Genotype information acquisition method, breeding method, device, equipment and medium

Abstract

The present invention discloses a method for obtaining genotype information, a breeding method, an apparatus, a device and a medium; wherein the method for obtaining genotype information comprises: obtaining genetic data of multiple sequencing samples of a target species; obtaining template reference genome data of the target species; comparing the genetic data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample; obtaining reference population genotype information of the target species; performing gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information; performing gene filling on the reference population genotype information to obtain reference population filled genotype information; performing gene filling on the sample genome filled genotype information of each sequencing sample according to the reference population filled genotype information to obtain target genotype information of each sequencing sample.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and more particularly to a method for obtaining genotype information, a breeding method, a device, an apparatus, and a medium. Background Art

[0002] With the development of modern biology, traditional empirical breeding has gradually evolved into genomic selection-assisted breeding, which relies on high-density molecular genetic markers. This has enabled quantitative, refined, and information-based breeding. The foundation of genomic selection technology is the acquisition of genotypes. Currently, gene chip technology is widely used in the breeding field to obtain genotypes. However, gene chip technology is relatively expensive and has a limited number of detection sites, making it difficult to meet current breeding needs. To address this issue, whole-genome sequencing technology has been developed, which can detect a large number of genotype sites, but it also has the disadvantage of higher costs.

[0003] If you want to reduce costs, you can do so by reducing the sequencing coverage of genes, but this also has an unavoidable defect, namely, it is difficult to accurately obtain whole-genome genotype information. Summary of the Invention

[0004] An object of embodiments of the present application is to solve at least the above-mentioned problems and to provide at least the advantages to be described later.

[0005] Another object of the embodiments of the present application is to provide a method for obtaining genotype information, a breeding method, an apparatus, a device and a medium, which can improve the accuracy of obtaining target genotype information while reducing the sequencing coverage of the sequencing sample.

[0006] In one aspect, the present invention provides a method for obtaining genotype information, comprising:

[0007] Obtain genetic data from multiple sequenced samples of the target species;

[0008] Obtain template reference genome data of the target species;

[0009] Comparing the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample;

[0010] Obtain genotype information of reference populations of target species;

[0011] Perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information;

[0012] Performing gene filling on the reference population genotype information to obtain reference population filled genotype information;

[0013] The already filled genotype information of the sample genome of each sequencing sample is gene-filled according to the filled genotype information of the reference population to obtain the target genotype information of each sequencing sample.

[0014] In some technical solutions, the gene data of each sequencing sample is compared with the template reference genome data to obtain the sample genome information of each sequencing sample; including:

[0015] Comparing the genetic data of each sequencing sample with the template reference genome data to determine the position of the sample genotype sequence of each sequencing sample in the genome;

[0016] According to the position information of one or more sample genotype sequences of each sequencing sample, the one or more sample genotype sequences are arranged to obtain the sample genome information of each sequencing sample.

[0017] In some technical solutions, gene filling is performed on the sample genome information of each sequenced sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information, including:

[0018] Obtaining gene information of the missing sites of the sequencing samples corresponding to the sample genome information of the sequencing samples;

[0019] Obtaining, from the reference population genotype information, gene information for filling missing sites in the sequencing sample that matches the gene information for missing sites in the sequencing sample;

[0020] The sample genome information of the sequencing sample is filled according to the gene information filling the missing sites of the sequencing sample to obtain the filled genotype information of the sample genome of the sequencing sample.

[0021] In some technical solutions, performing gene filling on the reference population genotype information to obtain the reference population filled genotype information includes:

[0022] Determining reference sample genotype information to be filled from a plurality of reference sample genotype information;

[0023] Obtaining the gene information of the missing site of the reference sample corresponding to the genotype information of the reference sample to be filled;

[0024] Comparing the genotype information of the reference sample to be filled with the genotype information of other reference samples in the multiple reference sample genotype information to obtain the reference sample missing site filling gene information with the highest matching degree with the reference sample missing site gene information;

[0025] Gene filling is performed on the genotype information of the reference sample to be filled according to the gene information of the missing sites of the reference sample.

[0026] In some technical solutions, the genotype information already filled in the sample genome of each sequencing sample is filled in according to the genotype information of the reference population to obtain the target genotype information of each sequencing sample; including:

[0027] Obtain the gene information of the missing sites of the sample genome that has been filled with genotype information for each sequenced sample;

[0028] The already filled genotype information of the sample genome of each sequencing sample is gene-filled according to the filled genotype information of the reference population to obtain the target genotype information of each sequencing sample.

[0029] In another aspect, an embodiment of the present application provides a genotype information acquisition device, comprising:

[0030] A gene data acquisition module is used to obtain gene data of multiple sequenced samples of the target species;

[0031] A template reference genome data acquisition module is used to obtain template reference genome data of the target species;

[0032] A sample genome information acquisition module is used to compare the gene data of each sequencing sample with the template reference genome data to obtain the sample genome information of each sequencing sample;

[0033] A reference population genotype information acquisition module is used to obtain the reference population genotype information of the target species;

[0034] A sample genome filled genotype information acquisition module is used to perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information;

[0035] A reference population filled genotype information acquisition module is used to perform gene filling on the reference population genotype information to obtain the reference population filled genotype information;

[0036] The target genotype information acquisition module is used to perform gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the reference population filled genotype information to obtain the target genotype information of each sequencing sample.

