An example of a resin composition includes a free radical curable resin matrix including an acrylate and a siloxane, and a free radical photoinitiator. When cured, the resin composition has low or no autofluorescence when exposed to blue excitation wavelengths ranging from about 380 nm to about 480 nm or green excitation wavelengths ranging from about 510 nm to about 560 nm.
C08L 63/00 - Compositions of epoxy resins; Compositions of derivatives of epoxy resins
C09D 153/00 - Coating compositions based on block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Coating compositions based on derivatives of such polymers
C09D 163/00 - Coating compositions based on epoxy resins; Coating compositions based on derivatives of epoxy resins
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
2.
NUCLEIC ACID SEQUENCING COMPONENTS INCLUDING A GLYCOLIPID BI-LAYER
An example of a nucleic acid sequencing component includes a support. A glycolipid bi-layer is attached to at least a portion of the support. First and second primers are respectively attached to the glycolipid bi-layer. In one example, the support is a substrate of a flow cell. In another example, the support is a core nanostructure that can be introduced into a flow cell.
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.
Detecting analytes using proximity-induced tagmentation, strand invasion, restriction, or ligation is provided herein. In some examples, detecting an analyte includes coupling a donor recognition probe to a first portion of the analyte. The donor recognition probe includes a first recognition element specific to the first portion of the analyte, a first oligonucleotide corresponding to the first portion, and a transposase coupled to the first recognition element and the first oligonucleotide. An acceptor recognition probe is coupled to a second portion of the analyte. The acceptor recognition probe includes a second recognition element specific to the second portion of the analyte and a second oligonucleotide coupled to the second recognition element and corresponding to the second portion. The transposase is used to generate a reporter polynucleotide including the first and second oligonucleotides. The analyte is detected based on the reporter including comprising the first and second oligonucleotides.
This disclosure describes methods, non-transitory computer readable media, and systems that can use a computationally efficient model to determine a corrected methylation-level value for a specific sample nucleotide sequence. For instance, the disclosed systems determine a false positive rate and a false negative rate at which a given methylation sequencing assay converts cytosine bases. Based on the determined false positive rate and false negative rate, the disclosed systems determine a corrected methylation-level value that corrects for a bias of the given methylation sequencing assay.
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.
This disclosure describes methods, non-transitory computer readable media, and systems that can generate genotype calls from a combined pipeline for processing nucleotide reads from multiple read types/sources for robust, accurate genotype calls. For example, the disclosed systems can train and/or utilize a genotype-call-integration machine-learning model to generate predictions for genotype calls based on data associated with a first type of nucleotide reads (e.g., short reads) and a second type of nucleotide reads (e.g., long reads). As disclosed, the disclosed systems can determine sequencing metrics and can utilize a genotype-call-integration machine-learning model to generate predictions (e.g., genotype probabilities, variant call classifications) for generating output genotype calls based on the sequencing metrics. The disclosed system can utilize multiple such genotype-call-integration machine-learning models to generate genotype calls for different variant types, such as SNPs and indels, where the genotype-call-integration machine-learning models generate different predictions for each variant type.
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 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
9.
DETECTING AND CORRECTING METHYLATION VALUES FROM METHYLATION SEQUENCING ASSAYS
This disclosure describes methods, non-transitory computer readable media, and systems that can use a computationally efficient model to determine a corrected methylation-level value for a specific sample nucleotide sequence. For instance, the disclosed systems determine a false positive rate and a false negative rate at which a given methylation sequencing assay converts cytosine bases. Based on the determined false positive rate and false negative rate, the disclosed systems determine a corrected methylation-level value that corrects for a bias of the given methylation sequencing assay.
An example of a flow cell includes a substrate and a reaction area defined in or over the substrate. The reaction area includes two angularly offset and non-perpendicular surfaces relative to a planar surface of the substrate, a polymeric hydrogel positioned over at least a portion of each of the two angularly offset and non-perpendicular surfaces; a first primer set attached to the polymeric hydrogel that is positioned over the portion of a first of the two angularly offset and non-perpendicular surfaces; and a second primer set attached to the polymeric hydrogel that is positioned over the portion of a second of the two angularly offset and non-perpendicular surfaces, wherein the first and second primer sets are orthogonal.
This disclosure relates to novel amplification compositions and methods, in particular for use in nucleic acid amplification and sequencing, preferably that do not involve reagents that are thermophilic.
This disclosure relates to novel thermophilic amplification compositions and methods, in particular for use in nucleic acid amplification and sequencing.
Gasket assemblies and related system and methods. An apparatus includes a system, a flow cell, and a plurality of gasket assemblies. The system includes a flow cell interface and the flow cell has one or more channels. Each channel has a first channel opening and a second channel opening. The first channel openings are positioned at a first end of the flow cell and the second channel openings are positioned at a second end of the flow cell. A gasket assembly coupled at each second channel opening. Each gasket assembly includes an adhesive stack and a gasket. The adhesive stack includes a first side bonded to the gasket and a second side bonded to the flow cell. The flow cell interface is engagable with the corresponding gaskets to establish a fluidic coupling between system and the flow cell.
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.
