Method and apparatus for detecting translocation

Patent metadata

Field	Value
Publication number	US-10443090-B2
Application number	US-201514949813-A
Country	US
Kind code	B2
Filing date	Nov 23, 2015
Priority date	Nov 25, 2014
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

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.

First claim

What is claimed is:

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

Assignees

• Electronics & Telecommunications Res Inst

Inventors

• Kim Min-Ho
• Kim Dae-Hee
• Jung Ho-Youl
• Kim Young-Won
• Lim Myung-Eun
• Choi Jae-Hun
• Han Young-Woong

Classifications

• G16B30/00

  ICT specially adapted for sequence analysis involving nucleotides or amino acids · CPC title

• C12Q1/6816

  characterised by the detection means (C12Q1/6804 takes precedence) · CPC title

• C12Q1/6827 Primary

  for detection of mutation or polymorphism · CPC title

• G16B20/00

  ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations · CPC title

• G16B30/10 Primary

  Sequence alignment; Homology search · CPC title