Abstract: The technology disclosed predicts quality of base calling during an extended optical base calling process. The base calling process includes pre-prediction base calling process cycles and at least two times as many post-prediction base calling process cycles as pre-prediction cycles. A plurality of time series from the pre-prediction base calling process cycles is given as input to a trained convolutional neural network. The convolutional neural network determines from the pre-prediction base calling process cycles, a likely overall base calling quality expected after post-prediction base calling process cycles. When the base calling process includes a sequence of paired reads, the overall base calling quality time series of the first read is also given as an additional input to the convolutional neural network to determine the likely overall base calling quality after post-prediction cycles of the second read.

Abstract: The technology disclosed uses neural networks to determine analyte metadata by (i) processing input image data derived from a sequence of image sets through a neural network and generating an alternative representation of the input image data, the input image data has an array of units that depicts analytes and their surrounding background, (ii) processing the alternative representation through an output layer and generating an output value for each unit in the array, (iii) thresholding output values of the units and classifying a first subset of the units as background units depicting the surrounding background, and (iv) locating peaks in the output values of the units and classifying a second subset of the units as center units containing centers of the analytes.

Abstract: The technology disclosed relates to artificial intelligence-based base calling of index sequences. The technology disclosed accesses index images generated for the index sequences during index sequencing cycles of a sequencing run. The index images depict intensity emissions generated as a result of nucleotide incorporation in the index sequences during the sequencing run. The technology disclosed normalizes an index image from a current index sequencing cycle based on (i) intensity values of index images from one or more preceding index sequencing cycles, (ii) intensity values of index images from one or more succeeding index sequencing cycles, and (iii) intensity values of index images from the current index sequencing cycle. The technology disclosed processes normalized versions of the index images through a neural network-based base caller and generates a base call for each of the index sequencing cycles, thereby producing index reads for the index sequences.

Abstract: The technology disclosed relates to artificial intelligence-based base calling. The technology disclosed relates to accessing a progression of per-cycle analyte channel sets generated for sequencing cycles of a sequencing run, processing, through a neural network-based base caller (NNBC), windows of per-cycle analyte channel sets in the progression for the windows of sequencing cycles of the sequencing run such that the NNBC processes a subject window of per-cycle analyte channel sets in the progression for the subject window of sequencing cycles of the sequencing run and generates provisional base call predictions for three or more sequencing cycles in the subject window of sequencing cycles, from multiple windows in which a particular sequencing cycle appeared at different positions, using the NNBC to generate provisional base call predictions for the particular sequencing cycle, and determining a base call for the particular sequencing cycle based on the plurality of base call predictions.

Abstract: The technology disclosed compresses a larger, teacher base caller into a smaller, student base caller. The student base caller has fewer processing modules and parameters than the teacher base caller. The teacher base caller is trained using hard labels (e.g., one-hot encodings). The trained teacher base caller is used to generate soft labels as output probabilities during the inference phase. The soft labels are used to train the student base caller.

Abstract: The technology disclosed relates to a system that comprises a spatial convolution network and a bus network. The spatial convolution network is configured to process a window of per-cycle sequencing image sets on a cycle-by-cycle basis by separately processing respective per-cycle sequencing image sets through respective spatial processing pipelines to generate respective per-cycle spatial feature map sets for respective sequencing cycles. The bus network is configured to form buses between spatial convolution layers within the respective spatial processing pipelines. The buses are configured to cause respective per-cycle spatial feature map sets generated by two or more spatial convolution layers in a particular sequence of spatial convolution layer for a particular sequencing cycle to combine into a combined per-cycle spatial feature map set, and provide the combined per-cycle spatial feature map set as input to another spatial convolution layer in the particular sequence of spatial convolution layer.

Abstract: The technology disclosed relates to an artificial intelligence-based method of base calling. In particular, it relates to processing, through a spatial network of a neural network-based base caller, a first window of per-cycle analyte channel sets in for a first window of sequencing cycles of a sequencing run, and generating respective sequences of spatial output sets for respective sequencing cycles in the first window of sequencing cycles, processing, through a compression network of the neural network-based base caller, respective final spatial output sets in the respective sequences of spatial output sets, and generating respective compressed spatial output sets for the respective sequencing cycles in the first window of sequencing cycles, and generating, based on the respective compressed spatial output sets, base call predictions for one or more sequencing cycles in the first window of sequencing cycles.

