Abstract: A system includes an image sensor structure and a flow cell. The image sensor structure includes an image layer disposed over a base substrate. A device stack is disposed over the image layer. A bond pad is disposed in the device stack. A passivation stack is disposed over the device stack and the bond pad. An array of nanowells is disposed in a top layer of the passivation stack. A through-silicon via (TSV) is in electrical contact with the bond pad. The TSV extends through the base substrate. A redistribution layer (RDL) is disposed on a bottom surface of the base substrate. The RDL is in electrical contact with the TSV. The flow cell is disposed upon the top layer of the passivation stack to form a flow channel therebetween. The flow channel is disposed over the array of nanowells and the bond pad.

Abstract: The technology disclosed relates to splice site prediction and aberrant splicing detection. In particular, it relates to a splice site predictor that includes a convolutional neural network trained on training examples of donor splice sites, acceptor splice sites, and non-splicing sites. An input stage of the convolutional neural network feeds an input sequence of nucleotides for evaluation of target nucleotides in the input sequence. An output stage of the convolutional neural network translates analysis by the convolutional neural network into classification scores for likelihoods that each of the target nucleotides is a donor splice site, an acceptor splice site, and a non-splicing site.

Abstract: A method may be implemented for in-tip flow-through magnetic bead processing. A biological solution may include a plurality of magnetic beads suspended therein. The biological solution may be introduced to a tube via an opening in a tip portion of the tube. The tip portion of the tube may include a magnetizable material arranged in a flow path of the biological solution. The magnetizable material may include a ferromagnetic matrix or a wire within the tip portion. A magnetic field may be applied proximate to the tip portion of the tube using an electromagnetic coil. The electromagnetic coil may be wound around the tip portion. The biological solution may be removed from the tube, for example, via the opening in the tip portion. The plurality of magnetic beads may be captured within the magnetizable material in the tip portion using the magnetic field.

Abstract: A composition for capturing target polynucleotides at a surface of a substrate is provided. The composition may include a plurality of capture primers coupled to the surface of the substrate and including modified nucleic acids; and a plurality of orthogonal capture primers coupled to the surface of the substrate and including modified nucleic acids. The modified nucleic acids of the capture primers may include locked nucleic acid (LNA), peptide nucleic acid (PNA), or super T. The modified nucleic acids of the orthogonal capture primers may include locked nucleic acid (LNA), peptide nucleic acid (PNA), or super T.

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for determining sequences of interest using unique molecular index (UMI) sequences that are uniquely associable with individual polynucleotide fragments, including sequences with low allele frequencies and long sequence length. In some implementations, the UMIs include both physical UMIs and virtual UMIs. In some implementations, the unique molecular index sequences include non-random sequences. System, apparatus, and computer program products are also provided for determining a sequence of interest implementing the methods disclosed.

Abstract: An apparatus includes a flow cell body, a plurality of electrodes, an imaging assembly, and one or more barrier features. The flow cell body defines one or more flow channels and a plurality of wells defined as recesses in the floor of each flow channel. Each well is fluidically coupled with the corresponding flow channel. The flow cell body further defines interstitial surfaces between adjacent wells. Each well defines a corresponding depth. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are to effect writing of polynucleotides in the wells. The imaging assembly is to capture images of polynucleotides written in the wells. The one or more barrier features are positioned in the wells, between the wells, or above the wells. The one or more barrier features contain reactions in each well, reduce diffusion between the wells, or reduce optical cross-talk between the wells.

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: We disclose computational models that alleviate the effects of human ascertainment biases in curated pathogenic non-coding variant databases by generating pathogenicity scores for variants occurring in the promoter regions (referred to herein as promoter single nucleotide variants (pSNVs)). We train deep learning networks (referred to herein as pathogenicity classifiers) using a semi-supervised approach to discriminate between a set of labeled benign variants and an unlabeled set of variants that were matched to remove biases.

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: The technology disclosed corrects inter-cluster intensity profile variation for improved base calling on a cluster-by-cluster basis. The technology disclosed accesses current intensity data and historic intensity data of a target cluster, where the current intensity data is for a current sequencing cycle and the historic intensity data is for one or more preceding sequencing cycles. A first accumulated intensity correction parameter is determined by accumulating distribution intensities measured for the target cluster at the current and preceding sequencing cycles. A second accumulated intensity correction parameter is determined by accumulating intensity errors measured for the target cluster at the current and preceding sequencing cycles. Based on the first and second accumulated intensity correction parameters, next intensity data for a next sequencing cycle is corrected to generate corrected next intensity data, which is used to base call the target cluster at the next sequencing cycle.

