Seven Bridges Genomics, Inc.

Wan-Ping Lee

Devin Locke

Alyssa Dayan

Kaushik Ghose

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.

Systems and methods for epigenetic analysis

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.

Systems and methods for adaptive local alignment for graph genomes

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.

Systems and methods for analyzing circulating tumor DNA

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.

Growing community of inventors

Somerville, MA, United States of America

Wan-Ping Lee