Abstract: The technology disclosed presents a deep learning-based framework, which identifies sequence patterns that cause sequence-specific errors (SSEs). Systems and methods train a variant filter on large-scale variant data to learn causal dependencies between sequence patterns and false variant calls. The variant filter has a hierarchical structure built on deep neural networks such as convolutional neural networks and fully-connected neural networks. Systems and methods implement a simulation that uses the variant filter to test known sequence patterns for their effect on variant filtering. The premise of the simulation is as follows: when a pair of a repeat pattern under test and a called variant is fed to the variant filter as part of a simulated input sequence and the variant filter classifies the called variant as a false variant call, then the repeat pattern is considered to have caused the false variant call and identified as SSE-causing.

Abstract: An apparatus includes a fluid reservoir and a laminate fluidic circuit positioned above the fluid reservoir. The laminate fluidic circuit includes two or more layers laminated together to define a substantially planar substrate and one or more channels defined within the substrate. The laminate fluidic circuit includes a flexible conduit defined by a portion of the substrate encompassing an extent of at least one of the channels that is partially separated or separable from the remainder of the substrate. The flexible conduit is deflectable with respect to the planar substrate toward the fluid reservoir such that the flexible conduit fluidly connects the at least one channel to the fluid reservoir.

Abstract: A method includes, under control of control circuitry implementing a mixing protocol, aspirating reagents from multiple different reagent reservoirs into a cache channel. Designated amounts of the reagents are automatically aspirated from the corresponding reagent reservoirs by corresponding sippers based on the mixing protocol implemented by the control circuitry. The method also includes discharging the reagents from the cache channel into a mixing reservoir, and mixing the reagents within the mixing reservoir to form a reagent mixture.

Abstract: The present disclosure relates to new nucleotide and oligonucleotide compounds and their use in nucleic acid sequencing applications.

Abstract: The present invention relates to a method for preparing a library of template polynucleotides and use thereof in methods of solid-phase nucleic acid amplification. More specifically, the invention relates to a method for preparing a library of template polynucleotides that have common sequences at their 5? ends and at their 3? ends.

Abstract: Valve assemblies and related systems are disclosed. An apparatus includes or comprises a system including or comprising an imaging system, a flow cell interface having a corresponding flow cell receptacle, a stage assembly, and a valve assembly including or comprising a valve and a valve drive assembly. The stage assembly moves the flow cell interface relative to the imaging system and the valve drive assembly is to drive the valve using shaped input signals to reduce vibration imposed on at least one of the stage assembly or another component of the apparatus based on movement of the valve.

Abstract: Polypeptide nanopores synthetically functionalized with positively charged species, and methods of making and using the same, are provided herein. In some examples, a polypeptide nanopore includes a first side, a second side, a channel extending through the first and second sides, and a mutated amino acid residue. The mutated amino acid residue may be synthetically functionalized with a positively charged species that inhibits translocation of cations through the channel.

Abstract: The determination of pharmacogenomics gene star alleles using high-throughput targeted genotyping includes obtaining input genetic sequence variation data from a high-throughput genotyping platform based on a pharmacogenomic genotyping of a sample, applying a Bayesian graphical model to determine a plurality of different star allele calls corresponding to the sample, and providing a respective quality score for each star allele call of the plurality of different star allele calls. For instance, the application of the Bayesian graphical model uses multi-solution integer programming to explore a model space of the Bayesian graphical model in a first phase that includes structural variant candidate identification and a second phase that includes star allele candidate identification based on the structural variant candidate identification, to determine the plurality of different star allele calls.

Abstract: Array-based targeted copy number detection, for instance detection on contaminated and/or variable concentration samples, includes obtaining a collection of intensity signals from assays of a set of input samples, performing a cross-sample calibration on the intensity signals based on reference sample(s), which calibration includes constructing a reference signal distribution based on intensity signals of the reference sample(s) and for one or more input samples calibrating a set of intensity signals corresponding to the input sample based on the reference signal distribution, determining, for the one or more input samples, and from a respective one or more calibrated sets of intensity signals corresponding to the one or more input samples, a respective at least one aggregated calibrated signal from targeted genomic region(s) to produce a collection of aggregated calibrated signals, and detecting variant(s) in the targeted genomic region(s) based on the collection of aggregated calibrated signals.

