Variant database

• US 8,812,422 B2
• Filed: 11/02/2012
• Issued: 08/19/2014
• Est. Priority Date: 04/09/2012
• Status: Active Grant

• Current Assignee: Invitae Corporation
• Original Assignee: Good Start Genetics, Inc. (Invitae Corporation)
• Inventors: Nizzari, Marcia M., Breton, Benjamin H., Tefft, David L., Haurie, Xavier S.
• Primary Examiner(s): Chaki, Kakali
• Assistant Examiner(s): Figueroa, Kevin W
• Application Number:
  US13/667,575
• Publication Number:
  US 20130268474A1
• Time in Patent Office: 655 Days
• US Class Current: 706/46
• CPC Class Codes: G06F 16/285 Clustering or classification
• CPC Class Codes: G06N 5/02 Knowledge representation; Symbolic representation
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/10 Ploidy or copy number detection
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/10 Ontologies; Annotations

Abstract

The invention provides a system and method for describing polymorphisms or genetic variants based on information about mutations and relationships among them. The invention uses object-oriented concepts to describe variants as variant objects and relations among those variants as variant relation object, each object being an instance of an abstract class of genomic feature and able to contain any number of other objects. Information about genetic disorders is stored in association with the object that represents the pathogenic variant. Genetic test results are used to access corresponding objects to provide a report based on variants or polymorphisms in a patient'"'"'s genetic material.

Claims

1. A method of providing a description of a variant in a patient'"'"'s genome, the method comprising:

receiving genetic data relating to the patient, the data representing at least a first mutation and a second mutation;

retrieving from one or more computer-readable storage devices a first variant object comprising a description of the first mutation as a first variant of a reference and a second variant object comprising a description of the second mutation as a second variant of the reference, each of the first and second variant objects being an instance of an abstract class of a genomic feature;

determining a relationship between the first and second mutations;

retrieving a third object comprising a description of the relationship, the third object also being an instance of the abstract class; and

providing a description of the variant based on the third object, wherein each object inherits a start position attribute from the abstract class.

2. The method of claim 1, further comprising:

retrieving a fourth object comprising a description of a genomic region; and

storing in the memory a fifth object comprising a description of a relationship between the genomic region and the first and second mutations, each object being an instance of the abstract class of genomic feature.

3. The method of claim 2, wherein the fourth object comprises a description of one selected from the list consisting of:

exon, intron, gene, ORF, epigenetically modified region, methylated sequence, regulatory region, promoter, splice site, protein motif, protein secondary structure, and non-coding region.

4. The method of claim 1, wherein each of the descriptions of the mutations comprises a systematic name comprising a numeral representing a distance from a start position, a specification of a mutation type, and one or more IUPAC characters representing nucleotides.

5. The method of claim 1, wherein the first mutation is a novel mutation and the second mutation is a known mutation.

6. The method of claim 5, further comprising:

creating a new object as an instance of the abstract class of genomic feature, the new object comprising a description of the novel mutation; and

storing the new object in the one or more computer storage devices.

7. A system for providing a description of a variant in a patient'"'"'s genome, the system comprising:

a processor; and

a computer-readable storage device containing instructions which when executed by the processor cause the system to

receive genetic data relating to the patient, the data representing at least a first mutation and a second mutation,

retrieve from a database a first object comprising a description of the first mutation as a first variant of a reference and a second object comprising a description of the second mutation as a second variant of the reference, each of the first and second objects being an instance of an abstract class of a genomic feature,

determine a relationship between the mutation and a second mutation,

retrieving a third object comprising a description of the relationship, the third object also being an instance of the abstract class, and

provide a description of the variant based on the third object, wherein each object inherits a start position attribute from the abstract class.

8. The system of claim 7, wherein the system is further configured to:

retrieve a fourth object comprising a description of a genomic region; and

store in the storage device a fifth object comprising a description of a relationship between the genomic region and the first and second mutations, each object being an instance of the abstract class of genomic feature.

9. The system of claim 8, wherein the fourth object comprises a description of one selected from the list consisting of:

exon, intron, gene, ORF, epigenetically modified region, methylated sequence, regulatory region, promoter, splice site, protein motif, protein secondary structure, and non-coding region.

