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
2.
PHOTO-SWITCHABLE CHEMISTRY FOR REVERSIBLE HYDROGELS AND REUSABLE FLOW CELLS
322H end group for dual functionality and/or pH responsiveness. For nucleic acid sequencing, amplification primers are grafted to photochemically-reversible hydrogels or nanogel particles reversibly bound to surfaces within a flow cell. After sequencing is complete, the photochemically-reversible hydrogel or nanogel particles is/are removable from the flow cell surfaces by irradiation, enabling the flow cell to be reusable.
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.
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.
An example of a flow cell includes a base support, a reversibly swellable resin positioned over the base support, and a depression defined in the reversibly swellable resin. The reversibly swellable resin includes at least one hydrophilic monomer selected from the group consisting of a poly(ethylene glycol) based monomer, poly(propylene glycol) based monomer, and combinations thereof. The depression has a first opening dimension when the reversibly swellable resin is in a non-swelled stated and has a second opening dimension, that is smaller than the first opening dimension, when the reversibly swellable resin is in a swelled state.
In an example of a method, a deoxyribonucleic acid sample is exposed to tagmentation in the presence of a tagmentation buffer including a divalent cation cofactor and a transposase enzyme to generate a tagmented DNA fragment complex. A chelator mixture is added to the tagmented DNA fragment complex. The chelator mixture includes a chelator of the divalent cation cofactor at a weight ratio that is at least 1:1 with the divalent cation cofactor; and has a pH ranging from 8 to 9. The tagmented DNA fragment complex is incubated in the chelator mixture at a temperature of at least 55°C for at least about 60 seconds, so that the transposase enzyme dissociates from a tagmented DNA fragment of the tagmented DNA fragment complex.
Some implementations of the disclosure describe an imaging system comprising: a camera including multiple image sensors that are spaced apart, each of the image sensors to capture an image of a respective sample location of multiple sample locations of a sample; and a fiber bundle comprising multiple fiber cores, each of the fiber cores to emit a light beam that is projected on a respective one of the sample locations.
G02B 6/04 - Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings formed by bundles of fibres
An example nanoimprint lithography (NIL) resin composition includes a total of three monomers, wherein two of the three monomers are selected from the group consisting of two different epoxy substituted silsesquioxane monomers; two different epoxy substituted cyclosiloxane monomers; and two different non-organosilicon epoxy monomers. A third of the three monomers is a fluorinated monomer that is present in an amount ranging from about from 0.5 mass% to about 4 mass%, based on a total solids content of the NIL resin composition. The NIL resin also includes a photoinitiator and a solvent.
An example of a sequencing nanoparticle includes a core of a negatively chargeable, hydrophobic polymer. Alternating layers of a positively charged acrylamide hydrogel and the negatively charged polymer are positioned on the core, wherein the positively charged acrylamide hydrogel forms an outer layer of the sequencing nanoparticle. A negatively charged primer set is attached to the outer layer.
A co-polymer includes a plurality of a first monomer including a terminal functional group that is to attach to at least two different primers; a plurality of a second monomer including a second functional group that is different from the terminal functional group, and that is selected from the group consisting of a phenyl group, methoxy propyl, glycosyl, vinyl pyrrolidone, and an imidazole group; and a plurality of a third monomer that is different from the first and second monomers. This co-polymer may be used in a flow cell, and may enhance the clustering efficiency and kinetics.
3'-blocked nucleotides, methods of deblocking the same, and methods of synthesizing polynucleotides using the same are provided herein. In some examples, a nucleotide is disposed within the aperture on the first side of a nanopore. The nucleotide may be coupled to a 3'-blocking group including a trigger. The trigger may be selectively activated using an initiator. The activated trigger may be used to remove the 3'-blocking group from the nucleotide.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to certain pharmacogenetic (PGX) genes. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to major histocompatibility complex (MHC) genes. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to an American College of Medical Genetics (ACMG) panel of genes. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to certain challenging medically relevant genes (CMRG). Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to certain genes throughout the genome and expressed regions with low mappability. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.
A transposome complex capable of producing size-controlled nucleic acid fragments is described herein. In some embodiments, the transposome complex includes multiple inactive transposomes with active transposomes on both ends of the multiple inactive transposomes. Applications, uses, and variations of the disclosed transposome complex include, but are not limited to, library preparation for a nucleic acid and tuning the length of the transposome complex to produce nucleic acid fragments of predetermined or desired lengths.
The present disclosure relates to a method, including providing one or more lyophilised microspheres in a mixing vessel at a first temperature and generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel, under conditions effective to encapsulate the one or more lyophilised microspheres with a coating formulation. In an example, the fluidized bed has a fluidization rate of between about 1 cubic meters per hour (m3/h) and about 30 m3/h. In another example, the fluidized bed has an environmental humidity of between about 10% and about 20%. In still another example, the coating formulation is applied at a spray rate of between about 1.5 grams per minute (g/min) and about 10 g/min. In yet another example, the coating formulation is applied at an atomizing rate of between about 0.5 bar and about 1.5 bar. In a further example, the fluidized bed is in a Wurster configuration, a top spray configuration, or a combination thereof. The present disclosure also relates to a system, including one or more lyophilised microspheres, a mixing vessel configured for holding the one or more lyophilised microspheres, a mixer for generating a fluidized bed of the one or more lyophilised microspheres in the mixing vessel at a location, and at least one spray nozzle configured to introduce a shell formulation into the mixing vessel at the location.
