METHOD AND APPARATUS FOR DETECTING TRANSLOCATION

• US 20160145680A1
• Filed: 11/23/2015
• Published: 05/26/2016
• Est. Priority Date: 11/25/2014
• Status: Active Grant

• Current Assignee: Electronics and Telecommunications Research Institute
• Original Assignee: Electronics and Telecommunications Research Institute
• Inventors: Kim, Min-ho, Kim, Dae-Hee, JUNG, Ho-Youl, Kim, Young-Won, Lim, Myung-Eun, Choi, Jae-Hun, Han, Young-Woong
• Granted Patent: US 10,443,090 B2
• Time in Patent Office: Days
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6827 for detection of mutation or polymorphism
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/10 Sequence alignment; Homology search

Abstract

Disclosed are a method and an apparatus for detecting a translocation. The apparatus acquires BAM for a first pair of chromosomes and a second pair of chromosomes. Also, the apparatus detects a translocation generated in at least one chromosome by selecting at least one translocation case corresponding to the translocation information produced on the basis of BAM from among multiple translocation cases in which a translocation may be generated in at least one of the first and the second chromosomes.

Claims

1. A method for detecting a translocation, comprising:

acquiring a binary version of sequence alignment/map (BAM) for a first pair of chromosomes and a second pair of chromosomes; and

detecting a translocation generated in at least one chromosome by selecting at least one translocation case corresponding to the translocation information produced on the basis of BAM from among multiple translocation cases in which a translocation is possibly generated in at least one of the first chromosome and the second chromosome.

2. The method of claim 1, wherein when at least one translocation occurs on at least one chromosome, the multiple translocation cases are expressed by the number of the chromosomes in the first paired chromosomes on which the translocation occurs, and the number of the chromosomes in the second paired chromosomes on which the translocation occurs.

3. The method of claim 1, wherein the translocation information contains discordant fragment (DF) information, the DF information showing at least one BP (break point) present in the first chromosome or the second chromosome.

4. The method of claim 3, wherein the detecting step comprises:

analyzing at least one BP with the aid of paired end (PE) information and split-read (SR) information of BAM to produce DF information about at least one BP; and

utilizing the DF information to select at least one corresponding to at least one BP from among all or a part of multiple translocation cases.

5. The method of claim 4, wherein:

when the DF information indicates presence of ‘

5 to 3’

BP on at least one of the first chromosomes and the second chromosome, at least one selected from among all or a part of the multiple translocation cases includes a translocation case in which a translocation is generated on at least one of the first paired chromosomes; and

when the DF information indicates presence of ‘

3 to 5’

BP on at least one of the first chromosome and the second chromosome, at least one selected from among all or a part of the multiple translocation cases includes a translocation case in which a translocation is generated on at least one of the second paired chromosomes.

6. The method of claim 1, wherein the translocation information contains ploidy information about a ploidy in a vicinity of a break point (BP) region on the first chromosome, and a ploidy in a vicinity of a BP region on the second chromosome.

7. The method of claim 6, wherein the detecting step comprises:

analyzing the RD information of BAM to determine a ploidy in a vicinity of a BP region on the first chromosome and in a vicinity of a BP region on the second chromosome; and

selecting at least one translocation case corresponding to the ploidy in a vicinity of a BP region on the first chromosome and at least one translocation case corresponding to the ploidy in a vicinity of a BP region on the second chromosome from among from all or a part of the multiple translocation cases.

8. The method of claim 7, wherein

when a ploidy in a vicinity of a BP region on the first chromosome is smaller than a mean RD, the at least one translocation case selected accounts for a translocation case in which a translocation is generated on the first chromosome among all or a part of the multiple translocation cases;

and

when a ploidy in a vicinity of a BP region on the second chromosomes is smaller than a mean RD, the at least one translocation case selected accounts for a translocation case in which a translocation is generated on the second chromosome among all or a part of the multiple translocation cases.

