KR102082360B1 - An apparatus for detecting structural variation of chromosome and a method of manufacturing the same - Google Patents

Abstract

The present invention is obtained by obtaining a sample of the target; A first calculating unit analyzing genetic information of a sample; A second operation unit for collating a result of the first operation unit with a sequence of a target reference chromosome; A detector for detecting a chromosomal structural variation from the collation result of the second calculator; And
The present invention relates to a chromosome structural variation detection device and a method for manufacturing the same, including an output unit defining and outputting a chromosomal structural variation obtained from the detection unit as a node and an edge around a breaking point. Through the apparatus of the present invention, by more accurately defining the variation of the genetic information of the desired sample to construct the data, the information on the variation can be categorized and a large amount of data can be easily constructed.

Description

An apparatus for detecting structural variation of chromosome and a method of manufacturing the same

The present invention relates to a chromosome structural variation detection device and a method of manufacturing the same.

After the completion of the human genome project, the DNA sequences of humans are deciphered and the various functions of human genes are revealed. In particular, research into human genomes is accelerating as a variety of genetic variations have been discovered that can not only cause differences in human traits, but can also cause specific diseases.

have. However, it is difficult to find out which of the vast genetic variations that can occur in the human genome can be the actual etiology.

With the development of Next Generation Sequencing (NGS), it is possible to decipher the entire genome of individual human genomes, and to extract disease-specific gene mutations through the comparative analysis of nucleotide sequences and mutations between disease and normal groups. It also became possible. In addition, unique molecular markers can be selected by selecting markers related to traits, identifying existing variations at the nucleotide level, and introducing selectable markers by introduction of one or more nucleotides at positions of the constant region of the marker by target nucleotide exchange. A method for the production of these plants was also used (see KR 10-2011-0094268). However, since there is no method to accurately type and diagram various types of structural variation, it is difficult to manage data and obtain new information in large quantities. In order to solve this problem, the inventors have completed the present invention.

The present invention provides a chromosome structural variation detection device and a method for manufacturing the same, which are defined as nodes and edges based on a cutting point in order to type mutant information of chromosomes and construct a large amount of information. For the purpose of

In addition, an object of the present invention is to provide information on the chromosomal structural variation that is defined and outputted as a node (edge) and the edge (edge) based on the cutting point of the chromosomal variation information.

In one embodiment, the obtaining unit for obtaining a sample of the target; A first calculating unit analyzing genetic information of a sample; A second operation unit for collating a result of the first operation unit with a sequence of a target reference chromosome; A detector for detecting a chromosomal structural variation from the collation result of the second calculator; And it provides a chromosomal structural variation detection device including an output unit for defining and outputting the chromosomal structural variation obtained from the detection unit as a node (node) and the edge (edge) around the breaking point (breaking point). In the above embodiment, the sample of interest provides a chromosomal structural variation detection device, characterized in that the human blood, the node provides a chromosomal structural variation detection device comprising the number and structural variation position of the chromosome, the edge is cut Provided is a chromosomal structural variation detection device comprising a point and an order, wherein the edge provides a chromosomal structural variation detection device including any one or more of one to three cutting points, wherein the order is the first order and the first Provided is a chromosomal structural variation detection device comprising two orders, wherein the order provides a chromosomal structural variation detection device represented by 0 and 1, wherein the chromosomal structural variation detection device is directed by a combination of the first and second orders. The present invention provides a device for detecting a chromosomal structural variation, wherein the directionality is any one of amphoteric, right, left, and non-directional, and the cleavage point is a cleavage point. And a chromosomal structural variation detection device for detecting a cleavage point of the structural variation using atypical read pair information, wherein the chromosomal structural variation is a chromosomal structural variation detection device having any one of gene deletion, insertion, inversion, and chromosomal translocation on a chromosome. to provide.

In one embodiment, the obtaining unit for obtaining a sample of the target; A first calculating unit analyzing genetic information of a sample; A second operation unit for collating a result of the first operation unit with a sequence of a target reference chromosome; A detector for detecting a chromosomal structural variation from the collation result of the second calculator; And it provides a method for producing a chromosome structural variation detection apparatus by combining the output unit to define and output the chromosomal structural variation obtained from the detection unit (node) and the edge (edge) around the breaking point (breaking point).

