Fracture point identification method and device for chromosome structure variation region, equipment, medium and program product

Abstract

The embodiment of the invention discloses a breaking point identification method and device for a chromosome structure variation region, equipment, a medium and a program product. The method comprises the steps that a chromosome structure variation region and at least two region windows are obtained, and the region windows are combined to surround the chromosome structure variation region; determining first information of a shared bar code among the region windows; and obtaining a read pair position of a read pair carried by the shared barcode according to the first information, and identifying a breaking point with chromosome structure variation in the chromosome structure variation region according to the read pair position. According to the technical scheme provided by the embodiment of the invention, the breaking point can be accurately identified for the chromosome structure variation region.

Description

Technical Field

[0001] Embodiments of the present invention relate to bioinformatics / fields, and in particular, to a method, device, equipment, medium, and program product for identifying breakpoints in chromosome structural variation regions. Background Art

[0002] The development of next-generation sequencing (NGS) technology has promoted the application of preimplantation genetic testing (PGT) in assisted reproductive technology (ART), which helps to reduce the birth of children with genetic diseases.

[0003] To address this issue, NGS technology, especially NGS technology based on long fragments (linked-reads), can be used to detect chromosome structural variation (SV) in infertile people before embryo implantation, and further identify the breakpoints of the detected chromosome structural variation regions.

[0004] However, accurate identification of breaking points is currently not possible and needs to be resolved. Summary of the invention

[0005] Embodiments of the present invention provide a method, device, equipment, medium and program product for identifying breakpoints in a chromosome structural variation region, so as to accurately identify breakpoints in a chromosome structural variation region.

[0006] According to one aspect of the present invention, a method for identifying breakpoints in a chromosome structural variation region is provided, which may include:

[0007] Acquire a chromosome structural variation region and at least two region windows, wherein each region window is merged to surround the chromosome structural variation region;

[0008] Determine first information of a shared barcode between each area window;

[0009] The read pair positions of the read pairs carried by the shared barcode are obtained according to the first information, and the breakpoints where the chromosome structural variation occurs in the chromosome structural variation region are identified according to the read pair positions.

[0010] According to another aspect of the present invention, a device for identifying breakpoints in a chromosome structural variation region is provided, which may include:

[0011] A region window acquisition module, used to acquire a chromosome structural variation region and at least two region windows, wherein each region window is combined to surround the chromosome structural variation region;

[0012] A first information determination module, used to determine first information of a shared barcode between each area window;

[0013] A breakpoint identification module is used to obtain the read pair position of the read pair carried by the shared barcode according to the first information, and identify the breakpoint where the chromosome structural variation occurs in the chromosome structural variation region according to the read pair position.

[0014] According to another aspect of the present invention, there is provided an electronic device, which may include:

[0015] at least one processor; and

[0016] a memory communicatively connected to at least one processor; wherein,

[0017] The memory stores a computer program that can be executed by at least one processor. The computer program is executed by at least one processor so that the at least one processor implements the breakpoint identification method for the chromosome structural variation region provided by any embodiment of the present invention when executing the computer program.

[0018] According to another aspect of the present invention, a computer-readable storage medium is provided, on which computer instructions are stored, and the computer instructions are used to enable a processor to implement the breakpoint identification method for a chromosome structural variation region provided by any embodiment of the present invention when executed.

[0019] According to another aspect of the present invention, a computer program product is provided, on which a computer program is stored. When the computer program is executed by a processor, the method for identifying breakpoints for a chromosome structural variation region provided in any embodiment of the present invention is implemented.

[0020] The technical solution of the embodiment of the present invention obtains the chromosome SV region and at least two regional windows, which can surround the chromosome SV region after merging; further, the first information of the shared barcode between the regional windows is determined, thereby obtaining the pos of the reads-pair carried by the shared barcode according to the first information, and identifying the breakpoint of the SV in the chromosome SV region according to the pos. The above technical solution uses the pos corresponding to the shared barcode between the regional windows on the chromosome SV region to achieve accurate identification of the breakpoint in the chromosome SV region.

[0021] It should be understood that the contents described in this section are not intended to identify the key or important features of the embodiments of the present invention, nor are they intended to limit the scope of the present invention. Other features of the present invention will become easily understood through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0023] Figure 1 is a flow chart of a method for identifying breakpoints in a chromosome structural variation region provided by an embodiment of the present invention;

[0024] Figure 2 is a flowchart of another method for identifying breakpoints in a chromosome structural variation region provided according to an embodiment of the present invention;

[0025] Figure 3a It is a schematic diagram of a visualization result of barcode distribution corresponding to chromosome 1 in another method for identifying breakpoints in a chromosome structural variation region provided according to an embodiment of the present invention;

[0026] Figure 3b is a schematic diagram of a visualization result of barcode distribution corresponding to chromosome 11 in another method for identifying breakpoints in a chromosome structural variation region provided according to an embodiment of the present invention;