B01J 13/04 - Making microcapsules or microballoons by physical processes, e.g. drying, spraying
B01J 8/18 - Chemical or physical processes in general, conducted in the presence of fluids and solid particles; Apparatus for such processes with fluidised particles
19.
DNA ORIGAMI STRUCTURE AND PROTEIN NANOPORE CONSTRUCT
The present application discloses a novel DNA origami structure and a nanopore construct associated with the DNA origami structure. The DNA origami structure includes a first hydrophilic section at a first end of the DNA origami structure, a stopper section adjacent the first hydrophilic section, a second hydrophilic section at a second end of the DNA origami structure, a hydrophobic section between the stopper section and the second hydrophilic section, and an open cavity running through the DNA origami structure from the first end to the second end. The stopper section is configured to lay against the membrane when the DNA origami structure is inserted through the membrane.
There is set forth herein, in one example, an apparatus. The apparatus can comprise, for example: a first reaction site and a second reaction site associated to a common pixel, wherein the pixel comprises a pixel sensor.
Aptamer detection techniques with dynamic range compression are described that permit removal of a portion of more abundant aptamers in an aptamer-based assay. In an embodiment, a mixture of tagged probes and dummy probes can be used such that the dummy probes bind abundant aptamers and in turn are not captured or amplified for detection in downstream steps. Other techniques are also contemplated, including targeted removal of or cleavage of probes that bind to excess aptamers.
The present disclosure is concerned with proteins, methods, compositions, and kits for mapping of methylation status of nucleic acids, including 5-methylcytosine and 5-hydroxymethyl cytosine (5hmC). In one embodiment, proteins are provided that selectively act on certain modified cytosines of target nucleic acids and converts them to thymidine or modified thymidine analogues. In another embodiment, proteins are provided that selectively act on certain modified cytosines of target nucleic acids and converts them to uracil or thymidine and selectively do not act on other certain modified cytosines of target nucleic acids. Also provided are compositions and kits that include one or more of the proteins and methods for using one or more of the proteins.
The application relates to DNA sequencing systems and methods. Systems and methods for determining the nucleotide sequence of a polynucleotide include attaching three different fluorescent dyes to three different nucleotides during incorporation. In particular, long Stokes shifted dyes may be used to determine the sequence of polynucleotides in a sequencing by synthesis system.
Embodiments of the present disclosure relate to compositions and methods for improving the intensity of the fluorescent signals during nucleic acid sequencing. In particular, at least one biotin-binding site of the labeled streptavidin is blocked to reduce fluorescent signal deflation.
The present application relates to chromenoquinoline dyes and their uses as fluorescent labels. For example, these dyes may be used to label nucleotides for nucleic acid sequencing.
The present disclosure is generally directed to strategies for template capture and amplification during sequencing. In some examples, a solid support is used for template capture and amplification.
Barriers including molecules covalently bonded to amphiphilic molecules, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids includes one or more layers comprising a plurality of amphiphilic molecules; and a first layer comprising a plurality of molecules covalently bonded to amphiphilic molecules of the plurality of amphiphilic molecules.
B01D 67/00 - Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
Embodiments of the present disclosure relate to compositions and kits for use in sequencing by synthesis to improve fluorescent signal intensity and reduce signal decay caused by short wavelength light source during the imaging events. Methods of sequencing using the compositions and kits described herein are also provided.
Embodiments of the present disclosure relate to modified extension primers for use in generating clustered polynucleotides for sequencing by synthesis. In particular, the disclosure relates to methods of chemically linearizing clustered polynucleotides in preparation for sequencing by cleavage of one or more strands of double-stranded polynucleotides immobilized on a solid support by a periodate salt.
Devices including osmotically balanced barriers, and methods of making and using the same, are provided herein. A fluidic well may include a barrier having first and second sides. A first fluid within the fluidic well may contact the first side of the barrier, and may have a first composition including a first concentration of a salt. A second fluid within the fluidic well may contact the second side of the barrier and may have a second composition including a second concentration of the salt that is different than the first concentration. The difference between the first and second concentrations of the salt may generate a first osmotic pressure across the barrier. The second composition further may include a concentration of a compound other than the salt. The concentration of the compound may generate a second osmotic pressure across the barrier that opposes and substantially balances the first osmotic pressure.
G01N 33/487 - Physical analysis of biological material of liquid biological material
31.
COMPOSITIONS INCLUDING AQUEOUS AMINE BORANE COMPLEXES AND POLYNUCLEOTIDES, AND METHODS OF USING THE SAME TO DETECT METHYLCYTOSINE OR HYDROXYMETHYLCYTOSINE
Disclosed herein are aqueous compositions that include a pyridine complex and a polynucleotide. The compositions can be used to detect methylcytosine and/or hydroxymethylcytosine in the polynucleotide. In some examples, the compositions may be used as part of a TET-assisted borane sequencing workflow.
Methods of inserting a nanopore into a polymeric membrane are provided herein. The membrane may be destabilized using a chaotropic solvent. The nanopore may be inserted into the destabilized polymer membrane. The chaotropic solvent may be removed to stabilize the polymer membrane with the nanopore inserted therein.
