alignement de séquenceRecherche d’homologie
G16B 40/00 - TIC spécialement adaptées aux biostatistiquesTIC 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
A system for sequencing nucleic acid comprising a plurality of stations and a system control. The system control configured to direct the first substrate to progress and retrogress between the first processing station and the imaging station, direct the second substrate to progress and retrogress between the second processing station and the imaging station, and direct a chemistry cycle of a first sequencing procedure to occur within one of the first processing station or the second processing station while an imaging cycle of a second sequencing procedure occurs within the imaging station.
Described herein are compositions and methods for enriching library fragments prepared for coronavirus sequences prepared from various samples. These methods may incorporate microfluidics and flowcells for greater case of use. Libraries enriched with the present methods may be used for sequencing. Also described are probes and methods for enzymatic depletion of unwanted RNA.
C12Q 1/70 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des virus ou des bactériophages
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6832 - Amélioration de la réaction d’hybridation
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p. ex. séquençage par hybridation [SBH]
Described herein are methods for depleting library fragments prepared from off-target RNA sequences. Libraries enriched or depleted with the present methods may be used for sequencing. Also described are probes and methods for depletion or supplementing depletion of off-target RNA from human and non-human samples.
Well assemblies and related systems and methods are disclosed. In accordance with an implementation, an apparatus includes a body having a first wall, a second wall, a cover, and an impermeable barrier. The first wall defines a well having a port and a distal end defining an opening having an opening perimeter. The second wall surrounds the first wall and has a distal end. The cover is coupled to the distal end of the first wall and covers the opening along the opening perimeter at a connected portion and uncoupled from the distal end of the first wall along the opening perimeter at an unconnected portion. The impermeable barrier is coupled to the distal end of the second wall and covers the well. The unconnected portion forms a vent that allows air flow out of the well.
An example of a flow cell includes a substrate including a surface and a dendron architecture. The dendron architecture includes a functionalized focal point of attachment that is attached to the substrate surface and a plurality of peripheral functional groups that are orthogonal to the functionalized focal point of attachment. The flow cell further includes a primer set attached to the dendron architecture via the plurality of peripheral functional groups.
C07F 9/6561 - Composés hétérocycliques, p. ex. contenant du phosphore comme hétéro-atome du cycle contenant des systèmes de plusieurs hétérocycles déterminants condensés entre eux ou condensés avec un carbocycle ou un système carbocyclique commun, avec ou sans autres hétérocycles non condensés
12.
CAPTURING AND AMPLIFYING POLYNUCLEOTIDES USING PARTICLES
In some examples, a method for capturing and amplifying a polynucleotide includes capturing the polynucleotide at a particle comprising a first region and a second region. The first region may include a first moiety that captures the polynucleotide. The second region may include a plurality of amplification primers and have a surface area which is substantially larger than the surface area of the first portion. The method includes using the plurality of amplification primers to amplify the captured polynucleotide.
Embodiments of the present disclosure relate to patterned substrates with functionalized surface such as flow cells, as well as methods of fabricating the patterned substrate. In particular, patterned substrates of the present disclosure may be prepared using two or more imprint resin layers, one of which acts as a photomask for the photoresist during substrate patterning, without the need of any metallic photomask. Embodiments of the patterned substrate may be used for simultaneous paired-end sequencing methods.
This application relates to functionalized magnetic particles and methods of using magnetic particles to generate amplicons. In some examples, a method of modifying a magnetic particle comprising a first functional group includes contacting the magnetic particle with a first molecule comprising a polymer coupled to second and third functional groups, wherein the first functional group reacts with the second functional group to form a bond via which the polymer is coupled to the magnetic particle. The method may include contacting the magnetic particle with a second molecule, the second molecule comprising an oligonucleotide coupled to a fourth functional group, wherein the third functional group reacts with the fourth functional group to form a bond via which the oligonucleotide is coupled to the magnetic particle.
A microreactor array is provided that includes a plurality of microreactors in a substrate. The plurality of microreactors is in fluid communication with a common fluid delivery channel. Each of the microreactors includes an electrode configured to generate one or more gaseous bubbles that can block reagent access to selected microreactors. A method for selective reactions in a microreactor array is also provided. The method includes flooding the array of microreactors with a first fluid selected to release a gas during electrolysis, applying a bias to the electrode associated with one or more selected microreactors in the array, thereby forming one or more gaseous bubbles at or near the electrode. The next step involves flushing the array with a second fluid, and carrying out a reaction in the microreactors that are not blocked by the bubble.
Embodiments of the present disclosure relate to patterned substrates with functionalized surface such as flow cells, as well as methods of fabricating the patterned substrate. In particular, patterned substrates of the present disclosure may be prepared using two or more imprint resin layers, one of which acts as a photomask for the photoresist during substate patterning, without the need of any metallic photomask. Embodiments of the patterned substrate may be used for simultaneous paired-end sequencing methods.
G03F 7/00 - Production par voie photomécanique, p. ex. photolithographique, de surfaces texturées, p. ex. surfaces impriméesMatériaux à cet effet, p. ex. comportant des photoréservesAppareillages spécialement adaptés à cet effet
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en généralAppareils appropriés
17.
SYSTEMS AND METHODS OF SEQUENCING POLYNUCLEOTIDES WITH ALTERNATIVE SCATTERPLOTS
The application relates to DNA sequencing systems and methods. Systems and methods for determining the nucleotide sequence of a polynucleotide may include introducing a fourth labelled nucleotide in a two-channel sequencing by synthesis system to create alternative X-Y scatterplot shapes where the x-axis represents the intensity of fluorescence at one wavelength (channel 1), and the y-axis represents intensity of fluorescence at another wavelength (channel 2 The alternative scatterplot shapes may allow for additional encoding space for empty well detection.
The application relates to DNA sequencing systems and methods. Systems and methods for determining the nucleotide sequence of a polynucleotide may include introducing a fourth labeled nucleotide in a two-channel sequencing by synthesis system that allows for encoding space for a detecting a fifth labeled nucleotide or empty well detection.
Methods are provided for assigning nucleic acid sequence reads to target polynucleotides, including providing a substrate having transposome complexes immobilized thereon, wherein the transposome complexes comprise a transposase and a first polynucleotide comprising an end sequence and a first tag; contacting the transposome complexes with target polynucleotides under conditions to fragment the target polynucleotides; amplifying the fragmented target polynucleotides to form a plurality of nucleic acid clusters on the substrate; obtaining location information for the plurality of nucleic acid clusters on the substrate; determining the nucleic acid sequence reads of the fragmented nucleic acids in each of the nucleic acid clusters; and assigning the nucleic acid sequence reads to the target polynucleotides using the obtained location information.
