Method and apparatus for detecting translocation

• US 10,443,090 B2
• Filed: 11/23/2015
• Issued: 10/15/2019
• 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
• Primary Examiner(s): Dunston, Jennifer
• Application Number:
  US14/949,813
• Publication Number:
  US 20160145680A1
• Time in Patent Office: 1,422 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, using the BAM, a translocation generated in at least one chromosome by selecting at least one translocation case from among multiple translocation cases, including;

determining, using the BAM, at least one Break Point (BP) of the pairs of chromosomes, each of the at least one BP corresponding to respective point where a translocation has occurred between the first and second pairs of chromosomes, including determining, using the BAM, Discordant Fragment (DF) information corresponding to the at least one BP;

determining, using the BAM, a Read Depth (RD) of a first region in the first pair of chromosomes, a RD of a second region in the second pair of chromosomes, an average RD of the BAM, and concordant fragment (CF) information of the second region indicating the presence of CFs for the second region;

selecting a first translocation case when the RD of the first region is 1.5 times the average RD, the RD of the second region is 0.5 times the average RD, the DF information indicates the presence of DFs in the second pair of chromosomes, and CFs are present for the first region and the second region; and

selecting a second translocation case when the RD of the first region is 2.0 times the average RD, the RD of the second region is zero, the DF information indicates the presence of DFs in the second pair of chromosomes, and CFs are present for the first region and absent for the second region,

wherein the first translocation case corresponds to a single translocation from the first pair of chromosomes to a first chromosome of the second pair of chromosomes, and

wherein the second translocation case corresponds to first and second translocations from the first pair of chromosomes to the first chromosome and a second chromosome, respectively, of the second pair of chromosomes.

2. The method of claim 1, wherein determining the DF information comprises:

analyzing the BP using paired end (PE) information and split-read (SR) information of the BAM to produce the DF information.

3. The method of claim 1, wherein the DF information includes information about the following:

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

4. The method of claim 1, detecting the translocation further including:

determining, using the BAM, CF information of the first region indicating the presence of CF for the first region;

selecting a third translocation case when the RD of the second region is 1.5 times the average RD, the RD of the first region is 0.5 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes, and CF is present for the first region and the second region,

wherein the third translocation case corresponds to a single translocation from the second pair of chromosomes to a first chromosome of the first pair of chromosomes.

5. The method of claim 4, detecting the translocation further including:

selecting a fourth translocation case when the RD of the first region is 1.0 times the average RD, the RD of the second region is 1.0 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is present for the first region and for the second region,

wherein the fourth translocation case corresponds to a first translocation from the second pair of chromosomes to the first pair of chromosomes and a second translocation from the first pair of chromosomes to the second pair of chromosomes.

6. The method of claim 4, detecting the translocation further including:

selecting a fifth translocation case when the RD of the first region is 1.5 times the average RD, the RD of the second region is 0.5 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is present for the first region and absent for the second region,

wherein the fifth translocation case corresponds to first and second translocations from the first pair of chromosomes to the first chromosome and a second chromosome, respectively, of the second pair of chromosomes and a single third translocation from the second pair of chromosomes to a first chromosome of the first pair of chromosomes.

7. The method of claim 4, detecting the translocation further including:

selecting a sixth translocation case when the RD of the first region is zero, the RD of the second region is 2.0 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes, and CF is absent for the first region and present for the second region,

wherein the sixth translocation case corresponds to first and second translocations from the second pair of chromosomes to the first chromosome and a second chromosome, respectively, of the first pair of chromosomes.

8. The method of claim 4, detecting the translocation further including:

selecting a seventh translocation case when the RD of the first region is 0.5 times the average RD, the RD of the second region is 1.5 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is absent for the first region and present for the second region,

wherein the seventh translocation case corresponds to first and second translocations from the second pair of chromosomes to the first chromosome and a second chromosome, respectively, of the first pair of chromosomes, and a single third translocation from the first pair of chromosomes to a first chromosome of the second pair of chromosomes.

9. The method of claim 4, detecting the translocation further including:

selecting an eighth translocation case when the RD of the first region is 1.0 times the average RD, the RD of the second region is 1.0 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is absent for the first region and the second region,

wherein the eighth translocation case corresponds to first and second translocations from the second pair of chromosomes to the first chromosome and a second chromosome, respectively, of the first pair of chromosomes and third and fourth translocations from the first pair of chromosomes to a first chromosome and a second chromosome, respectively, of the second pair of chromosomes.