Nanopore devices including barriers using diblock or triblock copolymers, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids is suspended by a barrier support defining an aperture. The barrier may include one or more layers suspended across the aperture and including molecules of a block copolymer. Each molecule of the block copolymer may include one or more hydrophilic blocks having an approximate length A and one or more hydrophobic blocks having an approximate length B. The hydrophilic blocks may form outer surfaces of the barrier and the hydrophobic blocks may be located within the barrier. The hydrophobic blocks may include a polymer selected from the group consisting of poly(dimethylsiloxane) (PDMS), polybutadiene (PBd), polyisoprene, polymyrcene, polychloroprene, hydrogenated polydiene, fluorinated polyethylene, polypeptide, and poly(isobutylene) (PIB).
Barriers including crosslinked amphiphilic molecules, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids includes at least one layer comprising a plurality of amphiphilic molecules. Amphiphilic molecules of the plurality of amphiphilic molecules are crosslinked to one another.
Nanopore devices including barriers using amphiphilic units, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids includes a first layer comprising a first plurality of amphiphilic units, a second layer comprising a second plurality of the amphiphilic units and contacting the first plurality of amphiphilic units. The amphiphilic units may be substantially the same size as one another. The amphiphilic units respectively may include hydrophobic blocks and hydrophilic blocks coupled to the hydrophobic blocks.
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
B01D 71/82 - Macromolecular material not specifically provided for in a single one of groups characterised by the presence of specified groups, e.g. introduced by chemical after-treatment
C08G 77/28 - Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen, and oxygen sulfur-containing groups
C08L 83/08 - Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen, and oxygen
C08G 81/00 - Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
C09D 187/00 - Coating compositions based on unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
36.
BARRIERS INCLUDING BIOLOGICAL NANOPORE FOR DNA SEQUENCING, THE BARRIERS BEING MADE OF CO-POLYMERS WITH END AND/OR MIDDLE GROUPS, AND METHODS OF MAKING THE SAME
Nanopore devices including barriers using polymers with end groups, and methods of making the same, are provided herein. In some examples, a barrier between first and second fluids is provided. The barrier may be suspended by a barrier support defining an aperture. The barrier may include one or more layers suspended across the aperture and including molecules of a block copolymer. Each molecule of the block copolymer may include one or more hydrophilic blocks having an approximate length A and one or more hydrophilic blocks having an approximate length B. The hydrophilic blocks may form outer surfaces of the barrier and the hydrophobic blocks being located within the barrier. End groups may be coupled to ends of the hydrophilic blocks that form outer surfaces of the barrier. The end groups may have a different hydrophilicity than the hydrophilic blocks.
B01D 69/02 - Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
C08G 77/28 - Polysiloxanes containing silicon bound to organic groups containing atoms other than carbon, hydrogen, and oxygen sulfur-containing groups
C08G 81/00 - Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
C09D 187/00 - Coating compositions based on unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
In an example method, an initial depression is defined in a first resin layer of a multi-layer stack including the first resin layer over a second resin layer or a base support. The first resin layer is resistant to silanization in an organic solvent, the second resin layer or the base support is reactive toward silanization in the organic solvent, and the first resin layer and the second resin layer or the base support are orthogonally etchable. A remaining portion of the first resin layer at the initial depression is anisotropically etched, using air or O2 plasma, through to expose a surface of the second resin layer or the base support and to form a depression. The multi-layer stack is exposed to a silane in the organic solvent to selectively silanizing the surface of the second resin layer or the base support at the depression.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
38.
SUBSTRATE WITH ORTHOGONALLY FUNCTIONAL NANODOMAINS
Embodiments of the present disclosure also relate to methods of fabricating flow cell substrates. Some exemplary workflows exploit orthogonal chemistries of substrate layers such that the process does not include polishing steps. Substrates prepared by the method described herein can include a first primer set and a second primer set compatible with simultaneous paired-end sequencing methods.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
The invention relates to methods and kits for use in nucleic acid sequencing, in particular methods for use in concurrent sequencing, and in particular concurrent sequencing of tandem insert libraries.
A method of determining sequence information from two or more polynucleotide sequence portions, the method comprising: selecting one of a plurality of classifications based on first and second intensity data, wherein each classification represents one or more possible combinations of respective nucleobases of the two or more polynucleotide sequence portions, and wherein at least one classification represents more than one possible combination of respective nucleobases.
The invention relates to methods and associated products for preparing polynucleotide sequences for detection of modified cytosines and sequencing said polynucleotides to detect modified cytosines. The methods comprise treatment of the target polynucleotide with a conversion reagent that is configured to convert a modified cytosine to thymine or a nucleobase which is read as thymine/uracil, and/or configured to convert an unmodified cytosine to uracil or a nucleobase which is read as thymine/uracil. In particular embodiments, portions of both strands of the treated target are sequenced concurrently.
A method of base calling nucleobases of two or more polynucleotide sequence portions, wherein said polynucleotide sequence portions have been selectively processed such that an intensity of the signals obtained based upon the respective first nucleobase is greater than an intensity of the signals obtained based upon the respective second nucleobase.
Systems and methods of identifying nucleobases in a template polynucleotide are disclosed. In one embodiment, such a method may include providing a substrate comprising a plurality of double stranded template polynucleotides in a cluster. Each double stranded template polynucleotide may comprise a first strand and a second strand. The method may further include contacting the plurality of double stranded template polynucleotides with first primers which bind to the first strand and second primers which bind to the second strand. The method may further include extending the first primers and the second primers by contacting the cluster with labeled nucleobases to form first labeled primers and second labeled primers. The method may further include stimulating light emissions from the first and second labeled primers, wherein an amplitude of the signal generated by the first labeled primers is greater than an amplitude of the signal generated by the second labeled primers. The method may further include identifying the labeled nucleobases added to the first primers and the second primers based on the amplitude of the signal generated by the labeled nucleobases.