This disclosure describes methods, non-transitory-computer readable media, and systems that can modify sequencing runs to ensure all genomic samples meet a target read-coverage level. The disclosed system can estimate read coverage for each genomic sample in a genomic pool based on (i) clusters belonging to each sample derived from indexing sequences and/or (ii) filter metrics corresponding to each sample within a flow-cell pool. The disclosed systems can modify a sequencing run based on the estimated read coverage and a target read coverage. For example, the disclosed systems can adjust a number of sequencing cycles within a sequencing run to ensure that all genomic samples meet the target read coverage. Additionally, or alternatively, the disclosed systems can determine a set of flow cell tiles to be imaged to ensure that all genomic samples meet the target read coverage.
21.
MACHINE-LEARNING MODEL FOR RECALIBRATING GENOTYPE CALLS CORRESPONDING TO GERMLINE VARIANTS AND SOMATIC MOSAIC VARIANTS
This disclosure describes methods, non-transitory computer readable media, and systems that can utilize a machine-learning model to recalibrate genotype calls (e.g., variant calls) corresponding to germline variants and somatic mosaic variants. For instance, based on sequencing metrics for nucleotide reads of a genomic sample, the disclosed systems can utilize a variant-call-recalibration machine-learning model to generate genotype probabilities for variants within genomic regions corresponding to candidate germline variants and candidate somatic mosaic variants. Further, the disclosed systems can generate genotype calls, such as variant calls corresponding to somatic mosaic variants, based on the generated genotype probabilities.
An imaging system includes a focus tracking module including: a light source to project a first pair of spots on a sample; and a first image sensor to obtain one or more first images of the first pair of spots; a second image sensor to obtain one or more second images of the sample; one or more mirrors optically coupled to the second image sensor, the one or more mirrors positioned in an optical path from the sample to the second image sensor; and a controller to: determine, using at least a first separation distance measurement of the first pair of spots from the one or more first images, a first sample tilt of the sample about a first axis of the imaging system; and actuate, based at least on the first sample tilt, the one or more mirrors to offset the first sample tilt about the first axis.
An example of a flow cell includes a substrate including a surface and a dendron architecture. The dendron architecture includes a functionalized focal point of attachment that is attached to the substrate surface and a plurality of peripheral functional groups that are orthogonal to the functionalized focal point of attachment. The flow cell further includes a primer set attached to the dendron architecture via the plurality of peripheral functional groups.
This application relates to methods and compositions for protecting fully functional nucleotides (ffNs) against degradation. In some examples, micelles or surfactants are used to protect ffNs. In some examples, bulky cation compounds are used to protect ffNs. In some examples, the compositions that protect ffNs are included in lyophilized material.
Systems and related reagent cartridge queuing methods are disclosed. In accordance with an implementation, an apparatus includes a first reagent cartridge, a second reagent cartridge, and a system. The system includes a sipper manifold assembly having a sipper, a queue to carry the first reagent cartridge and the second reagent cartridge, a cartridge moving assembly, and a cartridge receptacle assembly. The cartridge moving assembly includes a gantry, a carriage actuator, and a carriage. The carriage is coupled to the gantry and the carriage actuator is to move the carriage relative to the gantry. The cartridge receptacle assembly has a cartridge receptacle to receive the first reagent cartridge or the second reagent cartridge. The carriage is to move the first reagent cartridge from the queue and position the first reagent cartridge into the cartridge receptacle.
G01N 35/02 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes Manipulation de matériaux à cet effet en utilisant une série de récipients à échantillons déplacés par un transporteur passant devant un ou plusieurs postes de traitement ou d'analyse
G01N 35/00 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes Manipulation de matériaux à cet effet
G01N 35/10 - Dispositifs pour transférer les échantillons vers, dans ou à partir de l'appareil d'analyse, p. ex. dispositifs d'aspiration, dispositifs d'injection
In some examples, a method for capturing and amplifying a polynucleotide includes capturing the polynucleotide at a particle comprising a first region and a second region. The first region may include a first moiety that captures the polynucleotide. The second region may include a plurality of amplification primers and have a surface area which is substantially larger than the surface area of the first portion. The method includes using the plurality of amplification primers to amplify the captured polynucleotide.
Described are DNA sequencing systems and methods. Systems and methods for determining the nucleotide sequence of a polynucleotide may include determining the sequence of a polynucleotide with more than four types of bases by increasing the number of encoding states in sequencing by synthesis (SBS) systems. The systems and methods may expand the encoding space of current systems by discretizing the amplitude space in a channel into more than two states, and/or by adding additional channels.
This application relates to functionalized magnetic particles and methods of using magnetic particles to generate amplicons. In some examples, a method of modifying a magnetic particle comprising a first functional group includes contacting the magnetic article with a first molecule comprising a polymer coupled to second and third functional groups, wherein the first functional group reacts with the second functional group to form a bond via which the polymer is coupled to the magnetic particle. The method may include contacting the magnetic particle with a second molecule, the second molecule comprising an oligonucleotide coupled to a fourth functional group, wherein the third functional group reacts with the fourth functional group to form a bond via which the ligonucleotide is coupled to the magnetic particle.
This disclosure describes methods, non-transitory-computer readable media, and systems that can simultaneously determine estimated methylation-level values for cytosine bases and genotype calls for a target genomic sample. The disclosed system can utilize a Bayesian method on a target genomic sample's nucleotide-read data to generate estimated methylation-level values that indicate genomic coordinates at which the target genomic sample comprises a reference cytosine base or a nucleobase that could be called as a cytosine. The disclosed system can estimate methylation-level values based on prior genotype probabilities and observed nucleobases at a genomic coordinate from a read pileup of a target genomic sample. Based on the estimated methylation-level values and base-call-quality metrics, the disclosed system may generate posterior genotype probabilities for the genomic sample at the genomic coordinate. Based on the posterior genotype probabilities, the disclosed system can generate a genotype call for the target genomic sample.
Methods, systems, and apparatus, including computer programs encoded on computer-storage media, for classification of a single cell from a biological sample of an entity. In one aspect, the method can include obtaining data indicating a plurality of reference positions where a known variant sequence exists for the entity in respective reference positions of the plurality of reference positions, obtaining a plurality of reads for the single cell from the biological sample of the entity, determining, for respective reads of the obtained plurality of reads, a score indicating whether a variant sequence in the respective reads of the biological sample of the entity matches the plurality of reference positions where the known variant sequence exists, and classifying the single cell as a tumor cell or normal cell based on an aggregation of the score determined for the respective reads of the obtained plurality of reads.
