Abstract: A method comprises: directing, using an objective and a first reflective surface, first autofocus light toward a sensor, the first autofocus light reflected from a first surface of a substrate; preventing second autofocus light from reaching the sensor, the second autofocus light reflected from a second surface of the substrate; and directing, using the objective and a second reflective surface, emission light toward the sensor, the emission light originating from a sample at the substrate.

Abstract: Presented herein are altered polymerase enzymes for improved incorporation of nucleotides and nucleotide analogues, in particular altered polymerases that maintain high fidelity under reduced incorporation times, as well as methods and kits using the same.

Abstract: A composition is provided that comprises a calcium carbonate slurry. The calcium carbonate slurry comprises a plurality of calcium carbonate particles suspended in a solution, where the solution comprises a dispersant and an anionic surfactant. The concentration of the calcium carbonate particles in the calcium carbonate slurry is equal to or less than about 2.0 wt. %.

Abstract: 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.

Abstract: Methods, systems, and apparatuses, including computer programs for generating and using a hash table configured to improve mapping of reads are disclosed that include obtaining a first seed of K nucleotides from a reference sequence, generating a seed extension tree having a nodes, wherein each node of the nodes corresponds to (i) an extended seed that is an extension of the first seed and has a nucleotide length of K* and (ii) one or more locations, in a seed extension table, that include data describing reference sequence locations that match the extended seed, and for each node: storing interval information at a location of the hash table that corresponds to an index key for the extended seed, wherein the interval information references one or more locations in the seed extension table that include reference sequence locations that match the extended seed associated with the node.

Abstract: The present disclosure relates to methods, compositions, and kits for generating a library of tagged nucleic acid fragments without using PCR amplification, including methods and compositions for fragmenting and tagging nucleic acids (e.g., DNA) using transposome complexes immobilized on solid support.

Abstract: A method of characterizing candidate agents including steps of (a) providing a library of candidate agents attached to nucleic acid tags; (b) contacting the library with a solid support to attach the candidate agents to the solid support, whereby an array of candidate agents is formed; (c) contacting the array with a screening agent, wherein one or more candidate agents in the array react with the screening agent; (d) detecting the array to determine that at least one candidate agent in the array reacts with the screening agent; (e) sequencing the nucleic acid tag to determine the tag sequences attached to candidate agents in the array; and (f) identifying the at least one candidate agent in the array that reacts with the screening agent based on the tag sequence that is attached to the at least one candidate agent.

Abstract: The technology disclosed relates to constructing a convolutional neural network-based classifier for variant classification. In particular, it relates to training a convolutional neural network-based classifier on training data using a backpropagation-based gradient update technique that progressively match outputs of the convolutional neural network-based classifier with corresponding ground truth labels. The convolutional neural network-based classifier comprises groups of residual blocks, each group of residual blocks is parameterized by a number of convolution filters in the residual blocks, a convolution window size of the residual blocks, and an atrous convolution rate of the residual blocks, the size of convolution window varies between groups of residual blocks, the atrous convolution rate varies between groups of residual blocks. The training data includes benign training examples and pathogenic training examples of translated sequence pairs generated from benign variants and pathogenic variants.

Abstract: Presented herein are methods and compositions for analyzing rare nucleic acid species. Some methods presented herein use DNA reassociation kinetics following thermal denaturation to define populations of nucleic acid sequences, e.g., highly abundant (e.g., cDNA from rRNA), moderately abundant, and less abundant or rare sequences (e.g., cDNA from mRNA).

Abstract: A flow cell includes a support and a heteropolymer attached to the support. The heteropolymer includes an acrylamide monomer including an attachment group to react with a functional group attached to a primer, and a monomer including a stimuli-responsive functional group. The monomer including the stimuli-responsive functional group may be pH-responsive, temperature-responsive, saccharide-responsive, nucleophile-responsive, and/or salt-responsive.

Abstract: Embodiments of the present disclosure relate to nucleotide and nucleoside molecules with acetal 3?-OH blocking groups. Also provided herein are methods to prepare such nucleotide and nucleoside molecules, and the uses of fully functionalized nucleotides containing the 3? acetal blocking group for sequencing applications.

