A method for displaying single-molecule chromatin microstructure

Abstract

The present application is applicable to the field of bioinformatics, and provides a method for displaying a single-molecule chromatin microstructure, the method comprising: obtaining target chromosome region information, and obtaining target single-molecule chromatin complex information; obtaining target single-molecule chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information; performing cluster analysis on the target single-molecule chromatin information to obtain clustering matrix information; obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, and displaying the display image. The above method clusters the single-molecule chromatin complex data to display the microstructure of chromatin, can intuitively browse the chromatin microstructure of multiple chromatin complexes in real time, and can conduct in-depth and intuitive exploration and analysis of the functions and characteristics of multiple chromatin complexes.

Description

Technical Field

[0001] The present application belongs to the field of bioinformatics, and in particular relates to a method for displaying single-molecule chromatin microstructure. Background Art

[0002] The one-dimensional linear genome sequence of the entire human genome is about 2 meters long when connected together, and is squeezed into a cell nucleus with a diameter of only about 10 microns. This 2-meter-long linear genome sequence is highly folded in the cell nucleus to regulate gene expression in an orderly manner, thereby ensuring the normal operation of cell life. Three-dimensional genomics is an emerging discipline that studies how the genome is folded and assembled into a high-dimensional structure in the cell nucleus to perform its functions.

[0003] The new generation of 3D genome interaction technologies such as GAM, SPRITE and ChIA-Drop can detect multi-site interactions and accurately analyze the spatial structure of chromatin. However, due to the complexity of the spatial structure of chromatin, it is impossible to conduct in-depth and intuitive exploration and analysis of multiple chromatin complexes after using existing analysis methods. Summary of the invention

[0004] The embodiments of the present application provide a method for displaying single-molecule chromatin microstructure, which can solve the above problems.

[0005] In a first aspect, the present invention provides a method for displaying a single-molecule chromatin microstructure, comprising:

[0006] Obtaining target chromosome region information and target single-molecule chromatin complex information;

[0007] Acquire the target single molecule chromatin information corresponding to the target chromosome region information from the target single molecule chromatin complex information;

[0008] Performing cluster analysis on the target single-molecule chromatin information to obtain cluster matrix information;

[0009] According to the clustering matrix information, a display image corresponding to the chromatin microstructure of the target chromosome region information is obtained, and the display image is displayed.

[0010] Furthermore, the obtaining of target single-molecule chromatin complex information includes:

[0011] Obtain initial single-molecule chromatin complex information;

[0012] The initial single-molecule chromatin complex information is formatted to obtain target single-molecule chromatin complex information; wherein the target single-molecule chromatin complex information includes a plurality of DNA interaction fragment information; the DNA interaction fragment information includes the region information and the complex encoding information.

[0013] Further, the step of obtaining the target single molecule chromatin information corresponding to the target chromosome region information from the target single molecule chromatin complex information includes:

[0014] Acquiring initial chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information;

[0015] The initial chromatin information is mapped to the target bins to generate target single-molecule chromatin information stored in an interaction matrix; wherein each row in the interaction matrix represents each chromatin complex, and each column in the interaction matrix represents a different target bin.

[0016] Furthermore, after obtaining the initial chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information, the method further includes:

[0017] The initial chromatin information is displayed.

[0018] Furthermore, the clustering analysis is performed on the target single-molecule chromatin information to obtain clustering matrix information, including:

[0019] A hierarchical clustering process is performed on each of the chromatin complexes in the interaction matrix to obtain first matrix information corresponding to the first dimensional data, and the first matrix information is used as clustering matrix information.

[0020] Furthermore, after performing hierarchical clustering processing on each of the chromatin complexes in the interaction matrix to obtain clustering matrix information corresponding to the first dimensional data, the method further includes:

[0021] If the first matrix information does not meet the preset condition, performing dimensionality reduction processing on the first matrix information according to a dimensionality reduction algorithm to obtain second dimensional data;

[0022] Perform cluster analysis on the second dimensional data to obtain second matrix information, and use the second matrix information as cluster matrix information.

[0023] Furthermore, obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information includes:

[0024] The clustering matrix information is subjected to data overlay processing to generate a cumulative coverage view of the target chromosome region information.

[0025] Further, after obtaining the display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, it also includes:

[0026] The cumulative coverage view and the target single-molecule chromatin information are interactively superimposed to generate a two-dimensional interactive map of the target chromosome region information.

[0027] Further, the display image includes a first heat map view and a first dimension data segment view;

[0028] The step of obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information includes:

[0029] Obtain a first heat map view according to first matrix information corresponding to the first dimensional data;

[0030] A first dimensional data segment view is obtained according to the first heat map view.

[0031] Further, the display image includes a second heat map view and a second dimension data segment view;

[0032] The step of obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information includes:

[0033] Obtain a second heat map view according to second matrix information corresponding to the second dimensional data;

[0034] A second dimensional data segment view is obtained according to the second heat map view.

[0035] Furthermore, the display image also includes one or more of a target region view, a gene transcription pattern view, a chromatin organization pattern view, a transcription regulation pattern view, and a shielding view.

[0036] Further, after obtaining the display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, it also includes:

[0037] According to the preset boundary definition rule and the display image, the target boundary information of the chromatin microstructure of the target chromosome region information is obtained.

[0038] Further, the display image includes a clustered segment view;

[0039] The step of obtaining target boundary information of the chromatin microdomain of the target chromosome region information according to the preset boundary definition rule and the display image comprises:

[0040] Acquiring DNA fragment information in the clustered fragment view;

[0041] Obtaining initial density contour lines corresponding to the probability distribution information of the DNA fragment information according to a preset two-dimensional kernel density preset algorithm;

[0042] Filtering out target density contour lines that meet preset filtering conditions from the initial density contour lines;

[0043] The target boundary information of the chromatin microstructure of the target chromosome region information is determined according to the target density contour line.