G16B 20/20 - Détection d’allèles ou de variantes, p. ex. détection de polymorphisme d’un seul nucléotide
G16B 30/10 - Alignement de séquenceRecherche d’homologie
G16H 50/20 - TIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicalesTIC 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 médicalesTIC spécialement adaptées à la détection, au suivi ou à la modélisation d’épidémies ou de pandémies pour le calcul des indices de santéTIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicalesTIC 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
31.
INTERLOCKING NUCLEIC ACIDS FOR TARGET HYBRIDIZATION
Interlocking nucleic acids for target hybridization are described. The interlocking nucleic acids include individual nucleic acids having respective capture regions that hybridize to the target nucleic acid and interlocking regions that bind to each other. In an embodiment, the interlocking nucleic acids are part of a probe set that specifically binds to a target nucleic acid to permit capture of the target nucleic acid. In an embodiment, the interlocking nucleic acids may be part of a primer used for amplification of the target nucleic acid.
C12Q 1/6818 - Tests d’hybridation caractérisés par les moyens de détection impliquant l’interaction de plusieurs marqueurs, p. ex. transfert d’énergie de résonance
In some examples, a method of capturing a polynucleotide on a particle that includes a capture primer includes transporting the particle to a first aperture between a first fluidic compartment and a second fluidic compartment. The particle may be located in the first fluidic compartment, and the polynucleotide may be at least partially located in the second fluidic compartment. The method may include transporting the polynucleotide from the second fluidic compartment to the first fluidic compartment through the first aperture. The method may include hybridizing the polynucleotide to the capture primer.
A methylation detection array includes a substrate having a plurality of depressions defined therein; a plurality of beads, each of the plurality of beads positioned within one of the plurality of depressions; a plurality of sample probes respectively attached to some of the plurality of beads; and a plurality of lambda phage control probes respectively attached to some other of the plurality of beads. The plurality of lambda phage control probes includes a probe set including an unmethylated probe and a corresponding methylated probe; and a single probe. Each of the plurality of lambda phage control probes targets a cytosine in a CH site of a lambda phage target sequence and is free of additional CpG sites. The plurality of lambda phage control probes make up from greater than 0% to less than 5% of a total of the sample probes and the control probes.
C12Q 1/6809 - Méthodes de détermination ou d’identification des acides nucléiques faisant intervenir la détection différentielle
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 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
Disclosed herein are formulations and methods for denaturing DNA that utilize betaine as the denaturant. In some examples, the formulations include additives other than betaine, such as, for example, dimethyl sulfoxide (DMSO) and/or diethylene glycol (DEG).
Reagent reservoirs and related systems and methods are disclosed. An apparatus includes a flexible container and a coupling. The flexible container includes an end and a tapered bottom. The flexible container includes an interior containing dried reagent. The coupling has a portion coupled to the end of the flexible container. The coupling has a port fluidly coupled to the interior of the flexible container. Rehydrating fluid is to flow through the port and into the interior of the flexible container. An interaction between the rehydrating fluid and the tapered bottom is to cause a vortex within the interior of the flexible container to rehydrate a substantial portion of the dried reagent.
B65D 75/58 - Dispositifs d'ouverture ou servant à retirer le contenu, ajoutés ou incorporés lors de la confection du paquet
B65D 75/30 - Objets ou matériaux enveloppés entre deux feuilles ou flans opposés à bords réunis, p. ex. par adhésifs à pression, pliage, thermosoudage ou soudage
36.
METHOD AND SYSTEM FOR ESTIMATING IMPACT OF MUTATIONS ON FITNESS, LIFESPAN, AND FECUNDITY
Techniques are described for estimating selection coefficients (700) for missense mutations (500) and PTVs (504). In certain embodiments, such estimates may be based on forward-time population modeling and/or deep learning to facilitate estimation of individual-level selection burdens (704) and/or to identify individuals with increased (or decreased) genetic risk of reduced fitness (712) (including lifespan (812) and/or fecundity (912) metrics) relative to a threshold (720), such as a statistically mean or median fitness, lifespan, or fecundity based on a subject's demographic data.
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 biostatistiquesTIC 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
G16H 50/30 - TIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicalesTIC spécialement adaptées à la détection, au suivi ou à la modélisation d’épidémies ou de pandémies pour le calcul des indices de santéTIC spécialement adaptées au diagnostic médical, à la simulation médicale ou à l’extraction de données médicalesTIC 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
37.
FLOW CELLS AND METHODS FOR PREPARING SURFACES THEREOF
An example flow cell includes a first substrate; a second substrate attached to the first substrate; a flow channel defined between the first substrate and the second substrate; a first primer set attached to the first substrate, the first primer set including an un-cleavable first primer and a cleavable second primer; a second primer set attached to the second substrate, the second primer set including a cleavable first primer and an un-cleavable second primer; and a removable blocking mechanism passivating i) the first primer set or the second primer set or ii) the cleavable first primer and the cleavable second primer.
Some examples herein provide a method that includes reacting an unsaturated cyclic dione with an indole or indazole to form a first adduct. One of a substrate and a functional group is coupled to the unsaturated cyclic dione, and the other of the substrate and the functional group is coupled to the indole or indazole. Forming the first adduct couples the functional group to the substrate. Some examples herein provide a composition that includes a substate, a functional group, and an adduct coupling the functional group to the substrate. The adduct may be a product of a reaction between an unsaturated cyclic dione and an indole or indazole.
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
C08F 283/12 - Composés macromoléculaires obtenus par polymérisation de monomères sur des polymères prévus par la sous-classe sur des polysiloxanes
The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.001% of the complex mixture, wherein the representational sample comprises a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of the sequences in the predetermined portion of one or more nucleic acids within the complex mixture. A method of selecting a representational sample of genomic sequences from a complete genome also is provided. The invention further provides a nucleic acid population that includes a representational sample having a complexity of less than 10% but more than 0.001% of a complex mixture, the representational sample comprising a nucleic acid copy having a proportion of each sequence in the copy relative to all other sequences in the copy substantially the same as the proportions of sequences in a predetermined portion of a sequence collectively present in one or more nucleic acids within the complex mixture.
A cartridge for use with chemical or biological analysis systems, as well as methods of using the same, is provided. The cartridge may include a floating microfluidic plate that is held in the cartridge using one or more floating support brackets that incorporate gaskets that may seal against fluidic ports on the microfluidic plate. The floating support brackets may include indexing features that may align the microfluidic plate with the seals.