10. An apparatus for detecting translocation, comprising:

a processor configured to;

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

detect, using the BAM, a translocation generated in at least one chromosome by selecting at least one translocation case from among multiple translocation cases, wherein the processor is configured to;

determine, using the BAM, at least one Break Point (BP) of the pairs of chromosomes, each of the at least one BP corresponding to respective point where a translocation has occurred between the first and second pairs of chromosomes, including determining, using the BAM, Discordant Fragment (DF) information corresponding to the at least one BP;

determine, using the BAM, a Read Depth (RD) of a first region in the first pair of chromosomes, a RD of a second region in the second pair of chromosomes, an average RD of the BAM, and concordant fragment (CF) information of the second region indicating the presence of CF for the second region;

select a first translocation case when the RD of the first region is 1.5 times the average RD, the RD of the second region is 0.5 times the average RD, the DF information indicates the presence of DFs in the second pair of chromosomes, and CF is present for the first region and the second region; and

select a second translocation case when the RD of the first region is 2.0 times the average RD, the RD of the second region is zero, the DF information indicates the presence of DFs in the second pair of chromosomes, and CF is present for the first region and absent for the second region,

wherein the first translocation case corresponds to a single translocation from the first pair of chromosomes to a first chromosome of the second pair of chromosomes, and

wherein the second translocation case corresponds to first and second translocations from the first pair of chromosomes to the first chromosome and a second chromosome, respectively, of the second pair of chromosomes.

11. The apparatus of claim 10, wherein the processor is configured to:

determine, using the BAM, CF information of the first region indicating the presence of CF for the first region; and

select a third translocation case when the RD of the second region is 1.5 times the average RD, the RD of the first region is 0.5 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes, and CF is present for the first region and for the second region,

wherein the third translocation case corresponds to a single translocation from the second pair of chromosomes to a first chromosome of the first pair of chromosomes.

12. The apparatus of claim 11, wherein the processor is configured to:

select a fourth translocation case when the RD of the first region is 1.0 times the average RD, the RD of the second region is 1.0 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is present for the first region and for the second region,

wherein the fourth translocation case corresponds to a first translocation from the second pair of chromosomes to the first pair of chromosomes and a second translocation from the first pair of chromosomes to the second pair of chromosomes.

13. The apparatus of claim 11, wherein the processor is configured to:

select a fifth translocation case when the RD of the first region is 1.5 times the average RD, the RD of the second region is 0.5 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is present for the first region and absent for the second region,

wherein the fifth translocation case corresponds to first and second translocations from the first pair of chromosomes to the first chromosome and a second chromosome, respectively, of the second pair of chromosomes and a single third translocation from the second pair of chromosomes to a first chromosome of the first pair of chromosomes.

14. The apparatus of claim 11, wherein the processor is configured to:

select a sixth translocation case when the RD of the first region is zero, the RD of the second region is 2.0 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes, and CF is absent for the first region and present for the second region,

wherein the sixth translocation case corresponds to first and second translocations from the second pair of chromosomes to the first chromosome and a second chromosome, respectively, of the first pair of chromosomes.

15. The apparatus of claim 11, wherein the processor is configured to:

select a seventh translocation case when the RD of the first region is 0.5 times the average RD, the RD of the second region is 1.5 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is absent for the first region and present for the second region,

wherein the seventh translocation case corresponds to first and second translocations from the second pair of chromosomes to the first chromosome and a second chromosome, respectively, of the first pair of chromosomes, and a single third translocation from the first pair of chromosomes to a first chromosome of the second pair of chromosomes.

16. The apparatus of claim 11, wherein the processor is configured to:

select an eighth translocation case when the RD of the first region is 1.0 times the average RD, the RD of the second region is 1.0 times the average RD, the DF information indicates the presence of DFs in the first pair of chromosomes and in the second pair of chromosomes, and CF is absent for the first region and the second region,

wherein the eighth translocation case corresponds to first and second translocations from the second pair of chromosomes to the first chromosome and a second chromosome, respectively, of the first pair of chromosomes and third and fourth translocations from the first pair of chromosomes to a first chromosome and a second chromosome, respectively, of the second pair of chromosomes.