A method for generating individual genome simulation data based on graph compression

By constructing individual genome simulation data through graph compression technology, the problem of low accuracy of individual genome simulation data in existing technologies is solved, and more accurate drug efficacy prediction and personalized medical support are achieved.

CN119785871BActive Publication Date: 2025-09-16HARBIN INST OF TECH
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Patent Information

Application Number
CN202411973780.8
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-12-30
Publication Date
2025-09-16
Estimated Expiration
2044-12-30

AI Technical Summary

Technical Problem

Existing individual genome simulation data has low accuracy in predicting the efficacy of drugs on different individuals and lacks biological basis, resulting in random generation of mutation types and lengths in the simulation data and random customization of sites.

Method used

Using graph compression technology, we acquire historical genomic datasets, construct a graph genome data structure, perform preprocessing, forward compression, and decompression, generate individual genome simulation data, and use the nodes and edges of the graph genome to represent genomic variations, achieving efficient simulation data output.

Benefits of technology

It improves the accuracy and biological basis of individual genome simulation data, enhances the accuracy of drug efficacy prediction, and supports the development of personalized medicine and precision medicine.

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Abstract

The present invention belongs to the field of bioinformatics, and in particular relates to a method for generating individual genome simulation data based on graph compression. The purpose of the present invention is to solve the problem of low accuracy of existing individual genome simulation data when used to predict the efficacy of drugs on different individuals. A method for generating individual genome simulation data based on graph compression is provided, comprising: S1: obtaining a historical genome dataset; S2: preprocessing the graph genome data in the historical genome dataset to obtain preprocessed graph genome data; S3: calculating the connectivity of the nodes in the preprocessed graph genome data, and performing forward compression processing on the preprocessed graph genome data according to the connectivity of the nodes to obtain forward compressed graph genome data; S4: generating individual genome simulation data based on the forward compressed graph genome data. This method solves the problem of low accuracy of existing individual genome simulation data when used to predict the efficacy of drugs on different individuals.
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Description

Technical Field

[0001] The present invention belongs to the field of bioinformatics, and in particular relates to a method for generating individual genome simulation data based on graph compression. Background Art

[0002] Individual genome simulation is of great value in the field of bioinformatics, especially in drug research and development. Genome simulation can help researchers gain a deeper understanding of the drug's mechanism of action, thereby accelerating the development of new drugs.

[0003] By simulating individual genomes, it is possible to predict drug efficacy for different individuals, improving the efficiency and precision of drug development. Furthermore, because each person's genome is unique, research based on simulation data and in-depth exploration of genetic information has the potential to provide patients with more personalized medical plans and achieve targeted disease prevention and treatment. Genome simulation is also crucial for efficient variant detection. In genetic research, rapid and accurate detection of genetic variants is crucial, and simulation data can serve as an effective dataset to help researchers discover new genetic variants and their functional impact. Furthermore, in genetic disease risk prediction, by studying the characteristics of simulation data, it is possible to assess an individual's risk of developing a genetic disease, thereby enabling early intervention and prevention. In summary, individual genome simulation plays an irreplaceable and important role in medical research and clinical practice. It can not only promote new drug development, but also advance personalized and precision medicine, providing powerful data support for genetic research and disease prevention.

[0004] However, existing individual genome simulation tools have had problems such as arbitrary simulation mechanisms, simple reference genomes, and mutations derived from custom scripts. As a result, the types and lengths of artificially introduced mutations are randomly generated, and the sites are randomly customized, lacking biological basis. This leads to low accuracy in predicting the efficacy of drugs on different individuals through simulating individual genomes. Summary of the Invention

[0005] The present invention aims to address the low accuracy of existing individual genome simulation data when used to predict drug efficacy for different individuals. A method for generating individual genome simulation data based on graph compression is provided, comprising:

[0006] S1: Acquisition of historical genomic datasets;

[0007] The genome data in the historical genome dataset is graph genome data;

[0008] The graph genome includes: a node set, an edge set, and a graph

[0009] The nodes represent sequence fragments in the genome

[0010] (k-mer, usually a DNA fragment of length k). These fragments can be of fixed length or can be adjusted according to specific mutation information. The node division in this invention is already divided in the historical data set;

[0011] The edges represent the connection relationship between nodes;

[0012] The graph represents the overall structure composed of nodes and edges

[0013] If two fragments are directly connected in the genome, an edge is added between them. The presence of an edge may reflect sequence connectivity, variation (such as insertions or deletions), or structural changes.