In some examples, a method of sequencing a polynucleotide includes hybridizing the polynucleotide to a first oligonucleotide coupled to a particle. The hybridized polynucleotide may be amplified using additional oligonucleotides coupled to the particle, to generate amplicons coupled to the particle. After the amplifying, the particle, having the amplicons coupled thereto, may be disposed within a flowcell. After disposing the particle within the flowcell, the particle may be dissolved, leaving the amplicons within the flowcell. The flowcell may be used to sequence the amplicons.
Methods, systems, and computer programs for compressing nucleic acid sequence data. A method can include obtaining nucleic acid sequence data representing: (i) a read sequence, and (ii) a plurality of quality scores, determining whether the read sequence includes at least one “N” base, based on a determination that the read sequence includes at least one “N” base, generating, by one or more computers, a first encoding data set by using a first encoding process to encode each set of four quality scores of the read sequence into a single byte of memory, and using a second encoding process to encode the first encoded data set, thereby compressing the data to be compressed.
An example flow cell includes a first substrate; a second substrate attached to the first substrate; a flow channel defined between the first substrate and the second substrate; a first primer set attached to the first substrate, the first primer set including an un-cleavable first primer and a cleavable second primer; a second primer set attached to the second substrate, the second primer set including a cleavable first primer and an un-cleavable second primer; and a removable blocking mechanism passivating i) the first primer set or the second primer set or ii) the cleavable first primer and the cleavable second primer.
Provided herein include various examples of a method for manufacturing aspects of a flow cell. The method may include bonding a die to a first carrier with a first bonding material, encapsulating the die with a molding material, bonding a second carrier to a surface of the molding material with a second bonding material, releasing the first carrier from the die encapsulated with the molding material to expose a surface that includes fanout regions, applying chemistry to the exposed surface of the die such that the given surface of the die becomes an active detection area for the flow cell, and placing a lidding layer over the exposed surface to form a space over the active detection area; the space defines a fluidic channel.
Well assemblies and related methods are disclosed. In accordance with an implementation, an apparatus includes a well assembly including a body and an insert. The body has a well and the insert includes a sidewall defining an opening and a venting membrane coupled to the insert and extending across the opening. The insert is received within the well and wherein a coupling is formed between the sidewall of the insert and the body.
A method for amplifying a target nucleic acid including providing a system having a crRNA or a derivative thereof, and a Cas protein or a variant thereof. The crRNA or the derivative thereof contains a target-specific nucleotide region substantially complementary to a region of the target nucleic acid, and contacting the target nucleic acid with the system to form a complex.
Techniques are described for dynamically correcting image distortion during imaging of a patterned sample having repeating spots. Different sets of image distortion correction coefficients may be calculated for different regions of a sample during a first imaging cycle of a multicycle imaging run and subsequently applied in real time to image data generated during subsequent cycles. In one implementation, image distortion correction coefficients may be calculated for an image of a patterned sample having repeated spots by: estimating an affine transform of the image; sharpening the image; and iteratively searching for an optimal set of distortion correction coefficients for the sharpened image, where iteratively searching for the optimal set of distortion correction coefficients for the sharpened image includes calculating a mean chastity for spot locations in the image, and where the estimated affine transform is applied during each iteration of the search.
G01B 11/16 - Dispositions pour la mesure caractérisées par l'utilisation de techniques optiques pour mesurer la déformation dans un solide, p. ex. indicateur optique de déformation
G06V 10/24 - Alignement, centrage, détection de l’orientation ou correction de l’image
G06V 20/69 - Objets microscopiques, p. ex. cellules biologiques ou pièces cellulaires
H04N 1/387 - Composition, repositionnement ou autre modification des originaux
H04N 1/401 - Compensation de la réponse inégale selon la position de la tête de lecture ou de reproduction
H04N 1/409 - Amélioration des contours ou des détailsSuppression du bruit ou des erreurs
H04N 25/61 - Traitement du bruit, p. ex. détection, correction, réduction ou élimination du bruit le bruit provenant uniquement de l'objectif, p. ex. l'éblouissement, l'ombrage, le vignettage ou le "cos4"
One example of a flow cell includes a base support and a multi-layer stack positioned over the base support. The multi-layer stack includes a resin layer positioned over the base support; and a hydrophobic layer positioned over the resin layer. A depression is defined in the multi-layer stack through the hydrophobic material and through a portion of the resin.
G03F 7/00 - Production par voie photomécanique, p. ex. photolithographique, de surfaces texturées, p. ex. surfaces impriméesMatériaux à cet effet, p. ex. comportant des photoréservesAppareillages spécialement adaptés à cet effet
G03F 7/09 - Matériaux photosensibles caractérisés par des détails de structure, p. ex. supports, couches auxiliaires
H01L 21/02 - Fabrication ou traitement des dispositifs à semi-conducteurs ou de leurs parties constitutives
H01L 31/08 - Dispositifs à semi-conducteurs sensibles aux rayons infrarouges, à la lumière, au rayonnement électromagnétique d'ondes plus courtes, ou au rayonnement corpusculaire, et spécialement adaptés, soit comme convertisseurs de l'énergie dudit rayonnement e; Procédés ou appareils spécialement adaptés à la fabrication ou au traitement de ces dispositifs ou de leurs parties constitutives; Leurs détails dans lesquels le rayonnement commande le flux de courant à travers le dispositif, p.ex. photo-résistances
The invention provides methods for measuring quantities of mRNA transcripts present in a sample, where sequence information for each molecule is read from what is essentially a random start site within that molecule and in which a short binning index (e.g., about 3 bases) is added to the sequence information. The binning index is useful to resolve any bias arising with the use of the intrinsic sequences to uniquely identify and count the molecules.
53.
CONCURRENT SEQUENCING WITH SPATIALLY SEPARATED RINGS
The invention relates to solid supports and methods for use in nucleic acid sequencing, in particular solid supports and methods for use in concurrent sequencing.
Disclosed herein are flow cells and methods of sequencing using flow cells. In some examples, the flow cells include a first surface that includes a first set of capture primers and a second set of capture primers, and a second surface that includes a first set of capture primers and a second set of capture primers.
An instrument includes a reagent management system. The reagent management system includes a plurality of reagent wells, each reagent well operable to contain a reagent of a plurality of reagents positioned therein. The reagent management system is operable to select a flow of reagent from one of the plurality of reagents. A flexible connection includes a laminate stack and includes a first flexible channel in fluid communication with the reagent management system. The first flexible channel is operable to route the flow of reagent therethrough. A flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is operable to route the flow of reagent over analytes positioned in the flow channel. The flexible connection enables the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.