[0027] Figure 4a is a schematic diagram of a visualization result of barcode distribution corresponding to the left region on chromosome 2 in another method for identifying breakpoints in a chromosome structural variation region provided according to an embodiment of the present invention;

[0028] Figure 4b It is a schematic diagram of a visualization result of barcode distribution corresponding to the right region on chromosome 2 in another method for identifying breakpoints in a chromosome structural variation region provided according to an embodiment of the present invention;

[0029] Figure 5 This is a structural block diagram of a device for identifying breakpoints in a chromosome structural variation region provided by an embodiment of the present invention;

[0030] Figure 6 It is a structural schematic diagram of an electronic device for implementing the breakpoint identification method for a chromosome structural variation region according to an embodiment of the present invention. DETAILED DESCRIPTION

[0031] In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work should fall within the scope of protection of the present invention.

[0032] It should be noted that the terms "first", "second", etc. in the specification and claims of the present invention and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present invention described herein can be implemented in an order other than those illustrated or described herein. The situations of "target", "original", etc. are similar and will not be repeated here. In addition, the terms "including" and "having" and any variations thereof are intended to cover non-exclusive inclusions, for example, a process, method, system, product or device comprising a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0033] Figure 1 It is a flow chart of a method for identifying breakpoints in a chromosome structural variation region provided by an embodiment of the present invention. This embodiment is applicable to the case of identifying breakpoints of SVs in a chromosome structural variation region (i.e., a chromosome SV region). The method can be performed by a device for identifying breakpoints in a chromosome structural variation region provided by an embodiment of the present invention, which can be implemented by software and / or hardware, and which can be integrated in an electronic device, which can be various user terminals or servers.

[0034] See also Figure 1 The method of the embodiment of the present invention specifically includes the following steps:

[0035] S110. Obtain a chromosome structural variation region and at least two region windows, wherein each region window is merged to surround the chromosome structural variation region.

[0036] The chromosome SV region can be understood as a region on a chromosome where SV occurs, and can further be understood as a region for identifying SV breakpoints on a chromosome (hereinafter referred to as breakpoints). It should be noted that the chromosome SV region can be obtained by any method, which is not specifically limited here.

[0037] The regional window can be understood as a window covering a local area in the chromosome SV region. The number of the windows can be two or more. The merging result of the two or more windows can completely surround the chromosome SV region. The two or more windows are obtained by sliding windows in the process of determining the chromosome SV region.

[0038] The chromosome SV region and the two or more region windows are obtained.

[0039] S120. Determine first information of a shared barcode between each area window.

[0040] Among them, the shared barcode (i.e., shared barcode) can be understood as a barcode shared by each regional window (i.e., all have), which is part of the sequencing result of the chromosome SV region. The number of the shared barcode can be one or more, especially multiple, which is related to the actual situation and is not specifically limited here.

[0041] For each shared barcode, the first information can be understood as the information of the shared barcode. In combination with the application scenarios that may be involved in the embodiments of the present invention, for example, it can be at least one of the barcode identifier of the shared barcode (i.e., barcode_id), whether the shared barcode (Yes / No) carries read pairs (reads-pair) that support SV, the read pair information of the reads-pair carried by the shared barcode (such as the number of read pairs, read pair positions (pos) and library length, etc.), the chromosome (chr) where the shared barcode is located, the start and end positions of the shared barcode on the chromosome, and the barcode length of the shared barcode.

[0042] In practical applications, optionally, the following method can be used to determine whether the shared barcode carries reads-pairs that support SV: max_len / median_len>20, Yes; max_len / median_len<=20, No. Wherein, max_len is the maximum library length of all reads pairs carried by the shared barcode, and median_len is the median value of the library length of all reads pairs carried by the shared barcode.

[0043] Determine the first information of each shared barcode separately. In practical applications, optionally, a corresponding information file can be generated in advance, and then the first information can be extracted from the information file. Optionally, after obtaining the first information, the first information can be sorted, and the sorted result format includes barcode_id, chr, pos. On this basis, it should be noted that due to the particularity of linked-reads library construction, a shared barcode can carry multiple reads-pairs, and the reads-pair can be understood as reads1 and reads2. Then a reads-pair has two pos (i.e., the pos of reads1 and the pos of reads2), so a shared barcode can correspond to multiple pos.

[0044] S130. Obtain the read pair positions of the read pairs carried by the shared barcode according to the first information, and identify the breakpoints where the chromosome structural variation occurs in the chromosome structural variation region according to the read pair positions.

[0045] The read pair position (pos) can be understood as the position of the reads-pair carried by the shared barcode on the chromosome, which can be obtained by comparing the reads-pair with the reference genome. The pos is obtained based on the first information, and the breakpoint in the chromosome SV region can be identified based on the pos.