Abstract: There is set forth herein a device comprising structure defining a detector surface configured for supporting biological or chemical substances, and a sensor array comprising light sensors and circuitry to transmit data signals using photons detected by the light sensors. The device can include one or more features for reducing fluorescence range noise in a detection band of the sensor array.

Abstract: Described herein is a polynucleotide for use as a sequencing template comprising multiple inserts. Also described herein are method of generating and using these polynucleotides and methods of use of such templates, including analysis of contiguity information. Further, sequencing templates comprising an insert sequence and a copy of the insert sequence can be used to correct for random errors generated during sequencing or amplification or to identify nucleobase damage or other mutation that leads to non-canonical base pairing in a double-stranded nucleic acid. Methods of performing methylation analysis are also described herein.

Abstract: Defocus is introduced during sequencing by synthesis by tilt of a flow cell and by variations in flatness of the flow cell. Effects of the defocus are reduced, and base calling quality is improved using techniques relating to dependence of base calling on flow cell tilt. For example, the flow cell surface height is measured throughout the flow cell. A focal height of an imager having a sensor for the sequencing is set, optionally adaptively, one or more times during the sequencing. Each image captured by the sensor is partitioned, e.g., based on differences between focal height and the measured flow cell surface height across areas of the sensor. Filters, e.g., related to defocus correction, are selected based at least in part on the difference between the focal height and the measured flow cell surface height at a particular area of the image being corrected for defocus.

Abstract: A flow cell package includes first and second surface-modified patterned wafers and a spacer layer. The first surface-modified patterned wafer includes first depressions separated by first interstitial regions, a first functionalized molecule bound to a first silane or silane derivative in at least some of the first depressions, and a first primer grafted to the first functionalized molecule in the at least some of the first depressions. The second surface-modified patterned wafer includes second depressions separated by second interstitial regions, a second functionalized molecule bound to a second silane or silane derivative in at least some of the second depressions, and a second primer grafted to the second functionalized molecule in the at least some of the second depressions. The spacer layer bonds at least some first interstitial regions to at least some second interstitial regions, and at least partially defines respective fluidic chambers of the flow cell package.

Abstract: A system includes a reagent selector valve controllable to select a reagent flow path from a plurality of reagent flow paths, and a pump coupled to the reagent flow path to draw a liquid through the reagent flow path in accordance with a prescribed test protocol. The system includes a discharge flow path to expel the drawn liquid, and a flow meter to measure liquid displaced by the pump and that outputs data representative of the measured flow. The system also includes a processor to access the data and to determine a volume of the liquid displaced by the pump.

Abstract: An integrated detection, flow cell and photonics (DFP) device is provided that comprises a substrate having an array of pixel elements that sense photons during active periods. The substrate and pixel elements form an IC photon detection layer. At least one wave guide is formed on the IC photo detection layer as a photonics layer. An optical isolation layer is formed over at least a portion of the wave guide. A collection of photo resist (PR) walls patterned to define at least one flow cell channel that is configured to direct fluid along a fluid flow path. The wave guides align to extend along the fluid flow path. The flow cell channel is configured to receive samples at sample sites that align with the array of pixel elements.

Abstract: In one example, a flow cell includes a substrate, an electrode positioned on the substrate, and a patterned material positioned on the electrode. In this example, the patterned material includes depressions separated by interstitial regions, and a functionalized surface of the electrode is exposed at each of the depressions. In this example, the flow cell further includes a primer grafted to the functionalized surface in each of the depressions. In another example, a flow cell includes a substrate and a patterned electrode positioned on the substrate. In this other example, the patterned electrode includes depressions separated by interstitial regions, and a functionalized surface of the substrate exposed at each of the depressions. In this other example, a primer is grafted to the functionalized surface in each of the depressions.

Abstract: The present disclosure relates to methods, compositions, and kits for treating target nucleic acids, including methods and compositions for fragmenting and tagging nucleic acid (e.g., DNA) using transposome complexes bound to a solid support.

Abstract: The present invention includes methods and materials for use in the detection preeclampsia and/or determining an increased risk for preeclampsia in a pregnant female, the method including identifying in a biosample obtained from the pregnant women circulating RNA (C-RNA) molecules associated with preeclampsia.

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.