Abstract: The technology disclosed relates to variant calling of sequenced reads of a sample of a target species against a reference genome of a pseudo-target species. Low-quality variants are identified as false positive variants that are present in the second set of variants but absent from the first set of variants.

Abstract: Disclosed herein are systems and methods for collapsing sequencing reads and identifying similar sequencing reads. In one example, a method includes generating a plurality of first identifier subsequences from a first identifier sequence of each nucleotide sequencing read and generating a first signature for the nucleotide sequencing read by applying hashing to the plurality of first identifier subsequences. The method may include assigning the nucleotide sequencing read to a first particular bin of a first data structure based on the first signature and determining a nucleotide sequence for each first particular bin of the first data structure with one or more nucleotide sequencing reads assigned.

Abstract: In some examples, an instrument for measuring a volume of a liquid is provided. A gas flow rate sensor may measure a rate of flow of a pressurized gas to a reservoir storing a liquid. A controller may be coupled to the gas flow rate sensor and may calculate a volume of the liquid that the flow of pressurized gas displaces from the reservoir. In some examples, a method of measuring a volume of a liquid is provided. Using a gas flow rate sensor, a flow of pressurized gas may be measured. The flow of the pressurized gas may be delivered to a reservoir storing a liquid. A volume of the liquid in the reservoir may be displaced using the flow of pressurized gas. The measurement of the flow of the pressurized gas may be used to calculate the volume of the liquid that is displaced.

Abstract: Flow cells systems and corresponding methods are provided. The flow cells systems may include a socket comprising a base portion, a plurality of electrical contacts and a cover portion that includes a first port. The flow cells systems may also include a flow cell device secured within an enclosure of the socket. The flow cell device may comprise a frameless light detection device comprising a base wafer portion, a plurality of dielectric layers, a reaction structure, a plurality of light guides, a plurality of light sensors, and device circuitry electrically coupled to the light sensors. The flow cell device may also comprise a lid forming a flow channel over the reaction structure that includes a second port in communication with the flow channel and the first port of the socket. The device circuitry of the light detection device may be electrically coupled to the electrical contacts of the socket.

Abstract: An example sensor includes a flow cell, a detection device, and a controller. The flow cell includes a passivation layer having opposed surfaces and a reaction site at a first of the opposed surfaces. The flow cell also includes a lid operatively connected to the passivation layer to partially define a flow channel between the lid and the reaction site. The detection device is in contact with a second of the opposed surfaces of the passivation layer, and includes an embedded metal layer that is electrically isolated from other detection circuitry of the detection device. The controller is to ground the embedded metal layer.

Abstract: Flexible authentication technologies customized to particular tenants of a data center network can be implemented. For example, an administrator can specify a primary authentication server and specify at which data centers different applications are to be hosted for a given tenant. End users can be shielded from the complexities of implementing such configuration details. For example, single sign-on authentication can be implemented, even when applications are configured to be hosted in different data centers. Enterprise tenants can thus control where applications are hosted and enforce data containment scenarios without encumbering users with additional tasks. Collaboration and application-to-application authentication can be achieved.

Abstract: An example of a flow cell includes a substrate; a first primer set attached to a first region on the substrate, the first primer set including an un-cleavable first primer and a cleavable second primer; and a second primer set attached to a second region on the substrate, the second primer set including a cleavable first primer and an un-cleavable second primer.

Abstract: The technology disclosed relates to systems and methods for avoiding post-processing of an image from extension of probes on beads during a sample evaluation run. The method includes receiving an image of beads in an array of tiles on a beadchip. The method includes calculating averages, over each tile in image channel, of full width at half max (FWHM) values of images of the beads. The method includes predicting from the average FWHM values of the tiles, a likelihood of failure score for the sample evaluation run. A trained classifier can be used to predict the likelihood of failure score. The method includes reporting the likelihood of failure score for the sample evaluation run.

Abstract: 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.

Abstract: This application describes methods of preparing an immobilized library of tagged RNA fragments. Also described herein are a number of methods of preparing DNA and RNA sequencing libraries from a single sample. These methods can include library preparation from single cells.

Abstract: Methods and systems for analysis of image data generated from various reference points. Particularly, the methods and systems provided are useful for real time analysis of image and sequence data generated during DNA sequencing methodologies.