Systems and methods of identifying nucleobases in a template polynucleotide are disclosed. In one embodiment, such a method may include providing a substrate comprising a plurality of the template polynucleotides in a cluster. The method may further include generating light to stimulate fluorescent emissions from the cluster. The method may further include receiving a first signal emitted at a first intensity from a first plurality of nucleotide analogs hybridized to the plurality of template polynucleotides at a first site. The method may further include receiving a second signal emitted at a second intensity from a second plurality of nucleotide analogs hybridized to the plurality of template polynucleotides at a second site. The method may further include identifying the nucleobases hybridized at the first and second sites of the template polynucleotide based on a combination of the first and second signals.
A functionalized nanostructure includes a metal nanostructure; an un-cleavable first primer and a cleavable second primer attached to a first region of the metal nanostructure through i) a first thiol linkage attached to a first polymer chain having a first polarity or ii) respective first thiol linkages attached to respective first polymer chains having the first polarity; and a cleavable first primer and an un-cleavable second primer attached to a second region of the metal nanostructure through i) a second thiol linkage attached to a second polymer chain having a second polarity different from the first polarity or ii) respective second thiol linkages attached to respective second polymer chains having the second polarity.
An apparatus includes a chassis, a frame, a sample support member, an imaging assembly, an actuation assembly, and a vibration capture assembly. The frame is coupled with the chassis. The sample support member is supported by the frame. The actuation assembly is supported by the frame and is operable to drive movement of the imaging assembly relative to the sample support member. The vibration capture assembly is operable to selectively transition between a plurality of modes, including a damping mode and an isolation mode. In the damping mode, the vibration capture assembly is configured to resist movement of the frame relative to the chassis in response to operation of the actuation assembly. In the isolation mode, the vibration capture assembly is configured to prevent transmission of vibrational movement in the chassis to the frame.
This disclosure describes methods, non-transitory computer readable media, and systems that can use a machine-learning to determine factors or scores indicating an error level with which a given methylation assay detects methylation of cytosine bases. For instance, the disclosed systems use a machine-learning model to generate a bias score indicating a degree to which a given methylation assay errs in detecting cytosine methylation when specific sequence contexts surround such cytosines compared to other sequence contexts. The machine-learning model may take various forms of models, including a decision-tree model, a neural network, or a combination of a decision-tree model and a neural network. In some cases, the disclosed system combines or uses bias scores from multiple machine-learning models to generate a consensus bias score.
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
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
Described herein are technologies for classifying a protein structure (such as technologies for classifying the pathogenicity of a protein structure related to a nucleotide variant). Such a classification is based on two-dimensional images taken from a three-dimensional image of the protein structure. With respect to some implementations, described herein are multi-view convolutional neural networks (CNNs) for classifying a protein structure based on inputs of two-dimensional images taken from a three-dimensional image of the protein structure. In some implementations, a computer-implemented method of determining pathogenicity of variants includes accessing a structural rendition of amino acids, capturing images of those parts of the structural rendition that contain a target amino acid from the amino acids, and, based on the images, determining pathogenicity of a nucleotide variant that mutates the target amino acid into an alternate amino acid.
G16H 50/20 - 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
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
54.
METHODS OF DETECTING METHYLCYTOSINE AND HYDROXYMETHYLCYTOSINE BY SEQUENCING
Embodiments of the present disclosure relates to various bisulfite-free chemical methods for detecting methylation of cytosine in the DNA sample. These methods convert methylated and hydroxymethylated cytosine in the nucleic acid sequence to a modified or pseudo thymine or a uracil moiety which then can be detected in sequencing.
Polynucleotide sequencing methods for sequencing one or more polynucleotide templates that uses primers bound to a surface as sequencing primers. The surface primers may include at least a portion of a surface oligonucleotide used during cluster formation. The sequencing methods may be used for single stranded sequencing or double stranded sequencing. Double stranded sequencing methods may employ an enzyme that has nick-translation activity. A kit includes all the reagents needed for sequencing does not include sequencing primers. The kit may be used to accomplish the sequencing methods of the present disclosure.
Imaging systems and related methods are disclosed. In accordance with an implementation, a system includes a flow cell receptacle to receive a flow cell that receives a sample and an imaging system having a light source assembly, and an imaging device. The light source assembly to form a substantially collimated beam. The optical assembly including an asymmetric beam expander group that includes one or more asymmetric elements or anamorphic elements disposed along an optical axis. The optical assembly to receive the substantially collimated beam from the light source assembly, and transform the substantially collimated beam into a shaped sampling beam having an elongated cross section in a far field at or near a focal plane of the optical assembly to optically probe the sample. The imaging device to obtain image data associated with the sample in response to the optical probing of the sample with the sampling beam.
The technology disclosed relates to accessing a multiple sequence alignment that aligns a query residue sequence to a plurality of non-query residue sequences, applying a set of periodically-spaced masks to a first set of residues at a first set of positions in the multiple sequence alignment, and cropping a portion of the multiple sequence alignment that includes the set of periodically-spaced masks at the first set of positions, and a second set of residues at a second set of positions in the multiple sequence alignment to which the set of periodically-spaced masks is not applied. The first set of residues includes a residue-of-interest at a position-of-interest in the query residue sequence.
