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: Genomic data is written to disk in a compact format by dividing the data into segments and encoding each segment with the smallest number of bits per character necessary for whatever alphabet of characters appears in that segment. A computer system dynamically chooses the segment boundaries for maximum space savings. A first one of the segments may use a different number of bits per character than a second one of the segments. In one embodiment, dividing the data into segments comprises scanning the data and keeping track of a number of unique characters, noting positions in the sequence where the number increases to a power of two, calculating a compression that would be obtained by dividing the genomic data into one of the plurality of segments at ones of the noted positions, and dividing the genomic data into the plurality of segments at the positions that yield the best compression.

Abstract: The invention provides methods for identifying rare variants near a structural variation in a genetic sequence, for example, in a nucleic acid sample taken from a subject. The invention additionally includes methods for aligning reads (e.g., nucleic acid reads) to a reference sequence construct accounting for the structural variation, methods for building a reference sequence construct accounting for the structural variation or the structural variation and the rare variant, and systems that use the alignment methods to identify rare variants. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long, or longer.

Abstract: In one embodiment, a method of processing a computational workflow comprises receiving a description of a computational workflow. The description comprises a plurality of steps, in which each step has at least one input and at least one output, and further wherein an input from a second step depends on an output from a first step. The description is translated into a static workflow graph stored in a memory, the static workflow graph comprising a plurality of nodes having input ports and output ports, wherein dependencies between inputs and outputs are specified as edges between input ports and output ports. Information about a first set of nodes is then extracted from the static workflow graph and placed into a dynamic graph. A first actionable job is identified from the dynamic graph and executed.

Abstract: The invention includes methods for aligning reads (e.g., nucleic acid reads, amino acid reads) to a reference sequence construct, methods for building the reference sequence construct, and systems that use the alignment methods and constructs to produce sequences. The method is scalable, and can be used to align millions of reads to a construct thousands of bases or amino acids long. The invention additionally includes methods for identifying a disease or a genotype based upon alignment of nucleic acid reads to a location in the construct.

Abstract: Techniques for identifying variations in sequence data relative to reference sequence data. The techniques include accessing information specifying multiple sets of variants in the sequence data relative to reference sequence data, each of the multiple sets of variants being generated by using a respective variant identification technique; and determining, using the information specifying the multiple sets of variants in the sequence data, a reconciled set of variants in the sequence data relative to the reference sequence data, the determining comprising: determining whether a first variant is present at a first position in the sequence data based, at least in part, on one or more variants at one or more other positions in the sequence data.

Abstract: The invention provides methods for comparing one set of genetic sequences to another without discarding any information within either set. A set of genetic sequences is represented using a directed acyclic graph (DAG) avoiding any unwarranted reduction to a linear data structure. The invention provides a way to align one sequence DAG to another to produce an alignment that can itself be stored as a DAG. DAG-to-DAG alignment is a natural choice wherever a set of genomic information consisting of more than one string needs to be compared to any non-linear reference. For example, a subpopulation DAG could be compared to a population DAG in order to compare the genetic features of that subpopulation to those of the population.

Abstract: A tool in a bioinformatics pipeline can include a smart wrapper and an executable. The smart wrapper can cause the executable to analyze the sequence data it receives and can also selectively change to the pipeline when circumstances warrant. In certain aspects, a system for genomic analysis includes a processor coupled to a non-transitory memory. The system is operable to present to a user a plurality of genomic tools organized into a pipeline. At least a first one of the tools comprises an executable and a wrapper script. The system can receive instructions from the user and sequence data—instructions that call for the sequence data to be analyzed by the pipeline—and select, using the wrapper script, a change to the pipeline.

Abstract: The invention provides methods for identifying rare variants near a structural variation in a genetic sequence, for example, in a nucleic acid sample taken from a subject. The invention additionally includes methods for aligning reads (e.g., nucleic acid reads) to a reference sequence construct accounting for the structural variation, methods for building a reference sequence construct accounting for the structural variation or the structural variation and the rare variant, and systems that use the alignment methods to identify rare variants. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long, or longer.