[0044] Further, the display image includes a clustered segment view;

[0045] The step of obtaining target boundary information of the chromatin microstructure of the target chromosome region information according to the preset boundary definition rule and the display image includes:

[0046] The clustered fragment view is input into a trained boundary definition model for processing to obtain target boundary information of the chromatin microdomain of the target chromosome region information.

[0047] In a second aspect, the present application provides a single-molecule chromatin microstructure device, comprising:

[0048] A first acquisition unit is used to acquire target chromosome region information and target single-molecule chromatin complex information;

[0049] A second acquisition unit is used to acquire the target single molecule chromatin information corresponding to the target chromosome region information from the target single molecule chromatin complex information;

[0050] A first processing unit is used to perform cluster analysis on the target single-molecule chromatin information to obtain cluster matrix information;

[0051] The second processing unit is used to obtain a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, and display the display image.

[0052] Furthermore, the first acquisition unit is specifically configured to:

[0053] Obtain initial single-molecule chromatin complex information;

[0054] The initial single-molecule chromatin complex information is formatted to obtain target single-molecule chromatin complex information; wherein the target single-molecule chromatin complex information includes a plurality of DNA interaction fragment information; the DNA interaction fragment information includes the region information and the complex encoding information.

[0055] Furthermore, the second acquisition unit is specifically used to:

[0056] Acquiring initial chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information;

[0057] The initial chromatin information is mapped to the target bins to generate target single-molecule chromatin information stored in an interaction matrix; wherein each row in the interaction matrix represents each chromatin complex, and each column in the interaction matrix represents a different target bin.

[0058] Furthermore, the second acquisition unit is further configured to:

[0059] The initial chromatin information is displayed.

[0060] Furthermore, the first processing unit is specifically configured to:

[0061] A hierarchical clustering process is performed on each of the chromatin complexes in the interaction matrix to obtain first matrix information corresponding to the first dimensional data, and the first matrix information is used as clustering matrix information.

[0062] Furthermore, the first processing unit is further configured to:

[0063] If the first matrix information does not meet the preset condition, performing dimensionality reduction processing on the first matrix information according to a dimensionality reduction algorithm to obtain second dimensional data;

[0064] Perform cluster analysis on the second dimensional data to obtain second matrix information, and use the second matrix information as cluster matrix information.

[0065] Furthermore, the second processing unit is specifically configured to:

[0066] The clustering matrix information is subjected to data overlay processing to generate a cumulative coverage view of the target chromosome region information.

[0067] Furthermore, the second processing unit is further configured to:

[0068] The cumulative coverage view and the target single-molecule chromatin information are interactively superimposed to generate a two-dimensional interactive map of the target chromosome region information.

[0069] Further, the display image includes a first heat map view and a first dimension data segment view; the second processing unit is specifically configured to:

[0070] Obtain a first heat map view according to first matrix information corresponding to the first dimensional data;

[0071] A first dimensional data segment view is obtained according to the first heat map view.

[0072] Furthermore, the display image includes a second heat map view and a second dimensional data segment view; the second processing unit is specifically configured to:

[0073] Obtain a second heat map view according to second matrix information corresponding to the second dimensional data;

[0074] A second dimensional data segment view is obtained according to the second heat map view.

[0075] Furthermore, the display image also includes one or more of a target region view, a gene transcription pattern view, a chromatin organization pattern view, a transcription regulation pattern view, and a shielding view.

[0076] Furthermore, the chromatin microdomain display device further comprises:

[0077] The third processing unit is used to obtain target boundary information of the chromatin microstructure of the target chromosome region information according to a preset boundary definition rule and the display image.

[0078] Further, the display image includes a clustered segment view;

[0079] The third processing unit is specifically configured to:

[0080] Acquiring DNA fragment information in the clustered fragment view;

[0081] Obtaining initial density contour lines corresponding to the probability distribution information of the DNA fragment information according to a preset two-dimensional kernel density preset algorithm;

[0082] Filtering out target density contour lines that meet preset filtering conditions from the initial density contour lines;

[0083] The target boundary information of the chromatin microstructure of the target chromosome region information is determined according to the target density contour line.

[0084] Further, the display image includes a clustered segment view;

[0085] The third processing unit is specifically configured to:

[0086] The clustered segment view is input into a trained boundary definition model for processing to obtain target boundary information of the chromatin microstructure of the target chromosome region information.

[0087] In a third aspect, an embodiment of the present application provides a device for displaying chromatin microdomains, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor implements the method described in the first aspect above when executing the computer program.

[0088] In a fourth aspect, an embodiment of the present application provides a computer-readable storage medium, wherein the computer-readable storage medium stores a computer program, and when the computer program is executed by a processor, the method described in the first aspect above is implemented.

