Abstract: Systems and methods for analyzing genomic information can include obtaining a sequence read including genetic information; identifying, within a graph representing a reference genome, a plurality of candidate mapping positions that relate to the genetic information, the graph comprising nodes representing genetic sequences and edges connecting pairs of nodes; determining, by means of a computer system, whether an alignment with the graph surrounding each of the plurality of candidate mapping positions is advanced or basic; and performing for each candidate mapping position, by means of the computer system, a local alignment based on whether the local alignment is advanced or basic. The advanced local alignment can include a first-local-alignment algorithm, and the basic local alignment includes a second-local-alignment algorithm. Based on the local alignments, the mapped position of the sequence read can be identified within the genome.

Abstract: The invention provides systems and methods for determining patterns of modification to a genome of a subject by representing the genome using a graph, such as a directed acyclic graph (DAG) with divergent paths for regions that are potentially subject to modification, profiling segments of the genome for evidence of epigenetic modification, and aligning the profiled segments to the DAG to determine locations and patterns of the epigenetic modification within the genome.

Abstract: Systems and methods for analyzing genomic information can include obtaining a sequence read including genetic information; identifying, within a graph representing a reference genome, a plurality of candidate mapping positions that relate to the genetic information, the graph comprising nodes representing genetic sequences and edges connecting pairs of nodes; determining, by means of a computer system, whether an alignment with the graph surrounding each of the plurality of candidate mapping positions is advanced or basic; and performing for each candidate mapping position, by means of the computer system, a local alignment based on whether the local alignment is advanced or basic. The advanced local alignment can include a first-local-alignment algorithm, and the basic local alignment includes a second-local-alignment algorithm. Based on the local alignments, the mapped position of the sequence read can be identified within the genome.

Abstract: The invention provides oncogenomic methods for detecting tumors by identifying circulating tumor DNA. A patient-specific reference directed acyclic graph (DAG) represents known human genomic sequences and non-tumor DNA from the patient as well as known tumor-associated mutations. Sequence reads from cell-free plasma DNA from the patient are mapped to the patient-specific genomic reference graph. Any of the known tumor-associated mutations found in the reads and any de novo mutations found in the reads are reported as the patient’s tumor mutation burden.

Abstract: The invention provides systems and methods for determining patterns of modification to a genome of a subject by representing the genome using a graph, such as a directed acyclic graph (DAG) with divergent paths for regions that are potentially subject to modification, profiling segments of the genome for evidence of epigenetic modification, and aligning the profiled segments to the DAG to determine locations and patterns of the epigenetic modification within the genome.

Abstract: The invention provides oncogenomic methods for detecting tumors by identifying circulating tumor DNA. A patient-specific reference directed acyclic graph (DAG) represents known human genomic sequences and non-tumor DNA from the patient as well as known tumor-associated mutations. Sequence reads from cell-free plasma DNA from the patient are mapped to the patient-specific genomic reference graph. Any of the known tumor-associated mutations found in the reads and any de novo mutations found in the reads are reported as the patient's tumor mutation burden.

Abstract: Techniques for detecting copy number variations (CNVs) in a genetic sequence, diagnosing disorders caused by CNVs, and treating disorders caused by CNVs are presented. The techniques include using a processor to perform steps of: scanning the genetic sequence to identify genetic regions corresponding to at least one autosomal chromosome, dividing the genetic sequence into bins, calculating a CNV status for each bin of the plurality of bins, and filtering the CNV statuses to identify at least one CNV in the genetic sequence.

Abstract: Various embodiments of the disclosure relate to systems and methods for aligning a sequence read to a graph reference. In one embodiment, the method comprises selecting a first node from a graph reference, the graph reference comprising a plurality of nodes connected by a plurality of directed edges, at least one node of the plurality of nodes having a nucleotide sequence. The method further comprises traversing the graph reference according to a depth-first search, and comparing a sequence read to nucleotide sequences generated from the traversal of the graph reference. The traversal of the graph is then modified in response to a determination that each and every node associated with a given nucleotide sequence was previously evaluated.

Abstract: The invention provides systems and methods for determining patterns of modification to a genome of a subject by representing the genome using a graph, such as a directed acyclic graph (DAG) with divergent paths for regions that are potentially subject to modification, profiling segments of the genome for evidence of epigenetic modification, and aligning the profiled segments to the DAG to determine locations and patterns of the epigenetic modification within the genome.

Abstract: The invention provides systems and methods for determining patterns of modification to a genome of a subject by representing the genome using a graph, such as a directed acyclic graph (DAG) with divergent paths for regions that are potentially subject to modification, profiling segments of the genome for evidence of epigenetic modification, and aligning the profiled segments to the DAG to determine locations and patterns of the epigenetic modification within the genome.

Abstract: The invention provides oncogenomic methods for detecting tumors by identifying circulating tumor DNA. A patient-specific reference directed acyclic graph (DAG) represents known human genomic sequences and non-tumor DNA from the patient as well as known tumor-associated mutations. Sequence reads from cell-free plasma DNA from the patient are mapped to the patient-specific genomic reference graph. Any of the known tumor-associated mutations found in the reads and any de novo mutations found in the reads are reported as the patient's tumor mutation burden.