[0014] S2: Preprocess the graph genome data in the historical genome dataset to obtain preprocessed graph genome data;

[0015] S3: Calculate the connectivity of the nodes in the preprocessed graph genome data, and perform forward compression on the preprocessed graph genome data according to the connectivity of the nodes to obtain forward compressed graph genome data;

[0016] S4: Generate individual genome simulation data based on the graph genome data after forward compression.

[0017] The beneficial effects of the present invention are:

[0018] The present invention proposes a method for generating individual genome simulation data based on graph compression. The method utilizes the high-quality data structure of the graph genome to perform graph compression and decompression transformations, and uses the interactive information between high- and low-level graphs to realize the output of a large amount of simulation data. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 A schematic flow chart of a method for generating individual genome simulation data based on graph compression according to the present invention. DETAILED DESCRIPTION

[0020] Specific implementation method 1: Combination Figure 1 - a figure illustrating the invention,

[0021] S1: Acquisition of historical genomic datasets;

[0022] The genome data in the historical genome dataset is graph genome data;

[0023] The sources of the historical genomic dataset are:

[0024] https: / / s3-us-west-2.amazonaws.com / human-pangenomics / pangenomes / freeze / freeze1 / minig raph-cactus / hprc-v1.1-mc-grch38 / hprc-v1.1-mc-grch38.gfa.gz;

[0025] Graph genomics refers to a method of representing and storing genomic data in the form of a graph structure. Compared with traditional genomic sequences, graph genomics not only contains the basic sequence information of the genome, but also can better represent the variation and diversity of the genome.

[0026] The following introduces the background and concept of graph genome

[0027] Genomes are usually represented as linear sequences (i.e., DNA base pair sequences). The genome of each species has a fixed "reference sequence," i.e., a representative genome. However, real genomes are often very diverse, with a variety of variations, such as single nucleotide polymorphisms (SNPs), insertions / deletions (Indels), and structural variations (e.g., inversions and duplications). Traditional linear reference genomes have difficulty capturing these variations, especially complex genomic variations.

[0028] Graph genomics attempts to solve this problem through graph structures. Graphs are used here to represent different versions of the genome and the mutation relationships between them, allowing for a more flexible and accurate description of the complexity of the genome.

[0029] The graph genome includes: a node set, an edge set, and a graph

[0030] The nodes represent sequence fragments in the genome

[0031] (k-mer, usually a DNA fragment of length k). These fragments can be of fixed length or can be adjusted according to specific mutation information. The node division in this invention is already divided in the historical data set;

[0032] The edges represent the connection relationship between nodes;

[0033] The graph represents the overall structure composed of nodes and edges

[0034] If two fragments are directly connected in the genome, an edge is added between them. The presence of an edge may reflect sequence connectivity, variation (such as insertions or deletions), or structural changes.

[0035] S2: Preprocess the graph genome data in the historical genome dataset to obtain preprocessed graph genome data;

[0036] S3: Calculate the connectivity of the nodes in the preprocessed graph genome data, and perform forward compression on the preprocessed graph genome data according to the connectivity of the nodes to obtain forward compressed graph genome data;

[0037] S4: Generate individual genome simulation data based on the graph genome data after forward compression;

[0038] Specific embodiment 2: The difference between this embodiment and specific embodiment 1 is that:

[0039] The specific process of preprocessing the graph genome data in the historical genome dataset in S2 to obtain the preprocessed graph genome data is as follows:

[0040] S2.1: Invert all nodes of the graph genome in the historical genome dataset to obtain inverted nodes, and add the inverted nodes to the original graph genome to obtain the expanded graph genome.

[0041] S2.2: Select a starting node in the expanded graph genome and use a breadth-first search method based on a queue data structure to search for nodes layer by layer in the expanded graph genome in order, ultimately obtaining a set of reachable nodes with the starting node as the root.

[0042] The starting node is fixed and is the starting point of the chromosome, has biological significance, and is well known to those skilled in the art. Simulation data for only one chromosome is obtained each time.

[0043] S2.3: Based on the reachable node set, delete the node set that cannot be found in the expanded graph genome to obtain the deleted graph genome;

[0044] S2.4: Screening and eliminating the deleted graph genome to obtain a pre-processed graph genome;

[0045] Other steps and parameters are the same as those in the first embodiment.