The motion of a mechanical stage may be directed in x-, y-, and/or z-dimensions such that excitation of a resonant frequency f is reduced. In particular, once a resonant frequency f is identified, the acceleration of the stage in the x-, y-, and/or z-dimensions may divided into an even number of acceleration segments or intervals, with the second of each pair of acceleration segments starting 1/(2f) seconds after the start of the initial acceleration segment. The acceleration intervals may be defined by a start time, an amplitude profile, and/or a time duration. In some implementations, the amplitude and time duration of each acceleration pulse may be different. The amplitude and time duration of acceleration steps may be determined and adjusted to compensate for the particular resonance frequency of an individual system, and programmed into a controller for the stage using motor programming controls.
Liquid reservoirs, cartridge assemblies and related systems and methods are disclosed. An example implementation includes an apparatus that includes a body, a cover, and a lid assembly. The body includes a top surface and a storage chamber having an opening at the top surface. The cover covers or is positioned within the opening of the storage chamber. The lid assembly is coupled to the top surface and covers the opening of the storage chamber. The top surface and the first portion define a plenum. The cover is at least one of piercable, breakable, or movable to allow the storage chamber to be fluidly coupled to the plenum without venting the plenum to atmosphere.
This disclosure describes methods, non-transitory computer readable media, and systems that can utilize a machine-learning model to refine structural variant calls of a call generation model. For example, the disclosed systems can train and utilize a structural variant refinement machine-learning model to reduce false positives and/or false negatives. Indeed, the disclosed systems can improve or refine structural variant calls (e.g., between 50-200 base pairs in length) determined by a call generation model by training and utilizing the structural variant refinement machine-learning model. As disclosed, the systems can determine sequencing metrics and can customize training data for a structural variant refinement machine-learning model to generate modified structural variant calls.
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.
Presented herein are techniques for indexing of nucleic acid, e.g., for use in conjunction with sequencing. The techniques include generating indexed nucleic acid fragments from an individual sample, whereby the index sequence incorporated into each index site of the nucleic acid fragment is selected from a plurality of distinguishable of index sequences and such that the population of generated nucleic acid fragments represents each index sequence from the plurality. In this manner, the generated indexed nucleic acid fragments from a single sample are indexed with a diverse mix of index sequences that reduce misassignment due to index read errors associated with low sequence diversity.
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.
Described herein are compositions and methods for enriching library fragments comprising viral sequences prepared from a variety of samples. These methods may incorporate microfluidics and flowcells for greater ease 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 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
23.
METHODS, COMPOSITIONS AND KITS TO IMPROVE SEEDING EFFICIENCY OF FLOW CELLS WITH POLYNUCLEOTIDES
The disclosure relates to methods, compositions, and kits for improving seeding efficiency of flow cells with polynucleotides, and applications thereof, including for sequencing.
Reusable flow cells for sequencing which exhibit signal intensity retention over numerous use cycles, the active surface of which contains poly-azide functional moieties, methods of treating flow cells surfaces with reagents to provide such poly-azide functional moieties, and reagents therefor.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C07D 207/46 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
25.
NANOGEL PARTICLES HAVING DUAL FUNCTIONALITY AND TEMPERATURE RESPONSIVENESS FOR PARTICLE CLUSTERING IN NUCLEIC ACID SEQUENCING SYSTEMS
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.
A microarray is designed to capture one or more molecules of interest at each of a plurality of sites on a substrate. The sites comprise base pads, such as polymer base pads, that promote the attachment of the molecules at the sites. The microarray may be made by one or more patterning techniques to create a layout of base pads in a desired pattern. Further, the microarrays may include features to encourage clonality at the sites.
C40B 50/18 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support using a particular method of attachment to the solid support
27.
BIOSENSORS FOR BIOLOGICAL OR CHEMICAL ANALYSIS AND SYSTEMS AND METHODS FOR SAME
A biosensor is provided including a detection device and a flow cell mounted to the detection device. The detection device has a detector surface with a plurality of reaction sites. The detection device also includes a filter layer. A method is providing including obtaining signal data from an array of light detectors; determining a crosstalk function for each of the light detectors of the array of light detectors; and determining characteristics of analytes of interest based on the signal data using the crosstalk functions.
The present invention provides a novel approach for storing, analyzing, and/or accessing biological data in a cloud computing environment. Sequence data generated by a particular sequencing device may be uploaded to the cloud computing environment during a sequencing run, which reduces the on-site storage needs for the sequence data. Analysis of the data may also be performed in the cloud computing environment, and the instructions for such analysis may be set at the originating sequencing device. The sequence data in the cloud computing environment may be shared according to permissions. Further, the sequence data may be modified or annotated by authorized secondary users.
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
G06F 21/62 - Protecting access to data via a platform, e.g. using keys or access control rules
G16B 50/30 - Data warehousing; Computing architectures
G16H 40/40 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the management of medical equipment or devices, e.g. scheduling maintenance or upgrades
G16H 40/63 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
This disclosure describes methods, non-transitory computer readable media, and systems that can generate genotype calls from a combined pipeline for processing nucleotide reads from multiple read types/sources for robust, accurate genotype calls. For example, the disclosed systems can train and/or utilize a genotype-call-integration machine-learning model to generate predictions for genotype calls based on data associated with a first type of nucleotide reads (e.g., short reads) and a second type of nucleotide reads (e.g., long reads). As disclosed, the disclosed systems can determine sequencing metrics and can utilize a genotype-call-integration machine-learning model to generate predictions (e.g., genotype probabilities, variant call classifications) for generating output genotype calls based on the sequencing metrics. The disclosed system can utilize multiple such genotype-call-integration machine-learning models to generate genotype calls for different variant types, such as SNPs and indels, where the genotype-call-integration machine-learning models generate different predictions for each variant type.