Abstract: Various embodiments of the disclosure relate to systems and methods for aligning a sequence read to a graph reference. In one embodiment, the method comprises selecting a first node from a graph reference, the graph reference comprising a plurality of nodes connected by a plurality of directed edges, at least one node of the plurality of nodes having a nucleotide sequence. The method further comprises traversing the graph reference according to a depth-first search, and comparing a sequence read to nucleotide sequences generated from the traversal of the graph reference. The traversal of the graph is then modified in response to a determination that each and every node associated with a given nucleotide sequence was previously evaluated.

Abstract: Systems and methods for analyzing genomic information can include obtaining a sequence read including genetic information; identifying, within a graph representing a reference genome, a plurality of candidate mapping positions that relate to the genetic information, the graph comprising nodes representing genetic sequences and edges connecting pairs of nodes; determining, by means of a computer system, whether an alignment with the graph surrounding each of the plurality of candidate mapping positions is advanced or basic; and performing for each candidate mapping position, by means of the computer system, a local alignment based on whether the local alignment is advanced or basic. The advanced local alignment can include a first-local-alignment algorithm, and the basic local alignment includes a second-local-alignment algorithm. Based on the local alignments, the mapped position of the sequence read can be identified within the genome.

Abstract: The invention provides oncogenomic methods for detecting tumors by identifying circulating tumor DNA. A patient-specific reference directed acyclic graph (DAG) represents known human genomic sequences and non-tumor DNA from the patient as well as known tumor-associated mutations. Sequence reads from cell-free plasma DNA from the patient are mapped to the patient-specific genomic reference graph. Any of the known tumor-associated mutations found in the reads and any de novo mutations found in the reads are reported as the patient's tumor mutation burden.

Abstract: Various embodiments of the disclosure relate to systems and methods for aligning a sequence read to a graph reference. In one embodiment, the method comprises selecting a first node from a graph reference, the graph reference comprising a plurality of nodes connected by a plurality of directed edges, at least one node of the plurality of nodes having a nucleotide sequence. The method further comprises traversing the graph reference according to a depth-first search, and comparing a sequence read to nucleotide sequences generated from the traversal of the graph reference. The traversal of the graph is then modified in response to a determination that each and every node associated with a given nucleotide sequence was previously evaluated.

Abstract: Techniques for generating a personalized reference sequence construct for an individual to align sequence reads obtained for the individual. The techniques include: obtaining a plurality of sequence reads for an individual; obtaining information identifying a plurality of locations; genotyping the plurality of sequence reads for the plurality of locations to obtain a first set of variants for the individual for at least some of the plurality of locations; identifying a second set of variants associated with the first set of variants; generating a personalized reference sequence construct using the second set of variants; and aligning the plurality of sequence reads to the personalized reference sequence construct.

Abstract: Various embodiments of the disclosure relate to systems and methods for aligning a sequence read to a graph reference. In one embodiment, the method comprises selecting a first node from a graph reference, the graph reference comprising a plurality of nodes connected by a plurality of directed edges, at least one node of the plurality of nodes having a nucleotide sequence. The method further comprises traversing the graph reference according to a depth-first search, and comparing a sequence read to nucleotide sequences generated from the traversal of the graph reference. The traversal of the graph is then modified in response to a determination that each and every node associated with a given nucleotide sequence was previously evaluated.

Abstract: The invention provides oncogenomic methods for detecting tumors by identifying circulating tumor DNA. A patient-specific reference directed acyclic graph (DAG) represents known human genomic sequences and non-tumor DNA from the patient as well as known tumor-associated mutations. Sequence reads from cell-free plasma DNA from the patient are mapped to the patient-specific genomic reference graph. Any of the known tumor-associated mutations found in the reads and any de novo mutations found in the reads are reported as the patient's tumor mutation burden.

Abstract: Systems and methods for analyzing genomic information can include obtaining a sequence read including genetic information; identifying, within a graph representing a reference genome, a plurality of candidate mapping positions that relate to the genetic information, the graph comprising nodes representing genetic sequences and edges connecting pairs of nodes; determining, by means of a computer system, whether an alignment with the graph surrounding each of the plurality of candidate mapping positions is advanced or basic; and performing for each candidate mapping position, by means of the computer system, a local alignment based on whether the local alignment is advanced or basic. The advanced local alignment can include a first-local-alignment algorithm, and the basic local alignment includes a second-local-alignment algorithm. Based on the local alignments, the mapped position of the sequence read can be identified within the genome.

Abstract: The invention provides systems and methods for determining patterns of modification to a genome of a subject by representing the genome using a graph, such as a directed acyclic graph (DAG) with divergent paths for regions that are potentially subject to modification, profiling segments of the genome for evidence of epigenetic modification, and aligning the profiled segments to the DAG to determine locations and patterns of the epigenetic modification within the genome.