In one embodiment, obtaining a sample of interest; Analyzing the genetic information of the sample; Contrasting the result obtained from the analyzing step with the sequence of the desired reference chromosome; It provides a method for providing information about the chromosomal structural variation comprising the step of expressing the chromosomal structural variation as a node (edge) and edge around the breaking point from the results obtained from the contrasting step do.

In the present invention, the “cutting point” refers to a point at which cleavage occurs unlike a chromosome of a normal person due to genetic mutations such as insertion, deletion, translocation, and inversion in a chromosome. We can find the cut point of the structural variation using.

In the present invention, the term "node" includes information on the chromosome number and structural variation position of the cutting point, and may include a plurality of cutting points.

In the present invention, the term "edge" refers to a relationship between cutting points, which is expressed as a contig, an order, or a link, and determines the direction between the cutting points.

In the present invention, the "order" is expressed as a specific value of the direction between the cutting point, one edge is displayed at different positions on the chromosome, mutually exclusive matching and unmatched (soft clipped) state If present, the match-matching order state is indicated by order 1, and the match-matching order state is indicated by order 0 (see FIG. 8).

In the present invention, "chromosomal structural variation" means that genes are not limited thereto, but the chromosome and genetic information of a normal person are changed due to genetic variation such as insertion, deletion, translocation, and inversion.

"Graph making" of the present invention is created according to the order values of the cutting point and the edge, and connects the cutting point and the cutting point from the order value 1 to the order value 0 (see FIGS. 9 and 1 to 7).

"Read" of the present invention is a sequence fragment obtained by amplifying the genetic information of the desired sample, and can be arbitrarily expressed like leader A and leader B.

Through the apparatus and the information providing method of the present invention, by more accurately defining the variation of the genetic information of the desired sample to construct the data, the information on the variation can be categorized and a large amount of data can be easily constructed. In addition, it is possible to easily grasp the relationship between the cutting points, to detect a conventional undiscovered cutting point, and to provide information about the pattern thereof.

Figure 1 is a graphical representation of the matching state, the cutting point and the edge when the new sequence is inserted into the cutting point.
Figure 2 is a graphical representation of the matching state, the cut point and the edge when the sequence is deleted at the cut point.
Figure 3 is a graphical representation of the matching state, the cutting point and the edge when the new sequence is inserted backwards at the cutting point.
FIG. 4 is a graphical representation of a sequence using a matching state, a cutting point, and an edge when a sequence moves within a chromosome identical to the cutting point.
5 to 7 are graphs expressed by using a matching state, a cutting point and an edge when a sequence is moved between different chromosomes at a cutting point.
8 is a diagram showing a relationship between a cutting point and a matching order.
9 is a specific example of the graph created through the cutting point and the matching order.

Hereinafter, the components and technical features of the present invention will be described in more detail with reference to the following examples. However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the invention.

Various embodiments described herein are described with reference to the drawings. In the following description, for a thorough understanding of the present invention, various specific details are described, such as specific forms, compositions, processes and the like. However, certain embodiments may be practiced without one or more of these specific details, or in conjunction with other known methods and forms. In other instances, well known processes and manufacturing techniques have not been described in particular detail in order to not unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "embodiment" means that a particular feature, form, composition or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, the context of the expression “in one embodiment” or “embodiment” in various places throughout this specification does not necessarily represent the same embodiment of the invention. In addition, particular features, forms, compositions, or properties may be combined in any suitable manner in one or more embodiments.

When a genetic mutation occurs in the chromosome, the insertion point, deletion, inversion, internal translocation, and external translocation of the genetic mutation can be graphically represented as the cutting point and the matching order values 0 and 1.

When a new sequence is inserted on a chromosome, one break point occurs, and a value of 0 or 1 may be given according to a matching state by matching a reference sequence and a read sequence, which is a desired sequence, to the reference sequence. It can be expressed as shown in the graph to the right of FIG.

