Abstract: Provided may be a computer-implemented method for estimating a tumor fraction in a patient sample, comprising the steps of obtaining a catalog of tumor specific variants and whole genome sequencing data from the patient sample. Further, the method may comprise aligning reads to a reference genome; determining a measure of the signal supporting the presence, in the patient sample read alignment file, of variants in the catalog of tumor specific variants; and determining a measure of the noise associated with variants similar to variants in the catalog of tumor specific variants in the patient sample read alignment file. The method may comprise estimating, over iterations, k, the fraction of tumor (eTF) DNA in the patient sample given the measure of the signal and the measure of the noise at all tumor specific positions; and generating a final eTF and a list of somatic variants in the patient sample.

Abstract: The simplification of neural network models is described. For example, a method for simplifying a neural network model includes providing the neural network model to be simplified, defining a first temporal filter for the conveyance of input from a neuron to an other spatially-extended neuron along the arborized projection, defining a second temporal filter for the conveyance of input from yet another neuron to the spatially-extended neuron along the arborized projection, replacing, in the neural network model, the first, spatially-extended neuron with a first, spatially-constrained neuron and the arborized projection with a first connection extending between the first, spatially-constrained neuron and the second neuron, wherein the first connection filters input from the second neuron in accordance with the first temporal filter and a second connection extending between the first spatially-constrained neuron and the third neuron.

Abstract: The simplification of neural network models is described. For example, a method for simplifying a neural network model includes providing the neural network model to be simplified, defining a first temporal filter for the conveyance of input from a neuron to an other spatially-extended neuron along the arborized projection, defining a second temporal filter for the conveyance of input from yet another neuron to the spatially-extended neuron along the arborized projection, replacing, in the neural network model, the first, spatially-extended neuron with a first, spatially-constrained neuron and the arborized projection with a first connection extending between the first, spatially-constrained neuron and the second neuron, wherein the first connection filters input from the second neuron in accordance with the first temporal filter and a second connection extending between the first spatially-constrained neuron and the third neuron.

Abstract: A genomic data analyzer may be configured to detect and characterize, with a variant analysis module, biallelic genomic alterations for at least one gene in next generation sequencing variant calling information for patient tumor samples characterized by different purity ratios of somatic genomic material. The variant analysis module may compare the observed variant fraction distributions of putative heterozygous germline mutations to the theoretical distributions corresponding to different chromosomal aberration events to detect a combination of genomic alteration events possibly causing the biallelic loss of function of the gene.

Abstract: A genomic data analyzer maybe configured to detect and characterize biallelic genomic alterations for at least one gene in next generation sequencing variant calling information for patient tumor samples characterized by different purity ratios of somatic genomic material. The variant analysis module may compare the observed variant fraction distributions of putative heterozygous germline mutations to the theoretical distributions corresponding to different chromosomal aberration events to detect a combination of genomic alteration events. The variant analysis module maybe used in next-generation-sequencing oncogenomics testing to identify biallelic loss of function on tumor suppressor genes to facilitate the biological understanding and choice of a personalized oncology treatment targeting the analyzed patient tumor solely from next generation sequencing data variant information, without requiring complementary germline analysis or biological assays.

Abstract: Methods are disclosed for adding adapters to fragmented nucleic acids for next generation sequencing, including providing numerical codes based on variable adapter molecular barcode lengths on both sides of the fragmented nucleic acids and identifying reads from the same fragment based on both barcodes. The methods and products allow for the amplification of the fragmented nucleic acids when there is a low yield of isolated fragmented nucleic acids and also for efficient and reliable detection of low-frequency mutations including in subpopulations of cells within a subject.

Abstract: A genomic data analyzer may be configured to detect and characterize, with a machine learning model such as a trained convolutional neural network, the presence of a genomic instability in a tumor sample. The genomic data analyzer may use whole genome sequencing reads as input data even at low sequencing coverage in a high throughput sequencing workflow as may be routinely employed in a diversity of clinical oncology setups. The genomic data analyzer may arrange the aligned read data coverage from chromosome arms or full chromosomes to form a coverage data signal array possibly as an image. The trained machine learning model may process the coverage data signal array to determine whether a chromosomal spatial instability (CSI) such as for instance a genomic instability caused by a homologous repair or recombination deficiency (HRD) is present in the tumor sample. The latter indication may guide the choice of a preferred anticancer treatment for the tumor.