Some examples relate to a method for characterizing polynucleotides in a sample. First polynucleotides coupled to a first substrate may be hybridized to second polynucleotides in a sample. First labeled nucleotides may be added to the first polynucleotides using a sequence of the second polynucleotides. A first signal intensity from the first labeled nucleotides is measured. Second labeled nucleotides are added to the first polynucleotides using the sequence of the second polynucleotides. A second signal intensity from the second labeled nucleotides is measured. The first signal intensity is normalized using the second signal intensity. The normalized first signal intensity characterizes the second polynucleotides in the sample.
C12Q 1/6818 - Tests d’hybridation caractérisés par les moyens de détection impliquant l’interaction de plusieurs marqueurs, p. ex. transfert d’énergie de résonance
C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme
The present disclosure relates to methods, systems and compositions directed to unspooling a substrate from a source coil and polishing a surface of the substrate, wherein before the polishing, the substrate includes depressions separated by interstices and a coating including a hydrogel disposed on the depressions and the interstices, and the polishing includes applying a slurry to the surface of the substrate and removing the hydrogel from the interstices but not the depressions by contacting the surface of the substrate with one or more polisher and introducing relative movement between the one or more polisher and the surface.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p. ex. verrerie de laboratoireCompte-gouttes
G03F 7/00 - Production par voie photomécanique, p. ex. photolithographique, de surfaces texturées, p. ex. surfaces impriméesMatériaux à cet effet, p. ex. comportant des photoréservesAppareillages spécialement adaptés à cet effet
In some examples, a method of sequencing a polynucleotide includes hybridizing the polynucleotide to a first oligonucleotide coupled to a particle. The hybridized polynucleotide may be amplified using additional oligonucleotides coupled to the particle, to generate amplicons coupled to the particle. After the amplifying, the particle, having the amplicons coupled thereto, may be disposed within a flowcell. After disposing the particle within the flowcell, the particle may be dissolved, leaving the amplicons within the flowcell. The flowcell may be used to sequence the amplicons.
In one aspect, the disclosed technology relates to systems and methods for compensating bias offset voltages of an amplifier array when using nanopore sensors to sequence polynucleotides. In one embodiment, the disclosed system for sequencing polynucleotides includes: a nanopore for sensing a polynucleotide; an amplifier configured to measure an electrical response associated with the nanopore, the amplifier having a bias offset voltage between a first input terminal and a second input terminal; and a bias compensation circuit coupled to the nanopore and the amplifier, the bias compensation circuit configured to store a voltage potential indicative of the bias offset voltage and compensate the bias offset voltage using the voltage potential.
Disclosed herein are flow cells and methods of sequencing using flow cells. In some examples, the flow cells include a first surface that includes a first set of capture primers and a second set of capture primers, and a second surface that includes a first set of capture primers and a second set of capture primers.
This disclosure relates to methods of identifying and mapping methylation sites. In some embodiments, these methods incorporate cytosine deamination and base excision repair. In some embodiments, these methods incorporate use of hairpin adapters. Methods of sequence analysis are also described herein.
Compounds of the disclosure include modified dideoxynucleotide triphosphates (ddNPT) including multiple binding unit containing arms to provide multivalent binding unit molecules.
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
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
63.
FRAGMENT SIZE CHARACTERIZATION OF CELL-FREE DNA MUTATIONS FROM CLONAL HEMATOPOIESIS
Methods and systems are provided for differentiating between cancer variants and somatic variants originating from hematopoietic cells in a cell free DNA sample. In some embodiments, the cancer variants can be distinguished from somatic variants originating from hematopoietic cells based on fragment size distribution.
C12N 15/11 - Fragments d'ADN ou d'ARNLeurs formes modifiées
A61K 35/13 - Cellules tumorales, quel que soit le tissu d’origine
C07K 16/28 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des récepteurs, des antigènes de surface cellulaire ou des déterminants de surface cellulaire
C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
A cartridge for use with chemical or biological analysis systems, as well as methods of using the same, is provided. The cartridge may include a floating microfluidic plate that is held in the cartridge using one or more floating support brackets that incorporate gaskets that may seal against fluidic ports on the microfluidic plate. The floating support brackets may include indexing features that may align the microfluidic plate with the seals.
Examples provided herein are related to detecting a methylated nucleotide using a quencher coupled to the methylated nucleotide. In some examples, a methylated nucleotide in a polynucleotide may be detected using a method that includes coupling a quencher to the methylated nucleotide. The method may include adding fluorescently labeled nucleotides to a primer hybridized to the polynucleotide. The method may include using the quencher to reduce fluorescence from at least one of the added, fluorescently labeled nucleotides. The method may include using the reduced fluorescence caused by the first quencher to detect the methylated nucleotide.
The technology relates in part to methods for determining copy number variations (CNVs) known or suspected to be associated with a variety of medical conditions. In some aspects, the technology relates to determining CNVs of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some aspects, the technology relates to determining CNVs known or suspected to be associated with a variety of medical conditions. In some aspects, methods to improve the sensitivity and/or specificity of sequence data analysis by deriving a fragment size parameter are provided. In some aspects, information from fragments of different sizes is used to evaluate copy number variations. In some aspects, information from fragments of different sizes is used to discriminate between fetal and maternal CNVs. In some aspects, the technology relates to systems and computer program products for evaluation of CNVs of sequences of interest.
In one aspect, the disclosed technology relates to systems and methods for estimating a copy number of repeat units in a target genomic region in a nucleic acid sample from a subject. In some embodiments, a machine learning model is trained to learn the relationship between the known copy numbers of repeat units in predetermined invariant tandem repeat loci and specific features of the predetermined loci and specific features of training genomic regions in the nucleic acid sample from the subject that correspond to the predetermined loci. The copy number of repeat units in the target genomic region can be estimated by applying the trained machine learning model to specific features of a tandem repeat locus corresponding to the target genomic region and specific features of the target genomic region. In another aspect, the disclosed technology relates to computer-readable media including instructions for performing the disclosed methods.
Methods, systems, and apparatus, including computer programs encoded on computer-storage media, for multi-region joint detection. In some implementations, a method for identifying variants using multi-region joint detection in genetic sample sequences includes generating a set of candidate diplotypes mapped to at least two different regions in a reference sequence; generating a set of joint diplotype candidates comprising two or more candidate diplotypes of the set of candidate diplotypes; querying, for diplotypes at one or more locations of the at least two different regions in the reference sequence, a population database comprising genetic sequences of previously sequenced organisms; determining one or more values representing the frequency of specific diplotypes occurring within the genetic sequences of previously sequenced organisms; and generating, using the one or more values, an indication that the variant of the first joint diplotype candidate is an actual variant.