The technology disclosed relates to generating species-differentiable evolutionary profiles using a weighting logic. In particular, the technology disclosed relates to determining a weighted summary statistic for a given residue category at a given position in a multiple sequence alignment based on one or more weights of one or more sequences in the multiple sequence alignment that have a residue of the given residue category at the given position.
The technology disclosed relates to determining feasibility of using a reference genome of a non-target species for variant calling a sample of a target species. In particular, the technology disclosed relates to mapping sequenced reads of a sample of a target species to a reference genome of a non-target species to detect a first set of variants in the sequenced reads of the sample of the target species, and mapping the sequenced reads of the sample of the target species to a reference genome of a pseudo-target species to detect a second set of variants in the sequenced reads of the sample of the target species.
The technology disclosed relates to inter-model prediction score recalibration. In one implementation, the technology disclosed relates to a system including a first model that generates, based on evolutionary conservation summary statistics of amino acids in a target protein sequence, a first pathogenicity score-to-rank mapping for a set of variants in the target protein sequence; and a second model that generates, based on epistasis expressed by amino acid patterns spanning the target protein sequence and a plurality of non-target protein sequences aligned in multiple sequence alignment, a second pathogenicity score-to-rank mapping for the set of variants. The system also includes a reassignment logic that reassigns pathogenicity scores from the first set of pathogenicity scores to the set of variants based on the first and second score-to-rank mappings, and an output logic to generate a ranking of the set of variants based on the reassigned scores.
The present disclosure relates to a method including exposing a composition comprising a wax-microsphere matrix to a first melt-condition, wherein said wax-microsphere matrix comprises a wax component and a plurality of lyophilised microspheres, wherein said plurality of lyophilised microspheres comprise one or more reagent, whereby exposing said composition comprising said wax-microsphere matrix to said first melt-condition melts the wax component; exposing said composition to a first release-condition to rehydrate at least one lyophilised microsphere; and exposing said at least one rehydrated lyophilised microsphere to a separation-condition to separate said wax component from said at least one rehydrated lyophilised microsphere. Also disclosed are methods of preparing a wax-microsphere matrix and releasing one or more reagent from a wax-microsphere matrix as well as compositions. Also disclosed are cartridges with a reagent reservoir including the compositions described herein. Also disclosed are systems for controlling release of one or more reagent including the compositions described herein.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
62.
DYNAMIC GRAPHICAL STATUS SUMMARIES FOR NUCELOTIDE SEQUENCING
This disclosure describes methods, non-transitory computer readable media, and systems that can query the status of various stages in an end-to-end sequencing process and generate a graphical status summary for the sequencing process that depicts icons indicating statuses of the various stages. For instance, the disclosed systems can generate a graphical status summary for a nucleotide sequencing taskset that includes icons depicting statuses of a sequencing run, a data transfer of base-call data to a device for variant analysis, and the variant analysis—each part of the same nucleotide sequencing taskset. By exchanging data with a sequencing device for read data and one or more servers for variant analysis, the disclosed system can quickly provide a graphical status summary of an end-to-end sequencing process marked by various tasks within a nucleotide sequencing taskset.
Embodiments of the present disclosure relates to periodate salt compositions for use in the chemical linearization of double-stranded polynucleotides in preparation for sequencing application, for example, sequencing-by-synthesis (SBS). Kits containing the periodate salt composition and methods of sequencing polynucleotides are also described.
An example of a flow cell includes a substrate having depressions separated by interstitial regions. First and second primers are immobilized within the depressions. First transposome complexes are immobilized within the depressions, and the first transposome complexes include a first amplification domain. Second transposome complexes are also immobilized within the depressions, and the second transposome complexes include a second amplification domain. Some of the first transposome complexes, or some of the second transposome complexes, or some of both of the first and second transposome complexes include a modification to reduce tagmentation efficiency.
This disclosure describes methods, non-transitory computer readable media, and systems that can facilitate execution of external workflows for diagnostic analysis of nucleotide sequencing data utilizing a container orchestration engine. For example, the disclosed systems can utilize a container orchestration engine to allow external systems (e.g., third-party systems) to generate and implement workflows for analyzing sequencing data. In executing individual workflow containers of a sequencing diagnostic workflow, the disclosed systems can isolate the workflow containers to prevent access to, or corruption of, other data while also orchestrating allocation of computing resources available at a genomic sequence processing device to execute the workflow containers.
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.
The present disclosure is directed to decoupling library capture (template seeding) from cluster generation to optimise both processes. This is achieved by introducing orthogonality between the seeding and clustering primer.
An iterative process may be implemented for incrementally aggregating available batches of sample data with previously available batches to perform sequencing analysis. Genomic variant call files associated with one or more samples may be received in batches from sequencing devices and aggregated for performing sequencing analysis. The aggregated genomic variant call files may be used to generate cohort files and census files that comprise summary information related to the genomic variant call files in each batch. The census data in census files may be aggregated into a global census file that includes summary genome variant data. Multi-sample variant call files may be generated based on the global census file, cohort files, and census files. The genomic variant call files may be processed using parallel processing at multiple compute nodes. The files may be further compressed and overlapping data may be efficiently stored in buffer positions.
