Abstract: The present disclosure relates to systems, non-transitory computer-readable media, and methods for generating a target-variant-reference panel comprising a target-variant position with target-variant indicators or using the target-variant-reference panel to impute a genotype call for the corresponding target variant. In particular, in one or more embodiments, the disclosed systems generate an initial reference panel including a variety of phased genomic samples of different haplotypes. The disclosed systems further add a target-variant position to the initial reference panel to indicate a presence or absence of a target variant, thereby creating a target-variant-reference panel comprising a target-variant position with target-variant indicators.

Abstract: Disclosed herein include systems, devices, and methods for calling overlapping copy number variants (CNVs) of a gene. The gene can comprise a plurality of regions. The gene can have a plurality of CNVs. Two alleles of the gene of a subject can be determined based on a number of copies of each region of the plurality of regions and all CNVs of the plurality of CNVs of the gene comprising the region.

Abstract: Disclosed herein include systems, devices, and methods for determining the total copy number of kringle IV type 2 (KIV-2) domain of LPA gene, and/or the copy number of KIV-2 domain of each allele of LPA gene, a subject from sequence reads (e.g., short reads) generated from a sample obtained from the subject.

Abstract: Disclosed herein include systems, devices, and methods for determining repeat expansion status (e.g., pathogenic, carrier, and benign) of a locus of a gene of interest (e.g., at, or at about, chr4:39348424 of hg38 for RFC1). After aligning sequence reads to a sequence graph, the number of occurrences of repeat sequences satisfying predetermined criteria and the frequency of a pathogenic repeat sequence can be determined, which are in turn used to determine a repeat expansion status.

Abstract: The present disclosure relates to systems, non-transitory computer-readable media, and methods for generating a graph reference genome customized for a particular sample genome and utilizing the customized graph reference genome to determine final nucleotide-base calls for the sample genome. To illustrate, the disclosed systems can generate a customized graph reference genome including various paths representing imputed haplotypes corresponding to a particular genomic region. Additionally, or alternatively, the disclosed system can determine and compare direct and imputed nucleotide-base calls for a sample genome as a basis for generating final nucleotide-base calls. In some such cases, the disclosed system weights (and selects between) direct nucleotide-base calls and imputed nucleotide-base calls for genomic coordinates based on sequencing metrics corresponding to the direct nucleotide-base calls or based on the variability of the genomic regions comprising the genomic coordinates.

Abstract: Disclosed herein include systems, devices, and methods for identifying recombinant variants (e.g., gene conversion variants) of genes such as GBA gene and CYP21A2 gene, the copy numbers of recombinant variants, and gene variant status (e.g., carrier, compound heterozygous, or homozygous).

Abstract: Disclosed herein include systems, devices, and methods for determining a variable number tandem repeat (VNTR) status. Haplotypes of a VNTR can be determined using long sequence reads of reference samples aligned to the VNTR in a reference. Short reads of a test sample of a test subject can be aligned to the haplotypes determined using the long sequence reads to determine a VNTR status (e.g., one or more haplotypes or a genotype of the test subject) of the test subject based on the probability indications of the haplotypes.

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for genotyping and visualizing repeat sequences such as medically significant short tandem repeats (STRs). Some implementations can be used to genotype and visualize repeat sequences each including two or more repeat sub-sequences. Some implementations provides a computer tool to generate sequence read pileups for visualizing repeat sequences for samples that have different genotypes of the repeat sequence, each sequence pileup including reads aligned to two or more different haplotypes.

Abstract: Disclosed herein include systems, devices, computer readable media, and methods for paralog genotyping, such as determining a copy number of survival of motor neuron 1 gene and genotyping cytochrome P450 family 2 subfamily D member 6 gene using a Gaussian mixture model comprising a plurality of Gaussians each representing a different integer copy number.

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for determining the presence or absence of repeat expansions of interest, including repeat expansions of repeat sequences that are medically significant. Some embodiments provide methods for identifying and calling medically relevant repeat expansions using anchored reads. An anchored read is a paired end read that is unaligned to a repeat sequence under consideration, but it is paired with an anchor read that is aligned to or near the repeat sequence. Some embodiments use both anchor and anchored reads to determine the presence or absence of the repeat expansions. System, apparatus, and computer program products are also provided for determining repeat expansion implementing the methods disclosed.

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for genotyping repeat sequences such as medically significant short tandem repeats (STRs). The methods involve aligning reads to a repeat sequence represented by a sequence graph, and using the aligned reads to genotype the repeat sequence. The sequence graph is a directed graph each including at least one self-loop representing a repeat sub-sequence. In some implementations, the reads are paired end reads, and both mates of each read pair may be used to genotype the repeat sequences. Some implementations can be used to determine degenerate codon repeats. Some implementations can be used to genotype repeat sequences each including two or more repeat sub-sequences. Some implementations can be used to genotype nucleic acid sequences each including at least one repeat sub-sequence and another genetic variant such as an insertion, deletion, or substitution.

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for determining the presence or absence of repeat expansions of interest, including repeat expansions of repeat sequences that are medically significant. Some embodiments provide methods for identifying and calling medically relevant repeat expansions using anchored reads. An anchored read is a paired end read that is unaligned to a repeat sequence under consideration, but it is paired with an anchor read that is aligned to or near the repeat sequence. Some embodiments use both anchor and anchored reads to determine the presence or absence of the repeat expansions. System, apparatus, and computer program products are also provided for determining repeat expansion implementing the methods disclosed.

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for determining the presence or absence of repeat expansions of interest, including repeat expansions of repeat sequences that are medically significant. Some embodiments provide methods for identifying and calling medically relevant repeat expansions using anchored reads. An anchored read is a paired end read that is unaligned to a repeat sequence under consideration, but it is paired with an anchor read that is aligned to or near the repeat sequence. Some embodiments use both anchor and anchored reads to determine the presence or absence of the repeat expansions. System, apparatus, and computer program products are also provided for determining repeat expansion implementing the methods disclosed.

Abstract: The present disclosure provides methods and systems for determining the presence or absence of aneuploidy in a fetus. In particular, the present disclosure provides noninvasive methods and systems for detecting the presence of fetal trisomy and other fetal chromosomal anomalies, paternity of a fetus and fetal genotype.