[0037] In another aspect, the present invention provides a genetic breeding method, comprising:

[0038] Obtain genetic data from multiple sequenced samples of the target species;

[0039] Obtain template reference genome data of the target species;

[0040] Comparing the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample;

[0041] Obtain genotype information of reference populations of target species;

[0042] Perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information;

[0043] Performing gene filling on the reference population genotype information to obtain reference population filled genotype information;

[0044] Performing gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the genotype information filled in the reference population to obtain target genotype information of each sequencing sample;

[0045] Gene breeding is performed according to the target genotype information.

[0046] In another aspect, the present invention provides a gene breeding device, comprising:

[0047] A gene data acquisition module is used to obtain gene data of multiple sequenced samples of the target species;

[0048] A template reference genome data acquisition module is used to obtain template reference genome data of the target species;

[0049] A sample genome information acquisition module is used to compare the gene data of each sequencing sample with the template reference genome data to obtain the sample genome information of each sequencing sample;

[0050] A reference population genotype information acquisition module is used to obtain the reference population genotype information of the target species;

[0051] A sample genome filled genotype information acquisition module is used to perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information;

[0052] A reference population filled genotype information acquisition module is used to perform gene filling on the reference population genotype information to obtain the reference population filled genotype information;

[0053] A target genotype information acquisition module is used to perform gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the reference population filled genotype information to obtain the target genotype information of each sequencing sample;

[0054] A breeding module is used to perform genetic breeding based on the target genotype information.

[0055] In another aspect, an embodiment of the present application provides an electronic device comprising: a memory, a processor, and a computer instruction program stored on the memory and executable on the processor, wherein the computer instruction program, when executed by the processor, implements the steps of the genotype information acquisition method described in the first aspect or the steps of the genetic breeding method described in the third aspect.

[0056] In another aspect, an embodiment of the present application provides a computer-readable storage medium, on which a computer instruction program is stored. When the computer instruction program is executed by a processor, the steps of the genotype information acquisition method described in the first aspect or the steps of the genetic breeding method described in the third aspect are implemented.

[0057] The beneficial effects that can be achieved by the embodiments of the present application include:

[0058] The embodiment of the present application not only supplements the genotype information of the missing sites corresponding to the reference population genome information, but also performs two gene filling operations on the sequencing samples, thereby making the obtained target genotype information more accurate.

[0059] For this reason, the genotype information acquisition method provided in the embodiments of the present application can reduce the predetermined sequencing coverage, thereby significantly reducing costs.

[0060] In addition, since the sequencing samples were gene-filled twice and the reference population genome information was supplemented with genotype information of missing sites, the accuracy of the genotype information obtained according to the embodiments of the present application is not greatly affected by the number of sequenced samples or the number of reference sample genotype information in the reference population genome. From this perspective, even if the number of sequencing samples or reference samples is greatly reduced, it will not have much impact on the accuracy of the target genotype information.

[0061] Other advantages, objectives and features of the present application will be reflected in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] Figure 1 A schematic diagram of a flow chart of a method for obtaining genotype information according to an embodiment of the present application;

[0063] Figure 2 This is another flow chart of the method for obtaining genotype information according to an embodiment of the present application;

[0064] Figure 3 This is another flow chart of the method for obtaining genotype information according to an embodiment of the present application;

[0065] Figure 4 This is another flow chart of the method for obtaining genotype information according to an embodiment of the present application;

[0066] Figure 5 This is another flow chart of the method for obtaining genotype information according to an embodiment of the present application;

[0067] Figure 6 This is another flowchart of the method for obtaining genotype information according to an embodiment of the present application. DETAILED DESCRIPTION

[0068] The present invention will be described in further detail below in conjunction with the accompanying drawings so that those skilled in the art can implement the invention with reference to the description.

[0069] The terms "first", "second" and "third" in the embodiments of the present application are used for descriptive purposes only and are not to be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. It should also be noted that in the present application, the meaning of "multiple" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined. In addition, the orientations or positional relationships indicated by "upper", "lower", "top", "bottom", "inside", "outside", etc. are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description. They do not indicate or imply that the device or device referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention.

[0070] Furthermore, the terms "comprise," "comprising," and any variations thereof, are intended to cover non-exclusive inclusions. For example, a process, method, system, product, or apparatus comprising a series of steps or elements is not limited to the listed steps or elements, but may optionally include steps or elements not listed, or may optionally include other steps or elements inherent to the process, method, product, or apparatus.