Abstract: The technology disclosed relates to a system that comprises a spatial convolution network and a temporal convolution network. The spatial convolution network is configured to process a window of per-cycle sequencing image sets and generate respective per-cycle spatial feature map sets. Trained coefficients of spatial convolution filters in spatial convolution filter banks of respective sequences of spatial convolution filter banks vary between sequences of spatial convolution layers in respective sequences of spatial convolution layers. The temporal convolution network is configured to process the per-cycle spatial feature map sets on a groupwise basis and generate respective per-group temporal feature map sets. Trained coefficients of temporal convolution filters in respective temporal convolution filter banks vary between temporal convolution filter banks in respective temporal convolution filter banks.

Abstract: A method includes grafting oligonucleotides to a flow cell and preparing a library of polynucleotides. Each polynucleotide has been written to contain retrievable information and includes a region complementary to one of the sequencing initiation primers grafted to the flow cell. Each polynucleotide is indexed to permit discrete identification of that polynucleotide and the information it contains over other polynucleotides in the library. Another method includes writing two polynucleotides including two sequences with reverse complementary joining sequences onto a flow cell. One of the polynucleotides is extended to generate a third polynucleotide comprising a sequence that is the combination of the first and second sequences. A fourth polynucleotide is written with a third joining sequence of a fourth sequence.

Abstract: Presented herein are methods and compositions for tagmentation of nucleic acids. The methods are useful for generating tagged DNA fragments that are qualitatively and quantitatively representative of the target nucleic acids in the sample from which they are generated.

Abstract: Presented herein are methods and compositions for tagmentation of nucleic acids. The methods are useful for generating tagged DNA fragments that are qualitatively and quantitatively representative of the target nucleic acids in the sample from which they are generated.

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: The technology disclosed uses neural networks to determine analyte metadata by (i) processing input image data derived from a sequence of image sets through a neural network and generating an alternative representation of the input image data, the input image data has an array of units that depicts analytes and their surrounding background, (ii) processing the alternative representation through an output layer and generating an output value for each unit in the array, (iii) thresholding output values of the units and classifying a first subset of the units as background units depicting the surrounding background, and (iv) locating peaks in the output values of the units and classifying a second subset of the units as center units containing centers of the analytes.

Abstract: The technology disclosed relates to generating ground truth training data to train a neural network-based template generator for cluster metadata determination task. In particular, it relates to accessing sequencing images, obtaining, from a base caller, a base call classifying each subpixel in the sequencing images as one of four bases (A, C, T, and G), generating a cluster map that identifies clusters as disjointed regions of contiguous subpixels which share a substantially matching base call sequence, determining cluster metadata based on the disjointed regions in the cluster map, and using the cluster metadata to generate the ground truth training data for training the neural network-based template generator for the cluster metadata determination task.

Abstract: The technology disclosed processes a first input through a first neural network and produces a first output. The first input comprises first image data derived from images of analytes and their surrounding background captured by a sequencing system for a sequencing run. The technology disclosed processes the first output through a post-processor and produces metadata about the analytes and their surrounding background. The technology disclosed processes a second input through a second neural network and produces a second output. The second input comprises third image data derived by modifying second image data based on the metadata. The second image data is derived from the images of the analytes and their surrounding background. The second output identifies base calls for one or more of the analytes at one or more sequencing cycles of the sequencing run.

Abstract: The technology disclosed processes input data through a neural network and produces an alternative representation of the input data. The input data includes per-cycle image data for each of one or more sequencing cycles of a sequencing run. The per-cycle image data depicts intensity emissions of one or more analytes and their surrounding background captured at a respective sequencing cycle. The technology disclosed processes the alternative representation through an output layer and producing an output and base calls one or more of the analytes at one or more of the sequencing cycles based on the output.

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: Presented herein are transposase enzymes and reaction conditions for improved fragmentation and tagging of nucleic acid samples, in particular altered transposases and reaction conditions which exhibit improved insertion sequence bias, as well as methods and kits using the same.

Abstract: Presented herein are transposase enzymes and reaction conditions for improved fragmentation and tagging of nucleic acid samples, in particular altered transposases and reaction conditions which exhibit improved insertion sequence bias, as well as methods and kits using the same.

Abstract: Presented herein are transposase enzymes and reaction conditions for improved fragmentation and tagging of nucleic acid samples, in particular altered transposases and reaction conditions which exhibit improved insertion sequence bias, as well as methods and kits using the same.