[0089] In the embodiment of the present application, the target chromosome region information is obtained, and the target single-molecule chromatin complex information is obtained; the target single-molecule chromatin information corresponding to the target chromosome region information is obtained from the target single-molecule chromatin complex information; the target single-molecule chromatin information is clustered and processed to obtain clustering matrix information; according to the clustering matrix information, the display image corresponding to the chromatin microstructure of the target chromosome region information is obtained, and the display image is displayed. The above method clusters the single-molecule chromatin complex data to display the microstructure of chromatin, and the chromatin microstructure of multiple chromatin complexes can be browsed intuitively and in real time, and the functions and characteristics of multiple chromatin complexes can be deeply and intuitively explored and analyzed. BRIEF DESCRIPTION OF THE DRAWINGS

[0090] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0091] Figure 1 is a schematic flow chart of a method for displaying a single-molecule chromatin microstructure provided in the first embodiment of the present application;

[0092] Figure 2 This is a specific schematic flow chart of S101 in a method for displaying a single-molecule chromatin microstructure provided in the first embodiment of the present application;

[0093] Figure 3 This is a specific schematic flow chart of S102 in a method for displaying a single-molecule chromatin microstructure provided in the first embodiment of the present application;

[0094] Figure 4is a schematic diagram of a display device for single-molecule chromatin microstructure provided in the second embodiment of the present application;

[0095] Figure 5 This is a schematic diagram of a display device for single-molecule chromatin microstructure provided in the third embodiment of the present application. DETAILED DESCRIPTION

[0096] In the following description, specific details such as specific system structures, technologies, etc. are provided for the purpose of illustration rather than limitation, so as to provide a thorough understanding of the embodiments of the present application. However, it should be clear to those skilled in the art that the present application may also be implemented in other embodiments without these specific details. In other cases, detailed descriptions of well-known systems, devices, circuits, and methods are omitted to prevent unnecessary details from obstructing the description of the present application.

[0097] It should be understood that when used in the present specification and the appended claims, the term "comprising" indicates the presence of described features, wholes, steps, operations, elements and / or components, but does not exclude the presence or addition of one or more other features, wholes, steps, operations, elements, components and / or combinations thereof.

[0098] It should also be understood that the term “and / or” used in the specification and appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes these combinations.

[0099] As used in the specification and appended claims of this application, the term "if" can be interpreted as "when" or "uponce" or "in response to determining" or "in response to detecting", depending on the context. Similarly, the phrase "if it is determined" or "if [described condition or event] is detected" can be interpreted as meaning "uponce it is determined" or "in response to determining" or "uponce [described condition or event] is detected" or "in response to detecting [described condition or event]", depending on the context.

[0100] In addition, in the description of the present application specification and the appended claims, the terms "first", "second", "third", etc. are only used to distinguish the descriptions and cannot be understood as indicating or implying relative importance.

[0101] References to "one embodiment" or "some embodiments" etc. described in the specification of this application mean that one or more embodiments of the present application include specific features, structures or characteristics described in conjunction with the embodiment. Therefore, the statements "in one embodiment", "in some embodiments", "in some other embodiments", "in some other embodiments", etc. that appear in different places in this specification do not necessarily refer to the same embodiment, but mean "one or more but not all embodiments", unless otherwise specifically emphasized in other ways. The terms "including", "comprising", "having" and their variations all mean "including but not limited to", unless otherwise specifically emphasized in other ways.

[0102] The implementation of the Human Genome Project has enabled us to obtain a one-dimensional linear base sequence of the entire human genome, which is about 2 meters long when connected, but is squeezed into a cell nucleus with a diameter of only about 10 microns. This 2-meter-long linear genome sequence is highly folded in the cell nucleus to regulate gene expression in an orderly manner, thereby ensuring the normal operation of cell life. Three-dimensional genomics is an emerging discipline that studies how the genome is folded and assembled into a high-dimensional structure in the cell nucleus to perform its functions. Traditional three-dimensional genomic technologies such as Hi-C, ChIA-PET and their derivative methods fully analyze the high-dimensional structure of chromatin, including chromatin topologically associated domains TAD, A / B chromosome compartments, and chromatin interaction loops. However, these technologies are based on "neighborhood connection" biotechnology, which detects the "two-to-two interactions" of chromatin. The data is the result of the superposition of group cells, so there is no way to truly analyze the structure of chromatin in a single cell. In recent years, a new generation of three-dimensional genome interaction technologies has emerged, such as GAM, SPRITE and ChIA-Drop. The new generation of three-dimensional genome interaction technologies does not rely on "neighborhood connection", so it can detect interactions at multiple sites and accurately analyze the spatial structure of chromatin. The new generation of 3D genome technology has solved the current hot and difficult problems of 3D genome, such as what the chromatin topology-associated domain TAD looks like at the single-cell level, whether each cell has the same TAD structure, and how super enhancers that cluster together regulate target genes. However, the information of single-molecule multi-site chromatin complexes detected by the new generation of 3D genome technology is complex, and there is currently no visualization tool that can directly observe and browse multiple chromatin complexes, which greatly limits the exploration and analysis of single-molecule multiple chromatin interaction data.

[0103] Therefore, the embodiments of the present application propose a method for displaying chromatin microdomains, which mainly displays the chromatin microdomains of single-molecule multiple chromatin complexes generated by the current new generation of three-dimensional genomic technologies GAM, SPRITE and ChIA-Drop in real time.

[0104] See also Figure 1 , Figure 1 : is a schematic flow chart of a method for displaying chromatin microdomains provided in the first embodiment of the present application. The execution subject of the method for displaying chromatin microdomains in this embodiment is a device with the function of displaying chromatin microdomains, such as a desktop computer, a server, etc. Figure 1 The method for displaying the chromatin microdomains shown may include:

[0105] S101: Obtain target chromosome region information and target single-molecule chromatin complex information.

[0106] The device obtains target chromosome region information, wherein the target chromosome region information is the chromosome region of the chromatin microdomain to be displayed in this embodiment, and the target chromosome region information includes the region position information of the chromosome to be displayed.

[0107] The device can obtain the display instructions triggered by the user on the operation end, and extract the target chromosome region information from the display instructions. For example, the user can open the display browser on the operation end, select the genomic region of interest on the display browser interface, and the operation end generates a display instruction based on the genomic region of interest selected by the user. The device obtains the display instruction, and extracts the region of interest to the user from the display instruction, which is the target chromosome region information.