[0071] In addition to the above, it is still important to emphasize that references to "embodiments" herein mean that a particular feature, structure, or characteristic described in conjunction with the embodiments may be included in at least one embodiment of the present application. The appearance of such phrases in various locations in the specification does not necessarily refer to the same embodiment, nor does it necessarily refer to independent or alternative embodiments that are mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0072] <Method for Acquiring Genotype Information>

[0073] like Figure 1 As shown, the embodiment of the present application provides a method for obtaining genotype information, comprising the following steps S101 to S107:

[0074] S101. Obtain genetic data of multiple sequencing samples of a target species.

[0075] It should be noted that each genetic data here refers to the sample genotype information of a corresponding sequencing sample. The genetic data of each sequencing sample includes multiple genotype sequence information. The genetic data is the sample genotype information obtained by sequencing the sequencing sample at a preset sequencing coverage.

[0076] In some embodiments, the sequencing sample can be an individual of the target species (for example, animals and plants such as pigs, dogs, mice, and rice), or a small amount of tissue or cells from the early development of the target species, such as animal embryonic cells or tissue cells of a newborn individual. It is easy to understand that the individual or its cells carry genotype information, so the corresponding genetic data, that is, the sample genotype information, can be obtained from the sequencing sample.

[0077] It should be noted that the source of the sequencing sample cannot be regarded as limiting the scope of protection of the present invention. For example, whether the genetic data is obtained from the embryonic system of the target species or other tissue cells, and the genotype information acquisition method provided in the embodiments of this application is implemented based on the genetic data, it should be regarded as falling within the scope of protection of this application.

[0078] In some embodiments, the preset sequencing coverage is less than or equal to 10X, further less than or equal to 1X, and further less than or equal to 0.5X.

[0079] It should be noted that among multiple sequencing samples, the location information of the genotype sequence of each sequencing sample on the genome is unclear and is in a disordered arrangement state.

[0080] In some embodiments, S101, obtaining genetic data of multiple sequenced samples of a target species, may include:

[0081] Obtain sequencing data of sequencing samples of target species;

[0082] The sequencing data is subjected to sequencing quality control to obtain the gene data. For example, sequences with low sequencing quality (<99%) and short sequencing length (<15) are deleted from the sequencing data.

[0083] S102. Obtain template reference genome data of the target species.

[0084] The template reference genome data includes multiple reference genotype sequence information and the positional information of the multiple reference genotype sequence information within the genome. In other words, the positional information of the multiple reference genotype sequences within the genome is clear within the template reference genome. It should be noted that the template reference genome data can be obtained by previous high-depth sequencing of the target species. This is highly accurate whole-genome information and can be downloaded from public databases.

[0085] S103: Compare the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample.

[0086] Since the position of one or more genotype sequences in the genetic data of each sequencing sample is unclear in the genome, it is difficult to form a gene chain with correct gene arrangement. Therefore, it is necessary to compare with the existing template reference genome to determine the position of all genotype sequences of each sequencing sample in the genome, and then arrange the multiple genotype sequences to form the sample genome information with the same gene position arrangement order as in the template reference genome.

[0087] For example, for a sequencing sample P, its genetic data includes four genotype sequences: A, B, C, and D. Their positions in the genome are unknown before alignment. During alignment with the template reference genome data, it is found that A, B, C, and D correspond to the four genotype sequences A1, B1, C1, and D1 in the template reference genome data, respectively. Therefore, by rearranging A, B, C, and D according to the positions of A1, B1, C1, D1, and E1, the sample genome information of sequencing sample P can be obtained. This can be understood by referring to the table below.

[0088]

[0089] In some embodiments, the sample genomic information is haplotype genetic information.

[0090] S104. Obtain genotype information of a reference population of the target species.

[0091] The reference population genotype information includes genotype information of multiple reference samples, each of which is selected from a reference sample. The genotype information of each reference sample is almost all known information, but some individual genotype information may be missing.

[0092] In some embodiments, the genotype information of each reference sample is different from the genome information of the sequencing sample, that is, the genotype information of each reference sample and the sequencing sample is not exactly the same, and there are differences.

[0093] In some embodiments, the reference sample genotype information is haplotype gene information.

[0094] S105 , performing gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information.

[0095] Because the sequencing sample genome information may not contain complete whole-genome information, it needs to be supplemented by the reference population genotype information. For example, the genotype information of multiple reference samples in the reference population genotype information can be used as a filling template. Each reference sample genotype information is sequentially compared with the sequencing sample genome information, and the genotype sequence information of the missing sites in the sequencing sample genome information is supplemented to obtain the filled genotype information of the sample genome for each sequencing sample.

[0096] For example, the multiple sequencing samples are specifically m sequencing samples, and the reference population genotype information includes n reference sample genotype information, where n is greater than or equal to 2, and m is greater than or equal to 2.

[0097] When performing gene filling on the i-th sequencing sample among m sequencing samples, the genotype information of the 1st to nth reference samples is used as filling templates to perform gene filling on the sample genome information of the i-th sequencing sample, obtaining the filled genotype information of the sample genome of the i-th sequencing sample, where i is greater than or equal to 1 and less than or equal to m. In other words, for the i-th sequencing sample, after performing gene filling on its sample genome information n times, the corresponding filled genotype information of the sample genome can be obtained.