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.
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
31.
PROBES FOR IMPROVING CORONAVIRUS SAMPLE SURVEILLANCE
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 ease 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 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Sequencing systems and methods are provided that include a nanopore well that includes a cis well associated with a cis electrode and a trans well associated with a trans electrode, a membrane separating the cis well and the trans well, and a nanopore well embedded in the membrane providing a channel through the membrane; a command node connected directly to the nanopore well. The command node is configured to apply a potential across the nanopore well and a command pulse. The system further includes an amplifier with a feedback loop coupled to the nanopore well and a switch disposed between the amplifier and the nanopore well. The switch is driven by a clock pulse and configured to ground an inverting input of the amplifier.
The present disclosure relates to systems, non-transitory computer-readable media, and methods for generating a target-variant-reference panel comprising a target-variant position with target-variant indicators or using the target-variant-reference panel to impute a genotype call for the corresponding target variant. In particular, in one or more embodiments, the disclosed systems generate an initial reference panel including a variety of phased genomic samples of different haplotypes. The disclosed systems further add a target-variant position to the initial reference panel to indicate a presence or absence of a target variant, thereby creating a target-variant-reference panel comprising a target-variant position with target-variant indicators. Additionally or alternatively, the disclosed systems can utilize the target-variant-reference panel to impute genotype calls indicating a presence or absence of a target variant within a target genomic sample based on a comparison of (i) haplotypes represented in the target-variant-reference panel and (ii) nucleotide reads corresponding to the target genomic sample.
A method of processing sequence data comprising a known location of the start of a copy number variant breakpoint to generate a prediction for the location of the end of the copy number variant breakpoint. The method comprises an encoder and a copy number variation (CNV) caller guide. The encoder processes an anchor sequence and corresponding subject candidate sequence to generate a learned representation of the anchor sequence and a learned representation of the corresponding subject candidate sequence. The CNV caller guide determines a similarity between the learned representation of the anchor sequence and a learned representation of the corresponding subject candidate sequence. Similarity between anchor sequence and subject candidate sequence is used as a proxy for likelihood that the end of the CNV breakpoint is located on the subject candidate sequence.
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
37.
COMPOSITIONS AND METHODS FOR REDUCING PHOTO DAMAGE DURING 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.
Presented herein are altered polymerase enzymes for improved incorporation of nucleotides and nucleotide analogues, in particular altered polymerases that maintain low error rate, low phasing rate, or increased incorporation rate for a second generation ffN under reduced incorporation times, as well as methods and kits using the same.
Protein complexes including a cytidine deaminase and a helicase. In some embodiments, the cytidine deaminase is an altered cytidine deaminase. In some embodiments, the protein complex converts 5 methylcytosine to thymine. Kits, compositions, and methods of use for the protein complexes including a cytidine deaminase and a helicase are also described.
Sequencing systems and methods are provided that include a nanopore well (320) that includes a cis well associated with a cis electrode and a trans well associated with a trans electrode, a membrane separating the cis well and the trans well, and a nanopore well embedded in the membrane providing a channel through the membrane; a command node (312) connected directly to the nanopore well. The command node is configured to apply a potential across the nanopore well and a command pulse. The system further includes an amplifier (340) with a feedback loop (342) coupled to the nanopore well and a switch (366) disposed between the amplifier and the nanopore well. The switch is driven by a clock (362) pulse and configured to ground an inverting input of the amplifier.
Some implementations of the disclosure relate to an imaging system including one or more image sensors and a Z-stage. The imaging system is configured to perform operations including: capturing, using the one or more image sensors, a first image of a first pair of spots projected at a first sample location of a sample; determining whether or not the first image of the first pair of spots is valid; and when the first image is determined to be valid: obtaining, based on the first image, a current separation distance measurement of the first pair of spots; and controlling, based at least on the current separation distance measurement, the Z-stage to focus the imaging system at the first sample location.
Provided herein are methods, compositions, and kits related to using a CpG binding protein. In one embodiment, the present disclosure includes methods, compositions, and kits related to using a CpG binding protein with a cytidine deaminase protein to identify methylated cytosine nucleotides. The cytidine deaminase can be an altered cytidine deaminase that includes an amino acid substitution mutation at a position functionally equivalent to (Tyr/Phe)130 in a wild-type APOBEC3A protein. In another embodiment, the present disclosure includes methods, compositions, and kits related to using a CpG binding protein with a ten-eleven translocase (TET) protein to identify methylated cytosine nucleotides.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 9/78 - Hydrolases (3.) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
C12N 15/52 - Genes encoding for enzymes or proenzymes
C12N 15/62 - DNA sequences coding for fusion proteins
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
This disclosure describes methods, non-transitory computer readable media, and systems that can utilize a machine-learning model to refine structural variant calls of a call generation model. For example, the disclosed systems can train and utilize a structural variant refinement machine-learning model to reduce false positives and/or false negatives. Indeed, the disclosed systems can improve or refine structural variant calls (e.g., between 50-200 base pairs in length) determined by a call generation model by training and utilizing the structural variant refinement machine-learning model. As disclosed, the systems can determine sequencing metrics and can customize training data for a structural variant refinement machine-learning model to generate modified structural variant calls.