Methods, systems, and apparatus, including computer programs encoded on computer-storage media, for region-ambiguous joint detection. In some implementations, identifying variants using region-ambiguous variant detection in a genetic sample includes generating a plurality of joint diplotype candidates comprising four or more haplotypes of the plurality of haplotypes, determining a posterior probability for each of the plurality of joint diplotype candidates, determining a preferred copy number configuration of the multiple different copy number configurations, wherein the preferred copy number configuration is a copy number configuration that occurs more frequently than any other copy number configuration in the plurality of joint diplotype candidates; determining a region-ambiguous quality score for the plurality of joint diplotype candidates in a given position in a given region, and determining whether a variant exists in at least one of the first or second region of the reference genome based on the determined region-ambiguous quality score.
Described herein are methods, compositions, and kits for removing false positive uracils due to the deamination of unmethylated cytosines in assays using engineered cytosine deaminases to deaminate methylated cytosines. The methods, compositions, and kits utilize a dual enzymatic process. After cytidine deaminase treatment, the DNA is first incubated with Uracil DNA Glycosylase (UDG), which generates abasic sites where dC to dU conversions have occurred. The DNA is then incubated with a high-fidelity polymerase supplemented with a deoxycytidyl transferase, such as Rev1, to repair the lesion with the installation of a cytidine.
This disclosure describes methods, non-transitory computer-readable media, and systems that can (i) identify reads that align with at least some portion of alternative contiguous sequences representing structural variant haplotypes within a structural variant reference genome and (ii) generate a structural-variant-alignment tag within an alignment file for such read alignments to guide identifying candidate structural-variant locations. In addition to employing structural-variant-alignment tags, the disclosed systems identify read fragments that align or overlap with portions of alternate contiguous sequences representing an insertion (or other structural variant) and further masks such insertion-overlapping read fragments as part of an alignment file. When a read aligns completely within an insertion-representing alternate contiguous sequence, the disclosed system can mark the genomic coordinate corresponding to a primary contiguous sequence at which the insertion alternate contiguous sequence is lifted over and generates an unaligned read base indicator indicating that such an insertion-aligned nucleotide read is masked.
Computer methods and systems for quantifying a nucleic acid sample comprising nucleic acid of one or more contributors to: receive nucleic acid sequence reads obtained from the nucleic acid sample and mapped to alleles at polymorphism loci; determine, using the nucleic acid sequence reads, allele counts for each of the alleles at the polymorphism loci; use a probabilistic mixture model that applies a probabilistic mixture model to the allele counts, and that uses probability distributions to model the allele counts at the polymorphism loci; quantify, using the probabilistic mixture model, one or more fractions of nucleic acid of the one or more contributors in the nucleic acid sample; determine a probability that a specific contributor among the one or more contributors has a specific genotype; and call, based on the posterior probability, that the nucleic acid sample includes nucleic acid from the specific contributor.
G16B 40/00 - TIC spécialement adaptées aux biostatistiquesTIC 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
73.
METHODS FOR DOUBLE-STRANDED SEQUENCING BY SYNTHESIS
Nucleotide sequencing methods for sequencing an oligonucleotide strand while the oligonucleotide strand is a part of a double-stranded complex. At least one strand of the double-stranded complex is immobilized on a surface. Sequencing primers may not be immobilized on a surface. Double stranded sequencing methods may employ an enzyme that has nick-translation activity.
This disclosure describes methods, non-transitory computer-readable media, and systems that can (i) identify reads that align with at least some portion of alternative contiguous sequences representing structural variant haplotypes within a structural variant reference genome and (ii) generate a structural-variant-alignment tag within an alignment file for such read alignments to guide identifying candidate structural-variant locations. In addition to employing structural-variant-alignment tags, the disclosed systems identify read fragments that align or overlap with portions of alternate contiguous sequences representing an insertion (or other structural variant) and further masks such insertion-overlapping read fragments as part of an alignment file. When a read aligns completely within an insertion-representing alternate contiguous sequence, the disclosed system can mark the genomic coordinate corresponding to a primary contiguous sequence at which the insertion alternate contiguous sequence is lifted over and generates an unaligned read base indicator indicating that such an insertion-aligned nucleotide read is masked.
Fluidic device includes a manifold body having first and second body sides. The first body side has receiving ports forming a port array that defines a reaction region. The second body side has open-sided recesses forming reaction chambers when the fluidic device is mounted onto a sample substrate. The reaction chambers form a chamber array that defines a fluid-delivery region. The reaction region is greater than the fluid-delivery region. The manifold body also includes vent openings that open to an exterior. The fluidic device also includes upstream channels extending through the manifold body. Each of the upstream channels fluidly couples a corresponding receiving port of the port array to a corresponding reaction chamber of the chamber array. The fluidic device also includes venting channels extending through the manifold body. Each of the venting channels fluidly couples a corresponding reaction chamber of the chamber array to a corresponding vent opening.
Embodiments of the present disclosure relate to methods of preparation of templates for polynucleotide sequencing. In particular, the disclosure relates to linearization of clustered polynucleotides in preparation for sequencing by cleavage of one or more first strands of double-stranded polynucleotides immobilized on a solid support by a transition metal complex, for example, a palladium complex or a nickel complex. Further disclosure relate to linearization of clustered polynucleotides by cleaving one or more second strands of double double-stranded polynucleotides immobilized on a solid support comprising azobenzene linker by Na2S2O4. Nucleotides and oligonucleotides comprising a 3′ phosphate moiety blocking group, and methods of removing the same using a fluoride reagent are also disclosed.
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 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6876 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes
77.
PERIODATE COMPOSITIONS AND METHODS FOR CHEMICAL CLEAVAGE OF SURFACE-BOUND POLYNUCLEOTIDES
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.