Embodiments of the present disclosure relate to method of chemical linearization of double stranded polynucleotides for sequencing by synthesis. In particular, a heterogenous cobalt catalyst is used to cleave one or more diol moieties at a predetermined cleavage site of one strand of the double stranded polynucleotides.
An example primer set includes first and second nuclease resistant primers. The first nuclease resistant primer includes a first sequence; a first cleavage site attached at a 3' end of the first sequence; and a first nuclease resistant modification incorporated between the first sequence and the first cleavage site. The second nuclease resistant primer includes a second sequence that is different from the first sequence; a second nuclease resistant modification incorporated at a 3' end of the second sequence; and a second cleavage site attached between the second sequence and the second nuclease resistant modification. The second cleavage site is different from the first cleavage site.
The technology disclosed relates to determining pathogenicity of nucleotide variants. In particular, the technology disclosed relates to specifying a particular amino acid at a particular position in a protein as a gap amino acid, and specifying remaining amino acids at remaining positions in the protein as non-gap amino acids, generating a gapped spatial representation of the protein that includes spatial configurations of the non-gap amino acids, and excludes a spatial configuration of the gap amino acid, determining an evolutionary conservation at the particular position of respective amino acids of respective amino acid classes based at least in part on the gapped spatial representation, and based at least in part on the evolutionary conservation of the respective amino acids, determining a pathogenicity of respective nucleotide variants that respectively substitute the particular amino acid with the respective amino acids in alternate representations of the protein.
The technology disclosed relates to determining pathogenicity of nucleotide variants. In particular, the technology disclosed relates to specifying a particular amino acid at a particular position in a protein as a gap amino acid, and specifying remaining amino acids at remaining positions in the protein as non-gap amino acids. The technology disclosed further relates to generating a gapped spatial representation of the protein that includes spatial configurations of the non-gap amino acids, and excludes a spatial configuration of the gap amino acid, and determining a pathogenicity of a nucleotide variant based at least in part on the gapped spatial representation, and a representation of an alternate amino acid created by the nucleotide variant at the particular position.
The technology disclosed relates to training a pathogenicity predictor. In particular, the technology disclosed relates to accessing a gapped training set that includes respective gapped protein samples for respective positions in a proteome, accessing a non-gapped training set that includes non-gapped benign protein samples and non-gapped pathogenic protein samples, generating respective gapped spatial representations for the gapped protein samples, and generating respective non-gapped spatial representations for the non-gapped benign protein samples and the non-gapped pathogenic protein samples, training a pathogenicity predictor over one or more training cycles and generating a trained pathogenicity predictor, wherein each of the training cycles uses as training examples gapped spatial representations from the respective gapped spatial representations and non-gapped spatial representations from the respective non-gapped spatial representations, and using the trained pathogenicity classifier to determine pathogenicity of variants.
A polynucleotide sequencing method includes a wash step that employs a composition including a polymerase. The composition may also include a plurality of nucleotides. The composition may be configured to prevent the polymerase from incorporating one of the plurality of nucleotides into a copy polynucleotide strand. The composition may be substantially free of Mg2.
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 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
An apparatus and method for imaging includes an imaging system formed of a movable objective stage proximal to a sample and positioned for providing an excitation beam onto and for capturing an emission from the sample. The movable objective stage includes an optical lens apparatus and a turn reflector optically coupled to the imaging optics, where at least one of the optical lens apparatus and the turn reflector are movable relative to one another for scanning the sample, and wherein the movement is achieved while maintaining a substantially fixed optical path length between the optical lens apparatus and a fixed plane in a fixed imaging optics stage.
G01N 21/63 - Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
G01N 21/17 - Systems in which incident light is modified in accordance with the properties of the material investigated
G02B 21/36 - Microscopes arranged for photographic purposes or projection purposes
An example flow cell includes a substrate having a surface. The flow cell also includes a polymeric hydrogel attached to at least a portion of the substrate surface, where the polymeric hydrogel includes a dark quencher. The flow cell further includes at least one primer set attached to the polymeric hydrogel.
The invention relates to methods of preventing renaturation of single-stranded nucleic acid libraries during storage, the method comprising using blocking oligonucleotides substantially complementary to adaptor sequences in the nucleic acid library.
Some of the resin compositions are ultraviolet light or thermally curable, while others are ultraviolet light curable. One example of the ultraviolet light or thermally curable resin composition consists of a predetermined mass ratio of a (meth)acrylate cyclosiloxane monomer and a non-siloxane (meth)acrylate based monomer ranging from about >0:<100 to about 80:20; from 0 mass% to about 10 mass%, based on a total solids content of the resin composition, of an initiator selected from the group consisting of an azo-initiator, an acetophenone, a phosphine oxide, a brominated aromatic acrylate, and a dithiocarbamate; a surface additive; and a solvent.
An example of an ultraviolet light curable resin composition includes a predetermined mass ratio of a first epoxy substituted polyhedral oligomeric silsesquioxane monomer and a second substituted polyhedral oligomeric silsesquioxane monomer, wherein the first and second epoxy substituted polyhedral oligomeric silsesquioxane monomers are different, and wherein the predetermined mass ratio ranges from about 3:7 to about 7:3; bis-(4-methylphenyl)iodonium hexafluorophosphate as a first initiator; a second initiator selected from the group consisting of a free radical initiator and a cationic initiator other than bis-(4- methylphenyl)iodonium hexafluorophosphate; a surface additive; and a solvent.
