Tiny residual focus detection device, storage medium and equipment

Abstract

The invention discloses a tiny residual focus detection device, a storage medium and equipment. The brand-new cancer operation tissue and postoperative blood pairing inspection method is designed, based on sequencing data, an embryonic system variation union set of two samples is obtained, pairing inspection of the two samples is carried out in combination with mutation abundance correlation and homozygosity and heterozygosity consistency, a specific construction and judgment scheme is designed, extra detection is not needed, and the method is simple and convenient to operate. The cancer postoperative blood and surgical tissue pairing inspection can be performed simply and accurately, and the method is applied to tiny residual focus detection to verify cancer surgical tissues and postoperative blood samples.

Description

Technical Field

[0001] The present invention belongs to the field of biotechnology and relates to a micro residual lesion detection device, a storage medium and equipment. Background Art

[0002] Minimal residual disease (MRD) testing is a new type of testing method based on next-generation sequencing that has emerged in recent years. The most commonly used technical route for this test is tissue-informed testing, in which patients need to collect three samples simultaneously: surgical tissue, white blood cell control (WBC), and postoperative blood for next-generation sequencing. Because postoperative blood is collected later than surgical tissue and WBC, there is a certain probability of sample delivery error, that is, the collected postoperative blood and surgical tissue are not from the same patient (i.e., pairing error), which in turn leads to erroneous MRD test results.

[0003] Existing technology generally adds a SNP array test containing dozens of common germline loci to surgical tissue and postoperative blood, using the pure heterozygous consistency of this SNP array as the basis for pairing. This technology has three disadvantages: (1) The additional test increases the testing cost; (2) The ctDNA content obtained from postoperative blood extraction is low, and there is often not enough for this SNP array test; (3) This additional test is limited by the technical defects of the SNP array and cannot obtain mutation abundance information. It can only use pure heterozygous consistency information, and its accuracy is lower than that of second-generation sequencing.

[0004] Germline variation refers to variations that develop in the ectoderm, mesoderm, and endoderm during embryogenesis. Germline variation is primarily used to differentiate between different populations in terms of appearance, blood type, and other aspects, and it also has a certain degree of familial inheritance. In the field of precision cancer treatment, NGS sequencing technology is becoming increasingly widely used, and major public databases have accumulated sequencing data for multiple types of cancer. Based on the sequencing results of cancer patients, doctors can determine whether the patient is suitable for targeted drug therapy. Distinguishing germline variation from somatic variation in the variation results detected in the patient is a key step in this process. However, there have been no reports on the use of germline variation information for paired blood and surgical tissue testing after cancer surgery.

[0005] In summary, the development of a simple and highly accurate method for paired examination of blood and surgical tissue after cancer surgery is of great significance in the field of minimal residual lesions detection. Summary of the Invention

[0006] In response to the deficiencies of the existing technology and actual needs, the present invention provides a minimal residual lesion detection device, storage medium and equipment, in order to achieve simple and highly accurate paired examination of blood and surgical tissue after cancer surgery, and then perform efficient minimal residual lesion detection.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides a minimal residual lesion detection device, the detection device being configured to perform the following steps:

[0009] (1) Obtain mutation detection results from cancer surgical tissues and postoperative blood samples;

[0010] (2) Determine whether the two samples are paired based on the mutation detection results of the two samples; if the two samples are paired correctly, dynamic monitoring is performed; otherwise, the detection is terminated, or,

[0011] Perform dynamic monitoring and determine whether the two samples are paired based on the mutation detection results of the two samples. If the two samples are paired correctly, output the dynamic monitoring results, otherwise end the detection.

[0012] The present invention designs a minimal residual lesion detection device, which implements a new minimal residual lesion detection scheme. The schematic diagram for comparison with the existing method is shown in FIG. Figure 1 As shown, the results of sequencing technology (such as second-generation sequencing technology) are directly analyzed and paired, and then efficient minimal residual lesions are detected, without the need for additional SNP array testing, and the accuracy is higher than SNP array testing.

[0013] Preferably, the dynamic monitoring includes monitoring of tumor burden before surgery, monitoring of recurrence after surgery, monitoring of tumor burden after drug treatment, monitoring of recurrence after drug treatment, etc. for tumors (for example, lung cancer, colorectal cancer, gastric cancer, etc., not listed one by one).