10. The system of claim 7, wherein the description of the mutation comprises a systematic name for a mutation comprising a numeral representing a distance from a start position, a specification of a mutation type, and one or more IUPAC characters representing nucleotides.

11. The system of claim 7, wherein the first mutation is a novel mutation and the second mutation is a known mutation.

12. The system of claim 7, further comprising:

creating a new object as an instance of the abstract class of genomic feature, the new object comprising a description of the novel mutation; and

storing the new object in the storage device.

13. A method of describing variants, the method comprising:

providing, using a computer comprising a memory coupled to a processor, code describing an abstract class of genomic feature object;

creating variant objects, each variant object being an instance of the abstract class of genomic feature object and comprising a description of a mutation;

creating relation objects, each relation object being an instance of the genomic feature object and comprising one or more genomic feature objects and a description of a relationship among the one or more genomic feature objects; and

providing descriptions of variants based on at least one of the relation objects.

14. The method of claim 13, wherein the abstract class of genomic feature object comprises a start position attribute.

15. The method of claim 13, further comprising:

receiving new information about a genetic mutation, the new information comprising a start position value and a mutation description;

instantiating and storing a new variant object, wherein the new variant object is-a genomic feature object and comprises a description of the genetic mutation.

16. The method of claim 13, further wherein a plurality of genomic feature objects can have a “

has-a”

relationship with a shared genomic feature object, the shared genomic feature object occupying a single place in memory.

17. The method of claim 13, further comprising:

instantiating a feature object that is-a genomic feature, the feature object inheriting the start position attribute and further comprising a feature attribute;

storing a start position value in the start position attribute of the feature object and storing a description of a feature in the feature attribute, wherein the feature is one selected from the list consisting of;

a gene, an exon, and an intron.

18. The method of claim 13, further comprising:

branding the objects with system version information; and

releasing the branded objects to a production system.

19. The method of claim 13, further comprising storing the objects without modifying existing data.

20. The method of claim 13, further comprising:

receiving information about a type of genomic feature, the type being not yet represented by an object in the one or more storage devices;

instantiating a type object that is-a genomic feature, the type object inheriting the start position attribute and further comprising the received information about the type of genomic feature.

21. The method of claim 13, wherein the mutation is a novel mutation.

22. A system for describing variants, the system comprising:

a processor; and

a computer-readable storage device containing instructions which when executed by the processor cause the system to

create variant objects, wherein each variant object is an instance of an abstract class of genomic feature object and comprises a description of a mutation;

create relation objects, wherein each relation object in an instance of the abstract class of genomic feature object and comprises one or more genomic feature objects and a description of a relationship among the one or more genomic feature objects; and

provide descriptions of variants based on at least one of the relation objects.

23. The system of claim 22, wherein the abstract class of genomic feature object comprises a start position attribute.

24. The system of claim 22, wherein the system is further operable to:

receive new information about a genetic mutation, the new information comprising a start position value and a mutation description;

create a new variant object, the new variant object being an instance of the abstract class of genomic feature object and comprising a description of the genetic mutation.

25. The system of claim 22 wherein the computer-readable storage device comprises a relational database.

26. The system of claim 25, further wherein a plurality of genomic feature objects can have a “

has-a”

relationship with a shared genomic feature object, the shared genomic feature object occupying a single place in memory.

27. The system of claim 22, wherein the system is further operable to:

instantiate a feature object that is-a genomic feature, the feature object inheriting the start position attribute and further comprising a feature attribute;

store a start position value in the start position attribute of the feature object and store a description of a feature in the feature attribute, wherein the feature is one selected from the list consisting of;

a gene, an exon, and an intron.

28. The system of claim 22, wherein the system is further operable to:

brand the objects with system version information; and

release the branded objects to a production system.

29. The system of claim 22, wherein the system is further operable to:

store the objects without modifying existing data.

30. The system of claim 22, wherein the system is further operable to:

receive information about a type of genomic feature, the type being not yet represented by an object in the one or more storage devices;

instantiate a type object that is-a genomic feature, the type object inheriting the start position attribute and further comprising the received information about the type of genomic feature.

31. The system of claim 22, wherein the mutation is a novel mutation.