[0046] Specific embodiment three: This embodiment differs from specific embodiment one in that:

[0047] In S2.1, all nodes of the graph genome in the historical genome dataset are inverted to obtain a set of inverted nodes. The inverted set of nodes is added to the original graph genome to obtain an expanded graph genome, which is expressed as:

[0048] V'={v'|v'∈V,S'(v')=f(S(v))}, G'=(V∪V′,E∪E')

[0049] Where v represents a node in the graph genome, v' represents a node after negation, V is the set of all nodes in the graph genome, V' represents the set of nodes after negation, E is the set of all edges in the graph genome, and E' represents the set of edges composed of negated nodes; f is the negation operation function, S(v) is the state attribute of node v; G' is the expanded graph genome; S'(v') represents the state attribute of node v' after negation; ∪ represents the union;

[0050] The state attributes of the node v include: the number of the node (positive or negative); the base sequence represented by the node (forward or reverse complement) is well known to those skilled in the art;

[0051] In S2.2, a starting node is selected in the expanded graph genome, and a breadth-first search method based on a queue data structure is used to search for nodes layer by layer in the expanded graph genome in hierarchical order, ultimately obtaining a set of reachable nodes with the starting node as the root. The specific process is as follows:

[0052] S2.2.1: Select a starting node in the expanded graph genome;

[0053] S2.2.2: Set the level of the selected starting node to 0, and search the expanded graph genome for nodes directly connected to the starting node to obtain the first-level node set; the specific process is as follows:

[0054] The neighboring nodes directly connected to the current node are the first-layer nodes, the unvisited nodes directly connected to the first-layer nodes are the second-layer nodes, and so on, all nodes are divided into k levels.

[0055] Prioritize visiting neighboring nodes directly connected to the current node (i.e., visiting nodes layer by layer in hierarchical order), and then gradually expand to more distant nodes until all reachable nodes are visited, obtaining a reachable node set with the starting node as the root; this is a process well known to those skilled in the art;

[0056] S2.2.3: Search the expanded graph genome for nodes directly connected to the upper-level nodes. The new nodes found are used as the next-level node set, and finally the reachable node set with the starting node as the root is obtained. The total number of levels is k, where k is a positive integer.

[0057] The k-th layer node set is obtained by searching the k-1th layer node set and the formula is expressed as:

[0058]

[0059] Where Rk represents the set of nodes in the kth layer, R k-1 represents the set of nodes in the k-1th layer, R i represents the set of nodes in the i-th layer; w represents the nodes in the k-th layer, u represents the nodes in the k-1-th layer; (u, w) represents the edge from node u to node w;

[0060] Note that the edge (u, w) here has a direction, from u to w, u is the forward connection of w, and w is the backward connection of u. The graph genome structure of the present invention is a directed graph structure;

[0061] In S2.3, based on the reachable node set, the node set that cannot be found is deleted from the expanded graph genome to obtain the deleted graph genome; this is expressed as:

[0062]

[0063] In the formula, G" represents the deleted graph genome,

[0064] The other steps and parameters are the same as those in the first and second embodiments.

[0065] Specific embodiment 4: This embodiment differs from specific embodiments 1 to 4 in that:

[0066] In S2.4, the obtained deleted graph genome is screened and eliminated to obtain a pre-processed graph genome; the specific process is as follows:

[0067] S2.4.1.: Set the termination node set and eliminate the iteration termination condition;

[0068] S2.4.2: Screen and remove leaf nodes from the deleted graph genome based on the termination node set and the iteration termination condition to obtain the preprocessed graph genome.

[0069] The other steps and parameters are the same as those in the first to third embodiments.

[0070] Specific embodiment 5: This embodiment differs from specific embodiments 1 to 4 in that:

[0071] The specific process of setting the termination node set and iteration termination condition in S2.4.1 is as follows:

[0072] S2.4.1.1: Set the set of terminal nodes T in the deleted graph genome.

[0073] The termination node is also a node with biological significance. The termination node set only includes this termination node, which is the end point of the chromosome and is well known to those skilled in the art.

[0074] Each chromosome is an endpoint, and the endpoint set here also refers to a single chromosome. The content described in this invention is all for a single chromosome. The total number of chromosomes actually generated is calculated as 22 autosomes + 2 sex chromosomes + 1 mitochondrial chromosome, a total of 25.