9. The method of claim 1, wherein the translocation information contains concordant fragment (CF) information, the CF information indicating whether or not a CF is present in a vicinity of a BP region on the first chromosome and whether or not a CF is present in a vicinity of a BP region one the second chromosome.

10. The method of claim 9, wherein the detecting step comprises:

utilizing BAM to produce information about the presence of CF in a vicinity of at least one BP present on the first chromosome or the second chromosome; and

selecting at least one translocation case corresponding to the information about CF presence from among from all or a part of the multiple translocation cases.

11. The method of claim 1, wherein the translocation information contains at least a part of DF information about the following:

a ploidy in a vicinity of a BP region on the first chromosome, a polidy in a vicinity of a BP region on the second chromosome, and information about CF presence, and the DF information shows at least one BP present in the first chromosome or the second chromosome.

12. The method of claim 11, wherein, when the DF information indicates the absence of ‘

5 to 3’

BP and the presence of ‘

3 to 5’

BP while the CF information means the presence of a CF in each of the first and the second chromosomes, the at least one translocation case selected is a translocation case in which a translocation exists in one of the second paired chromosomes, but not in any of the first paired chromosomes.

13. The method of claim 11, wherein, when it is determined that the ploidy in a vicinity of a BP region on the first chromosome is two times the mean RD and the ploidy in a vicinity of a BP region on the second chromosome is zero, the at least one translocation case selected is a translocation case in which a translocation exists in both of the second paired chromosomes, but not in any of the first paired chromosomes.

14. The method of claim 11, wherein, when the DF information indicates the presence of ‘

5 to 3’

BP and the absence of ‘

3 to 5’

BP while the CF information indicates the presence of CF in each of the first and the second chromosomes, the at least one translocation case selected is a translocation case in which a translocation is present in one of the first paired chromosomes and absent in both of the second paired chromosomes.

15. The method of claim 11, wherein, when the DF information produced explains the presence of both ‘

5 to 3’

BP and ‘

3 to 5’

BP while the CF information indicates the presence of CF in each of the first and the second chromosome, the at least one translocation case selected is a translocation case in which a translocation is present in one of the first paired chromosomes and in one of the second paired chromosomes.

16. The method of claim 11, wherein, when the DF information explains the presence of both ‘

5 to 3’

BP and ‘

3 to 5’

BP while the CF information indicates the presence of CF in the first chromosome and the absence of CF in the second chromosome, the at least one translocation case selected is a translocation case of in which a translocation is present in one of the first paired chromosomes and in both of the second paired chromosomes.

17. The method of claim 11, wherein, when it is determined that the ploidy in a vicinity of a BP region on the first chromosomes is zero and the ploidy in a vicinity of a BP region on the second chromosomes is two times the mean RD, the at least one translocation case selected is a translocation case of in which a translocation exists in both of the first paired chromosomes, but not in any of the second paired chromosomes.

18. The method of claim 11, wherein, when the DF information explains the presence of both ‘

5 to 3’

BP and ‘

3 to 5’

BP while the CF information indicates the absence of CF in each of the first chromosome and the presence of CF in the second chromosome, the at least one translocation case selected is a translocation case in which a translocation is present in both of the first paired chromosomes and in one of the second paired chromosomes.

19. The method of claim 11, wherein, when the DF information explains the presence of both ‘

5 to 3’

BP and ‘

3 to 5’

BP while the CF information indicates the absence of CF in both the first and the second chromosomes, the at least one translocation case selected is a translocation case in which a translocation is present in both of the first paired chromosomes and in both of the second paired chromosomes.

20. An apparatus for detecting a translocation, comprising:

an acquirement unit for acquiring binary version of sequence alignment/map (BAM) for a first pair of chromosomes and a second pair of chromosomes; and

a detection unit for detecting a translocation generated in at least one chromosome by selecting at least one translocation case corresponding to the translocation information produced on the basis of BAM from among multiple translocation cases in which a translocation may be generated in at least one of the first and the second chromosomes.