Abstract: The invention provides methods for identifying rare variants near a structural variation in a genetic sequence, for example, in a nucleic acid sample taken from a subject. The invention additionally includes methods for aligning reads (e.g., nucleic acid reads) to a reference sequence construct accounting for the structural variation, methods for building a reference sequence construct accounting for the structural variation or the structural variation and the rare variant, and systems that use the alignment methods to identify rare variants. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long, or longer.

Abstract: The invention provides methods for comparing one set of genetic sequences to another without discarding any information within either set. A set of genetic sequences is represented using a directed acyclic graph (DAG) avoiding any unwarranted reduction to a linear data structure. The invention provides a way to align one sequence DAG to another to produce an alignment that can itself be stored as a DAG. DAG-to-DAG alignment is a natural choice wherever a set of genomic information consisting of more than one string needs to be compared to any non-linear reference. For example, a subpopulation DAG could be compared to a population DAG in order to compare the genetic features of that subpopulation to those of the population.

Abstract: Methods of analyzing a transcriptome that involves obtaining at least one pair of paired-end reads from a transcriptome from an organism, finding an alignment with an optimal score between a first read of the pair and a node in a directed acyclic data structure (the data structure has nodes representing RNA sequences such as exons or transcripts and edges connecting pairs of nodes), identifying candidate paths that include the node connected to a downstream node by a path having a length substantially similar to an insert length of the pair of paired-end reads, and aligning the paired-end rends to the candidate paths to determine an optimal-scoring alignment.

Abstract: The invention generally provides systems and methods for analysis of RNA-Seq reads in which an annotated reference is represented as a directed acyclic graph (DAG) or similar data structure. Features such as exons and introns from the reference provide nodes in the DAG and those features are linked as pairs in their canonical genomic order by edges. The DAG can scale to any size and can in fact be populated in the first instance by import from an extrinsic annotated reference.

Abstract: The invention generally provides systems and methods for analysis of RNA-Seq reads in which an annotated reference is represented as a directed acyclic graph (DAG) or similar data structure. Features such as exons and introns from the reference provide nodes in the DAG and those features are linked as pairs in their canonical genomic order by edges. The DAG can scale to any size and can in fact be populated in the first instance by import from an extrinsic annotated reference.

Abstract: Methods of analyzing a transcriptome that involves obtaining at least one pair of paired-end reads from a transcriptome from an organism, finding an alignment with an optimal score between a first read of the pair and a node in a directed acyclic data structure (the data structure has nodes representing RNA sequences such as exons or transcripts and edges connecting pairs of nodes), identifying candidate paths that include the node connected to a downstream node by a path having a length substantially similar to an insert length of the pair of paired-end reads, and aligning the paired-end rends to the candidate paths to determine an optimal-scoring alignment.

Abstract: The invention generally relates to tools for genomic analysis and particularly to a pipeline editor that can turn pipelines into standalone tools for use in other pipelines. The invention provides systems and methods for genomic analysis in which individual analytical tools can be arranged into analytical pipelines that can then be “collapsed” into standalone tools, which themselves can be put into the pool of individual tools for use in further building of pipelines. Aspects of the invention provide a system that includes a server computer system operable to present to a user a plurality of genomic tools, receive input from the user arranging the tools into a pipeline, create a new tool that includes the pipeline, and offer the new tool along with the plurality of genomic tools.

Abstract: The invention includes methods for aligning reads (e.g., nucleic acid reads, amino acid reads) to a reference sequence construct, methods for building the reference sequence construct, and systems that use the alignment methods and constructs to produce sequences. The method is scalable, and can be used to align millions of reads to a construct thousands of bases or amino acids long. The invention additionally includes methods for identifying a disease or a genotype based upon alignment of nucleic acid reads to a location in the construct.

Abstract: The invention provides methods for identifying rare variants near a structural variation in a genetic sequence, for example, in a nucleic acid sample taken from a subject. The invention additionally includes methods for aligning reads (e.g., nucleic acid reads) to a reference sequence construct accounting for the structural variation, methods for building a reference sequence construct accounting for the structural variation or the structural variation and the rare variant, and systems that use the alignment methods to identify rare variants. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long, or longer.