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p. ex. séquençage par hybridation [SBH]
C07D 233/58 - Composés hétérocycliques contenant des cycles diazole-1, 3 ou diazole-1, 3 hydrogéné, non condensés avec d'autres cycles comportant deux liaisons doubles entre chaînons cycliques ou entre chaînons cycliques et chaînons non cycliques avec uniquement des atomes d'hydrogène ou des radicaux ne contenant que des atomes d'hydrogène et de carbone, liés aux atomes de carbone du cycle avec uniquement des atomes d'hydrogène ou des radicaux ne contenant que des atomes d'hydrogène et de carbone, liés aux atomes d'azote du cycle
C07D 323/00 - Composés hétérocycliques contenant plus de deux atomes d'oxygène comme uniques hétéro-atomes du cycle
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p. ex. pour test de réaction en chaîne par polymérase [PCR]
An apparatus includes a sample stage region, an optical assembly, and a camera assembly. The optica! assembly includes an objective element, a tube lens, a first dichroic element, and a compensating element. The objective dement provides a field of view including the object plane. The tube lens is configured to receive light transmitted through the objective element. The optical assembly is configured to transmit light in at least a first color channel, a second color channel, a third color channel, and a fourth color channel from the tube lens toward the first dichroic element. The first dichroic element is configured to transmit light of the first and third color channels while reflecting light of the second and fourth color channels. The compensating element is configured to induce an astigmatism in the first and third color channels offsetting an astigmatism induced by the dichroic element.
C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques
G01N 21/01 - Dispositions ou appareils pour faciliter la recherche optique
G02B 21/18 - Aménagements avec plus d'un parcours de lumière, p. ex. pour comparer deux échantillons
The present disclosure is concerned with compositions, articles, kits, and methods for producing an array that includes clonal clusters. In one embodiment, methods include producing clonal clusters on an array that preserves methylation status, such as the methylation state of methylated CpG dinucleotides of the seed DNA molecules.
Actuation systems and methods are disclosed. An apparatus includes a housing, a printed circuit board, and a plurality of shape memory alloy actuators. The printed circuit board is coupled to the housing. Each shape memory alloy actuator has a pair of wire mounts, an actuator rod, a shape memory alloy wire, and a latch assembly. The pair of wire mounts are coupled to opposing sides of the printed circuit board and the actuator rod has a wire guide. The shape memory alloy wire is coupled to the wire mounts and positioned around the wire guide. The latch assembly is coupled to the printed circuit board. Applying a voltage to the shape memory alloy wire retracts the shape memory alloy wire and causes the corresponding actuator rod to move between a first position and a second position. The latch assembly is to hold the actuator rods in the second position.
F15B 13/02 - Dispositifs de distribution ou d'alimentation du fluide caractérisés par leur adaptation à la commande de servomoteurs
F15B 15/14 - Dispositifs actionnés par fluides pour déplacer un organe d'une position à une autreTransmission associée à ces dispositifs caractérisés par la structure de l'ensemble moteur le moteur étant du type à cylindre droit
F15B 15/22 - Autres parties constitutives pour accélérer ou ralentir le mouvement
H05K 7/14 - Montage de la structure de support dans l'enveloppe, sur cadre ou sur bâti
81.
METHODS FOR DOUBLE-STRANDED SEQUENCING BY SYNTHESIS
Nucleotide sequencing methods for sequencing an oligonucleotide strand while the oligonucleotide strand is a part of a double-stranded complex. At least one strand of the double-stranded complex is immobilized on a surface. Sequencing primers may not be immobilized on a surface. Double stranded sequencing methods may employ an enzyme that has nick-translation activity.
Methods, system, and computer programs for reducing a resource metric of a multireference genome. The method includes obtaining a set of augmentations of the multireference genome, performing one or more optimization operations on the set of augmentations to create a candidate augmentation optimization, determining (i) whether the candidate augmentation optimization deviates from a preferred variant tuple set and (ii) whether the candidate augmentation optimization reduces a resource metric of the multireference genome by a threshold amount, and based on a determination (i) that the candidate augmentation optimization does not deviate from the preferred variant tuple set and (ii) that the candidate augmentation optimization reduces a resource metric of the multireference genome by a threshold amount: committing the candidate augmentation optimization to the multireference genome to reduce the resource metric of the multireference genome.
This disclosure describes methods, non-transitory computer readable media, and systems that can utilize one or more machine learning models to predict relationships between human genes and phenotypes. For example, the disclosed systems can generate for human genes in relation to various clinical phenotypes. As a basis for generating such predictions, the disclosed systems can train a gene embedding neural network to determine relationships between genes and phenotypes using a two-stage training process that includes a supervised training stage and an unsupervised fine-tuning stage. In addition, the disclosed systems can utilize the gene embedding neural network to generate gene-to-phenotype scores indicating relationships between genes and phenotypes based on similarities among genes (as represented by gene embeddings). Further, the disclosed systems can utilize a diagnostic variant model to determine whether genomic samples exhibit diagnostic variants based on gene-to-phenotype scores as well as other variant-level features of the genomic samples.
Methods of making barriers including nanopores and crosslinked amphiphilic molecules, and barriers made using the same, are provided herein. In some examples, a method of forming a barrier between first and second fluids includes forming at least one layer comprising a plurality of amphiphilic molecules, wherein the amphiphilic molecules comprise reactive moieties. The method may include using first crosslinking reactions of the reactive moieties to only partially crosslink amphiphilic molecules of the plurality to one another. The method may include, after using the first crosslinking reactions, inserting the nanopore into the at least one layer. The method may include, after inserting the nanopore, using second crosslinking reactions of the reactive moieties to further crosslink amphiphilic molecules of the plurality to one another.
C08L 23/26 - Compositions contenant des homopolymères ou des copolymères d'hydrocarbures aliphatiques non saturés ne possédant qu'une seule liaison double carbone-carboneCompositions contenant des dérivés de tels polymères modifiées par post-traitement chimique
86.
METHODS FOR DISCRIMINATING BETWEEN FETAL AND MATERNAL EVENTS IN NON-INVASIVE PRENATAL TEST SAMPLES
The technology relates in part to methods for determining copy number variations (CNVs) known or suspected to be associated with a variety of medical conditions. In some aspects, the technology relates to determining CNVs of fetuses using maternal samples comprising maternal and fetal cell free DNA. In some aspects, the technology relates to determining CNVs known or suspected to be associated with a variety of medical conditions. In some aspects, methods to improve the sensitivity and/or specificity of sequence data analysis by deriving a fragment size parameter are provided. In some aspects, information from fragments of different sizes is used to evaluate copy number variations. In some aspects, information from fragments of different sizes is used to discriminate between fetal and maternal CNVs. In some aspects, the technology relates to systems and computer program products for evaluation of CNVs of sequences of interest.