[0046] The technical solution of the embodiment of the present invention obtains the chromosome SV region and at least two regional windows, which can surround the chromosome SV region after merging; further, the first information of the shared barcode between the regional windows is determined, thereby obtaining the pos of the reads-pair carried by the shared barcode according to the first information, and identifying the breakpoint of the SV in the chromosome SV region according to the pos. The above technical solution uses the pos corresponding to the shared barcode between the regional windows on the chromosome SV region to achieve accurate identification of the breakpoint in the chromosome SV region.

[0047] Figure 2It is a flowchart of another method for identifying breakpoints in a chromosome structural variation region provided in an embodiment of the present invention. This embodiment is optimized based on the above-mentioned technical solutions. In this embodiment, optionally, the read pair position of the read pair carried by the shared barcode is obtained according to the first information, and the breakpoint of the chromosome structural variation in the chromosome structural variation region is identified according to the read pair position, including: for each regional window, determining the local area covered by the regional window on the chromosome structural variation region, sliding the window on the local area, and obtaining multiple first windows; for each first window, according to the first information, obtaining the read pair position of the read pair carried by the shared barcode under the first window, and the first number of shared barcodes under the first window; according to the read pair positions and the first number corresponding to the multiple first windows, the breakpoint of the chromosome structural variation in the local area is identified. Among them, the explanation of the terms that are the same or corresponding to the above-mentioned embodiments is not repeated here.

[0048] See also Figure 2 The method of this embodiment may specifically include the following steps:

[0049] S210. Obtain a chromosome structural variation region and at least two region windows, wherein each region window is merged to surround the chromosome structural variation region.

[0050] S220. Determine first information of the shared barcode between each area window.

[0051] S230. For each regional window, determine the local area covered by the regional window on the chromosome structural variation region, and perform sliding window on the local area to obtain multiple first windows.

[0052] For each acquired region window, S230-S250 are used to perform relevant processing of the region window. Here, any region window is taken as an example, and the following processing is performed in this step:

[0053] Determine the local area covered by the regional window on the chromosome SV region, that is, the local area can be understood as the area covered by the regional window in the chromosome SV region; then, use a first window of fixed size to slide the window on the local area to obtain multiple first windows.

[0054] In combination with the application scenarios that may be involved in the embodiments of the present invention, the local regions obtained for different regional windows may be located on the same chromosome or on different chromosomes. This is related to the specific type of SV and is not specifically limited here. For example, if the SV involves a balanced translocation of two chromosomes, then different local regions are distributed on the two chromosomes. At this time, the processing of a local region is equivalent to the processing of the corresponding chromosome; if the SV involves an inversion of a chromosome, then different local regions are distributed on a chromosome, and the different local regions can be understood as the left region (left region) and the right region (right region) on the chromosome. At this time, the result format of the arrangement described above can be added to the barcode_id, chr, pos. Region (left / right), the region (left / right) can represent whether the local region where the pos is located is the left region or the right region.

[0055] S240. For each first window, obtain, according to the first information, the read pair positions of the read pairs carried by the shared barcodes in the first window and the first number of shared barcodes in the first window.

[0056] Here, each first window obtained is processed separately by this step. Taking any first window as an example, according to the first information, the pos of the reads-pair carried by the shared barcode under the first window and the first number of the shared barcode under the first window are obtained, that is, the first number can be understood as the number of shared barcodes under the first window.

[0057] S250. Identify breakpoints where chromosome structural variation occurs in the local region according to the positions and first quantities of read pairs corresponding to the plurality of first windows, respectively.

[0058] After obtaining the pos and the first number respectively corresponding to each first window, the breakpoint can be identified according to the pos and the first number.

[0059] The technical solution of the embodiment of the present invention realizes the regional identification of the breakpoint by processing each regional window separately, thereby further improving the accuracy of the breakpoint identification; and further improves the accuracy of the breakpoint identification in the corresponding area by continuing to slide the window on the basis of a regional window and combining the first number of shared barcodes under each first window on the basis of POS.

[0060] An optional technical solution, identifying the breakpoints where the chromosome structural variation occurs in the local region according to the positions and the first quantities of read pairs respectively corresponding to the plurality of first windows, comprises:

[0061] Merging first windows that are adjacent in window position and close in first quantity among the plurality of first windows, and dividing the local area into at least one segment based on the merging result;

[0062] For each segment, an average number is obtained according to the first numbers respectively corresponding to the first windows on the segment, so as to filter the segments according to the average numbers respectively corresponding to the segments;

[0063] For the retained fragments after filtering in each fragment, the window position of the first window on each retained fragment is obtained, so as to construct a position range based on the minimum window position and the maximum window position of all the window positions;

[0064] Target positions located within the position range among the read pair positions corresponding to the plurality of first windows are determined, and breakpoints where chromosome structural variation occurs in the local region are identified based on the target positions.