[0075] S2.4.1.2: Set the termination condition for the elimination iteration, expressed as:

[0076] or So that (v,u)∈E (h)

[0077] In S2.4.2, the leaf nodes in the deleted graph genome are screened and removed according to the termination node set and the iteration termination condition to obtain the preprocessed graph genome. The specific process is as follows:

[0078] S2.4.2.1: Set initial situation

[0079] G (0) =(V (0) ,E (0) )(V (0) =V”,E (0) =E”)

[0080] S2.4.2.2: Obtain the leaf node set L that needs to be removed in the hth round based on the terminal node set T (h) ;h∈[0,f-1];

[0081] According to the leaf node set L that needs to be removed in the h round (h) For the remaining node set V in round h (h) Perform elimination processing to obtain the h+1th round remaining node set V (h+1) and the edge set E consisting of the remaining nodes in round h+1 (h+1) ,

[0082] When the remaining node set in round f meets the iteration termination condition, the iteration stops and the preprocessed graph genome is obtained, which can be expressed as:

[0083] and

[0084] V (h+1) =V (h) \L (h)

[0085] E (h+1) =E (h) \{(u,v)|u∈V (h) ,v∈L (h)}

[0086] So that (v,u)∈E (f)}

[0087] Where T represents the set of terminal nodes, V (h) represents the set of remaining nodes in round h, E (h) represents the edge set consisting of the remaining nodes in round h, \ represents the elimination process; V (f) represents the set of remaining nodes in round f;

[0088] The other steps and parameters are the same as those in the first to fourth embodiments.

[0089] Specific embodiment 6: This embodiment differs from specific embodiments 1 to 5 in that:

[0090] In S3, the connectivity of the nodes in the preprocessed graph genome data is calculated, and the preprocessed graph genome data is forward compressed according to the connectivity of the nodes to obtain the forward compressed graph genome data. The specific process is as follows:

[0091] S3.1: Calculate the connectivity of all nodes in the preprocessed graph genome;

[0092] The connectivity of a node is the sum of the number of parent nodes and child nodes that the node has;

[0093] The parent node of the node is the node to which the node is forward connected, and the child node of the node is the node to which the node is backward connected;

[0094] In an undirected graph, degree is the number of edges connected to a node; in a directed graph, degree can be further divided into in-degree (number of parent nodes) and out-degree (number of child nodes). The preprocessed graph genome in the present invention is a directed graph, so the connectivity of a node in the present invention is the sum of the number of parent nodes and child nodes of the node;

[0095] S3.2: The first-category child nodes in the preprocessed graph genome are determined based on the connectivity of all nodes, and all the first-category child nodes constitute the first-category child node set;

[0096] The first-type child node is a node with only one parent node. The parent node of the first-type child node is called a first-type parent node. All first-type parent nodes constitute a first-type parent node set.

[0097] S3.3: Use the first-class parent node to inherit all the connection information of the corresponding first-class child node; get the inherited first-class parent node,

[0098] It can be expressed as:

[0099] if vc Has a unique v p

[0100] Where B represents the backward connection information; v c Represents the first type of child node, v p Represents the first-class parent node, Indicates the first type of parent node after inheritance;

[0101] S3.4: Remove the first type of child nodes from the preprocessed graph genome to obtain a removed graph genome;

[0102] At the same time, the corresponding first-category parent node after inheritance creates a merged node set;

[0103] Among them, the first type of parent node after the i-th inheritance The created merge node set is represented as

[0104] The merged node set records the inheritance information of the first type of child nodes that are removed;

[0105] The existence of this set ensures that the merge relationship between nodes is traceable and maintains information consistency. Furthermore, when a child node contains the merge information of other nodes (that is, the child node has a merge node set), these merge sets will also be merged into the parent node set. This process makes node merging transitive and completes closure isolation, allowing the relationship between nodes to be gradually compressed through multiple rounds of iteration until no node has a unique parent node, and finally a unified parent node set is formed. C(v c ) is v c The merged node set.

[0106] C′(v p )=C(v p )∪{v c}∪C(v c )

[0107] S3.5: Calculate the connectivity of all nodes in the removed graph genome.

[0108] According to the connectivity of all nodes, determine whether all nodes in the removed graph genome have no unique parent node.

[0109] If all the nodes in the removed graph genome do not have a unique parent node, the forward-compressed graph genome data is obtained;

[0110] If any node in the removed graph genome has a unique parent node, return to S3.2;

[0111] It is well known in the art to determine whether all nodes in the removed graph genome have no unique parent node based on the connectivity of all nodes. The connectivity of a node includes the number of parent nodes that the node has.

[0112] ; Other steps and parameters are the same as those in one of the specific implementation methods one to five.