[0098] According to the above method, gene filling of sample genome information of m sequenced samples can be achieved, and m sample genomes can be filled with genotype information.

[0099] It is easy to understand that since the genotype information filled in the sample genome of each sequencing sample is formed based on the filling of genotype information of multiple reference samples, the accuracy and completeness of the genotype information filled in the sample genome are improved.

[0100] S106. Perform gene filling on the reference population genotype information to obtain reference population filled genotype information.

[0101] It is easy to understand that the reference population filling genotype information is formed based on the reference population genotype information, so the reference population filling genotype information includes multiple reference sample filling genotype information, wherein the multiple reference sample filling genotype information corresponds one-to-one to the multiple reference sample genotype information, and each reference sample filling genotype information is formed based on the corresponding reference sample genotype information.

[0102] Since the reference sample genotypes in the reference population genotype information may be flawed, if the accuracy of gene filling is to be improved, the reference sample genotype information needs to be completed.

[0103] Specifically, the completion work can be implemented as follows: for each reference sample genotype information to be filled, all other reference sample genotype information in the multiple reference sample genotype information are used as filling templates to perform gene filling on the reference sample genotype information to be filled.

[0104] For example, the reference population genotype information includes n reference sample genotype information. When the k-th reference sample genotype information needs to be completed, all reference sample genotype information except the k-th reference sample genotype information is used as a filling template to perform gene filling on the k-th reference sample genotype information, wherein n is greater than or equal to 2, and k is greater than or equal to 1 and less than or equal to n. More specifically, in certain embodiments, n is equal to 3 and k is equal to 2, and the first and third reference sample genotype information are used as filling templates to perform gene filling on the k-th reference sample genotype information. In this way, all reference sample filling genotype information in the reference population filling genotype information is fully filled to obtain the reference population filling genotype information.

[0105] S107 , performing gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the filled genotype information of the reference population to obtain target genotype information of each sequencing sample.

[0106] As described above, the reference population genotype information includes multiple reference sample genotype information. Therefore, in this step, each of the multiple reference sample genotype information is used as a filling template to perform gene filling on the already filled genotype information of the sample genome of each sequenced sample, thereby obtaining the corresponding target genotype information. The specific process of gene filling has been described in more detail in steps S105 and S106, and will not be repeated here. Please refer to the similarities above for understanding.

[0107] It should also be noted that the target genotype information can be whole genome genotype information, or whole genome level SNP information.

[0108] When sequencing coverage is very low, genotype sequence information for some sites in the sequenced sample cannot be obtained, resulting in incomplete data and making it difficult to obtain accurate whole-genome information. Furthermore, the reference population genome information may be missing genotype sequences at certain sites. Therefore, using conventional methods to fill in the genetic data of the sequenced sample makes it difficult to obtain highly accurate target genotype information.

[0109] Precisely to address the above-mentioned defects, after obtaining the sample genome information of the sequencing sample, the embodiment of the present application performs a first gene filling on the sample genome information through the reference population genome information to obtain the sample genome-filled genotype information, and also fills the reference population genotype information to form the reference population-filled genotype information. Then, according to the reference population-filled genotype information, a second gene filling is performed on the sample genome-filled genotype information of each sequencing sample to obtain the target genotype information of each sequencing sample.

[0110] In other words, the present embodiment not only supplements the missing site genotype information corresponding to the reference population genome information, but also performs two gene filling operations on the sequenced samples, thereby making the obtained target genotype information more accurate. Therefore, when using the target genotype information for genetic breeding, it can also improve the accuracy of breeding work.

[0111] For this reason, the genotype information acquisition method provided in the embodiments of the present application can reduce the predetermined sequencing coverage, thereby significantly reducing costs.

[0112] In addition, since the sequencing samples were gene-filled twice and the reference population genome information was supplemented with genotype information of missing sites, the accuracy of the genotype information obtained according to the embodiments of the present application is not greatly affected by the number of sequenced samples or the number of reference sample genotype information in the reference population genome. From this perspective, even if the number of sequencing samples or reference samples is greatly reduced, it will not have much impact on the accuracy of the target genotype information.

[0113] In summary, the genotype information acquisition method provided in the embodiments of the present application can accurately obtain the target genotype information of the sequencing sample while reducing costs.

[0114] In some embodiments, the number of sequencing samples is less than or equal to 5.

[0115] In some embodiments, the number of reference samples is less than or equal to 200.

[0116] In some embodiments, as Figure 2As shown, step S103, comparing the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample; specifically, it may include S1031-S1032:

[0117] S1031. Compare the genetic data of each sequencing sample with the template reference genome data to determine the position of the sample genotype sequence of each sequencing sample in the genome.

[0118] It is easy to understand that the genetic data of each sequencing sample includes one or more sample genotype sequences with unclear positions, and the template reference genome data includes multiple template genotype sequences with clear positions.