[0065] Among them, for the first windows that are adjacent in window position and close in first quantity among the multiple first windows, since these first windows have similar properties in window position and first quantity, they can be merged together to obtain a new first window. Exemplarily, assuming that the multiple first windows include window 1, window 2, window 3, window 4 and window 5, if the first quantity of window 1 is close to that of window 2, and is not close to the first quantity of window 3, then window 1 and window 2 are merged to obtain window 12. Further, if the first quantity of window 3 is not close to that of window 4, there is no need to merge window 3 and window 4, and it is continued to be determined whether the first quantity of window 4 is close to that of window 5, so as to determine whether to merge.

[0066] Further, based on the merging result, the local area is divided into at least one segment, that is, based on the new first window obtained after merging and the first window that is not merged, the local area is divided into at least one segment. Here, still taking the above example as an example, assuming that window 4 and window 5 are merged into window 45, the local area can be divided into 3 segments based on window 12, window 3 and window 45.

[0067] Furthermore, for each segment obtained, the average of the first quantities corresponding to the original first windows on the segment can be used as the average quantity (seg.mean) of the segment. Exemplarily, taking the segment divided by window 12 as an example, the seg.mean of the segment can be obtained according to the first quantities corresponding to window 1 and window 2, respectively. Thus, all segments can be filtered according to the seg.mean corresponding to each segment, for example, filtering out segments whose seg.mean is less than a preset quantity threshold, that is, filtering out segments with low barcode coverage. These segments are mostly located at the head and tail of the local area, and the pos therein are mostly abnormal pos, which are easy to interfere with the subsequent processing process.

[0068] Furthermore, the segments retained after filtering are referred to as retained segments (i.e., retained segments). For each retained segment, the window position of the first window on the retained segment in the local area can be obtained, and then the minimum window position and the maximum window position can be found from the window positions corresponding to each retained segment, and then the position range is constructed based on the minimum window position and the maximum window position. On this basis, according to the above description, most of the pos outside the position range are abnormal pos. Therefore, in order to ensure the accuracy of the breakpoint identification, the target position within the position range can be determined from all pos, and then the breakpoint identification is performed based on the target position.

[0069] The above technical solution further improves the accuracy of breaking point identification by filtering out abnormal POS from all POS and then identifying breaking points based on the retained POS (ie normal POS) obtained after filtering.

[0070] On this basis, optionally, the breakpoints where chromosome structural variation occurs in the local region are identified based on the target location, including:

[0071] Based on the target position, the minimum position and the maximum position of all the read pair positions corresponding to each shared barcode in the local area are obtained, so as to divide all the shared barcodes into at least two groups according to the minimum position and the maximum position corresponding to all the shared barcodes;

[0072] For each group, the breakpoints where the chromosome structural variation occurs in the local region are identified based on the second information of each group barcode classified into the group among all the shared barcodes.

[0073] Among them, for each shared barcode in the local area, the shared barcode carries one or more reads-pairs, and one reads-pair corresponds to 2 pos. Here, the minimum position (i.e., the minimum pos) and the maximum position (i.e., the maximum pos) are found from all the pos corresponding to the shared barcode.

[0074] Further, all the shared barcodes are divided into at least two groups (or at least two categories) according to the minimum position and the maximum position corresponding to all the shared barcodes. On this basis, optionally, in theory, the grouping results of the same shared barcode in different local areas should be consistent, but due to deviations in the grouping process, the grouping results of the same shared barcode in different local areas may be inconsistent, and this inconsistency will affect the accuracy of breaking point identification. In this regard, after all the shared barcodes are divided into at least two groups, it also includes: for each shared barcode, when the grouping results of the shared barcode for different local areas are inconsistent, the shared barcode is deleted from the group where the shared barcode is located. That is, the shared barcode with inconsistent grouping results in different local areas is deleted from the corresponding grouping results, that is, the subsequent breaking point identification process no longer considers the shared barcode, thereby avoiding the shared barcode from affecting the accuracy of breaking point identification.

[0075] For each group, the shared barcodes in all shared barcodes that are divided into the group are called group barcodes (i.e., group barcodes), and the second information can be understood as the information of the group barcode. Therefore, the breakpoints on the group can be identified based on the second information.

[0076] The above technical solution, based on the breakpoint identification by region, divides the shared barcodes in a local area into at least two groups, and then identifies the breakpoints of each group separately, that is, the breakpoint identification is performed on a single group in a single local area. Compared with the breakpoint identification of a single local area, the more refined breakpoint identification process further improves the accuracy of breakpoint identification.

[0077] On this basis, optionally, according to the second information of each group barcode divided into groups among all the shared barcodes, the breakpoints where the chromosome structural variation occurs in the local region are identified, including:

[0078] According to the second information of each group barcode divided into groups among all the shared barcodes, a sub-region is determined from the local region, and a sliding window is performed on the sub-region to obtain a plurality of second windows;

[0079] For each second window, the window identifier of the second window and the second number of grouped barcodes under the second window are used as a set of data, so as to perform linear fitting according to the data respectively corresponding to the plurality of second windows to obtain a fitting slope;

[0080] According to the fitting slope and the second quantities respectively corresponding to the plurality of second windows, the breakpoints where the chromosome structural variation occurs in the sub-region are identified.