[0108] The operating end may be a local device or a device connected to the local device via a network.

[0109] The device obtains the target single-molecule chromatin complex information, and the target single-molecule chromatin complex information includes the information corresponding to all the single-molecule chromatin complexes required in this embodiment. Among them, each row of the target single-molecule chromatin complex information represents a single-molecule chromatin complex, and each column represents the interactive genomic position. The device can store the target single-molecule chromatin complex information in the background database, and when the target chromosome region information is obtained, the target chromosome information corresponding to the target chromosome region information is extracted from the target single-molecule chromatin complex information.

[0110] Among them, when obtaining the target single-molecule chromatin complex information, high-throughput sequencing data can be obtained through the new generation of three-dimensional genome technology GAM, SPRITE and ChIA-Drop. The data obtained by the second-generation sequencing technology Illumina double-end sequencing can ultimately obtain the target single-molecule chromatin complex information according to the data processing software.

[0111] In one embodiment, in order to obtain the target chromosome information corresponding to the target chromosome region information from the target single molecule chromatin complex information more accurately and quickly, the device can perform format conversion processing on the initial data. Specifically, the step of obtaining the target single molecule chromatin complex information in S101 may include S1011 to S1012, such as Figure 2 As shown, S1011 to S1012 are as follows:

[0112] S1011: Obtain initial single-molecule chromatin complex information.

[0113] The device obtains initial single-molecule chromatin complex information. The specific acquisition method can refer to the description in S101 and will not be repeated here.

[0114] S1012: Convert the format of the initial single-molecule chromatin complex information to obtain target single-molecule chromatin complex information; wherein the target single-molecule chromatin complex information includes multiple DNA interaction fragment information; the DNA interaction fragment information includes the region information and the complex encoding information.

[0115] The device performs format conversion on the initial single-molecule chromatin complex information to obtain the target single-molecule chromatin complex information. Format conversion refers to the transformation of the information arrangement of the initial single-molecule chromatin complex information to obtain single-molecule chromatin complex information in a preset format as the target single-molecule chromatin complex information. Specifically, the device converts the initial single-molecule chromatin complex information into a fixed format. The converted target single-molecule chromatin complex information contains multiple DNA interaction fragment information, each line represents a DNA interaction fragment information, and the DNA interaction fragment information includes the region information where the DNA fragment is located and the complex encoding information to which the DNA fragment belongs.

[0116] In one embodiment, in order to obtain the target chromosome information corresponding to the target chromosome region information from the target single-molecule chromatin complex information more accurately and quickly, the device can divide the target single-molecule chromatin complex information into corresponding sub-files according to the chromosome name, and compress these sub-files into RDS format files proprietary to the R language and store them in the same directory for data input.

[0117] The device can store the file in RDS format in the directory where the display browser program mentioned above is located, so that the user can find the directory name of the data in the drop-down menu that appears when entering the area of ​​interest, which is convenient for operation.

[0118] S102: Acquire target single-molecule chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information.

[0119] The target chromosome region information includes the regional position information of the chromosome to be displayed. The device can locate the chromosome data where the target chromosome region information is located from the target single-molecule chromatin complex information according to the regional position information, and obtain the target single-molecule chromatin information corresponding to the target chromosome region information.

[0120] In one embodiment, in order to better display the data, the device may further process the single-molecule chromatin complex corresponding to the acquired target chromosome region information. Specifically, S102 may include S1021 to S1022, such as Figure 3 As shown, S1021 to S1022 are specifically as follows:

[0121] S1021: Acquire initial chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information.

[0122] The device obtains initial chromatin information. The specific acquisition method can refer to the description in S102, which will not be repeated here. The initial chromatin information obtained here is not specially processed and is only the original chromosome data.

[0123] In order to enable users to obtain information more intuitively, further, after S1021, the device can display the initial chromosome information. When displaying, you can select DNA fragments whose ends fall into this area for display. In this way, real-time visualization of single-molecule multiple staining interaction data is achieved, and the chromatin assembly pattern and gene regulation pattern in the cell nucleus are displayed.

[0124] S1022: Mapping the initial chromatin information to the target bins to generate target single-molecule chromatin information stored in an interaction matrix; wherein each row in the interaction matrix represents each chromatin complex, and each column in the interaction matrix represents a different target bin.

[0125] The device maps the initial chromatin information to the target bins, generating the target single-molecule chromatin information stored in the interaction matrix. The device divides the region corresponding to the target chromosome region information into several bins of equal length to obtain the target bins.

[0126] The device maps the initial chromatin information to its corresponding target bin according to the position of the initial chromosome information to generate the target chromatin information. The target single-molecule chromatin information is stored in the interaction matrix. Each row in the interaction matrix represents each chromatin complex, and each column in the interaction matrix represents a different target bin, that is, each row in the matrix represents a chromatin complex, each column is a bin, and multiple non-empty bins in each row represent the interacting DNA fragments in the complex.

[0127] S103: Perform cluster analysis on the target single-molecule chromatin information to obtain cluster matrix information.

[0128] In order to better analyze the target single-molecule chromatin information, the device stores a preset clustering analysis strategy, and the device performs clustering analysis on the target single-molecule chromatin information according to the preset clustering analysis strategy to obtain clustering matrix information. Among them, the preset clustering analysis strategy can include a clustering analysis strategy for high-dimensional space and a clustering analysis strategy for low-dimensional space. The clustering matrix contains the clustering grouping results of the target single-molecule chromatin information.

[0129] Specifically, under the premise of S1021 to S1022, the device obtains the target single-molecule chromatin information stored in the interaction matrix. During the clustering analysis process, the device can perform hierarchical clustering processing on each chromatin complex in the interaction matrix to obtain the first matrix information corresponding to the first dimension data, and use the first matrix information as the clustering matrix information.