[0014] Preferably, determining whether two samples are paired includes:

[0015] Select the union of germline variants in the variant detection results;

[0016] Obtain germline variants and centralize the raw mutation abundance at each variant site;

[0017] Calculating the Pearson correlation coefficient between cancer surgical tissue and postoperative blood samples based on the raw mutation abundance, i.e., the mutation abundance correlation;

[0018] Performing pure heterozygous determination on the germline variation and each variation site in the set according to the original mutation abundance, and calculating the proportion of the same pure heterozygous determination in the germline variation and set between the cancer surgical tissue and the postoperative blood sample, which is pure heterozygous consistency;

[0019] The pairing of cancer surgical tissue and postoperative blood samples was determined based on mutation abundance correlation and pure heterozygosity consistency.

[0020] Preferably, the method for determining whether the cancer surgical tissue and the postoperative blood sample are paired comprises:

[0021] Substitute the values ​​of the mutation abundance correlation and pure heterozygous consistency into formula (1). If formula (1) is satisfied, the cancer surgical tissue and the postoperative blood sample are determined to be paired; otherwise, they are not paired.

[0022] 5×mutation abundance correlation + 4×homozygous consistency ≥ 7.6 formula (1).

[0023] Preferably, the method for selecting the germline variation union includes:

[0024] The mutation detection results of cancer surgical tissue and postoperative blood samples are obtained, and the mutation sites with mutation abundance not less than a threshold in the mutation detection results are selected as the germline mutation union. The threshold is 25% to 38% (for example, it can be 26%, 27%, 28%, 29%, 30%, 31%, 32%, 35% or 37%, etc., not listed one by one).

[0025] Preferably, the criteria for determining pure heterozygosity include: original mutation abundance ≥ 0.95.

[0026] Preferably, the method for calculating the mutation abundance correlation includes:

[0027] Where X represents the original mutation abundance of cancer surgical tissue, represents the mean of X; Y represents the original mutation abundance of postoperative blood, represents the mean value of Y, and the correlation r between the mutation abundances of the two is calculated by formula (2):

[0028]

[0029] Preferably, the method for calculating the pure heterozygous consistency includes:

[0030] X represents the original mutation abundance of cancer surgical tissue. If X < 0.05, the mutation is marked as "homozygous wild type" in the cancer surgical tissue; if 0.05 ≤ X < 0.95, the mutation is marked as "heterozygous" in the cancer surgical tissue; if X ≥ 0.95, the mutation is marked as "homozygous mutant" in the cancer surgical tissue.

[0031] Y represents the original mutation abundance in postoperative blood. If Y≤0.05, the mutation is marked as "homozygous wild type" in postoperative blood; if 0.05<Y≤0.95, the mutation is marked as "heterozygous" in postoperative blood; if Y>0.95, the mutation is marked as "homozygous mutant type" in postoperative blood.

[0032] For a mutation, the markers of two samples were compared and the homozygous consistency was calculated according to formula (3):

[0033] Homozygous consistency = number of mutations with the same marker ÷ total number of mutations (Formula (3)).

[0034] Preferably, the detection device is also used to perform the steps of obtaining cancer surgical tissue and postoperative blood samples and performing sequencing.

[0035] Preferably, the method for obtaining the variation detection result includes:

[0036] Variation detection is performed on sequencing data of cancer surgical tissue and postoperative blood samples to obtain the variation detection results.

[0037] Preferably, the variation detection software includes any one of in-house software, GATK, samtools, varScan, varDict or TNscope.

[0038] Preferably, the method for obtaining sequencing data includes:

[0039] Cancer surgical tissues and postoperative blood samples were sequenced to obtain raw data, which were preprocessed and the mutation abundance was calculated based on the SNP site information in the preprocessed data.

[0040] Preferably, the preprocessing includes data splitting, data pasting, sorting and deduplication.

[0041] In a second aspect, the present invention provides an electronic device comprising one or more processors and a memory for storing executable instructions, wherein the one or more processors are configured to call the executable instructions stored in the memory to implement the functions of the minimal residual lesion detection device described in the first aspect.

[0042] In a third aspect, the present invention provides a computer-readable storage medium having computer program instructions stored thereon, which, when executed by a processor, implement the functions of the minimal residual lesion detection device described in the first aspect.

[0043] In a fourth aspect, the present invention provides a method for pairing cancer surgical tissue and postoperative blood based on dynamic monitoring, the method comprising:

[0044] The mutation detection results of cancer surgical tissue and postoperative blood samples are obtained. The variant sites with a mutation abundance not less than a threshold value (the threshold value can be 25% to 38%, for example, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 35%, or 37%, etc., are not listed here) are selected as the germline variant union. Based on the genomic coordinates of the variant sites in the germline variant union, the raw mutation abundance at each variant site in the cancer surgical tissue and postoperative blood samples is obtained.

