Abstract: The present invention relates to a sequencing method which allows for increased rates of sequencing and an increase in the density of sequencing data. The system may be based on next generation sequencing methods such as sequencing by synthesis (SBS) but uses multiple primers bound at different positions on the same nucleic acid strand.

Abstract: The invention relates to methods for pairwise sequencing of a polynucleotide template which result in the sequential determination of nucleotide sequence in two distinct and separate regions of the polynucleotide template.

Abstract: The invention relates to methods for pairwise sequencing of a polynucleotide template which result in the sequential determination of nucleotide sequence in two distinct and separate regions of the polynucleotide template.

Abstract: 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.

Abstract: Presented herein are methods and compositions surface-based tagmentation. In particular embodiments, methods of preparing an immobilized library of fragmented and tagged DNA molecules on a solid surface are presented. In particular embodiments, the solid surface comprises immobilized transposomes in a dried format, suitable for reconstitution upon contact with liquid, such as a liquid sample.

Abstract: The present disclosure relates to new compounds and their use as fluorescent labels. The compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.

Abstract: 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.

Abstract: 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.

Abstract: An example of an array includes a support, a cross-linked epoxy polyhedral oligomeric silsesquioxane (POSS) resin film on a surface of the support, and a patterned hydrophobic polymer layer on the cross-linked epoxy POSS resin film. The patterned hydrophobic polymer layer defines exposed discrete areas of the cross-linked epoxy POSS resin film, and a polymer coating is attached to the exposed discrete areas. Another example of an array includes a support, a modified epoxy POSS resin film on a surface of the support, and a patterned hydrophobic polymer layer on the modified epoxy POSS resin film. The modified epoxy POSS resin film includes a polymer growth initiation site, and the patterned hydrophobic polymer layer defines exposed discrete areas of the modified epoxy POSS resin film. A polymer brush is attached to the polymer growth initiation site in the exposed discrete areas.

Abstract: 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.

Abstract: A method for detecting different analytes includes mixing different analytes with sensing probes, wherein at least some of the sensing probes are specific to respective ones of the analytes. The analytes respectively are captured by the sensing probes that are specific to those analytes. Fluorophores respectively are coupled to sensing probes that captured respective analytes. The sensing probes are mixed with beads, wherein the beads are specific to respective ones of the sensing probes, and wherein the beads include different codes identifying the analytes to which those sensing probes are specific. The sensing probes respectively are coupled to beads that are specific to those sensing probes. The beads are identified that are coupled to the sensing probes that captured analytes using at least fluorescence from the fluorophores coupled to those sensing probes. The analytes that are captured are identified.

Abstract: Method includes positioning a first carrier assembly on a system stage. The carrier assembly includes a support frame having an inner frame edge that defines a window of the support frame. The first carrier assembly includes a first substrate that is positioned within the window and surrounded by the inner frame edge. The first substrate has a sample thereon. The method includes detecting optical signals from the sample of the first substrate. The method also includes replacing the first carrier assembly on the system stage with a second carrier assembly on the system stage. The second carrier assembly includes the support frame and an adapter plate held by the support frame. The second carrier assembly has a second substrate held by the adapter plate that has a sample thereon. The method also includes detecting optical signals from the sample of the second substrate.

Abstract: A system includes at least a voxelizer, an alternative allele encoder, an evolutionary conservation encoder, and a convolutional neural network. The voxelizer accesses a three-dimensional structure of a reference amino acid sequence of a protein and fits a three-dimensional grid of voxels on atoms in the three-dimensional structure on an amino acid-basis to generate amino acid-wise distance channels. The alternative allele encoder encodes an alternative allele sequence to each voxel in the three-dimensional grid of voxels. The evolutionary conservation encoder encodes an evolutionary conservation sequence to each voxel in the three-dimensional grid of voxels. The convolutional neural network applies three-dimensional convolutions to a tensor that includes the amino acid-wise distance channels encoded with the alternative allele sequence and respective evolutionary conservation sequences and determines a pathogenicity of a variant nucleotide based at least in part on the tensor.

Abstract: 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.

Abstract: 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.

Abstract: The technology disclosed relates to efficiently determining which atoms in a protein are nearest to voxels in a grid. The atoms have three-dimensional (3D) atom coordinates, and the voxels have 3D voxel coordinates. The technology disclosed generates an atom-to-voxels mapping that maps, to each of the atoms, a containing voxel selected based on matching 3D atom coordinates of a particular atom of the protein to the 3D voxel coordinates in the grid. The technology disclosed generates a voxel-to-atoms mapping that maps, to each of the voxels, a subset of the atoms. The subset of the atoms mapped to a particular voxel in the grid includes those atoms in the protein that are mapped to the particular voxel by the atom-to-voxels mapping. The technology disclosed includes using the voxel-to-atoms mapping to determine, for each of the voxels, a nearest atom in the protein.

Abstract: The invention relates to modified polymerase enzymes which exhibit improved incorporation of nucleotide analogues bearing substituents at the 3? position of the sugar moiety that are larger in size than the naturally occurring 3? hydroxyl group. Also described are methods of using the polymerases to incorporate nucleotides into polynucleotides, particularly in the context of DNA sequencing.

Abstract: The present invention is concerned with compositions and methods for improving the rate of correct sample identification in indexed nucleic acid library preparations for multiplex next generation sequencing by exonuclease treatment and optionally blocking the 3? ends of pooled indexed polynucleotides from multiple samples prior to amplification and sequencing.

Abstract: Presented herein are methods and compositions surface-based tagmentation. In particular embodiments, methods of preparing an immobilized library of fragmented and tagged DNA molecules on a solid surface are presented. In particular embodiments, the solid surface comprises immobilized transposomes in a dried format, suitable for reconstitution upon contact with liquid, such as a liquid sample.

Abstract: Novel rhodamine dye compounds, labelled conjugates comprising the dyes are described, together with methods for their use. The dyes and labelled conjugates are useful as molecular probes in a variety of applications, such as in assays involving staining of cells, protein binding, and analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.