[0113] Specific embodiment 7: This embodiment differs from specific embodiments 1 to 6 in that:

[0114] The specific process of generating individual genome simulation data based on the forward-compressed graph genome data in S4 is as follows:

[0115] S4.1: Annotate the merged child node set corresponding to each inherited first-category parent node in the forward-compressed graph genome in the preprocessed graph genome to obtain the annotated preprocessed graph genome;

[0116] Among them, the node corresponding to the inherited first-category parent node in the preprocessed graph genome is called the second-category parent node;

[0117] The node number of the second-class parent node is marked; for example, the first-class parent node inherited in the forward-compressed graph genome The first parent node after inheritance The merge node set created is

[0118] The corresponding node in the preprocessed graph genome is v p , marked with v p ( )

[0119] S4.2: Based on the annotated pre-processed graph genome, construct a subgraph genome with the second-category parent node as the first node and n terminal nodes as the last nodes;

[0120] In the forward-compressed graph genome, each inherited parent node represents a subgraph genome;

[0121] Among them, the first type of parent node after the i-th inheritance The subgraph genome represented by

[0122] A subgraph genome has a second-class parent node and n terminal nodes, n∈T; assuming that there are m inherited parent nodes in the forward-compressed graph genome, then the m parent nodes corresponding to the annotated preprocessed graph genome have m subgraphs; each subgraph corresponds to an inherited parent node;

[0123] S4.3: Select the first inherited parent node corresponding to the starting node in the forward compressed graph genome And the first type of parent node after inheritance corresponding to the terminal node According to the first parent node after inheritance and the first parent node after inheritance Perform a deep search on the graph genome after forward compression to obtain the individual genome compression path;

[0124] The start node and the end node are the starting point and the end point of the chromosome, which have biological significance and are well known to those skilled in the art. The purpose of this step is to select the individual genome compression path from the start point to the end point of the chromosome in the forward compressed graph genome;

[0125] Because the number of nodes in the forward-compressed graph genome is smaller, finding a path in the forward-compressed graph genome, given a starting point and an end point, has a lower space complexity than finding a path in the uncompressed graph genome, and consumes less time and computing resources.

[0126] S4.4: Decompress the individual compressed genome path obtained in S4.3 to obtain the individual genome path; perform base processing on the individual genome path to obtain the individual genome structure data in the standard FASTA file format as the individual genome simulation data;

[0127] The other steps and parameters are the same as those in the first to sixth embodiments.

[0128] Specific embodiment eight: This embodiment differs from specific embodiments one to seven in that:

[0129] In the step S4.3, the first type of inherited parent node corresponding to the starting node is selected in the graph genome after forward compression. And the first type of parent node after inheritance corresponding to the terminal node According to the first parent node after inheritance and the first parent node after inheritance Perform a deep search on the graph genome after forward compression to obtain the individual genome compression path;

[0130] The specific process is:

[0131] S4.3.1: Use bitwise storage nodes to define the access status of each inherited first-class parent node in the forward-compressed graph genome.

[0132] When the bit operation storage node of the node is 1, it means that the node has been visited, and when the bit operation storage node of the node is 0, it means that the node has not been visited; this is a processing process well known to those skilled in the art.

[0133] S4.3.2: Select the first inherited parent node of the starting node in the forward compressed graph genome

[0134] Select the first type of parent node after inheritance corresponding to the terminal node in the graph genome after forward compression

[0135] According to the access status of each inherited first-category parent node in the forward-compressed graph genome, a deep search is performed in the forward-compressed graph genome to obtain an individual genome compression path;

[0136] The individual genome compression path includes m inherited first-category parent nodes, where m is a positive integer;

[0137] The starting point of the individual genome compression path is represented as As the starting point, the end point of the individual genome compression path is expressed as

[0138] The specific process is:

[0139] That is, each node has an attribute value. If it has not been visited, it is 0. If it has been visited once, it is recorded as 1. If it is visited again, the 1 is carried to 0, and the access status of all nodes that are 1 are also returned to 0. The principle of starting the search again when encountering a duplicate node during the search process is to finally find a arrive Individual genome compression pathways;

[0140] The other steps and parameters are the same as those in the first to seventh embodiments.

[0141] Specific embodiment 9: This embodiment differs from specific embodiments 1 to 8 in that:

[0142] In S4.4, the individual compressed genome path obtained in S4.3 is decompressed to obtain the individual genome path; the individual genome path is subjected to base processing to obtain the individual genome structure data in a standard FASTA file format as the individual genome simulation data. The specific process is as follows:

[0143] S4.4.1: Convert the m inherited first-category parent nodes in the individual compressed genome path obtained in S4.3 into m individual genome subpaths;

[0144] Among them, the first type of parent node after the i-th inheritance The corresponding individual genome subpathway is denoted as Pi;

[0145] S4.4.2: Merge the m individual genome subpaths to obtain the individual genome path;

[0146] S4.4.3: Perform base processing on the individual genome path to obtain the individual genome structure data in the standard FASTA file format as the individual genome simulation data.