[0081] For each group, a sub-region is determined from the local region according to the second information of each group barcode in all shared barcodes that are divided into the group. The sub-region can be understood as the region where each group barcode is located on the local region. A sliding window is performed on the sub-region to obtain multiple second windows.

[0082] Then, a unique window identifier is assigned to each second window, and the second number of grouped barcodes under each second window is counted. On this basis, for each second window, the window identifier and the second number corresponding to the second window are used as a set of data, so that a linear fit can be performed based on the data corresponding to the multiple second windows to obtain a fitting slope. Exemplarily, for the linear equation y=kx+b, y is the second number, x is the window identifier, and k is the fitting slope, then a linear fit is performed based on the above multiple sets of data to solve k. Further, according to the fitting slope and the second numbers corresponding to the multiple second windows, the breakpoints in the sub-region are identified. For example, the target window corresponding to the largest second number can be found from the multiple second windows, and when the fitting slope is greater than 0, the largest pos of the target window is taken as the breakpoint in the sub-region, otherwise the smallest pos of the target window is taken as the breakpoint in the sub-region.

[0083] The above technical solution, for a sub-region corresponding to a grouping result in a local area, continues to slide the window on the sub-region, thereby identifying the breakpoint based on the grouping barcode in a smaller second window, thereby further improving the accuracy of breakpoint identification.

[0084] In order to prove that the above-mentioned technical solutions can accurately identify breakpoints, the following is an exemplary description combined with an example of balanced translocation, an example of inversion, and a comparative example of SV breakpoint identification results of different software.

[0085] Example 1: Balanced translocation example: Breakpoint identification of balanced translocation between chromosomes 1 and 11. The karyotype result is t(1;11)(1q31.2;11q25). The distribution of the barcodes of the SVs supporting this karyotype result on the genome is as follows: Figure 3a and Figure 3b As shown, the red dotted line indicates the location of the breakpoint, and the horizontal axis indicates the genome position. Figure 3a chr1 and Figure 3b The same vertical coordinate position in chr11 represents the distribution of the same barcode across two breakpoints.

[0086] Example 2: Inversion example: Identification of the breakpoints of the inversion of chromosome 2. Its karyotype result is inv(2)(q12q24.2). The distribution of the barcodes of the SVs supporting this karyotype result on the genome is as follows: Figure 4a and Figure 4b As shown, the red dotted line is the location of the breakpoint, and the horizontal axis represents the genome position. Figure 4a left and Figure 4b The same vertical coordinate position in the right represents the distribution of the same barcode across two breakpoints.

[0087] Example 3: Comparison of SV breakpoint recognition results of different software: Using two related existing software and the software of this case compiled based on the above technical solutions, the breakpoints of the SVs shown in the above two examples are respectively recognized, and the recognition results are shown in the following table. After experimental verification, compared with the existing software, the software of this case can more accurately recognize the SV breakpoint.

[0088] Table 1 Comparison of SV breakpoint recognition results of various software

[0089]

[0090] Figure 5 This is a structural block diagram of a device for identifying breakpoints in chromosome structural variation regions provided in an embodiment of the present invention. The device is used to execute the method for identifying breakpoints in chromosome structural variation regions provided in any of the above embodiments. The device and the method for identifying breakpoints in chromosome structural variation regions in the above embodiments belong to the same inventive concept. For details not described in detail in the embodiment of the device for identifying breakpoints in chromosome structural variation regions, reference can be made to the embodiment of the method for identifying breakpoints in chromosome structural variation regions. Figure 5 The device may specifically include: a region window acquisition module 410, a first information determination module 420 and a breakpoint identification module 430.

[0091] A region window acquisition module 410 is used to acquire a chromosome structural variation region and at least two region windows, wherein each region window is combined to surround the chromosome structural variation region;

[0092] A first information determination module 420, used to determine first information of a shared barcode between each area window;

[0093] The breakpoint identification module 430 is used to obtain the read pair positions of the read pairs carried by the shared barcode according to the first information, and identify the breakpoints where the chromosome structural variation occurs in the chromosome structural variation region according to the read pair positions.

[0094] Optionally, the breakpoint identification module 430 may include:

[0095] A first window obtaining submodule is used to determine, for each regional window, a local area covered by the regional window on the chromosome structural variation region, and to perform sliding window operation on the local area to obtain multiple first windows;

[0096] A first quantity obtaining submodule, configured to obtain, for each first window, according to the first information, the read pair positions of the read pairs carried by the shared barcodes under the first window and the first quantity of the shared barcodes under the first window;

[0097] The breakpoint identification submodule is used to identify the breakpoints where chromosome structural variation occurs in the local area according to the positions and the first quantities of read pairs respectively corresponding to the plurality of first windows.