The present disclosure relates to compositions including a shell surrounding an interior compartment, wherein said interior compartment comprises one or more reagent and wherein said shell releases said interior compartment when said shell is exposed to a first release condition, wherein said interior compartment releases said one or more reagent when said interior compartment is exposed to a second release condition, and wherein said first release condition is different from said second release condition. Also disclosed are compositions including a dissolvable first shell, and a dissolvable second shell, the second shell comprising one or more reagent. Also disclosed are methods for controlling release of one or more reagent using the compositions described herein. The present disclosure further relates to cartridges that include a reagent reservoir including the compositions described herein. Also disclosed are systems for controlling release of one or more reagent including the compositions described herein.
Disclosed herein include methods, compositions, reaction mixtures, kits and systems for identification of methylated cytosines in nucleic acids using a bisulfite-free, one-step chemoenzymatic modification of methylated cytosines.
Presented herein are altered polymerase enzymes for improved incorporation of nucleotides and nucleotide analogues, in particular altered polymerases that maintain low pre-phasing rates when using ambiently stored polymerases, as well as methods and kits using the same.
Provided herein are various examples of a method of coupling oligonucleotides to a polymer. The method may include selectively irradiating first inactive moieties in a one or more first region of a polymer with light, while not irradiating second inactive moieties in a one or more second region of the polymer, to generate first active moieties in the one or more first region of the polymer. The method may also include coupling the first active moieties to first oligonucleotides. The method may further include irradiating the second inactive moieties in the one or more second region of the polymer with light to generate second active moieties in the one or more second region of the polymer. The method may also include coupling the second active moieties to second oligonucleotides.
A61K 47/50 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
C08F 8/00 - Chemical modification by after-treatment
C08F 220/00 - Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide, or nitrile thereof
An example of a kit includes a flow cell, a primer fluid, and a cleaving fluid. The flow cell includes at least one surface functionalized with a polymeric hydrogel including azide functional groups or amine functional groups. The primer fluid includes a plurality of alkyne-containing primers, each alkyne-containing primer having an amino cleavable group attaching a primer sequence of the alkyne-containing primer to an alkyne-containing moiety of the alkyne-containing primer. The cleaving fluid includes a substance that is reactive with the amino cleavable group.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
86.
MACHINE-LEARNING MODEL FOR GENERATING CONFIDENCE CLASSIFICATIONS FOR GENOMIC COORDINATES
This disclosure describes methods, non-transitory computer readable media, and systems that can train a genome-location-classification model to classify or score genomic coordinates or regions by the degree to which nucleobases can be accurately identified at such genomic coordinates or regions. For instance, the disclosed systems can determine sequencing metrics for sample nucleic-acid sequences or contextual nucleic-acid subsequences surrounding particular nucleobase calls. By leveraging ground-truth classifications for genomic coordinates, the disclosed systems can train a genome-location-classification model to relate data from one or both of the sequencing metrics and contextual nucleic-acid subsequences to confidence classifications for such genomic coordinates or regions. After training, the disclosed systems can also apply the genome-location-classification model to sequencing metrics or contextual nucleic-acid subsequences to determine individual confidence classifications for individual genomic coordinates or regions and then generate at least one digital file comprising such confidence classifications for display on a computing device.
The present approach relates generally to image-based approaches for detecting deviations from a linear movement when scanning a surface. More particularly, the approach relates to the use of linear fiducials to detect, in real-time, deviations from a linear scan path during operation of a scanning imaging system. Such linear fiducials may include both sample sites and blank regions or sites or, in certain embodiments, may utilize elongated sample sites (e.g., linear features) within the linear fiducial.
The present disclosure relates to a composition including one or more modified nucleotide, wherein the modified nucleotide comprises a purine or pyrimidine base and a sugar moiety having a 3'- hydroxy blocking group, and a radical scavenger, wherein the composition is lyophilised. The present disclosure further relates to a composition including one or more functional protein; one or more functional protein activator; and one or more non-reducing sugar, wherein the composition is lyophilised. Also disclosed are methods of rehydration of one or more compositions described herein and kits including one or more compositions described herein. Further disclosed are cartridges including a flow cell comprising one or more reagent reservoirs, where the one or more reagent reservoirs include one or more compositions described herein.
Embodiments of the present application relate to substrate comprising a surface-bound azido functionalized organosilane wherein the substrate is free or substantially free of a hydrogel or a hydrophilic polymer. Methods of preparing such substrate surface for sequencing applications are also disclosed.
In an example of a method for making a flow cell, a light sensitive material is deposited over a resin layer including depressions separated by interstitial regions, wherein the depressions overlie a first resin portion having a first thickness and the interstitial regions overlie a second resin portion having a second thickness that is greater than the first thickness. A predetermined ultraviolet light dosage that is based on the first and second thicknesses is directed through the resin layer, whereby the light sensitive material overlying the depressions is exposed to ultraviolet light and the second resin portion absorbs the ultraviolet light, thereby defining an altered light sensitive material at a first predetermined region over the resin layer. The altered light sensitive material is utilized to generate a functionalized layer at the first predetermined region or at a second predetermined region over the resin layer.