[0147] The individual genome path is the path from the start node to the end node in the preprocessed graph genome: through the directed path in the graph genome, a continuous node path is extracted from the start node to the end node.

[0148] The base conversion process refers to integrating the base information of each node in these pathways into a standard DNA sequence.

[0149] Finally, the processed DNA sequence is saved in FASTA format; which is well known to those skilled in the art.

[0150] The other steps and parameters are the same as those in the first to eighth embodiments.

[0151] Specific embodiment 10: This embodiment differs from specific embodiments 1 to 9 in that:

[0152] The specific process of converting the j inherited first-category parent nodes in the individual compressed genome path into the j-th individual genome sub-path in S4.4.1 is as follows:

[0153] S4.4.1.1: Select the first parent node after the jth inheritance and the first type of parent node after the j+1th inheritance

[0154] S4.4.1.2: Based on the first parent node after j+1 inheritance The corresponding second-category parent node v in the annotated preprocessed graph genome pj+1 , determine the end point of the j-th individual genome subpath Pj;

[0155] S4.4.1.3: Obtain the jth individual genome subpath Pj based on the endpoint of the jth individual genome subpath Pj;

[0156] The first type of parent node after j+1 inheritance in S4.4.1.2 The corresponding second-category parent node v in the annotated preprocessed graph genome pj+1 , determine the end point of the j-th individual genome subpath Pj; the specific process is:

[0157] We call the first-class parent node after inheritance a high-dimensional node, and the second-class parent node a low-dimensional node. This is because a high-dimensional node may be connected to several high-dimensional nodes in the compressed graph, and specifically to the subgraph inside the high-dimensional node, it may be connected to different high-dimensional graphs behind it through different terminal nodes in the subgraph. Therefore, the terminal node of the subgraph represented by this high-dimensional node must be determined by a certain high-dimensional node behind this high-dimensional node. For example, the first-class parent node after inheritance of two connections and pass Sure Subgraph genome represented

[0158] Selected subgraph genomes The terminal node of , as the end point of the j-th individual genome subpath Pj,

[0159] In S4.4.1.3, the j-th individual genome subpath Pj is obtained according to the end point of the j-th individual genome subpath Pj. The specific process is:

[0160] Subgraph genome Directly perform unrestricted forward random search to ensure that the search efficiency is not reduced by additional conditions. The output low-dimensional subgraph path end point must converge to the subgraph starting node, which is the representative node in the high-level graph.

[0161] That is, we know the end point and starting point of the individual genome subpath, and through the search algorithm we can obtain a reverse individual genome subpath. Then we invert the node path of the reverse search to obtain the jth individual genome subpath Pj. This path inversion operation is based on the reversibility of graph path search to ensure the logical consistency of the low-dimensional path.

[0162] By analogy, all individual genome subpaths P1 to Pm are finally obtained, and then all the individual genome subpaths are merged to obtain the individual genome path.

[0163] The other steps and parameters are the same as those in the first to ninth embodiments.

[0164] The above only describes the preferred embodiments of the present invention. It should be understood that the present invention is not limited to the above-mentioned specific implementation methods. Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. Any technician familiar with this profession can make some changes or modifications to equivalent embodiments of equivalent changes using the technical content disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent replacements and improvements made to the above embodiments without departing from the content of the technical solution of the present invention, based on the technical essence of the present invention, within the spirit and principles of the present invention, still fall within the scope of protection of the technical solution of the present invention.