Abstract: The disclosure provides for structured illumination microscopy (SIM) imaging systems. In one set of implementations, a SIM imaging system may be implemented as a multi-arm SIM imaging system, whereby each arm of the system includes a light emitter and a beam splitter (e.g., a transmissive diffraction grating) having a specific, fixed orientation with respect to the system's optical axis. In a second set of implementations, a SIM imaging system may be implemented as a multiple beam splitter slide SIM imaging system, where one linear motion stage is mounted with multiple beam splitters having a corresponding, fixed orientation with respect to the system's optical axis. In a third set of implementations, a SIM imaging system may be implemented as a pattern angle spatial selection SIM imaging system, whereby a fixed two-dimensional diffraction grating is used in combination with a spatial filter wheel to project one-dimensional fringe patterns on a sample.

Abstract: 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.

Abstract: Coordinated application processing includes obtaining a plurality of images and distributing them to processing engines to perform image processing. The plurality of images cover an image area, with different sub-areas, in which a biological sample to be sequenced is present. The image processing proceeds across multiple cycles to process a respective set of images, of the plurality of images, of each sub-area of the different sub-areas, and therefore of the respective area, of the flow cell, to which that sub-area correlates. The distributing the plurality of images includes, for each sub-area of the different sub-areas, distributing, across the multiple cycles of the image processing, the images of the respective set of images of that sub-area to a respective processing engine, of a plurality of processing engines, associated with, and selected for, processing images of that sub-area.

Abstract: Provided herein are compositions and methods for electronically sequencing polynucleotides using partially double-stranded polymer bridges. The bridges may span the space between first and second electrodes. A plurality of nucleotides may be coupled to corresponding labels. A polymerase may add nucleotides to a first polynucleotide using at least a sequence of a second polynucleotide. The labels corresponding to those nucleotides respectively may hybridize to a portion of the bridge that is not double-stranded. Detection circuitry may detect a sequence in which the polymerase adds the nucleotides to the first polynucleotide using at least changes in an electrical signal through the bridge, the changes being responsive to the respective hybridizations between the non-double stranded portion of the bridge and the labels corresponding to those nucleotides.

Abstract: In some examples, a device includes first and second electrodes separated from one another by a space; a particle coupled to the first electrode via a first plurality of bonds, and coupled to the second electrode via a second plurality of bonds; and a polymerase coupled to the particle. In some examples, a composition includes first and second electrodes separated from one another by a space; a fluid including a first electrically conductive label having a length at least as long as a length of the space; and detection circuitry to generate a first signal responsive to transient formation, using the first electrically conductive label, of a first electrically conductive bridge between the first and second electrodes.

Abstract: An example of a method includes providing a substrate with an exposed surface comprising a first chemical group, wherein the providing optionally comprises modifying the exposed surface of the substrate to incorporate the first chemical group; reacting the first chemical group with a first reactive group of a functionalized polymer molecule to form a functionalized polymer coating layer covalently bound to the exposed surface of the substrate; grafting a primer to the functionalized polymer coating layer by reacting the primer with a second reactive group of the functionalized polymer coating layer; and forming a water-soluble protective coating on the primer and the functionalized polymer coating layer. Examples of flow cells incorporating examples of the water-soluble protective coating are also disclosed herein.

Abstract: Some embodiments provided herein include methods and compositions for the detection of target ligands on an array. In some embodiments, a capture probe specifically binds to a target ligand from a sample, the location of a bead comprising the capture probe in an array is determined, and the bead is decoded to identify the capture probe and the sample. In some embodiments, a barcode is indicative of a capture probe attached to a bead; and an index is indicative of a subpopulation of beads. In some embodiments, the barcode and the index are determined by sequencing.

Abstract: An example method includes reacting a first solution and a different, second solution on a flow cell by flowing the first solution over amplification sites on the flow cell and subsequently flowing the second solution over the amplification sites. The first solution includes target nucleic acids and a first reagent mixture that comprises nucleoside triphosphates and replication enzymes. The target nucleic acids in the first solution transport to and bind to the amplification sites at a transport rate. The first reagent mixture amplifies the target nucleic acids that are bound to the amplification sites to produce clonal populations of amplicons originating from corresponding target nucleic acids. The amplicons are produced at an amplification rate that exceeds the transport rate. The second solution includes a second reagent mixture and lacks the target nucleic acids. The second solution is to increase a number of the amplicons at the amplification sites.