Abstract: The simplification of neural network models is described. For example, a method for simplifying a neural network model includes providing the neural network model to be simplified, defining a first temporal filter for the conveyance of input from a neuron to an other spatially-extended neuron along the arborized projection, defining a second temporal filter for the conveyance of input from yet another neuron to the spatially-extended neuron along the arborized projection, replacing, in the neural network model, the first, spatially-extended neuron with a first, spatially-constrained neuron and the arborized projection with a first connection extending between the first, spatially-constrained neuron and the second neuron, wherein the first connection filters input from the second neuron in accordance with the first temporal filter and a second connection extending between the first spatially-constrained neuron and the third neuron.

Abstract: The simplification of neural network models is described. For example, a method for simplifying a neural network model includes providing the neural network model to be simplified, defining a first temporal filter for the conveyance of input from a neuron to an other spatially-extended neuron along the arborized projection, defining a second temporal filter for the conveyance of input from yet another neuron to the spatially-extended neuron along the arborized projection, replacing, in the neural network model, the first, spatially-extended neuron with a first, spatially-constrained neuron and the arborized projection with a first connection extending between the first, spatially-constrained neuron and the second neuron, wherein the first connection filters input from the second neuron in accordance with the first temporal filter and a second connection extending between the first spatially-constrained neuron and the third neuron.

Abstract: A genomic data analyzer may process the next generation sequencing data of a patient sample to identify whether a variant is present (positive variant calling), absent at a high confidence (negative variant calling), or equivocal (possible false negative calling) as falling under a calculated limit of detection (LOD). This LOD estimate corresponds the lowest variant allele fraction (VAF) detectable at the required sensitivity (true positive rate). The presently disclosed genomic data analyzer may improve any legacy variant caller by automatically calculating the limitations of variant calling detection for a user-defined sensitivity and minimal VAF of interest for any variant genomic position and/or mutation, depending on analytical factors of the NGS assay and workflow such as the sample type, the DNA sample amount and the NGS assay library conversion rate (LCR), and/or its molecular barcoding capability, as well as its NGS assay error profile.

Abstract: A genomic data analyzer may be configured to detect and characterize, with a machine learning model such as a trained convolutional neural network, the presence of a genomic instability in a tumor sample. The genomic data analyzer may use whole genome sequencing reads as input data even at low sequencing coverage in a high throughput sequencing workflow as may be routinely employed in a diversity of clinical oncology setups. The genomic data analyzer may arrange the aligned read data coverage from chromosome arms or full chromosomes to form a coverage data signal array possibly as an image. The trained machine learning model may process the coverage data signal array to determine whether a chromosomal spatial instability (CSI) such as for instance a genomic instability caused by a homologous repair or recombination deficiency (HRD) is present in the tumor sample. The latter indication may guide the choice of a preferred anticancer treatment for the tumor.

Abstract: A genomic data analyzer may be configured to detect and characterize, with a machine learning model such as a trained convolutional neural network, the presence of a genomic instability in a tumor sample. The genomic data analyzer may use whole genome sequencing reads as input data even at low sequencing coverage in a high throughput sequencing workflow as may be routinely employed in a diversity of clinical oncology setups. The genomic data analyzer may arrange the aligned read data coverage from chromosome arms or full chromosomes to form a coverage data signal array possibly as an image. The trained machine learning model may process the coverage data signal array to determine whether a chromosomal spatial instability (CSI) such as for instance a genomic instability caused by a homologous repair or recombination deficiency (HRD) is present in the tumor sample. The latter indication may guide the choice of a preferred anticancer treatment for the tumor.

Abstract: A genomic data analyzer maybe configured to detect and characterize, with a variant analysis module, biallelic genomic alterations for at least one gene in next generation sequencing variant calling information for patient tumor samples characterized by different purity ratios of somatic genomic material. The variant analysis module may compare the observed variant fraction distributions of putative heterozygous germline mutations to the theoretical distributions corresponding to different chromosomal aberration events to detect a combination of genomic alteration events possibly causing the biallelic loss of function of the gene.

Abstract: The simplification of neural network models is described. For example, a method for simplifying a neural network model includes providing the neural network model to be simplified, defining a first temporal filter for the conveyance of input from a neuron to an other spatially-extended neuron along the arborized projection, defining a second temporal filter for the conveyance of input from yet another neuron to the spatially-extended neuron along the arborized projection, replacing, in the neural network model, the first, spatially-extended neuron with a first, spatially-constrained neuron and the arborized projection with a first connection extending between the first, spatially-constrained neuron and the second neuron, wherein the first connection filters input from the second neuron in accordance with the first temporal filter and a second connection extending between the first spatially-constrained neuron and the third neuron.