Claims

1. A method for generating individual genome simulation data based on graph compression, characterized in that: include: S1: Acquisition of historical genomic datasets; The genome data in the historical genome dataset is graph genome data; The graph genome includes: a node set, an edge set and a graph; The nodes represent sequence fragments in the genome; The edges represent the connection relationship between nodes; The graph represents an overall structure consisting of nodes and edges; S2: Preprocess the graph genome data in the historical genome dataset to obtain preprocessed graph genome data; S3: Calculate the connectivity of the nodes in the preprocessed graph genome data, and perform forward compression on the preprocessed graph genome data according to the connectivity of the nodes to obtain forward compressed graph genome data. The specific process is as follows: S3.1: Calculate the connectivity of all nodes in the preprocessed graph genome; The connectivity of a node is the sum of the number of parent nodes and child nodes that the node has; The parent node of the node is the node to which the node is forward connected, and the child node of the node is the node to which the node is backward connected; S3.2: The first-category child nodes in the preprocessed graph genome are determined based on the connectivity of all nodes, and all the first-category child nodes constitute the first-category child node set; The first-type child node is a node with only one parent node. The parent node of the first-type child node is called a first-type parent node. All first-type parent nodes constitute a first-type parent node set. S3.3: Use the first-category parent node to inherit the connection information of the corresponding first-category child node; the inherited first-category parent node is obtained, which is expressed as follows: ifv c Has a unique v p Where B represents the backward connection information; v c Represents the first type of child node, v p Represents the first-class parent node, Indicates the first type of parent node after inheritance; S3.4: Remove the first-category child nodes from the preprocessed graph genome, and create a merged node set for the corresponding inherited first-category parent nodes to obtain the removed graph genome. Among them, the first type of parent node after the i-th inheritance The created merge node set is represented as The merged node set records the inheritance information of the first type of child nodes that are removed; S3.5: Calculate the connectivity of all nodes in the removed graph genome, and determine whether all nodes in the removed graph genome have no unique parent node based on the connectivity of all nodes. If all the nodes in the removed graph genome do not have a unique parent node, the forward-compressed graph genome data is obtained; If any node in the removed graph genome has a unique parent node, return to S3.2; S4: Generate individual genome simulation data based on the forward-compressed graph genome data; the specific process is as follows: S4.1: Annotate the merged child node set corresponding to each inherited first-category parent node in the forward-compressed graph genome in the preprocessed graph genome to obtain the annotated preprocessed graph genome; Among them, the node corresponding to the inherited first-category parent node in the preprocessed graph genome is called the second-category parent node; S4.2: Based on the annotated preprocessed graph genome, construct a subgraph genome with the second-category parent node as the first node and n terminal nodes as the last nodes; n is a positive integer; In the forward-compressed graph genome, each inherited parent node represents a subgraph genome; Among them, the first type of parent node after the i-th inheritance The subgraph genome represented by S4.3: Select the first inherited parent node corresponding to the starting node in the forward compressed graph genome And the first type of parent node after inheritance corresponding to the terminal node According to the first parent node after inheritance and the first parent node after inheritance Perform a deep search on the graph genome after forward compression to obtain the individual genome compression path; the specific process is as follows: S4.3.1: Use bitwise storage nodes to define the access status of each inherited first-class parent node in the forward-compressed graph genome. S4.3.2: Select the first inherited parent node of the starting node in the forward compressed graph genome Select the first type of parent node after inheritance corresponding to the terminal node in the graph genome after forward compression According to the access status of each inherited first-category parent node in the forward-compressed graph genome, a deep search is performed in the forward-compressed graph genome to obtain an individual genome compression path; The individual genome compression path includes m inherited first-category parent nodes, where m is a positive integer; The starting point of the individual genome compression path is represented as The end point of the individual genome compression path is expressed as S4.4: Decompress the individual compressed genome path obtained in S4.3 to obtain the individual genome path; perform base processing on the individual genome path to obtain the individual genome structure data in the standard FASTA file format as the individual genome simulation data; the specific process is as follows: S4.4.1: Convert the m inherited first-category parent nodes in the individual compressed genome path obtained in S4.3 into m individual genome subpaths; Among them, the first type of parent node after the i-th inheritance The corresponding individual genome subpath is represented as Pi; the specific process is: S4.4.1.1: Select the first parent node after the jth inheritance and the first parent node after the j+1th inheritance S4.4.1.2: Based on the first parent node after j+1 inheritance The corresponding second-category parent node v in the annotated preprocessed graph genome pj+1 , determine the end point of the j-th individual genome subpath Pj; S4.4.1.3: Obtain the jth individual genome subpath Pj based on the end point of the jth individual genome subpath Pj; S4.4.2: Merge the m individual genome subpaths to obtain the individual genome path; S4.4.3: Perform base processing on the individual genome path to obtain the individual genome structure data in the standard FASTA file format as the individual genome simulation data.