[0130] Among them, hierarchical clustering is a method that decomposes a given data set hierarchically until a certain condition is met. Specifically, it can be divided into two schemes: "bottom-up" and "top-down". For example, in the "bottom-up" scheme, each data record initially forms a separate group. In the next iteration, it merges those adjacent groups into one group until all records form a group or a certain condition is met. Representative algorithms include: BIRCH algorithm, CURE algorithm, CHAMELEON algorithm, etc.

[0131] The device regards each column (bin) of the interaction matrix as a characteristic dimension of the data, so the interaction matrix can be regarded as high-dimensional data, that is, first-dimensional data. Each row in the interaction matrix represents a chromatin complex, and the device directly performs hierarchical clustering on the rows of the interaction matrix to obtain a clustering matrix of sorted high-dimensional data, that is, the first matrix information corresponding to the first-dimensional data.

[0132] Furthermore, the device performs hierarchical clustering processing on each chromatin complex in the interaction matrix, and after obtaining the first matrix information corresponding to the first dimension data, the first matrix information can be detected. If the first matrix information does not meet the preset conditions, for example, the device detects that the grouping of the first matrix information obtained by clustering does not meet the preset conditions, the first matrix information is subjected to dimensionality reduction processing according to a dimensionality reduction algorithm (such as TSNE, UMAP, etc.) to obtain second dimensional data. The device performs cluster analysis on the second dimensional data to obtain second matrix information, and uses the second matrix information as cluster matrix information. Among them, the second dimensional data is two-dimensional data, and when performing cluster analysis on the second dimensional data, algorithms such as hk-means and HCPC can be used.

[0133] S104: Obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, and displaying the display image.

[0134] The device obtains a display image corresponding to the chromatin microstructure of the target chromosome region information based on the clustering matrix information, and processes the clustering matrix information according to a preset processing rule to obtain a corresponding display image. The device displays the display image to the user.

[0135] In one implementation, the device performs data overlay processing on the clustering matrix information to generate a cumulative coverage view of the target chromosome region information. The device performs data overlay processing on the clustering matrix information by column (bin) to generate a cumulative coverage view of the target chromosome region information.

[0136] Then, the device interactively superimposes the cumulative coverage view and the target single-molecule chromatin information, that is, the cumulative coverage view is combined with DNA fragments and superimposed on each other to generate a two-dimensional interactive map of the target chromosome region information. The two-dimensional interactive map includes a two-dimensional interactive heat map and a two-dimensional interactive ring map.

[0137] In one embodiment, the display image includes a first heat map view and a first dimensional data segment view. The device obtains the first heat map view based on the first matrix information corresponding to the first dimensional data, and the first dimensional data is high-dimensional data, that is, the device clusters the high-dimensional data to obtain the first heat map view. Then, the device obtains the first dimensional data segment view based on the first heat map view. Specifically, the first dimensional data segment view is a high-dimensional data segment view of the original DNA segment data re-derived by the device according to the compound arrangement order of the first heat map view.

[0138] In one embodiment, the display image includes a second heat map view and a second dimensional data segment view. The device obtains the second heat map view based on the second matrix information corresponding to the second dimensional data, and the second dimensional data is low-dimensional data, that is, the device clusters the low-dimensional data to obtain the second heat map view. Then, the device obtains the second dimensional data segment view based on the second heat map view. Specifically, the second dimensional data segment view is a low-dimensional data segment view of the original DNA fragment data re-derived by the device according to the compound arrangement order of the second heat map view.

[0139] In addition to the types of display images mentioned above, in an embodiment of the present application, the display image may also include one or more of a target area view, a gene transcription pattern view, a chromatin organization pattern view, a transcription regulation pattern view, and a shielded view. Specifically, the device filters the current data by target area to obtain a complex with DNA fragments in the target area, and re-sorts the complexes according to the length of the region. Including: a target area view that filters the target area (such as the probe area of ​​DNA FISH); a gene transcription pattern view that filters the promoter region of the gene; a chromatin organization pattern view that filters the interaction interval of a factor (such as CTCF); a transcription regulation pattern view that explores the regulatory pattern of super enhancers; a shielded view that selects / does not select clusters.

[0140] The types of display views provided in this embodiment can provide high-resolution clustering data display at single-molecule accuracy, and can be applied to cluster single-molecule multi-fragment data into different microdomains within a certain domain area. Users can also filter or hide the data according to research purposes and needs.

[0141] Furthermore, in this embodiment, after displaying the chromatin microdomain, the boundaries of the displayed chromatin microdomain can also be defined, and the chromatin microdomain can be automatically defined to obtain cell-specific or gene-specific chromatin microdomains, providing a new research method for precision medicine. After S104, it can also include: according to the preset boundary definition rules and the displayed image, the target boundary information of the chromatin microstructure of the target chromosome region information is obtained.

[0142] The device pre-stores preset boundary definition rules, which are used to divide and define the boundaries of the chromatin microstructure of the target chromosome region information. The device does not limit the preset boundary definition rules, and can process the data through an algorithm to determine the boundaries, or use a deep convolutional network to determine the boundaries. The device obtains the target boundary information of the chromatin microstructure domain of the target chromosome region information based on the preset boundary definition rules and the displayed image.

[0143] In one embodiment, the displayed image includes a clustered fragment view. The device performs boundary definition of unsupervised machine learning based on the data itself through a two-dimensional kernel density prediction algorithm. The device obtains DNA fragment information in the clustered fragment view, and the device obtains initial density contour lines corresponding to the probability distribution information of the DNA fragment information according to a preset two-dimensional kernel density preset algorithm; the device selects target density contour lines that meet preset screening conditions from the initial density contour lines; and determines the target boundary information of the chromatin microstructure of the target chromosome region information according to the target density contour lines.