[0098] On this basis, optional breakpoint identification submodules include:

[0099] A local area division unit, configured to merge first windows that are adjacent in window position and similar in first quantity among a plurality of first windows, and divide the local area into at least one segment based on the merging result;

[0100] a fragment filtering unit, configured to obtain an average quantity for each fragment according to the first quantities respectively corresponding to the first windows on the fragment, so as to filter each fragment according to the average quantities respectively corresponding to each fragment;

[0101] a position range construction unit, for obtaining the window position of the first window on each of the retained fragments after filtering in each of the fragments, so as to construct a position range based on the minimum window position and the maximum window position of all the window positions;

[0102] The breakpoint identification unit is used to determine the target positions located within the position range among the read pair positions corresponding to the plurality of first windows, and to identify the breakpoints where the chromosome structural variation occurs in the local region based on the target positions.

[0103] On this basis, the optional breakpoint identification unit includes:

[0104] The shared barcode division subunit is used to obtain the minimum position and the maximum position of all the read segment pair positions corresponding to each shared barcode in the local area based on the target position, so as to divide all the shared barcodes into at least two groups according to the minimum position and the maximum position corresponding to all the shared barcodes;

[0105] The breakpoint identification subunit is used to identify the breakpoint where the chromosome structural variation occurs in the local area according to the second information of each group barcode divided into the group among all the shared barcodes for each group.

[0106] On this basis, an optional breakpoint recognition subunit is specifically used to:

[0107] According to the second information of each group barcode divided into groups among all the shared barcodes, a sub-region is determined from the local region, and a sliding window is performed on the sub-region to obtain a plurality of second windows;

[0108] For each second window, the window identifier of the second window and the second number of grouped barcodes under the second window are used as a set of data, so as to perform linear fitting according to the data respectively corresponding to the plurality of second windows to obtain a fitting slope;

[0109] According to the fitting slope and the second quantities respectively corresponding to the plurality of second windows, the breakpoints where the chromosome structural variation occurs in the sub-region are identified.

[0110] Alternatively, the above-mentioned breakpoint identification unit further includes:

[0111] The shared barcode deletion subunit is used to delete the shared barcode from the group where the shared barcode is located after all the shared barcodes are divided into at least two groups, if the grouping results of the shared barcode for different local areas are inconsistent.

[0112] The breakpoint identification device for the chromosome structural variation region provided by the embodiment of the present invention obtains the chromosome SV region and at least two regional windows through the regional window acquisition module, and the at least two regional windows can surround the chromosome SV region after merging; further, through the mutual cooperation of the first information determination module and the breakpoint identification module, the first information of the shared barcode between each regional window is determined, thereby obtaining the pos of the reads-pair carried by the shared barcode according to the first information, and identifying the breakpoint of the SV in the chromosome SV region according to the pos. The above device uses the pos corresponding to the shared barcode between each regional window on the chromosome SV region to achieve accurate identification of the breakpoint in the chromosome SV region.

[0113] The breakpoint identification device for chromosome structural variation regions provided by the embodiment of the present invention can execute the breakpoint identification method for chromosome structural variation regions provided by any embodiment of the present invention, and has the corresponding functional modules and beneficial effects of the execution method.

[0114] It is worth noting that in the above-mentioned embodiment of the breakpoint identification device for the chromosome structural variation region, the various units and modules included are only divided according to functional logic, but are not limited to the above-mentioned division, as long as the corresponding functions can be achieved; in addition, the specific names of the functional units are only for the convenience of distinguishing each other, and are not used to limit the scope of protection of the present invention.

[0115] Figure 6 A schematic diagram of the structure of an electronic device 10 that can be used to implement an embodiment of the present invention is shown. The electronic device is intended to represent various forms of digital computers, such as laptop computers, desktop computers, workstations, personal digital assistants, servers, blade servers, mainframe computers, and other suitable computers. The electronic device can also represent various forms of mobile devices, such as personal digital processing, cellular phones, smart phones, wearable devices (such as helmets, glasses, watches, etc.) and other similar computing devices. The components shown herein, their connections and relationships, and their functions are merely examples and are not intended to limit the implementation of the present invention described and / or required herein.

[0116] like Figure 6 As shown, the electronic device 10 includes at least one processor 11, and a memory connected to the at least one processor 11, such as a read-only memory (ROM) 12, a random access memory (RAM) 13, etc., wherein the memory stores a computer program that can be executed by at least one processor, and the processor 11 can perform various appropriate actions and processes according to the computer program stored in the read-only memory (ROM) 12 or the computer program loaded from the storage unit 18 to the random access memory (RAM) 13. In the RAM 13, various programs and data required for the operation of the electronic device 10 can also be stored. The processor 11, the ROM 12, and the RAM 13 are connected to each other through a bus 14. An input / output (I / O) interface 15 is also connected to the bus 14.