A method of processing sequence data comprising a known location of the start of a copy number variant breakpoint to generate a prediction for the location of the end of the copy number variant breakpoint. The method comprises an encoder and a copy number variation (CNV) caller guide. The encoder processes an anchor sequence and corresponding subject candidate sequence to generate a learned representation of the anchor sequence and a learned representation of the corresponding subject candidate sequence. The CNV caller guide determines a similarity between the learned representation of the anchor sequence and a learned representation of the corresponding subject candidate sequence. Similarity between anchor sequence and subject candidate sequence is used as a proxy for likelihood that the end of the CNV breakpoint is located on the subject candidate sequence.
An example of a flow cell includes a substrate and a reaction area defined in or over the substrate. The reaction area includes two angularly offset and non-perpendicular surfaces relative to a planar surface of the substrate, a polymeric hydrogel positioned over at least a portion of each of the two angularly offset and non-perpendicular surfaces; a first primer set attached to the polymeric hydrogel that is positioned over the portion of a first of the two angularly offset and non-perpendicular surfaces; and a second primer set attached to the polymeric hydrogel that is positioned over the portion of a second of the two angularly offset and non-perpendicular surfaces, wherein the first and second primer sets are orthogonal.
An apparatus includes a flow cell, an imaging assembly, and a processor. The flow cell includes a channel and a plurality of reaction sites. The imaging assembly is operable to receive light emitted from the reaction sites in response to an excitation light. The processor is configured to drive relative movement between at least a portion of the imaging assembly and the flow cell along a continuous range of motion to thereby enable the imaging assembly to capture images along the length of the channel. The processor is also configured to activate the imaging assembly to capture one or more calibration images of one or more calibration regions of the channel, during a first portion of the continuous range of motion. The processor is also configured to activate the imaging assembly to capture images of the reaction sites during a second portion of the continuous range of motion.
Some implementations of the disclosure relate to an imaging system including one or more image sensors and a Z-stage. The imaging system is configured to perform operations including: capturing, using the one or more image sensors, a first image of a first pair of spots projected at a first sample location of a sample; determining whether or not the first image of the first pair of spots is valid; and when the first image is determined to be valid: obtaining, based on the first image, a current separation distance measurement of the first pair of spots; and controlling, based at least on the current separation distance measurement, the Z-stage to focus the imaging system at the first sample location.
The presently described techniques relate generally to providing motion feedback (e.g., motion system calibration and/or sample alignment) in the context of an imaging system (such as a time delay and integration (TDI) based imaging system). The architecture and techniques discussed may achieve nanoscale control and calibration of a movement feedback system without a high-resolution encoder subsystem or, in the alternative embodiments, with a lower resolution (and correspondingly less expensive) encoder subsystem than might otherwise be employed. By way of example, certain embodiments described herein relate to ascertaining or calibrating linear motion of a sample holder surface using nanoscale features (e.g., sample sites or nanowells or lithographically patterned features) provided on a surface of the sample holder.
ffff) seconds after the start of the initial acceleration segment. The acceleration intervals may be defined by a start time, an amplitude profile, and/or a time duration. In some implementations, the amplitude and time duration of each acceleration pulse may be different. The amplitude and time duration of acceleration steps may be determined and adjusted to compensate for the particular resonance frequency of an individual system, and programmed into a controller for the stage using motor programming controls.
An apparatus includes a flow cell, an imaging assembly, and a processor. The flow cell includes a channel and a plurality of reaction sites. The imaging assembly is operable to receive light emitted from the reaction sites in response to an excitation light. The processor is configured to drive relative movement between at least a portion of the imaging assembly and the flow cell along a continuous range of motion to thereby enable the imaging assembly to capture images along the length of the channel. The processor is also configured to activate the imaging assembly to capture one or more calibration images of one or more calibration regions of the channel, during a first portion of the continuous range of motion. The processor is also configured to activate the imaging assembly to capture images of the reaction sites during a second portion of the continuous range of motion.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
Liquid reservoirs, cartridge assemblies and related systems and methods are disclosed. An example implementation includes an apparatus that includes a body, a cover, and a lid assembly. The body includes a top surface and a storage chamber having an opening at the top surface. The cover covers or is positioned within the opening of the storage chamber. The lid assembly is coupled to the top surface and covers the opening of the storage chamber. The top surface and the first portion define a plenum. The cover is at least one of piercable, breakable, or movable to allow the storage chamber to be fluidly coupled to the plenum without venting the plenum to atmosphere.
The present disclosure is concerned with proteins, methods, compositions, and kits for mapping of methylation status of nucleic acids. In one embodiment, proteins are provided that selectively act on certain modified cytosines of target nucleic acids and converts them to thymine. Also provided are compositions and kits that include one or more of the proteins and methods for using one or more of the proteins.
Disclosed herein are methods and systems for determining a score for the copy number of repeat units in a variable number tandem repeat (VNTR) locus in a target polynucleotide. Also disclosed herein are methods and systems for determining the nucleotide sequence of a sample nucleic acid having repeat units, where the methods and systems may utilize the most likely copy number of repeat units determined according to the aforementioned methods and systems. Also disclosed herein are methods and systems for predicting a feature of a subject, wherein the methods and systems may utilize the score for the copy number of repeat units in a VNTR locus in a target polynucleotide determined according to the aforementioned methods and systems.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
56.