[0144] Specifically, the device regards each DNA fragment information in the clustered fragment view as a data point, and then uses the two-dimensional kernel density prediction method to evaluate its probability distribution based on the data point distribution of each subclass (microstructure) and obtain density contours. The device then filters out the target density contours according to the preset screening conditions. For example, the device can select density contours containing a suitable proportion of data points as target density contours. The device can then use the minimum and maximum genomic positions in the horizontal direction of the target density contour as the boundaries of the microstructure domain to obtain the target boundary information of the chromatin microstructure of the target chromosome region information.

[0145] In one embodiment, the displayed image includes a clustered fragment view, and the device performs target detection on the chromatin microstructure domain and its boundaries at the image level through computer vision based on a deep convolutional network, thereby defining the chromatin microstructure domain. In this embodiment, the Faster R-CNN method of deep computer vision target detection is used for the first time to define the three-dimensional domain of the genome. The device inputs the clustered fragment view into the trained boundary definition model for processing, and obtains the target boundary information of the chromatin microstructure of the target chromosome region information.

[0146] Specifically, in this embodiment, the boundary definition model can use the Faster R-CNN method. The trained boundary definition model can be pre-trained by the device, or it can be trained by other devices and then transplanted to the local device after the model parameters are frozen. When training the boundary definition model, first select a batch of clustered fragment view images of the structural domain as training images, and use the image annotation tool to outline the boundaries of the microstructure as a reference standard box; then input the training images and annotation files into the initial model to train its shared deep convolutional network to obtain the boundary definition model; then use the remaining clustered fragment view images of the structural domain as the detection set to detect using the trained boundary definition model, so as to detect the image boundary position of the microstructure; according to the detection results, adjust the parameters of the boundary definition model to improve it.

[0147] In the embodiment of the present application, the target chromosome region information is obtained, and the target single-molecule chromatin complex information is obtained; the target single-molecule chromatin information corresponding to the target chromosome region information is obtained from the target single-molecule chromatin complex information; the target single-molecule chromatin information is clustered and processed to obtain clustering matrix information; according to the clustering matrix information, the display image corresponding to the chromatin microstructure of the target chromosome region information is obtained, and the display image is displayed. The above method clusters the single-molecule chromatin complex data to display the microstructure of chromatin, and the chromatin microstructure of multiple chromatin complexes can be browsed intuitively and in real time, and the functions and characteristics of multiple chromatin complexes can be deeply and intuitively explored and analyzed.

[0148] It should be understood that the size of the serial numbers of the steps in the above embodiments does not mean the order of execution. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0149] See also Figure 4 , Figure 4 Schematic diagram of a display device for chromatin microdomains provided in the second embodiment of the present application. The units included are used to perform Figures 1 to 3 For details, please refer to the steps in the corresponding embodiment. Figures 1 to 3 For the convenience of explanation, only the parts related to this embodiment are shown. Figure 4 , the chromatin microdomain display device 4 comprises:

[0150] A first acquisition unit 410 is used to acquire target chromosome region information and target single-molecule chromatin complex information;

[0151] A second acquisition unit 420 is used to acquire the target single molecule chromatin information corresponding to the target chromosome region information from the target single molecule chromatin complex information;

[0152] A first processing unit 430 is used to perform cluster analysis on the target single-molecule chromatin information to obtain cluster matrix information;

[0153] The second processing unit 440 is used to obtain a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, and display the display image.

[0154] Furthermore, the first acquiring unit 410 is specifically configured to:

[0155] Obtain initial single-molecule chromatin complex information;

[0156] The initial single-molecule chromatin complex information is formatted to obtain target single-molecule chromatin complex information; wherein the target single-molecule chromatin complex information includes a plurality of DNA interaction fragment information; the DNA interaction fragment information includes the region information and the complex encoding information.

[0157] Furthermore, the second acquiring unit 420 is specifically configured to:

[0158] Acquiring initial chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information;

[0159] The initial chromatin information is mapped to the target bins to generate target single-molecule chromatin information stored in an interaction matrix; wherein each row in the interaction matrix represents each chromatin complex, and each column in the interaction matrix represents a different target bin.

[0160] Furthermore, the second acquiring unit 420 is further configured to:

[0161] The initial chromatin information is displayed.

[0162] Furthermore, the first processing unit 430 is specifically configured to:

[0163] A hierarchical clustering process is performed on each of the chromatin complexes in the interaction matrix to obtain first matrix information corresponding to the first dimensional data, and the first matrix information is used as clustering matrix information.

[0164] Furthermore, the first processing unit 430 is further configured to:

[0165] If the first matrix information does not meet the preset condition, performing dimensionality reduction processing on the first matrix information according to a dimensionality reduction algorithm to obtain second dimensional data;

[0166] Perform cluster analysis on the second dimensional data to obtain second matrix information, and use the second matrix information as cluster matrix information.

[0167] Furthermore, the second processing unit 440 is specifically configured to:

[0168] The clustering matrix information is subjected to data overlay processing to generate a cumulative coverage view of the target chromosome region information.

[0169] Furthermore, the second processing unit 440 is further configured to:

[0170] The cumulative coverage view and the target single-molecule chromatin information are interactively superimposed to generate a two-dimensional interactive map of the target chromosome region information.

[0171] Further, the display image includes a first heat map view and a first dimension data segment view; the second processing unit 440 is specifically configured to:

[0172] Obtain a first heat map view according to first matrix information corresponding to the first dimensional data;

[0173] A first dimensional data segment view is obtained according to the first heat map view.