When the sequence is deleted on the chromosome, two cleavage points occur, and at the two cleavage points, the reference sequence and the lead sequence of the sample do not match, and thus a value of 0 or 1 is assigned, and the two match points are matched. The state value can be expressed as shown in the graph to the right of FIG. 2.

When a new sequence is inserted upside down on the chromosome, two cleavage points are generated and a match is made for the sequence between the cleavage points but not outside the two cleavage points, but outside the two cleavage points, but a match is made between the cleavage points. There is a lead that does not match, which can be expressed as shown in the right side of Figure 3, in this case has two edges.

When the sequence is shifted on the same chromosome, three cleavage points occur and have two edges (see FIG. 4).

When the sequence is shifted on different chromosomes, two cleavage points occur and have two edges (see FIGS. 5-6).

In one embodiment, when the gene is inserted, it is represented by a cutting point and a line connecting the same as shown in the right figure of FIG. 1, and may be stored in a computational database as follows.

Node BP_att1 BP_att2 BP1 Chr1 123456

edge BP1 Order 1 Lead A BP1 One Lead B BP1 0

At this time,

BP1 is any break point on the node,

BP_att1 and BP_att1 are information about the chromosome number and the position of the structural variation.

Read A and B are sequence fragments amplified genetic information of the desired sample,

Order value 1 is a specific value of the direction between the cutting points, for example, a value of 1 is an order of matching-unmatching, and an order value of 0 is an order of mismatching-matching.

In one embodiment, the deletion is represented by two cutting points and a line connecting the same, as shown in the right figure of FIG. 2, and may be stored in the computational database as follows.

Node BP_att1 BP_att2 BP1 Chr1 123456 BP2 Chr1 4567890

edge BP1 BP2 Order 1 Order 2 Lead A BP1 BP2 One 0

At this time,

BP1 and BP2 are arbitrary breakpoints on the node,

BP_att1 and BP_att1 are information about the chromosome number and the position of the structural variation.

Read A is a sequence fragment amplified genetic information of the desired sample,

Order value 1 is a specific value of the direction between the cutting points, for example, a value of 1 is an order of matching-unmatching, and an order value of 0 is an order of mismatching-matching.

In one embodiment, the inversion is represented by two cutting points and a line connecting the same, as shown in the right figure of FIG. 3, and may be stored in the computational database as follows.

Node BP_att1 BP_att2 BP1 Chr1 123456 BP2 Chr1 4567890

edge BP1 BP2 Order 1 Order 2 Lead A BP1 BP2 One One Lead B BP1 BP2 0 0

At this time,

BP1 and BP2 are arbitrary breakpoints on the node,

BP_att1 and BP_att1 are information about the chromosome number and the position of the structural variation.

Read A and B are sequence fragments amplified genetic information of the desired sample,

Order value 1 is a specific value of the direction between the cutting points, for example, a value of 1 is an order of matching-unmatching, and an order value of 0 is an order of mismatching-matching.

In one embodiment, when the sequence is shifted within the same chromosome, as shown in the upper right picture of Figure 4, it is represented by three cutting points and a line connecting them, it can be stored in a computerized database as follows

Node BP_att1 BP_att2 BP1 Chr1 111111 BP2 Chr1 200000 BP3 Chr1 200100

edge BP1 BP2 Order 1 Order 2 Lead A BP1 BP2 One 0 Lead B BP1 BP3 0 One

At this time,

BP1, BP2 and BP3 are any breakpoints on the node,

BP_att1 and BP_att1 are information about the chromosome number and the position of the structural variation.

Read A and B are sequence fragments amplified genetic information of the desired sample,

Order value 1 is a specific value of the direction between the cutting points, for example, a value of 1 is an order of matching-unmatching, and an order value of 0 is an order of mismatching-matching.

In one embodiment, when the sequence is reversed in the same chromosome, as shown in the lower right of Figure 4, it is represented by three cutting points and a line connecting them, it can be stored in a computational database as follows

Node BP_att1 BP_att2 BP1 Chr1 111111 BP2 Chr1 200000 BP3 Chr1 200100

edge BP1 BP2 Order 1 Order 2 Lead A BP1 BP3 One One Lead B BP1 BP2 0 0

At this time,

BP1, BP2 and BP3 are any breakpoints on the node,

BP_att1 and BP_att1 are information about the chromosome number and the position of the structural variation.