[0117] A number of components in the electronic device 10 are connected to the I / O interface 15, including: an input unit 16, such as a keyboard, a mouse, etc.; an output unit 17, such as various types of displays, speakers, etc.; a storage unit 18, such as a disk, an optical disk, etc.; and a communication unit 19, such as a network card, a modem, a wireless communication transceiver, etc. The communication unit 19 allows the electronic device 10 to exchange information / data with other devices through a computer network such as the Internet and / or various telecommunication networks.

[0118] The processor 11 may be a variety of general and / or special processing components with processing and computing capabilities. Some examples of the processor 11 include, but are not limited to, a central processing unit (CPU), a graphics processing unit (GPU), various special artificial intelligence (AI) computing chips, various processors running machine learning model algorithms, a digital signal processor (DSP), and any appropriate processor, controller, microcontroller, etc. The processor 11 executes the various methods and processes described above, such as the above-mentioned breakpoint identification method.

[0119] In some embodiments, the above-described breakpoint identification method may be implemented as a computer program, which is tangibly contained in a computer-readable storage medium, such as a storage unit 18. In some embodiments, part or all of the computer program may be loaded and / or installed on the electronic device 10 via the ROM 12 and / or the communication unit 19. When the computer program is loaded into the RAM 13 and executed by the processor 11, one or more steps of the above-described breakpoint identification method may be performed. Alternatively, in other embodiments, the processor 11 may be configured to perform the above-described breakpoint identification method in any other appropriate manner (e.g., by means of firmware).

[0120] Various implementations of the systems and techniques described above herein can be implemented in digital electronic circuit systems, integrated circuit systems, field programmable gate arrays (FPGAs), application specific integrated circuits (ASICs), application specific standard products (ASSPs), systems on chips (SOCs), load programmable logic devices (CPLDs), computer hardware, firmware, software, and / or combinations thereof. These various implementations can include: being implemented in one or more computer programs that can be executed and / or interpreted on a programmable system including at least one programmable processor, which can be a special purpose or general purpose programmable processor that can receive data and instructions from a storage system, at least one input device, and at least one output device, and transmit data and instructions to the storage system, the at least one input device, and the at least one output device.

[0121] Computer programs for implementing the methods of the present invention may be written in any combination of one or more programming languages. These computer programs may be provided to a processor of a general-purpose computer, a special-purpose computer, or other programmable data processing device, so that when the computer program is executed by the processor, the functions / operations specified in the flow chart and / or block diagram are implemented. The computer program may be executed entirely on the machine, partially on the machine, partially on the machine as a stand-alone software package and partially on a remote machine, or entirely on a remote machine or server.

[0122] In the context of the present invention, a computer-readable storage medium may be a tangible medium that may contain or store a computer program for use by or in combination with an instruction execution system, device or equipment. A computer-readable storage medium may include, but is not limited to, electronic, magnetic, optical, electromagnetic, infrared, or semiconductor systems, devices or equipment, or any suitable combination of the foregoing. Alternatively, a computer-readable storage medium may be a machine-readable signal medium. A more specific example of a machine-readable storage medium may include an electrical connection based on one or more lines, a portable computer disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disk read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing.

[0123] To provide interaction with a user, the systems and techniques described herein may be implemented on an electronic device having: a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) for displaying information to the user; and a keyboard and a pointing device (e.g., a mouse or trackball) through which the user can provide input to the electronic device. Other types of devices may also be used to provide interaction with the user; for example, the feedback provided to the user may be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user may be received in any form (including acoustic input, voice input, or tactile input).

[0124] The systems and techniques described herein may be implemented in a computing system that includes backend components (e.g., as a data server), or a computing system that includes middleware components (e.g., an application server), or a computing system that includes frontend components (e.g., a user computer with a graphical user interface or a web browser through which a user can interact with implementations of the systems and techniques described herein), or a computing system that includes any combination of such backend components, middleware components, or frontend components. The components of the system may be interconnected by any form or medium of digital data communication (e.g., a communication network). Examples of communication networks include: a local area network (LAN), a wide area network (WAN), a blockchain network, and the Internet.

[0125] A computing system may include a client and a server. The client and the server are generally remote from each other and usually interact through a communication network. The client and server relationship is generated by computer programs running on the corresponding computers and having a client-server relationship with each other. The server may be a cloud server, also known as a cloud computing server or cloud host, which is a host product in the cloud computing service system to solve the defects of difficult management and weak business scalability in traditional physical hosts and VPS services.

[0126] It should be understood that the various forms of processes shown above can be used to reorder, add or delete steps. For example, the steps described in the present invention can be executed in parallel, sequentially or in different orders, as long as the desired results of the technical solution of the present invention can be achieved, and this document does not limit this.