B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
In an example of a method for making a flow cell, a metal material is sputtered over a transparent substrate including depressions separated by interstitial regions to form a metal film having a first thickness over the interstitial regions and having a second thickness over the depressions, the second thickness being about 30 nm or less and being at least 1/3 times smaller than the first thickness. A light sensitive material is deposited over the metal film; and the metal film is used to develop the light sensitive material through the transparent substrate to define an altered light sensitive material at a first predetermined region over the transparent substrate. The altered light sensitive material is utilized to generate a functionalized layer at the first predetermined region or at a second predetermined region over the transparent substrate.
B01J 19/00 - Chemical, physical or physico-chemical processes in general; Their relevant apparatus
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
A method for purifying nucleotides is provided, that includes preparing a solution comprising (a) 3'-blocked nucleotides, (b) 3'-OH nucleotides, (c) a polishing polymerase, and (d) a template. The polishing polymerase and the template are used to selectively polymerize the 3'-OH nucleotides and thus reduce a concentration in the solution of the 3 '-OH nucleotides relative to the 3'-blocked nucleotides.
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
93.
OLIGO-MODIFIED NUCLEOTIDE ANALOGUES FOR NUCLEIC ACID PREPARATION
Nucleic acid techniques are disclosed. Embodiments include modified nucleotides 12 with oligonucleotide adapters 24 that are coupled via cleavable linkers 20. Incorporation of the modified nucleotide 12 at a 3' end of a nucleic acid permits end-adapterization via ligation of a free 5' end of the oligonucleotide adapter 24 to a 3' reactive group of the modified nucleotide 12 and cleavage at the cleavable linker 20 to liberate a free 3' end.
In one example, a method of preparing a fluidic channel includes covalently coupling a first region of a substrate to a first region of a cover using first moieties covalently coupled to the first region of the substrate and second moieties covalently coupled to the first region of the cover. The covalent coupling between the first region of the substrate and the first region of the cover suspends a second region of the cover over a second region of the substrate to form a fluidic channel.
C09J 5/00 - Adhesive processes in general; Adhesive processes not provided for elsewhere, e.g. relating to primers
C09J 5/02 - Adhesive processes in general; Adhesive processes not provided for elsewhere, e.g. relating to primers involving pretreatment of the surfaces to be joined
C09J 5/06 - Adhesive processes in general; Adhesive processes not provided for elsewhere, e.g. relating to primers involving heating of the applied adhesive
C08J 5/12 - Bonding of a preformed macromolecular material to the same or other solid material such as metal, glass, leather, e.g. using adhesives
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
95.
COMPOSITIONS AND METHODS FOR SEQUENCING BY SYNTHESIS
The present application relates to compositions and methods for sequencing by synthesis, where one or more palladium scavengers were used to improve sequencing metrics such phasing and prephasing values.
The present application relates to substituted dyes containing bis-boron fused heterocycles and their uses as fluorescent labels. These compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.
A61K 31/196 - Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
C09B 23/01 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain
C09B 23/04 - Methine or polymethine dyes, e.g. cyanine dyes characterised by the methine chain containing an odd number of CH groups one CH group, e.g. cyanines, isocyanines, pseudocyanines
C09B 23/12 - Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain being branched
C09B 57/00 - Other synthetic dyes of known constitution
An example method includes introducing a first fluid to a flow channel of a flow cell including a working electrode having a surface that is at least partially exposed to the flow channel, the surface being unmodified or modified with a first member of a transition metal complex binding pair, whereby a linking moiety of a complex present in the first fluid chemically attaches the complex to the surface to form a temporarily modified surface of the working electrode; performing a sensing operation involving the complex of the temporarily modified surface; and applying a desorption voltage of the linking moiety to the working electrode, thereby detaching the linking moiety and regenerating the surface.
Nucleic acid amplification techniques are disclosed. Embodiments include generating concatenated nucleic acids using rolling circle amplification of templates, e.g., starting from a cDNA of a full-length mRNA or from synthetic templates, and sequencing and/or detecting the concatenated nucleic acids. In some embodiments, the technology disclosed includes amplification reactions that include CRISPR-Cas interactions that generate primers as a result of the CRISPR-Cas interactions, whereby primers are in turn used as part of detectable amplification reactions. The disclosed amplification techniques may use synthetic oligonucleotides or primers.
An example of a flow cell includes a substrate and a pattern of two different silanes on at least a portion of a surface of the substrate. A first polymer is attached to a first of the two different silanes and a second polymer is attached to a second of the two different silanes. The first and second polymers respectively include a first functional group and a second functional group of a functional group pair, the functional group pair being selected from the group consisting of an activated ester functional group and an azide functional group, a tetrazine functional group and an activated ester functional group, and a tetrazine functional group and an azide functional group. A first primer set is grafted to the first polymer and a second primer set is grafted to the second polymer. The first and second primer sets are different.
The technology disclosed relates to determining pathogenicity of variants. In particular, the technology disclosed relates to generating amino acid-wise distance channels for a plurality of amino acids in a protein. Each of the amino acid-wise distance channels has voxel-wise distance values for voxels in a plurality of voxels. A tensor includes the amino acid-wise distance channels and at least an alternative allele of the protein expressed by a variant. A deep convolutional neural network determines a pathogenicity of the variant based at least in part on processing the tensor. The technology disclosed further augments the tensor with supplemental information like a reference allele of the protein, evolutionary conservation data about the protein, annotation data about the protein, and structure confidence data about the protein.
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
patents