NUCLEIC ACID SEQUENCING COMPONENTS INCLUDING A GLYCOLIPID BI-LAYER
An example of a nucleic acid sequencing component includes a support. A glycolipid bi-layer is attached to at least a portion of the support. First and second primers are respectively attached to the glycolipid bi-layer. In one example, the support is a substrate of a flow cell. In another example, the support is a core nanostructure that can be introduced into a flow cell.
The present disclosure relates to systems, non-transitory computer-readable media, and methods for generating a target-variant-reference panel comprising a target-variant position with target-variant indicators or using the target-variant-reference panel to impute a genotype call for the corresponding target variant. In particular, in one or more embodiments, the disclosed systems generate an initial reference panel including a variety of phased genomic samples of different haplotypes. The disclosed systems further add a target-variant position to the initial reference panel to indicate a presence or absence of a target variant, thereby creating a target-variant-reference panel comprising a target-variant position with target-variant indicators. Additionally or alternatively, the disclosed systems can utilize the target-variant-reference panel to impute genotype calls indicating a presence or absence of a target variant within a target genomic sample based on a comparison of (i) haplotypes represented in the target-variant-reference panel and (ii) nucleotide reads corresponding to the target genomic sample.
This disclosure relates to novel thermophilic amplification compositions and methods, in particular for use in nucleic acid amplification and sequencing.
This disclosure relates to novel amplification compositions and methods, in particular for use in nucleic acid amplification and sequencing, preferably that do not involve reagents that are thermophilic.
The presently described techniques relate generally to providing motion feedback (e.g., motion system calibration and/or sample alignment) in the context of an imaging system (such as a time delay and integration (TDI) based imaging system). The architecture and techniques discussed may achieve nanoscale control and calibration of a movement feedback system without a high-resolution encoder subsystem or, in the alternative embodiments, with a lower resolution (and correspondingly less expensive) encoder subsystem than might otherwise be employed. By way of example, certain embodiments described herein relate to ascertaining or calibrating linear motion of a sample holder surface using nanoscale features (e.g., sample sites or nanowells or lithographically patterned features) provided on a surface of the sample holder.
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.
An example flow cell includes a patterned substrate having an active region and a bonding region that at least partially surrounds the active region. The active region includes first depressions defined in a layer of the patterned substrate, surface chemistry positioned in the first depressions, and first interstitial regions surrounding the first depressions. The bonding region includes second depressions defined in the layer and second interstitial regions surrounding the second depressions. An adhesive is positioned over the second depressions and over the second interstitial regions. A cover is attached to the adhesive such that a flow channel is defined between a portion of the cover and the active region.
A method includes flowing an incorporation reagent through a reagent management system and a flow cell of an instrument. The flow cell having a first polynucleotide positioned therein. The incorporation reagent adding a first base onto a sequence of bases. The sequence of bases includes a second polynucleotide complementary to the first polynucleotide. An image of an identification signal emanating from the first base is captured after the first base has been added onto the second polynucleotide. A cleavage reagent is flowed through the reagent management system and flow cell to remove a first terminator from the first base in order to enable a subsequent base in the sequence of bases to be added to the second polynucleotide. A buffer reagent is flowed through the reagent management system and flow cell in a plurality of cycles of consecutive forward and reverse flow directions.
The invention relates to deformable polymers comprising immobilised primers, particularly for use in nucleic acid sequencing, such as concurrent sequencing.
Versions of a sequencing system may be monitored to enable changing of a version of a server subsystem operating the sequencing system to service requests from client subsystems for performing analysis of sequencing data. A monitor subsystem may be utilized for receiving and authorizing requests from client subsystems. The monitor subsystem may identify a version associated with a server subsystem operating the sequencing system to be implemented for servicing the request. The monitor subsystem may allow the server subsystem to be accessed for servicing the request from the client subsystem when the version associated with the client subsystem is compatible with the version associated with the server subsystem. The monitor subsystem may prevent the server subsystem from being accessed when the version associated with the client subsystem is incompatible with the version associated with the server subsystem.
G16B 50/00 - ICT programming tools or database systems specially adapted for bioinformatics
G16B 50/30 - Data warehousing; Computing architectures
G06F 21/57 - Certifying or maintaining trusted computer platforms, e.g. secure boots or power-downs, version controls, system software checks, secure updates or assessing vulnerabilities
G06F 8/71 - Version control ; Configuration management
G06F 21/62 - Protecting access to data via a platform, e.g. using keys or access control rules
A system and method for imaging biological samples on multiple surfaces of a support structure are disclosed. The support structure may be a flow cell through which a reagent fluid is allowed to flow and interact with the biological samples. Excitation radiation from at least one radiation source may be used to excite the biological samples on multiple surfaces. In this manner, fluorescent emission radiation may be generated from the biological samples and subsequently captured and detected by detection optics and at least one detector. The detected fluorescent emission radiation may then be used to generate image data. This imaging of multiple surfaces may be accomplished either sequentially or simultaneously. In addition, the techniques of the present invention may be used with any type of imaging system. For instance, both epifluorescent and total internal reflection methods may benefit from the techniques of the present invention.
Systems, methods, and apparatus are described herein for performing sequencing of one or more biological samples in at least two flow cells on a sequencing device. A sequencing system may comprise one or more of a scheduling engine, the sequencing device, and a display. The scheduling engine may maintain scheduling information of a state of compute resources and non-compute resources. The sequencing device may receive the scheduling information from the scheduling engine; determine the state of the compute resources and non-compute resources; determine a sequencing analysis priority associated with performing analysis of the at least two flow cells on the sequencing device; and perform the sequencing task related to the one or more biological samples in the at least two flow cells according to the sequencing analysis priority. The display may display real-time feedback associated with completion of the sequencing task for each flow cell.