Abstract: The disclosed embodiments concern index oligonucleotides configured to identify sources of samples of nucleic acids and methods, apparatus, systems and computer program products for identifying and making the index oligonucleotides. In some implementations, the index oligonucleotides include a set of index sequences, a Hamming distance between any two index sequences of the set of index sequences meeting one or more criteria. System, apparatus, and computer program products are also provided for determining a sequence of interest using the index oligonucleotides.

Abstract: Systems and methods for conducting designated reactions that include a fluidic network having a sample channel, a reaction chamber, and a reservoir. The sample channel is in flow communication with a sample port. The system also includes a rotary valve that has a flow channel and is configured to rotate between first and second valve positions. The flow channel fluidically couples the reaction chamber and the sample channel when the rotary valve is in the first valve position and fluidically couples the reservoir and the reaction chamber when the rotary valve is in the second valve position. A pump assembly induces a flow of a biological sample toward the reaction chamber when the rotary valve is in the first valve position and induces a flow of a reaction component from the reservoir toward the reaction chamber when the rotary valve is in the second valve position.

Abstract: Provided herein are methods for preparing a sequencing library that includes nucleic acids from a plurality of single cells. In one embodiment, the sequencing library includes whole genome nucleic acids from the plurality of single cells. In one embodiment, the method includes generating nucleosome-depleted nuclei by chemical treatment while maintaining integrity of the nuclei. Also provided herein are compositions, such as compositions that include chemically treated nucleosome-depleted isolated nuclei.

Abstract: An electrowetting-based droplet actuator includes top and bottom substrates, a droplet-operation gap between the top and bottom substrates, the droplet-operation gap including a gradually-reduced gap height in a direction of droplet flow when in use, and spaced electrodes embedded in the bottom substrate spanning a region thereof corresponding to the gradually-reduced gap height. A method includes gradually reducing a gap height in section(s) of a droplet-operation gap between top and bottom substrates of an electrowetting-based droplet actuator, the gradually reducing being in a direction of droplet flow when in use from a large-gap inlet to a small-gap outlet (relative sizes), the large-gap inlet being larger in height, the bottom substrate including spaced electrodes embedded therein spanning a region of the bottom substrate corresponding to the gradually reduced gap height, and moving dispensed droplet(s) of liquid in the direction of droplet flow using the spaced electrodes and an applied voltage.

Abstract: A sensing system includes a charge sensor including two electrodes and an electrically conductive channel connecting the two electrodes. The sensing system also includes a charged molecule attached to the electrically conductive channel. The charged molecule includes a recognition site to reversibly bind a label of a labeled nucleotide; has an unbound favored conformation associated with an unbound charge configuration; and has a favored conformation associated with a charge configuration when the recognition site is bound to the label. The charge configuration is different from the unbound charge configuration. The sensing system further includes a polymerase attached to the electrically conductive channel or to the charged molecule.

Abstract: An example of a flow cell includes a substrate, a plurality of chambers defined on or in the substrate, and a plurality of depressions defined in the substrate and within a perimeter of each of the plurality of chambers. The depressions are separated by interstitial regions. Primers are attached within each of the plurality of depressions, and a capture site is located within each of the plurality of chambers.

Abstract: Light detection devices and related methods are provided. The devices may comprise a reaction structure for containing a reaction solution with a relatively high or low pH and a plurality of reaction sites that generate light emissions. The devices may comprise a device base comprising a plurality of light sensors, device circuitry coupled to the light sensors, and a plurality of light guides that block excitation light but permit the light emissions to pass to a light sensor. The device base may also include a shield layer extending about each light guide between each light guide and the device circuitry, and a protection layer that is chemically inert with respect to the reaction solution extending about each light guide between each light guide and the shield layer. The protection layer prevents reaction solution that passes through the reaction structure and the light guide from interacting with the device circuitry.

Abstract: Presented herein are polymerase enzymes for improved incorporation of nucleotide analogues, in particular nucleotides which are modified at the 3? sugar hydroxyl, as well as methods and kits using the same.