[0119] Step S1031 can be further implemented in the following manner: determine whether there is a template genotype sequence corresponding to each sample genotype sequence of the sequencing sample in the template reference genome data; if so, use the gene position of the template genotype sequence in the template reference genome as the gene position of the corresponding sample genotype sequence in the whole genome.

[0120] For example, if it is determined that a sample genotype sequence A and a template genotype sequence A1 of a sequencing sample correspond to the same gene, the position P1 of the template genotype sequence A1 in the genome is determined to be the position of the sample genotype sequence A in the whole genome.

[0121] In some embodiments, determining whether a template genotype sequence corresponding to each sample genotype sequence of the sequenced sample exists in the template reference genome data comprises:

[0122] Determining whether there is a template genotype sequence in the template reference genome data that is within a preset similarity to the genotype sequence of each sample of the sequencing sample;

[0123] If it exists, the template genotype sequence with the greatest similarity to the sample genotype sequence is obtained from the template genotype sequences within the preset similarity;

[0124] The position of the template genotype sequence with the greatest similarity is taken as the template genotype sequence corresponding to the sample genotype sequence.

[0125] S1032. Arrange the one or more sample genotype sequences according to the position information of the one or more sample genotype sequences of each sequenced sample to obtain the sample genome information of each sequenced sample.

[0126] In some embodiments, as Figure 3As shown, step S105, gene filling is performed on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information, specifically including S1051-S1053:

[0127] S1051. Obtain gene information of the missing site of the sequencing sample corresponding to the sample genome information of the sequencing sample.

[0128] Specifically, the sample genome information of the sequencing sample can be compared with the template reference genome data to obtain the sequencing sample missing site gene information. For example, the template reference genome has template genes at n gene sites such as A1, A2, A3... An, and the sequencing sample genome has sequencing genes at A1, A3... An, etc. (n-1) based sites. By comparing the template reference genome data and the sample genome information of the sequencing sample, it can be found that the sample genome information of the sequencing sample lacks genes at gene site A2. Therefore, A2 is a missing gene site of the sample genome of the sequencing sample, and the gene information missing at A2 is a sequencing sample missing site gene information. It is easy to understand that if the sequencing sample genome is missing genes at multiple gene sites, then accordingly, the number of sequencing sample missing site gene information is multiple.

[0129] S1052. Obtaining, from the reference population genotype information, gene information for filling missing sites in the sequencing sample that matches the gene information for filling missing sites in the sequencing sample.

[0130] It should be noted that the reference population genotype information includes multiple reference sample genotype information, and each reference sample genotype information includes multiple reference genes.

[0131] Since each reference sample genome information may contain a reference gene corresponding to the missing site in the sequenced sample genome, the reference gene with the highest correlation with the missing gene site in the sequenced sample genome can be selected as the filling gene for the missing site in the sequenced sample. Specifically, taking the missing gene site A2 as an example, the method shown in S10521-S10523 below can be implemented. Figure 4 .

[0132] S10521. Determine the previous gene site A1 adjacent to the deleted gene site A2.

[0133] S10522. Obtain the sequenced gene at the previous gene site A1 of the sample genome of the sequenced sample as the gene to be compared.

[0134] S10523. Obtain one or more reference genes located at the previous gene site A1 from the genotype information of multiple reference samples, perform comparison tests with the genes to be compared respectively, and select the gene at A2 corresponding to the reference gene with the highest comparison similarity as the gene to fill the missing site of the sequencing sample.

[0135] It should be noted that, since the genotype information of each reference sample in the multiple reference sample genotype information is not exactly the same, some reference sample genotype information may not have a reference gene at the previous gene locus A1. Therefore, the number of reference genes located at the previous gene locus A1 obtained from the multiple reference sample genotype information may be one or more.

[0136] S1053: Fill the sample genome information of the sequencing sample according to the gene information for filling missing sites of the sequencing sample to obtain the filled genotype information of the sample genome of the sequencing sample. That is, copy the gene information for filling missing sites of the sequencing sample to the missing sites in the genome information of the sequencing sample.

[0137] In certain embodiments, the reference population genotype information in S105 further includes: sample genome information of other sequenced samples in addition to the sequenced sample to be filled in, which can further improve the accuracy of gene filling.

[0138] In some embodiments, as Figure 5 As shown, the gene filling of the genotype information of each reference sample includes the following steps S1061-S1064:

[0139] S1061. Determine reference sample genotype information to be filled from multiple reference sample genotype information.

[0140] S1062. Obtain the gene information of the missing site of the reference sample corresponding to the genotype information of the reference sample to be filled.

[0141] Specifically, the genotype information of the reference sample to be filled has been compared with the template reference genome data, and the gene information of the missing site of the reference sample is obtained by checking whether each site has displayed genotype information.

[0142] S1063. Compare the reference sample genotype information to be filled with other reference sample genotype information in the plurality of reference sample genotype information to obtain the reference sample missing site filling gene information that has the highest matching degree with the reference sample missing site gene information.

