Systems and methods for genetic analysis

Abstract

The invention relates to using a graph database in genetic analyses to link mutation data to extrinsic data. Entities such as mutations, patients, samples, alleles, and clinical information are individually represented and stored as nodes and relationships between entities are also individually represented and stored. Each node and relationship can be stored using a fixed-size record and nodes can be flexibly invoked to represent any entity without disrupting the existing data. Systems and methods of the invention may be used for obtaining data representing a mutation in an individual and using a node in a graph database to store a description of the mutation. The node has stored within it a pointer to an adjacent node that provides information about a clinical significance of the variant. The graph database can be queried to provide a report of the clinical significance of the mutation.

What is claimed is: 
     
         1 . A system for describing genetic information, the system comprising:
 at least one computer comprising memory coupled to a processor, the system having at least a portion of a graph database stored therein, wherein the system is operable to:
 obtain data representing a mutation in a genome of an individual; 
 use a node in the graph database to store a description of the mutation; 
 store, in the node, a pointer to an adjacent node that provides information about a clinical significance of the mutation; and 
 query the graph database to provide a report of the clinical significance of the mutation in the genome of the individual. 
   
     
     
         2 . The system of  claim 1 , wherein the system is operable to obtain the data representing the mutation by receiving at least one sequence read file that includes the data. 
     
     
         3 . The system of  claim 2 , further operable to represent, in the graph database, a biological sample from the individual using a sample node and connect the sample node via a pointer to a read file node representing the sequence read file. 
     
     
         4 . The system of  claim 1 , wherein the data representing the mutation is obtained as part of a file. 
     
     
         5 . The system of  claim 4 , wherein the file has a format selected from the group consisting of variant call format; sequence alignment map; binary alignment map; FASTA; and FASTQ. 
     
     
         6 . The system of  claim 4 , operable to represent the file as a file node in the graph database and store, in the variant node, a pointer to the file node. 
     
     
         7 . The system of  claim 6 , further operable to represent, in the graph database, a biological sample from the individual using a sample node and connect the sample node via a pointer to a read file node representing the sequence read file. 
     
     
         8 . The system of  claim 1 , wherein the data representing the mutation comprises a description of the mutation as a variant of a reference human genome. 
     
     
         9 . The system of  claim 8 , wherein the description of the mutation is obtained from a VCF record in a VCF file. 
     
     
         10 . The system of  claim 9 , further operable to represent, in the graph database, a biological sample from the individual using a sample node and connect the sample node via a pointer to a read file node representing the sequence read file. 
     
     
         11 . The system of  claim 1 , further operable to:
 obtain sequencing data representing a plurality of mutations in the genome of the individual, the plurality of mutations being represented as variant calls relative to a human genome reference;   use, for each of the plurality of mutations, a corresponding variant node in the graph database to store a description of that mutation; and   link the individual to an allele node based on the plurality of mutations.   
     
     
         12 . The system of  claim 11 , wherein the graph database comprises:
 nodes representing people, nodes representing genomic variants relative to a reference, and nodes representing literature reports on medical relevance of the genomic variants; and   edges defining relationships between pairs of the nodes.   
     
     
         13 . The system of  claim 12 , further operable to represent, in the graph database, a biological sample from the individual using a sample node and connect the sample node via a pointer to a read file node representing the sequence read file. 
     
     
         14 . The system of  claim 1 , wherein the graph database comprises:
 nodes representing people, nodes representing genomic variants relative to a reference, and nodes representing literature reports on medical relevance of the genomic variants; and   edges defining relationships between pairs of the nodes.   
     
     
         15 . The system of  claim 14 , further operable to represent, in the graph database, a biological sample from the individual using a sample node and connect the sample node via a pointer to a read file node representing the sequence read file. 
     
     
         16 . A method for analyzing mutations, the method comprising:
 obtaining data representing a mutation in a genome of an individual;   using a node in a graph database to store a description of the mutation;   storing, in the node, a pointer to an adjacent node that provides information about a clinical significance of the mutation; and   querying the graph database to provide a report of the clinical significance of the mutation in the genome of the individual.   
     
     
         17 . The method of  claim 16 , wherein obtaining the data representing the mutation comprises
 obtaining a sample that includes a nucleic acid from the individual; and   sequencing the nucleic acid to obtain a sequence read file that includes the data.   
     
     
         18 . The method of  claim 17 , further comprising representing the sample in the graph database using a sample node and connecting the sample node via a pointer to a read file node representing the sequence read file and metadata associated with the data. 
     
     
         19 . The method of  claim 16 , wherein the data representing a mutation is obtained as part of a file. 
     
     
         20 . The method of  claim 19 , wherein the file has a format selected from the group consisting of variant call format; sequence alignment map; binary alignment map; FASTA; and FASTQ. 
     
     
         21 . The method of  claim 19 , further comprising representing the file as a file node in the graph database and storing in the mutation node a pointer to the file node. 
     
     
         22 . The method of  claim 16 , wherein the data representing a mutation comprises a description of the mutation as a variant of a reference human genome. 
     
     
         23 . The method of  claim 22 , wherein the description of the mutation is provided as a VCF record in a VCF file. 
     
     
         24 . The method of  claim 16 , further comprising:
 obtaining sequencing data representing a plurality of mutations in the genome of the individual, each of the plurality of mutations being represented as variant calls relative to a human genome reference; and   using, for each of the plurality of mutations, a corresponding variant node in the graph database to store a description of that mutation.   
     
     
         25 . The method of  claim 16 , wherein the graph database comprises:
 nodes representing people, nodes representing genomic variants relative to a reference, and nodes representing literature reports on medical relevance of the genomic variants; and   edges defining relationships between pairs of the nodes.