[0174] Furthermore, the display image includes a second heat map view and a second dimensional data segment view; the second processing unit 440 is specifically configured to:

[0175] Obtain a second heat map view according to second matrix information corresponding to the second dimensional data;

[0176] A second dimensional data segment view is obtained according to the second heat map view.

[0177] Furthermore, the display image also includes one or more of a target region view, a gene transcription pattern view, a chromatin organization pattern view, a transcription regulation pattern view, and a shielding view.

[0178] Furthermore, the chromatin microdomain display device 4 further comprises:

[0179] The third processing unit is used to obtain target boundary information of the chromatin microstructure of the target chromosome region information according to a preset boundary definition rule and the display image.

[0180] Further, the display image includes a clustered segment view;

[0181] The third processing unit is specifically configured to:

[0182] Acquiring DNA fragment information in the clustered fragment view;

[0183] Obtaining initial density contour lines corresponding to the probability distribution information of the DNA fragment information according to a preset two-dimensional kernel density preset algorithm;

[0184] Filtering out target density contour lines that meet preset filtering conditions from the initial density contour lines;

[0185] The target boundary information of the chromatin microstructure of the target chromosome region information is determined according to the target density contour line.

[0186] Further, the display image includes a clustered segment view;

[0187] The third processing unit is specifically configured to:

[0188] The clustered segment view is input into a trained boundary definition model for processing to obtain target boundary information of the chromatin microstructure of the target chromosome region information.

[0189] Figure 5 Schematic diagram of a display device for chromatin microdomains provided in the third embodiment of the present application. Figure 5 As shown, the chromatin microdomain display device 5 of this embodiment includes: a processor 50, a memory 51, and a computer program 52 stored in the memory 51 and executable on the processor 50, such as a chromatin microdomain display program. When the processor 50 executes the computer program 52, the steps in the above-mentioned chromatin microdomain display method embodiments are implemented, such as Figure 2 Alternatively, when the processor 50 executes the computer program 52, the functions of each module / unit in the above-mentioned device embodiments are realized, for example, Figure 4 Functions of modules 410 to 440 are shown.

[0190] Exemplarily, the computer program 52 can be divided into one or more modules / units, and the one or more modules / units are stored in the memory 51 and executed by the processor 50 to complete the present application. The one or more modules / units can be a series of computer program instruction segments that can complete specific functions, and the instruction segments are used to describe the execution process of the computer program 52 in the display device 5 of the chromatin microstructure domain. For example, the computer program 52 can be divided into a first acquisition unit, a second acquisition unit, a first processing unit, and a second processing unit, and the specific functions of each unit are as follows:

[0191] A first acquisition unit is used to acquire target chromosome region information and target single-molecule chromatin complex information;

[0192] A second acquisition unit is used to acquire the target single molecule chromatin information corresponding to the target chromosome region information from the target single molecule chromatin complex information;

[0193] A first processing unit is used to perform cluster analysis on the target single-molecule chromatin information to obtain cluster matrix information;

[0194] The second processing unit is used to obtain a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, and display the display image.

[0195] The display device of the chromatin microdomain may include, but is not limited to, a processor 50 and a memory 51. A person skilled in the art will understand that Figure 5It is only an example of the display device 5 of the chromatin microstructure domain and does not constitute a limitation of the display device 5 of the chromatin microstructure domain. It may include more or fewer components than shown in the figure, or a combination of certain components, or different components. For example, the display device of the chromatin microstructure domain may also include input and output devices, network access devices, buses, etc.

[0196] The processor 50 may be a central processing unit (CPU), or other general-purpose processors, digital signal processors (DSP), application-specific integrated circuits (ASIC), field-programmable gate arrays (FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. A general-purpose processor may be a microprocessor or any conventional processor, etc.

[0197] The memory 51 can be an internal storage unit of the display device 5 of the chromatin microstructure domain, such as a hard disk or memory of the display device 5 of the chromatin microstructure domain. The memory 51 can also be an external storage device of the display device 5 of the chromatin microstructure domain, such as a plug-in hard disk, a smart memory card (Smart Media Card, SMC), a secure digital (Secure Digital, SD) card, a flash card (FlashCard), etc. equipped on the display device 5 of the chromatin microstructure domain. Further, the display device 5 of the chromatin microstructure domain can also include both the internal storage unit of the display device 5 of the chromatin microstructure domain and an external storage device. The memory 51 is used to store the computer program and other programs and data required for the display device of the chromatin microstructure domain. The memory 51 can also be used to temporarily store data that has been output or is to be output.

[0198] It should be noted that the information interaction, execution process, etc. between the above-mentioned devices / units are based on the same concept as the method embodiment of the present application. Their specific functions and technical effects can be found in the method embodiment part and will not be repeated here.

[0199] An embodiment of the present application also provides a network device, which includes: at least one processor, a memory, and a computer program stored in the memory and executable on the at least one processor, wherein the processor implements the steps in any of the above-mentioned method embodiments when executing the computer program.

[0200] An embodiment of the present application further provides a computer-readable storage medium, wherein the computer-readable storage medium stores a computer program, and when the computer program is executed by a processor, the steps in the above-mentioned method embodiments can be implemented.

[0201] An embodiment of the present application provides a computer program product. When the computer program product runs on a mobile terminal, the mobile terminal can implement the steps in the above-mentioned method embodiments when executing the computer program product.