[0143] S1064. Gene filling is performed on the genotype information of the reference sample to be filled according to the gene information of the missing sites of the reference sample.

[0144] In some embodiments, as Figure 6 As shown, step S107, performing gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the genotype information filled in the reference population to obtain the target genotype information of each sequencing sample; specifically including S1071-S1072:

[0145] S1071. Obtain the gene information of the missing sites of the sample genome of each sequenced sample that has been filled with genotype information.

[0146] S1072. Perform gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the filled genotype information of the reference population to obtain target genotype information of each sequencing sample.

[0147] In certain embodiments, the reference population populated genotype information in S107 further includes: sample genome information of other sequencing samples other than the sequencing sample to be populated, or sample genome populated genotype information, which can further improve the accuracy of gene populating.

[0148] For example, the beneficial effects achieved by the embodiments of the present application can also be achieved through the following Genotype information The information acquisition experiment was used to verify the

[0149] Genotype information acquisition experiment

[0150] 200 sequencing samples were randomly selected to carry out genotype filling experiments under different sequencing coverage conditions. Here we simulated data filling from 0.001X to 0.5X. Since only a few sequencing samples in the data set have a sequencing coverage exceeding 1X, we randomly selected 15 sequencing samples to simulate data with a coverage between 1X and 10X. From the results, it can be seen that the method of the embodiment of the present application has a higher filling accuracy on the data of different sequencing coverages. In the case of high sequencing coverage (10X, 5X), the filling accuracy is 99.39% and 99.29%. In the case of ultra-low coverage (0.3X, 0.2X, 0.1X, 0.05X, 0.01X, 0.005X, 0.001X), we also obtained a higher filling accuracy, which was 98.03%, 97.36%, 95.50%, 93.09%, 88.58%, 85.83%, and 73.89% respectively. From sequencing coverage 10X to 0.1X, when sequencing coverage is reduced by 100 times, filling accuracy is only reduced by 3.89%. When sequencing coverage is reduced by 1000 times (10X to 0.01X), genotype filling accuracy decreases by 10.81%. When sequencing coverage is reduced by 10,000 times (10X to 0.001X), genotype filling accuracy decreases by 25.25%. When sequencing coverage is so low, still a higher filling accuracy is obtained. And the data filling difference between samples is smaller. In the case of 0.001X, the filling accuracy standard error between 200 test samples is 0.097. Compared to other methods, the method of the embodiment of the present application has significantly improved accuracy in terms of ultra-low coverage data filling.

[0151] Using the aforementioned 200 samples as the test set, we randomly sampled different numbers of reference data sets (100, 200, 500, 1000, 1500, and 2000) from the 2669 reference data sets for data filling. Each reference set size was sampled five times for data testing. The filling accuracy of the 200 samples was 98.03%, 97.99%, 97.89%, 97.75%, 97.49%, 97.17%, and 96.98% for the reference sample sizes of 2000, 1500, 1000, 500, 200, and 100, respectively. When the reference data set decreases 10 times from 2000 to 200, the filling accuracy only decreases by 0.86%; when the reference data set decreases 20 times (2000 to 100), the filling accuracy decreases by 1.05%. This shows that the method of the embodiment of the present application has a high filling accuracy and does not require a high number of reference samples. When there are fewer reference groups (200), the sample filling accuracy is still high.

[0152] In some research institutions and breeding companies, the number of samples that need to be sequenced to obtain genotypes at one time is not too many. In this case, the embodiment of the present application also tests different numbers of sequencing samples. Specifically, 7 gradients are set, from 1 to 100 sequencing samples. One sample is randomly selected each time, and the test is repeated 20 times. 5-100 samples are repeated 5 times, and 200 samples use the results of Fig.2A. The genotype filling accuracy of 100, 50, 30, 15, 20, 5, and 1 sequencing samples is 98.33%, 98.48%, 98.55%, 98.67%, 98.66%, 98.61%, and 98.29%. The number of sequencing samples is reduced, and the genotype filling accuracy does not decrease. This allows us to sequence a small number of samples each time and perform genotype filling on these small samples, which is an improvement compared to existing filling methods. This is very useful for some breeding studies.

[0153] <Genotype Information Acquisition Device>

[0154] Based on the same inventive concept as the first embodiment, the second embodiment of the present application provides a genotype information acquisition device, comprising:

[0155] The genetic data acquisition module is used to obtain genetic data from multiple sequencing samples of the target species. The sequencing sample can be a single individual of the target species (e.g., pig, dog, mouse, rice, or other animals and plants), or a small amount of tissue or cells from the early development of the target species, such as animal embryonic cells or tissue cells from a newly born individual.

[0156] A template reference genome data acquisition module is used to obtain template reference genome data of the target species;

[0157] A sample genome information acquisition module is used to compare the gene data of each sequencing sample with the template reference genome data to obtain the sample genome information of each sequencing sample;

[0158] A reference population genotype information acquisition module is used to obtain the reference population genotype information of the target species;

[0159] A sample genome filled genotype information acquisition module is used to perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information;

[0160] A reference population filled genotype information acquisition module is used to perform gene filling on the reference population genotype information to obtain the reference population filled genotype information;

[0161] The target genotype information acquisition module is used to perform gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the reference population filled genotype information to obtain the target genotype information of each sequencing sample.