[0127] The above specific implementations do not constitute a limitation on the protection scope of the present invention. It should be understood by those skilled in the art that various modifications, combinations, sub-combinations and substitutions can be made according to design requirements and other factors. Any modification, equivalent substitution and improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for identifying breakpoints in chromosome structural variation regions. It is characterized in that include: Acquire a chromosome structural variation region and at least two region windows, wherein each of the region windows merges to surround the chromosome structural variation region; Determine first information of a shared barcode between the area windows; The read pair positions of the read pairs carried by the shared barcode are obtained according to the first information, and the breakpoints where the chromosome structural variation occurs in the chromosome structural variation region are identified according to the read pair positions.

2. The method according to claim 1, It is characterized in that The obtaining, according to the first information, the read pair positions of the read pairs carried by the shared barcode, and identifying the breakpoints where the chromosome structural variation occurs in the chromosome structural variation region according to the read pair positions, comprises: For each of the regional windows, determining a local area covered by the regional window on the chromosome structural variation region, and sliding a window on the local area to obtain a plurality of first windows; For each of the first windows, obtaining, according to the first information, read pair positions of the read pairs carried by the shared barcodes in the first window and a first number of the shared barcodes in the first window; According to the positions and the first quantities of read pairs respectively corresponding to the plurality of the first windows, the breakpoints where the chromosome structural variation occurs in the local region are identified.

3. The method according to claim 2, It is characterized in that The step of identifying the breakpoints where the chromosome structural variation occurs in the local region according to the positions and the first quantities of the read pairs respectively corresponding to the plurality of the first windows comprises: Merging the first windows that are adjacent in window position and close in the first number among the plurality of the first windows, and dividing the local area into at least one segment based on the merging result; For each of the segments, an average number is obtained according to the first numbers respectively corresponding to the first windows on the segment, so as to filter the segments according to the average numbers respectively corresponding to the segments; For the retained fragments retained after filtering in each of the fragments, the window position of the first window on each of the retained fragments is obtained, so as to construct a position range based on the smallest window position and the largest window position among all the window positions; A target position located within the position range among the read pair positions corresponding to the plurality of first windows is determined, and a breakpoint where a chromosome structural variation occurs in the local region is identified based on the target position.

4. The method according to claim 3, It is characterized in that The step of identifying the breakpoint where the chromosome structural variation occurs in the local region based on the target position comprises: Based on the target position, obtaining the minimum position and the maximum position of all the read segment pair positions corresponding to each of the shared barcodes on the local area, so as to divide all the shared barcodes into at least two groups according to the minimum position and the maximum position corresponding to all the shared barcodes; For each of the groups, the breakpoints where the chromosome structural variation occurs in the local region are identified based on the second information of the barcodes of each group divided into the group among all the shared barcodes.

5. The method according to claim 4, It is characterized in that The step of identifying the breakpoints where the chromosome structural variation occurs in the local region according to the second information of each group barcode divided into the group among all the shared barcodes comprises: According to the second information of each group barcode divided into the group in all the shared barcodes, a sub-region is determined from the local region, and a sliding window is performed on the sub-region to obtain a plurality of second windows; For each second window, the window identifier of the second window and the second number of the grouped barcodes under the second window are taken as a set of data, so as to perform linear fitting according to the data respectively corresponding to the plurality of second windows to obtain a fitting slope; According to the fitting slope and the second numbers respectively corresponding to the plurality of second windows, the breakpoints where the chromosome structural variation occurs in the sub-region are identified.

6. The method according to claim 4, It is characterized in that After dividing all the shared barcodes into at least two groups, the method further includes: For each of the shared barcodes, when the grouping results of the shared barcodes for different local areas are inconsistent, the shared barcode is deleted from the group where the shared barcode is located.

7. A device for identifying breakpoints in chromosome structural variation regions, It is characterized in that include: A region window acquisition module, used to acquire a chromosome structural variation region and at least two region windows, wherein each of the region windows merges to surround the chromosome structural variation region; A first information determination module, used to determine first information of a shared barcode between the area windows; A breakpoint identification module is used to obtain the read pair position of the read pair carried by the shared barcode according to the first information, and identify the breakpoint where the chromosome structural variation occurs in the chromosome structural variation region according to the read pair position.

8. An electronic device, It is characterized in that include: at least one processor; as well as a memory communicatively connected to the at least one processor; wherein, The memory stores a computer program executable by the at least one processor, and the computer program is executed by the at least one processor so that the at least one processor performs the breakpoint identification method for a chromosome structural variation region according to any one of claims 1 to 6.

9. A computer-readable storage medium, It is characterized in that The computer-readable storage medium stores computer instructions, and the computer instructions are used to enable a processor to implement the breakpoint identification method for a chromosome structural variation region as described in any one of claims 1 to 6 when executed.

10. A computer program product, It is characterized in that The computer program product comprises a computer program, and when the computer program is executed by a processor, the computer program implements the breakpoint identification method for a chromosome structural variation region according to any one of claims 1 to 6.

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