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: Genomes of different species may be embodied as a graph in which conserved parts of multiple genomes are stored at a fixed location in memory and accessed via spatial addressing. The graph branches into plural paths, each defined by pointers to other fixed locations in the memory, where the genomes diverge due to either divergent homology or non-homologous portions. The graph can represent whole genomic information for multiple species with the natural relationships among parts of the genomes being represented by the structure of the graph. Newly obtained sequences such as output from NGS instruments can be mapped onto the graph for assembly or identification.

Abstract: The invention provides methods of analyzing an individual's mtDNA by transforming available reference sequences into a directed graph that compactly represents all the information without duplication and comparing sequence reads from the mtDNA to the graph to identify the individual or describe their mtDNA. A directed graph can represent all of the genetic variation found among the mitochondrial genomes across all of a number of reference organisms while providing a single article to which sequence reads can be aligned or compared. Thus any sequence read or other sequence fragment can be compared, in a single operation, to the article that represents all of the reference mitochondrial sequences.

Abstract: The invention provides systems and methods for analyzing viruses by representing viral genetic diversity with a directed acyclic graph (DAG), which allows genetic sequencing technology to detect rare variations and represent otherwise difficult-to-document diversity within a sample. Additionally, a host-specific sequence DAG can be used to effectively segregate viral nucleic acid sequence reads from host sequence reads when a sample from a host is subject to sequencing. Known viral genomes can be represented using a viral reference DAG and the viral sequence reads from the sample can be compared to viral DAG to identify viral species or strains from which the reads were derived. Where the viral sequence reads indicate great genetic diversity in the virus that was infecting the host, those reads can be assembled into a DAG that itself properly represents that diversity.

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 methods for identifying a microorganism by aligning sequence reads to a graph, such as a directed acyclic graph (DAG), that contains condensed sequence information of a conserved region from multiple known microorganisms. The DAG can be constructed by obtaining sequence information of known reference microorganisms. The DAG also includes the identities of the known microorganisms that correspond to particular paths. Sequence reads obtained from an unknown sample can thus be aligned to paths in the DAG using an alignment algorithm, and the identity of a microorganism in the sample can be determined based on which path in the DAG to which the sequence reads align best.