[0162] <Gene breeding method>

[0163] A third aspect of the embodiments of the present application provides a genetic breeding method, comprising:

[0164] S201. Obtain genetic data for multiple sequencing samples of a target species. The sequencing sample can be a single individual of the target species (e.g., animals or plants such as pigs, dogs, mice, and rice), or a small amount of tissue or cells from the early development of the target species, such as animal embryonic cells or tissue cells from a newly born individual. Step S201 is similar to step S101 and can be implemented with reference to step S101.

[0165] S202, obtaining template reference genome data of the target species; step S202 is similar to step S102 and can be implemented with reference to step S102;

[0166] S203, comparing the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample; step S203 is similar to step S103 and can be implemented with reference to step S103;

[0167] S204, obtaining genotype information of a reference population of the target species; Step S204 is similar to step S104 and can be implemented with reference to step S104;

[0168] S205, performing gene filling on the sample genome information of each sequencing sample according to the genotype information of the reference population to obtain the corresponding sample genome filled with genotype information; step S205 is similar to step S105 and can be implemented with reference to step S105;

[0169] S206, performing gene filling on the reference population genotype information to obtain reference population filled genotype information; step S206 is similar to step S106 and can be implemented with reference to step S106;

[0170] S207, performing gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the genotype information filled in the reference population to obtain target genotype information of each sequencing sample; step S207 is similar to step S107 and can be implemented with reference to step S107;

[0171] S208. Perform genetic breeding according to the target genotype information.

[0172] <Gene Breeding Device>

[0173] Based on the same inventive concept as the third aspect of the embodiment, the fourth aspect of the embodiment of the present application provides a gene breeding device, comprising:

[0174] The genetic data acquisition module is used to obtain genetic data from multiple sequencing samples of the target species. The sequencing sample can be a single individual of the target species (e.g., pig, dog, mouse, rice, etc.), or a small amount of tissue or cells from the early development of the target species, such as animal embryonic cells or tissue cells from a newly born individual.

[0175] A template reference genome data acquisition module is used to obtain template reference genome data of the target species;

[0176] A sample genome information acquisition module is used to compare the gene data of each sequencing sample with the template reference genome data to obtain the sample genome information of each sequencing sample;

[0177] A reference population genotype information acquisition module is used to obtain the reference population genotype information of the target species;

[0178] A sample genome filled genotype information acquisition module is used to perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information;

[0179] A reference population filled genotype information acquisition module is used to perform gene filling on the reference population genotype information to obtain the reference population filled genotype information;

[0180] A target genotype information acquisition module is used to perform gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the reference population filled genotype information to obtain the target genotype information of each sequencing sample;

[0181] A breeding module is used to perform genetic breeding based on the target genotype information.

[0182] <Electronic equipment>

[0183] The fifth aspect of an embodiment of the present application provides an electronic device, comprising: a memory, a processor, and a computer instruction program stored on the memory and executable on the processor, wherein when the computer instruction program is executed by the processor, the steps of the genotype information acquisition method described in the first aspect or the steps of the genetic breeding method described in the third aspect are implemented.

[0184] <Computer-readable storage medium>

[0185] The sixth aspect of the embodiments of the present application provides a computer-readable storage medium, on which a computer instruction program is stored. When the computer instruction program is executed by a processor, the steps of the genotype information acquisition method described in the first aspect or the steps of the genetic breeding method described in the third aspect are implemented.

[0186] Although the embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the description and implementation methods. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and illustrations shown and described herein.

Claims

1. A method for obtaining genotype information, characterized in that: include: Obtain genetic data from multiple sequenced samples of the target species; Obtain template reference genome data of the target species; Comparing the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample; Obtain genotype information of reference populations of target species; Perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information; Performing gene filling on the reference population genotype information to obtain reference population filled genotype information; Perform gene filling on the sample genome of each sequencing sample based on the reference population filled genotype information to obtain the target genotype information of each sequencing sample. The sample genome information of each sequencing sample is gene-filled according to the reference population genotype information to obtain the corresponding sample genome-filled genotype information, including: Obtaining gene information of the missing sites of the sequencing samples corresponding to the sample genome information of the sequencing samples; Obtaining, from the reference population genotype information, gene information for filling missing sites in the sequencing sample that matches the gene information for missing sites in the sequencing sample; Filling the sample genome information of the sequencing sample according to the gene filling information of the missing site of the sequencing sample to obtain the genotype information of the sample genome of the sequencing sample. Performing gene filling on the reference population genotype information to obtain reference population filled genotype information; comprising: Determining reference sample genotype information to be filled from a plurality of reference sample genotype information; Obtaining the gene information of the missing site of the reference sample corresponding to the genotype information of the reference sample to be filled; Comparing the genotype information of the reference sample to be filled with the genotype information of other reference samples in the multiple reference sample genotype information to obtain the reference sample missing site filling gene information with the highest matching degree with the reference sample missing site gene information; Gene filling is performed on the genotype information of the reference sample to be filled according to the gene information of the missing sites of the reference sample.