2. The method for generating individual genome simulation data based on graph compression according to claim 1, characterized in that: The specific process of preprocessing the graph genome data in the historical genome dataset in S2 to obtain the preprocessed graph genome data is as follows: S2.1: Invert all nodes of the graph genome in the historical genome dataset to obtain inverted nodes, and add the inverted nodes to the original graph genome to obtain the expanded graph genome. S2.2: Select a starting node in the expanded graph genome and use a breadth-first search method based on a queue data structure to search for nodes layer by layer in the expanded graph genome in order, ultimately obtaining a set of reachable nodes with the starting node as the root. S2.3: Based on the reachable node set, delete the node set that cannot be found in the expanded graph genome to obtain the deleted graph genome; S2.4: Screening and eliminating the deleted graph genome to obtain a preprocessed graph genome.

3. The method for generating individual genome simulation data based on graph compression according to claim 2, characterized in that: In S2.1, all nodes of the graph genome in the historical genome dataset are inverted to obtain a set of inverted nodes. The inverted set of nodes is added to the original graph genome to obtain an expanded graph genome, which is expressed as: V′={v′∣v′∈V,S′(v′)=f(S(v))}, G′=(V∪V′,E∪E′) Where v represents a node in the graph genome, v′ represents a node after negation, V is the set of all nodes in the graph genome, V′ represents the set of nodes after negation, E is the set of all edges in the graph genome, and E′ represents the set of edges composed of negated nodes; f is the negation operation function, S(v) is the state attribute of node v; G′ is the expanded graph genome; S′(v′) represents the state attribute of node v′ after negation; ∪ represents the union; In S2.2, a starting node is selected in the expanded graph genome, and a breadth-first search method based on a queue data structure is used to search for nodes layer by layer in the expanded graph genome in hierarchical order, ultimately obtaining a set of reachable nodes with the starting node as the root. The specific process is as follows: S2.2.1: Select a starting node in the expanded graph genome; S2.2.2: Set the level of the selected starting node to 0, search the expanded graph genome for nodes directly connected to the starting node, and obtain the first-level node set; S2.2.3: Search the expanded graph genome for nodes directly connected to the upper-level nodes. The new nodes found are used as the next-level node set, and finally the reachable node set with the starting node as the root is obtained. The total number of levels is k, where k is a positive integer. The k-th layer node set is obtained by searching the k-1th layer node set and is expressed as follows: Where R k represents the set of nodes in the kth layer, R k-1 represents the set of nodes in the k-1th layer, R i represents the set of nodes in the i-th layer; w represents the nodes in the k-th layer, u represents the nodes in the k-1-th layer; (u, w) represents the edge from node u to node w; In S2.3, based on the reachable node set, the node set that cannot be found is deleted from the expanded graph genome to obtain the deleted graph genome; this is expressed as: Where G' represents the deleted graph genome.

4. The method for generating individual genome simulation data based on graph compression according to claim 3, characterized in that: In S2.4, the obtained deleted graph genome is screened and eliminated to obtain a pre-processed graph genome; the specific process is as follows: S2.4.1.: Set the termination node set and eliminate the iteration termination condition; S2.4.2: Screen and remove the leaf nodes in the deleted graph genome according to the termination node set and the iteration termination condition to obtain the preprocessed graph genome.

5. The method for generating individual genome simulation data based on graph compression according to claim 4, characterized in that: The specific process of setting the termination node set and iteration termination condition in S2.4.1 is as follows: S2.4.1.1: Set the set of terminal nodes T in the deleted graph genome. S2.4.1.2: Set the termination condition for the elimination iteration, expressed as: or So that (v,u)∈E (h) In S2.4.2, the leaf nodes in the deleted graph genome are screened and removed according to the termination node set and the iteration termination condition to obtain the preprocessed graph genome. The specific process is as follows: S2.4.2.1: Set initial situation G (0) =(V (0) ,E (0) )(V (0) =V”,E (0) "=E") S2.4.2.2: Obtain the leaf node set L that needs to be removed in the hth round based on the terminal node set T (h) ;h∈[0,f-1]; According to the leaf node set L that needs to be removed in the h round (h) For the remaining node set V in round h (h) Perform elimination processing to obtain the h+1th round remaining node set V (h+1) and the edge set E consisting of the remaining nodes in round h+1 (h+1) , When the remaining node set in round f meets the iteration termination condition, the iteration stops and the preprocessed graph genome is obtained, which can be expressed as: and V (h+1) =V (h) \L (h) E (h+1) =E (h) \{(u,v)∣u∈V (h) ,v∈L (h) } So that (v,u)∈E (f) } Where T represents the set of terminal nodes, V (h) represents the set of remaining nodes in round h, E (h) represents the edge set consisting of the remaining nodes in round h, \ represents the elimination process; V (f) Represents the set of remaining nodes in round f.

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