Abstract: The assembly includes a docking console and a manifold. The docking console includes a cartridge support surface having a first end and a second end. The manifold has one or more wells defined therein. The docking console further includes a manifold retention bracket to releasably hold the manifold against a fluid cartridge supported on the cartridge support surface at an interface position such that the one or more wells are in fluid communication with the fluid cartridge and a biased seal bar to press the fluid cartridge against the manifold held by the manifold retention bracket. A hydrophilic porous frit disposed within at least one of the wells and is to permit liquid to flow through the outlet aperture but prevent gas from passing through the outlet aperture.

Abstract: 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.

Abstract: An instrument includes a reagent management system. The reagent management system includes a plurality of reagent wells, each reagent well operable to contain a reagent of a plurality of reagents positioned therein. The reagent management system is operable to select a flow of reagent from one of the plurality of reagents. A flexible connection includes a laminate stack and includes a first flexible channel in fluid communication with the reagent management system. The first flexible channel is operable to route the flow of reagent therethrough. A flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is operable to route the flow of reagent over analytes positioned in the flow channel. The flexible connection enables the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.

Abstract: Fixtures and related system and methods are disclosed. In accordance with an implementation, a method includes applying a resin onto a substrate and positioning the substrate on over a chuck of a base of a fixture. The method also includes moving a mold into engagement with the resin and curing the resin. The method also includes detaching the mold and the resin and, while detaching the mold and the resin, determining a detachment force applied as a function of a distance of detachment between the mold and the resin.

Abstract: A method for amplifying a target nucleic acid including providing a system having a crRNA or a derivative thereof, and a Cas protein or a variant thereof. The crRNA or the derivative thereof contains a target-specific nucleotide region substantially complementary to a region of the target nucleic acid, and contacting the target nucleic acid with the system to form a complex.

Abstract: Provided herein are processes for preparing fluorescent 1-cyano-2-substituted isoindole compounds or N-substituted phthalazinium compounds, comprising reacting an aromatic dialdehyde or aromatic aldehyde-ketone compound with a material that contains primary amino or hydrazine groups, and assaying methods involving the processes thereof.

Abstract: The present disclosure relates to polymer coatings covalently attached to the surface of a substrate and the preparation of the polymer coatings, such as poly(N-(5-azidoacetamidylpentyl)acrylamide-co-acrylamide) (PAZAM), in the formation and manipulation of substrates, such as molecular arrays and flow cells. The present disclosure also relates to methods of preparing a substrate surface by using beads coated with a covalently attached polymer, such as PAZAM, and the method of determining a nucleotide sequence of a polynucleotide attached to a substrate surface described herein.

Abstract: 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.

Abstract: The invention provides methods for controlling the density of different molecular species on the surface of a solid support. A first mixture of different molecular species is attached to a solid support under conditions to attach each species at a desired density, thereby producing a derivatized support having attached capture molecules. The derivatized support is treated with a second mixture of different molecular species, wherein different molecular species in the second mixture bind specifically to the different capture molecules attached to the solid support. One or more of the capture molecules can be reversibly modified such that the capture molecules have a different activity before and after the second mixture of molecular species are attached. In particular embodiments, the different molecular species are nucleic acids that are reversibly modified to have different activity in an amplification reaction.

Abstract: In one example, an unsaturated cyclic dione is coupled to the substrate, and is reacted with an indole or indazole including a first functional group to form a first adduct coupling the first functional group to the substrate. In another example, an unsaturated cyclic dione is coupled to a substrate and reacted with a diene including a functional group to form an adduct coupling the functional group to the substrate. In another example, an indole or indazole is coupled to a substrate, and is reacted with an unsaturated cyclic dione including an oligonucleotide to form an adduct coupling the oligonucleotide to the substrate. In another example, a diene is coupled to a substrate, and is reacted with an unsaturated cyclic dione including an oligonucleotide to form an adduct coupling the oligonucleotide to the substrate.

Abstract: Disclosed in one example is an apparatus including a substrate, a sensor over the substrate including an active surface and a sensor bond pad, a molding layer over the substrate and covering sides of the sensor, the molding layer having a molding height relative to a top surface of the substrate that is greater than a height of the active surface of the sensor relative to the top surface of the substrate, and a lidding layer over the molding layer and over the active surface. The lidding layer and the molding layer form a space over the active surface of the sensor that defines a flow channel.