Reusable flow cells for sequencing which exhibit signal intensity retention over numerous use cycles, the active surface of which contains poly-azide functional moieties, methods of treating flow cells surfaces with reagents to provide such poly-azide functional moieties, and reagents therefor.
Systems, methods, and apparatus are described herein for performing sequencing of one or more biological samples in at least two flow cells on a sequencing device. A sequencing system may comprise one or more of a scheduling engine, the sequencing device, and a display. The scheduling engine may maintain scheduling information of a state of compute resources and non-compute resources. The sequencing device may receive the scheduling information from the scheduling engine; determine the state of the compute resources and non-compute resources; determine a sequencing analysis priority associated with performing analysis of the at least two flow cells on the sequencing device; and perform the sequencing task related to the one or more biological samples in the at least two flow cells according to the sequencing analysis priority. The display may display real-time feedback associated with completion of the sequencing task for each flow cell.
The technology disclosed is directed to cluster segmentation and base calling. The technology disclosed describes a computer-implemented method including segmenting a population of clusters into a plurality of subpopulations of clusters based on one or more prior bases called at one or more prior sequencing cycles of a sequencing run. At a current sequencing cycle of the sequencing run, the method includes applying a mixture of four distributions to current sequenced data of each subpopulation of clusters in the plurality of subpopulations of clusters, the four distributions corresponding to four bases adenine (A), cytosine (C), guanine (G), and thymine (T), and the current sequenced data being generated at the current sequencing cycle. The method further includes base calling clusters in a particular subpopulation of clusters using a corresponding mixture of four distributions.
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
In one aspect, the disclosed technology relates to systems and methods for sequencing polynucleotides. In one embodiment, the disclosed technology relates to a nanopore sensor device for identifying nucleotides, the nanopore sensor device including: one or more cis wells; one or more cis electrodes associated with the one or more cis wells; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid or solid-state membrane having a nanopore; a plurality of field effect transistors (FETs), each of the plurality of FETs associated with one of the plurality of trans wells; an electrical source configured to provide alternating current (AC) inputs between the one or more cis electrodes and the source terminals of the plurality of FETs; and a controller operably coupled to the plurality of FETs, the controller configured to measure AC responses of the plurality of FETs, wherein the AC responses depend on the identities of the nucleotides within or near the nanopores.
Versions of a sequencing system may be monitored to enable changing of a version of a server subsystem operating the sequencing system to service requests from client subsystems for performing analysis of sequencing data. A monitor subsystem may be utilized for receiving and authorizing requests from client subsystems. The monitor subsystem may identify a version associated with a server subsystem operating the sequencing system to be implemented for servicing the request. The monitor subsystem may allow the server subsystem to be accessed for servicing the request from the client subsystem when the version associated with the client subsystem is compatible with the version associated with the server subsystem. The monitor subsystem may prevent the server subsystem from being accessed when the version associated with the client subsystem is incompatible with the version associated with the server subsystem.
H04L 67/00 - Network arrangements or protocols for supporting network services or applications
G06F 8/71 - Version control ; Configuration management
H04L 41/082 - Configuration setting characterised by the conditions triggering a change of settings the condition being updates or upgrades of network functionality
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.
There is set forth herein a device comprising structure defining a detector surface configured for supporting biological or chemical substances, and a sensor array comprising light sensors and circuitry to transmit data signals using photons detected by the light sensors. The device can include one or more features for reducing fluorescence range noise in a detection band of the sensor array.
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 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups
79.
ERROR SUPPRESSION IN SEQUENCED DNA FRAGMENTS USING REDUNDANT READS WITH UNIQUE MOLECULAR INDICES (UMIS)
The disclosed embodiments concern methods, apparatus, systems and computer program products for determining sequences of interest using unique molecular index (UMI) sequences that are uniquely associable with individual polynucleotide fragments, including sequences with low allele frequencies and long sequence length. In some implementations, the UMIs include both physical UMIs and virtual UMIs. In some implementations, the unique molecular index sequences include non-random sequences. System, apparatus, and computer program products are also provided for determining a sequence of interest implementing the methods disclosed.
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.
C07K 14/195 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
C08F 293/00 - Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule
81.
METHODS AND COMPOSITIONS FOR SELECTIVE CLEAVAGE OF NUCLEIC ACIDS WITH RECOMBINANT NUCLEASES
Some embodiments of the methods and compositions provided herein relate to the selective cleavage of a target nucleic acid. Some such embodiments include the selective cleavage of a target nucleic acid that is associated with a DNA-binding protein or comprises a methylated CpG island, with a recombinant nuclease. In some embodiments, the DNA-binding protein comprises a chromatin protein. Some embodiments also include the enrichment of non-target nucleic acids in a sample by selective cleavage of target nucleic acids in the sample, and removal of the cleaved target nucleic acids from the sample.
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
Some embodiments of the methods and compositions provided herein relate to blocked substrates in which non-specific binding of nucleic acids to the substrate is reduced. Some embodiments include use of carrier nucleic acids. More embodiments include the use of beads contacted with an oligonucleotide, such as an oligonucleotide containing one or more phosphorothioate bonds. Such substrates are useful in methods for obtaining long-read information from short reads of a target nucleic acid.