2. The method for obtaining genotype information according to claim 1, wherein: Comparing the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample; including: Comparing the genetic data of each sequencing sample with the template reference genome data to determine the position of the sample genotype sequence of each sequencing sample in the genome; According to the position information of one or more sample genotype sequences of each sequencing sample, the one or more sample genotype sequences are arranged to obtain the sample genome information of each sequencing sample.

3. The method for obtaining genotype information according to claim 1, wherein: Performing gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the reference population filled genotype information to obtain target genotype information of each sequencing sample; comprising: Obtain the gene information of the missing sites of the sample genome that has been filled with genotype information for each sequenced sample; The already filled genotype information of the sample genome of each sequencing sample is gene-filled according to the filled genotype information of the reference population to obtain the target genotype information of each sequencing sample.

4. A genetic breeding method, characterized in that: include: Obtain genetic data from multiple sequenced samples of the target species; Obtain template reference genome data of the target species; Comparing the gene data of each sequencing sample with the template reference genome data to obtain sample genome information of each sequencing sample; Obtain genotype information of reference populations of target species; Perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information; Performing gene filling on the reference population genotype information to obtain reference population filled genotype information; Performing gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the genotype information filled in the reference population to obtain target genotype information of each sequencing sample; Perform genetic breeding according to the target genotype information, The sample genome information of each sequencing sample is gene-filled according to the reference population genotype information to obtain the corresponding sample genome filled genotype information, including: Obtaining gene information of the missing sites of the sequencing samples corresponding to the sample genome information of the sequencing samples; Obtaining, from the reference population genotype information, gene information for filling missing sites in the sequencing sample that matches the gene information for missing sites in the sequencing sample; Filling the sample genome information of the sequencing sample according to the gene filling information of the missing site of the sequencing sample to obtain the genotype information of the sample genome of the sequencing sample. Performing gene filling on the reference population genotype information to obtain reference population filled genotype information; comprising: Determining reference sample genotype information to be filled from a plurality of reference sample genotype information; Obtaining the gene information of the missing site of the reference sample corresponding to the genotype information of the reference sample to be filled; Comparing the genotype information of the reference sample to be filled with the genotype information of other reference samples in the multiple reference sample genotype information to obtain the reference sample missing site filling gene information with the highest matching degree with the reference sample missing site gene information; Gene filling is performed on the genotype information of the reference sample to be filled according to the gene information of the missing sites of the reference sample.

5. A genotype information acquisition device, characterized in that: The method for obtaining genotype information according to claim 1 comprises: A gene data acquisition module is used to obtain gene data of multiple sequenced samples of the target species; A template reference genome data acquisition module is used to obtain template reference genome data of the target species; A sample genome information acquisition module is used to compare the gene data of each sequencing sample with the template reference genome data to obtain the sample genome information of each sequencing sample; A reference population genotype information acquisition module is used to obtain the reference population genotype information of the target species; A sample genome filled genotype information acquisition module is used to perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information; A reference population filled genotype information acquisition module is used to perform gene filling on the reference population genotype information to obtain the reference population filled genotype information; The target genotype information acquisition module is used to perform gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the reference population filled genotype information to obtain the target genotype information of each sequencing sample.

6. A gene breeding device, characterized in that: The method for obtaining genotype information according to claim 1 comprises: A gene data acquisition module is used to obtain gene data of multiple sequenced samples of the target species; A template reference genome data acquisition module is used to obtain template reference genome data of the target species; A sample genome information acquisition module is used to compare the gene data of each sequencing sample with the template reference genome data to obtain the sample genome information of each sequencing sample; A reference population genotype information acquisition module is used to obtain the reference population genotype information of the target species; A sample genome filled genotype information acquisition module is used to perform gene filling on the sample genome information of each sequencing sample according to the reference population genotype information to obtain the corresponding sample genome filled genotype information; A reference population filled genotype information acquisition module is used to perform gene filling on the reference population genotype information to obtain the reference population filled genotype information; A target genotype information acquisition module is used to perform gene filling on the already filled genotype information of the sample genome of each sequencing sample according to the reference population filled genotype information to obtain the target genotype information of each sequencing sample; A breeding module is used to perform genetic breeding based on the target genotype information.

7. An electronic device, characterized in that include: A memory, a processor, and a computer instruction program stored in the memory and executable on the processor, wherein the computer instruction program, when executed by the processor, implements the steps of the genotype information acquisition method according to any one of claims 1 to 3 or the steps of the genetic breeding method according to claim 4.

8. A computer-readable storage medium, characterized in that The computer-readable storage medium stores a computer instruction program, which, when executed by a processor, implements the steps of the genotype information acquisition method according to any one of claims 1 to 3 or the steps of the genetic breeding method according to claim 4.

Images