[0202] If the integrated unit is implemented in the form of a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the present application implements all or part of the processes in the above-mentioned embodiment method, which can be completed by instructing the relevant hardware through a computer program. The computer program can be stored in a computer-readable storage medium, and the computer program can implement the steps of the above-mentioned various method embodiments when executed by the processor. Among them, the computer program includes computer program code, and the computer program code can be in source code form, object code form, executable file or some intermediate form. The computer-readable medium can at least include: any entity or device that can carry the computer program code to the camera / terminal device, recording medium, computer memory, read-only memory (ROM, Read-Only Memory), random access memory (RAM, RandomAccess Memory), electric carrier signal, telecommunication signal and software distribution medium. For example, a USB flash drive, a mobile hard disk, a magnetic disk or an optical disk. In some jurisdictions, according to legislation and patent practice, computer-readable media cannot be electric carrier signals and telecommunication signals.

[0203] In the above embodiments, the description of each embodiment has its own emphasis. For parts that are not described or recorded in detail in a certain embodiment, reference can be made to the relevant descriptions of other embodiments.

[0204] Those of ordinary skill in the art will appreciate that the units and algorithm steps of each example described in conjunction with the embodiments disclosed herein can be implemented in electronic hardware, or a combination of computer software and electronic hardware. Whether these functions are performed in hardware or software depends on the specific application and design constraints of the technical solution. Professional and technical personnel can use different methods to implement the described functions for each specific application, but such implementation should not be considered to be beyond the scope of this application.

[0205] In the embodiments provided in the present application, it should be understood that the disclosed devices / network equipment and methods can be implemented in other ways. For example, the device / network equipment embodiments described above are merely schematic. For example, the division of the modules or units is only a logical function division. There may be other division methods in actual implementation, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some interfaces, indirect coupling or communication connection of devices or units, which can be electrical, mechanical or other forms.

[0206] The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0207] The embodiments described above are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application, and should all be included in the protection scope of the present application.

Claims

1. A method for displaying single-molecule chromatin microstructure, characterized in that: include: Obtaining target chromosome region information and target single-molecule chromatin complex information; Acquire the target single molecule chromatin information corresponding to the target chromosome region information from the target single molecule chromatin complex information; Performing cluster analysis on the target single-molecule chromatin information to obtain cluster matrix information; Obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, and displaying the display image; The step of obtaining target single-molecule chromatin complex information comprises: Obtain initial single-molecule chromatin complex information; The initial single-molecule chromatin complex information is formatted to obtain target single-molecule chromatin complex information; wherein the target single-molecule chromatin complex information includes a plurality of DNA interaction fragment information; the DNA interaction fragment information includes the region information and the complex encoding information; The step of obtaining the target single molecule chromatin information corresponding to the target chromosome region information from the target single molecule chromatin complex information includes: Acquiring initial chromatin information corresponding to the target chromosome region information from the target single-molecule chromatin complex information; The initial chromatin information is mapped to the target bins to generate target single-molecule chromatin information stored in an interaction matrix; wherein each row in the interaction matrix represents each chromatin complex, and each column in the interaction matrix represents a different target bin.

2. The method for displaying single-molecule chromatin microstructure according to claim 1, characterized in that: The clustering analysis process is performed on the target single-molecule chromatin information to obtain clustering matrix information, including: A hierarchical clustering process is performed on each of the chromatin complexes in the interaction matrix to obtain first matrix information corresponding to the first dimensional data, and the first matrix information is used as clustering matrix information.

3. The method for displaying single-molecule chromatin microstructure according to claim 2, characterized in that: After performing hierarchical clustering processing on each of the chromatin complexes in the interaction matrix to obtain clustering matrix information corresponding to the first dimensional data, the method further includes: If the first matrix information does not meet the preset condition, performing dimensionality reduction processing on the first matrix information according to a dimensionality reduction algorithm to obtain second dimensional data; Perform cluster analysis on the second dimensional data to obtain second matrix information, and use the second matrix information as cluster matrix information.

4. The method for displaying single-molecule chromatin microstructure according to claim 1, characterized in that: The step of obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information includes: Performing data overlay processing on the clustering matrix information to generate a cumulative coverage view of the target chromosome region information; The cumulative coverage view and the target single-molecule chromatin information are interactively superimposed to generate a two-dimensional interactive map of the target chromosome region information.

5. The method for displaying single-molecule chromatin microstructure according to claim 2, characterized in that: The display image includes a first heat map view and a first dimension data segment view; The step of obtaining a display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information includes: Obtain a first heat map view according to first matrix information corresponding to the first dimensional data; A first dimensional data segment view is obtained according to the first heat map view.

6. The method for displaying single-molecule chromatin microstructure according to claim 1, characterized in that: The displayed image also includes one or more of a target region view, a gene transcription pattern view, a chromatin organization pattern view, a transcription regulation pattern view, and a shielding view.

7. The method for displaying single-molecule chromatin microstructure according to claim 1, characterized in that: After obtaining the display image corresponding to the chromatin microstructure of the target chromosome region information according to the clustering matrix information, the method further includes: According to the preset boundary definition rule and the display image, the target boundary information of the chromatin microstructure of the target chromosome region information is obtained.

8. The method for displaying single-molecule chromatin microstructure according to claim 7, characterized in that: The display image includes a clustered segment view; The step of obtaining target boundary information of the chromatin microstructure of the target chromosome region information according to the preset boundary definition rule and the display image includes: Acquiring DNA fragment information in the clustered fragment view; Obtaining initial density contour lines corresponding to the probability distribution information of the DNA fragment information according to a preset two-dimensional kernel density preset algorithm; Filtering out target density contour lines that meet preset filtering conditions from the initial density contour lines; Determining target boundary information of the chromatin microstructure of the target chromosome region information according to the target density contour line; or, The clustered segment view is input into a trained boundary definition model for processing to obtain target boundary information of the chromatin microstructure of the target chromosome region information.

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