A method for spatially tagging nucleic acids of a biological specimen, including steps of (a) providing a solid support comprising different nucleic acid probes that are randomly located on the solid support, wherein the different nucleic acid probes each includes a barcode sequence that differs from the barcode sequence of other randomly located probes on the solid support; (b) performing a nucleic acid detection reaction on the solid support to locate the barcode sequences on the solid support; (c) contacting a biological specimen with the solid support that has the randomly located probes; (d) hybridizing the randomly located probes to target nucleic acids from portions of the biological specimen; and (e) modifying the randomly located probes that are hybridized to the target nucleic acids, thereby producing modified probes that include the barcode sequences and a target specific modification, thereby spatially tagging the nucleic acids of the biological specimen.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
84.
METHODS OF MODIFYING METHYLCYTOSINE OR DERIVATIVE THEREOF USING A NUCLEOPHILIC MOLECULE, AND METHODS OF USING THE SAME TO DETECT THE METHYLCYTOSINE OR DERIVATIVE THEREOF IN A POLYNUCLEOTIDE
Disclosed herein are methods of modifying 5-methylcytosine (5-mC), 5- hydroxymethylcytosine (5-hmC), or 5-formlcytosine (5-fC) in a polynucleotide. The method may include oxidizing the 5-mC, 5-hmC, or 5-fC to 5-carboxylcytosine (5-caC); activating the 5-carboxyl group of the 5-caC; and reacting the activated 5-carboxyl group with a nucleophilic molecule to form a product. In some examples, the product may be used to detect the 5-mC, 5-hmC, or 5-fC in the polynucleotide.
An example flow cell includes a patterned substrate having an active region and a bonding region that at least partially surrounds the active region. The active region includes first depressions defined in a layer of the patterned substrate, surface chemistry positioned in the first depressions, and first interstitial regions surrounding the first depressions. The bonding region includes second depressions defined in the layer and second interstitial regions surrounding the second depressions. An adhesive is positioned over the second depressions and over the second interstitial regions. A cover is attached to the adhesive such that a flow channel is defined between a portion of the cover and the active region.
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 technology disclosed assigns quality scores to bases called by a neural network-based base caller by (i) quantizing classification scores of predicted base calls produced by the neural network-based base caller in response to processing training data during training, (ii) selecting a set of quantized classification scores, (iii) for each quantized classification score in the set, determining a base calling error rate by comparing its predicted base calls to corresponding ground truth base calls, (iv) determining a fit between the quantized classification scores and their base calling error rates, and (v) correlating the quality scores to the quantized classification scores based on the fit.
G06F 18/23211 - Non-hierarchical techniques using statistics or function optimisation, e.g. modelling of probability density functions with adaptive number of clusters
G06F 18/2415 - Classification techniques relating to the classification model, e.g. parametric or non-parametric approaches based on parametric or probabilistic models, e.g. based on likelihood ratio or false acceptance rate versus a false rejection rate
G06N 3/084 - Backpropagation, e.g. using gradient descent
G06N 7/01 - Probabilistic graphical models, e.g. probabilistic networks
G06V 10/44 - Local feature extraction by analysis of parts of the pattern, e.g. by detecting edges, contours, loops, corners, strokes or intersections; Connectivity analysis, e.g. of connected components
G06V 10/75 - Image or video pattern matching; Proximity measures in feature spaces using context analysis; Selection of dictionaries
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/77 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using data integration or data reduction, e.g. principal component analysis [PCA] or independent component analysis [ICA] or self-organising maps [SOM]; Blind source separation
G06V 10/778 - Active pattern-learning, e.g. online learning of image or video features
G06V 10/82 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using neural networks
G06V 10/98 - Detection or correction of errors, e.g. by rescanning the pattern or by human intervention; Evaluation of the quality of the acquired patterns
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
88.
Flexible Seed Extension for Hash Table Genomic Mapping
Methods, systems, and apparatuses, including computer programs for generating and using a hash table configured to improve mapping of reads are disclosed that include obtaining a first seed of K nucleotides from a reference sequence, generating a seed extension tree having a nodes, wherein each node of the nodes corresponds to (i) an extended seed that is an extension of the first seed and has a nucleotide length of K* and (ii) one or more locations, in a seed extension table, that include data describing reference sequence locations that match the extended seed, and for each node: storing interval information at a location of the hash table that corresponds to an index key for the extended seed, wherein the interval information references one or more locations in the seed extension table that include reference sequence locations that match the extended seed associated with the node.
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.
Methods are used for obtaining, cataloguing, and/or storing data derived from a biological source using a flow cell body, electrodes, and an imaging assembly. The data may include DNA and/or RNA obtained from a biological source, such as from the cells of an organism. The methods may be used to obtain, catalog, and/or store data such as DNA or RNA sequence from a pathogen such as a virus and/or a bacteria, human health data over time, and immune system information from an individual. The data obtained using the disclosed methods may be used for a variety of different purposes, including the manufacture of vaccine compositions, and for restoring the immune system of an individual who has undergone an immune system depleting event. The methods may be used for storage of biological cells, which may be used for the screening of compounds, such as small molecules with potential for therapeutic indications.
There is set forth herein a light energy exciter that can include one or more light sources. A light energy exciter can emit excitation light directed toward a detector surface that can support biological or chemical samples.