Read A and B are sequence fragments amplified genetic information of the desired sample,

Order value 1 is a specific value of the direction between the cutting points, for example, a value of 1 is an order of matching-unmatching, and an order value of 0 is an order of mismatching-matching.

In one embodiment, when the sequence is shifted in different chromosomes, as shown in the right figure of FIG.

Node BP_att1 BP_att2 BP1 Chr1 123456 BP2 Chr2 456789

edge BP1 BP2 Order 1 Order 2 Lead A BP1 BP2 One One Lead B BP1 BP2 0 0

At this time,

BP1 and BP2 are arbitrary breakpoints on the node,

BP_att1 and BP_att1 are information about the chromosome number and the position of the structural variation.

Read A and B are sequence fragments amplified genetic information of the desired sample,

Order value 1 is a specific value of the direction between the cutting points, for example, a value of 1 is an order of matching-unmatching, and an order value of 0 is an order of mismatching-matching.

In one embodiment, when the sequence is shifted in different chromosomes, as shown in the right figure of FIG.

Node BP_att1 BP_att2 BP1 Chr1 123456 BP2 Chr2 456789

edge BP1 BP2 Order 1 Order 2 Lead A BP1 BP2 One 0 Lead B BP1 BP2 0 One

At this time,

BP1 and BP2 are arbitrary breakpoints on the node,

BP_att1 and BP_att1 are information about the chromosome number and the position of the structural variation.

Read A and B are sequence fragments amplified genetic information of the desired sample,

Order value 1 is a specific value of the direction between the cutting points, for example, a value of 1 is an order of matching-unmatching, and an order value of 0 is an order of mismatching-matching.

Claims (13)

Obtaining section for obtaining a sample of the target;
A first calculating unit analyzing genetic information of a sample;
A second operation unit for collating a result of the first operation unit with a sequence of a target reference chromosome;
A detector for detecting a chromosomal structural variation from the collation result of the second calculator; And
And an output unit for defining and outputting the chromosomal structural variation obtained from the detection unit as a node and an edge around a breaking point.
The edge includes a cutting point and an order,
The order is displayed as different order values according to the matching sequence when the sequence fragments amplified the genetic information of the target sample,
Chromosome structural variation detection device that determines whether or not the arrow is displayed according to the order value. The method of claim 1,
Chromosome structural variation detection device, characterized in that the target sample is human blood. The method of claim 1,
Node is a chromosome structural variation detection device comprising a chromosome number and a structural variation position. delete The method of claim 1,
Edge detection device for chromosomal structural variation comprising any one or more of one to three cutting points. The method of claim 1,
Order is a chromosome structural variation detection device comprising a first order and a second order.
The method of claim 1,
Order is a chromosome structural variation detection device is represented by 0 and 1. The method of claim 6,
An apparatus for detecting a chromosomal structural variation in which orientation occurs by combining a first order and a second order. The method of claim 8,
A device for detecting chromosomal structural alterations in which the aromaticity is any one of amphoteric, right, left and non-directional. The method of claim 1,
A cut point detects a cut point of a structural variation using cutting lead and atypical lead pair information. The method of claim 1,
Chromosomal structural alteration is a chromosomal structural variation detection device, wherein any one of a gene deletion, insertion, inversion and chromosomal translocation on the chromosome. delete Obtaining a sample of interest;
Analyzing the genetic information of the sample;
Contrasting the result obtained from the analyzing step with the sequence of the desired reference chromosome;
Expressing the chromosomal structural variation as a node and an edge around a breaking point from the result obtained from the collating step,
The edge includes a cutting point and an order,
The order is displayed as different order values according to the matching sequence when the sequence fragments amplified the genetic information of the target sample,
A method for providing information on chromosomal structural variation in which an arrow is displayed or an arrow direction is determined according to the order value.

Images