An apparatus includes a sample stage region, an optical assembly, and a camera assembly. The optical assembly includes an objective element, a tube lens, a first dichroic element, and a compensating element. The objective element provides a field of view including the object plane. The tube lens is configured to receive light transmitted through the objective element. The optical assembly is configured to transmit light in at least a first color channel, a second color channel, a third color channel, and a fourth color channel from the tube lens toward the first dichroic element. The first dichroic element is configured to transmit light of the first and third color channels while reflecting light of the second and fourth color channels. The compensating element is configured to induce an astigmatism in the first and third color channels offsetting an astigmatism induced by the dichroic element.
G02B 27/14 - Systèmes divisant ou combinant des faisceaux fonctionnant uniquement par réflexion
G02B 13/18 - Objectifs optiques spécialement conçus pour les emplois spécifiés ci-dessous avec des lentilles ayant une ou plusieurs surfaces non sphériques, p. ex. pour réduire l'aberration géométrique
G02B 27/00 - Systèmes ou appareils optiques non prévus dans aucun des groupes ,
Valve assemblies and related systems are disclosed. A method includes imaging a flow cell of a flow cell assembly carried by a flow cell interface using an imaging system of an apparatus and moving the flow cell assembly relative to the imaging system using a stage assembly based on a command from an associated controller. The method also includes driving a motor of the apparatus using shaped input signals to reduce vibration imposed on at least one of the stage assembly or another component of the apparatus based on movement of the motor.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p. ex. verrerie de laboratoireCompte-gouttes
G01N 35/10 - Dispositifs pour transférer les échantillons vers, dans ou à partir de l'appareil d'analyse, p. ex. dispositifs d'aspiration, dispositifs d'injection
Methods, systems, and apparatus, including computer programs encoded on computer-storage media, for multi-region joint detection. In some implementations, a method for identifying variants using multi-region joint detection in genetic sample sequences includes generating a set of candidate diplotypes mapped to at least two different regions in a reference sequence; generating a set of joint diplotype candidates comprising two or more candidate diplotypes of the set of candidate diplotypes; querying, for diplotypes at one or more locations of the at least two different regions in the reference sequence, a population database comprising genetic sequences of previously sequenced organisms; determining one or more values representing the frequency of specific diplotypes occurring within the genetic sequences of previously sequenced organisms; and generating, using the one or more values, an indication that the variant of the first joint diplotype candidate is an actual variant.
Actuation systems and methods are disclosed. An apparatus includes a housing, a printed circuit board, and a plurality of shape memory alloy actuators. The printed circuit board is coupled to the housing. Each shape memory alloy actuator has a pair of wire mounts, an actuator rod, a shape memory alloy wire, and a latch assembly. The pair of wire mounts are coupled to opposing sides of the printed circuit board and the actuator rod has a wire guide. The shape memory alloy wire is coupled to the wire mounts and positioned around the wire guide. The latch assembly is coupled to the printed circuit board. Applying a voltage to the shape memory alloy wire retracts the shape memory alloy wire and causes the corresponding actuator rod to move between a first position and a second position. The latch assembly is to hold the actuator rods in the second position.
Methods, systems, and apparatus, including computer programs, for region-ambiguous joint detection. The method can include actions of obtaining a plurality of haplotypes, generating a plurality of joint diplotype candidates, wherein at least two of the plurality of haplotypes are associated with a first region of a reference genome and at least two of the other haplotypes are associated with a second region of the reference genome, the plurality of joint diplotype candidates comprising multiple different copy number configurations, determining a posterior probability for each of the plurality of joint diplotype candidates, determining a preferred copy number configuration of the multiple different copy number configurations, determining a region-ambiguous quality score for the plurality of joint diplotype candidates in a given position, and determining whether a variant exists in at least one of the first or second region of the reference genome based on the determined region-ambiguous quality score.
An interposer for a flow cell comprises a base layer having a first surface and a second surface opposite the first surface. The base layer comprises black polyethylene terephthalate (PET). A first adhesive layer is disposed on the first surface of the base layer. The first adhesive layer comprises methyl acrylic adhesive. A second adhesive layer is disposed on the second surface of the base layer. The second adhesive layer comprises methyl acrylic adhesive. A plurality of microfluidic channels extends through each of the base layer, the first adhesive layer, and the second adhesive layer.
Presented herein are methods and compositions for multiplexed single cell gene expression analysis. Some methods and compositions include the use of droplets and/or beads bearing unique barcodes such as unique molecular barcodes (UMI).
Methods of making barriers including nanopores and crosslinked amphiphilic molecules, and barriers made using the same, are provided herein. In some examples, a method of forming a barrier between first and second fluids includes forming at least one layer comprising a plurality of amphiphilic molecules, wherein the amphiphilic molecules comprise reactive moieties. The method may include using first crosslinking reactions of the reactive moieties to only partially crosslink amphiphilic molecules of the plurality to one another. The method may include, after using the first crosslinking reactions, inserting the nanopore into the at least one layer. The method may include, after inserting the nanopore, using second crosslinking reactions of the reactive moieties to further crosslink amphiphilic molecules of the plurality to one another.
Artificial transposon sequences having code tags and target nucleic acids containing such sequences. Methods for making artificial transposons and for using their properties to analyze target nucleic acids.
Methods and systems that include training a machine learning model for detecting biological constituents in a sample are provided. A computer-implemented method, and systems executing the method, may include collecting metagenomic data that includes biological constituents obtained from a sample; generating a first molecular data set of covariates; generating a second molecular data set of covariates; generating a training set comprising the first and second covariates as well as combined covariates; and training the machine learning model using aggregate molecular covariates to predict biological constituents from metagenomics data.
G16B 40/00 - TIC spécialement adaptées aux biostatistiquesTIC 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
97.
PERIODATE COMPOSITIONS AND METHODS FOR CHEMICAL CLEAVAGE OF SURFACE-BOUND POLYNUCLEOTIDES
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.
Described is a multi-regional, multi-omics approach to uncovering the mechanisms of immune escape in carcinoma. Immunotherapy with ant-PD1 and anti-CTLA4 elicits a heterogeneous immunological response across different regions of the tumor. Several genetic alterations associated with high intra-tumoral heterogeneity (ITH) shape tumor microenvironment (TME).
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p. ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
99.
MACHINE LEARNING-BASED PREDICTION OF BIOLOGICAL CONSTITUENTS IN A SAMPLE
Methods and systems that include training a machine learning model for detecting biological constituents in a sample are provided. A computer-implemented method, and systems executing the method, may include collecting metagenomic data that includes biological constituents obtained from a sample; generating a first molecular data set of covariates; generating a second molecular data set of covariates; generating a training set comprising the first and second covariates as well as combined covariates; and training the machine learning model using aggregate molecular covariates to predict biological constituents from metagenomics data.