An integrated detection, flow cell and photonics (DFP) device is provided that comprises a substrate having an array of pixel elements that sense photons during active periods. The substrate and pixel elements form an IC photon detection layer. At least one wave guide is formed on the IC photo detection layer as a photonics layer. An optical isolation layer is formed over at least a portion of the wave guide. A collection of photo resist (PR) walls patterned to define at least one flow cell channel that is configured to direct fluid along a fluid flow path. The wave guides align to extend along the fluid flow path. The flow cell channel is configured to receive samples at sample sites that align with the array of pixel elements.
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
H01L 31/107 - Devices sensitive to infrared, visible or ultraviolet radiation characterised by only one potential barrier or surface barrier the potential barrier working in avalanche mode, e.g. avalanche photodiode
G01S 7/4863 - Detector arrays, e.g. charge-transfer gates
H01L 31/055 - Optical elements directly associated or integrated with the PV cell, e.g. light-reflecting means or light-concentrating means where light is absorbed and re-emitted at a different wavelength by the optical element directly associated or integrated with the PV cell, e.g. by using luminescent material, fluorescent concentrators or up-conversion arrangements
G01S 7/4865 - Time delay measurement, e.g. time-of-flight measurement, time of arrival measurement or determining the exact position of a peak
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
Embodiments of the present disclosure relate to six-nucleobase libraries having a third Watson-Crick base pair. Also provided herein are methods to prepare such six-nucleobase libraries, and their use for sequencing and modified nucleobase detection applications.
The technology disclosed relates to splice site prediction and aberrant splicing detection. In particular, it relates to a splice site predictor that includes a convolutional neural network trained on training examples of donor splice sites, acceptor splice sites, and non-splicing sites. An input stage of the convolutional neural network feeds an input sequence of nucleotides for evaluation of target nucleotides in the input sequence. An output stage of the convolutional neural network translates analysis by the convolutional neural network into classification scores for likelihoods that each of the target nucleotides is a donor splice site, an acceptor splice site, and a non-splicing site.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G06N 3/04 - Architecture, e.g. interconnection topology
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
The present invention relates to a method for selective differentiation from a pluripotent stem cell to hindbrain tissue, the method comprising a step of selective differentiation into hindbrain tissue, in which embryoid bodies formed from pluripotent stem cells are cultured in the presence of a hindbrain tissue induction medium containing endogenous WNT secretion inhibitors and WNT signaling agonists.
The present invention relates to a method for selective differentiation into dorsal-metencephalic tissue from embryoids derived from pluripotent stem cells, the method comprising the step of selective differentiation into dorsal-metencephalic tissues in which embryoids derived from pluripotent stem cells are cultured in the presence of a dorsal-metencephalic tissue-inducing medium containing a sonic hedgehog (SHh) signaling pathway inhibitor.
The technology disclosed relates to artificial intelligence-based base calling. The technology disclosed relates to accessing a progression of per-cycle analyte channel sets generated for sequencing cycles of a sequencing run, processing, through a neural network-based base caller (NNBC), windows of per-cycle analyte channel sets in the progression for the windows of sequencing cycles of the sequencing run such that the NNBC processes a subject window of per-cycle analyte channel sets in the progression for the subject window of sequencing cycles of the sequencing run and generates provisional base call predictions for three or more sequencing cycles in the subject window of sequencing cycles, from multiple windows in which a particular sequencing cycle appeared at different positions, using the NNBC to generate provisional base call predictions for the particular sequencing cycle, and determining a base call for the particular sequencing cycle based on the plurality of base call predictions.
The present invention relates to a method for preparing a cerebellar organoid, comprising: (A) a step of selective differentiation into hindbrain tissues, in which an embryonic body formed from pluripotent stem cells is cultured in the presence of a hindbrain tissue induction medium including an endogenous WNT secretion inhibitor and a WNT signaling activator; (B) a step of selective differentiation into dorsal hindbrain tissues, in which the embryonic body is cultured in the presence of a dorsal hindbrain tissue induction medium including a sonic hedgehog (SHh) signaling pathway inhibitor; and (C) a basal surface-apex surface polarization step of inducing basal surface-apex surface polarization, in which polarization of the embryonic body is induced in the presence of a basal surface-apex surface induction medium including an extracellular matrix-based hydrogel.
Non-contact dispensers and related systems and methods are disclosed. In accordance with an implementation, an apparatus includes a pump having a body that defines an inlet, an outlet, and a flow path fluidly coupling the inlet and the outlet. A first displacement member is movable from a first position to a second position within the flow path to urge a first volume of the fluid out of the outlet. A second displacement member is movable from a first position to a second position within the flow path to urge a second volume of the fluid out of the outlet.
Actuation systems and methods are disclosed. An apparatus includes a system including a flow cell receptacle and a valve drive assembly including a shape memory alloy actuator including a pair of shape memory alloy wires and a flow cell disposable within the flow cell receptacle and having a membrane valve. The system actuates the membrane valve, via the shape memory alloy actuator, by causing a voltage to be applied to a first one of the shape memory alloy wires and the system not applying the voltage to a second one of the shape memory alloy wires.
F03G 7/06 - Mechanical-power-producing mechanisms, not otherwise provided for or using energy sources not otherwise provided for using expansion or contraction of bodies due to heating, cooling, moistening, drying, or the like