[0045] The Pearson correlation coefficient between the cancer surgical tissue and the postoperative blood sample is calculated based on the original mutation abundance, which is the mutation abundance correlation; the germline variation and each mutation site are judged as pure heterozygous based on the original mutation abundance, and the proportion of the cancer surgical tissue and the postoperative blood sample with the same pure heterozygous judgment in the germline variation and the set is calculated, which is the pure heterozygous consistency;

[0046] Substitute the values ​​of the mutation abundance correlation and pure heterozygous consistency into formula (1). If formula (1) is satisfied, the cancer surgical tissue and the postoperative blood sample are determined to be paired; otherwise, they are not paired.

[0047] 5×mutation abundance correlation + 4×homozygous consistency ≥ 7.6 formula (1).

[0048] In the present invention, a new method for paired examination of cancer surgical tissue and postoperative blood is designed. Based on sequencing data, the union of germline variations of the two samples is obtained, and the two-sample paired examination is performed in combination with mutation abundance correlation and pure heterozygous consistency. A specific construction and judgment scheme is designed, and no additional testing is required. It can realize simple and highly accurate paired examination of cancer postoperative blood and surgical tissue, which can be applied to the detection of minimal residual lesions and the verification of cancer surgical tissue and postoperative blood samples.

[0049] In the present invention, since surgical tissue samples contain a certain amount of tumor cells, the chromosome ploidy of some cells may change, causing the mutation abundance of some heterozygous mutant sites to deviate from 0.5, resulting in errors in the pure heterozygous consistency judgment. The introduction of the mutation abundance correlation dimension can effectively improve the accuracy.

[0050] Preferably, the criteria for determining pure heterozygosity include: original mutation abundance ≥ 0.95;

[0051] Preferably, the method for calculating the mutation abundance correlation includes:

[0052] Where X represents the original mutation abundance of cancer surgical tissue, represents the mean of X; Y represents the original mutation abundance of postoperative blood, represents the mean value of Y, and the correlation r between the mutation abundances is calculated by the following formula:

[0053]

[0054] Preferably, the method for calculating the pure heterozygous consistency includes:

[0055] X represents the original mutation abundance of cancer surgical tissue. If X < 0.05, the mutation is marked as "homozygous wild type" in the cancer surgical tissue; if 0.05 ≤ X < 0.95, the mutation is marked as "heterozygous" in the cancer surgical tissue; if X ≥ 0.95, the mutation is marked as "homozygous mutant" in the cancer surgical tissue.

[0056] Y represents the original mutation abundance in postoperative blood. If Y≤0.05, the mutation is marked as "homozygous wild type" in postoperative blood; if 0.05<Y≤0.95, the mutation is marked as "heterozygous" in postoperative blood; if Y>0.95, the mutation is marked as "homozygous mutant type" in postoperative blood.

[0057] For a mutation, the marker comparison between two samples was performed and the homozygous consistency was calculated as follows:

[0058] Homozygous consistency = number of mutations with the same marker ÷ total number of mutations (Formula (3)).

[0059] Preferably, the method for obtaining the variation detection result includes:

[0060] Variation detection is performed on sequencing data of cancer surgical tissue and postoperative blood samples to obtain the variation detection results.

[0061] It is understood that in the present invention, common methods or software in the art can be used to perform variation detection without special limitations.

[0062] Preferably, the variation detection software includes any one of in-house software, GATK, samtools, varScan, varDict or TNscope.

[0063] It is understood that in the present invention, methods or software commonly used in the art can be used to perform sequencing and data processing operations, as long as the calculation of mutation abundance can be achieved, without any special limitations.

[0064] Preferably, the method for obtaining sequencing data includes:

[0065] Cancer surgical tissues and postoperative blood samples were sequenced to obtain raw data, which were preprocessed and the mutation abundance was calculated based on the SNP site information in the preprocessed data.

[0066] Preferably, the sequencing method includes a second-generation sequencing method, etc.

[0067] Preferably, the preprocessing includes data splitting, data pasting, sorting and deduplication.

[0068] Preferably, the data splitting software includes bcl2fastq software and the like.

[0069] Preferably, the data reply software includes bwa software and the like.

[0070] Preferably, the software for calculating the mutation abundance includes samtools software, etc.

[0071] In a fifth aspect, the present invention provides a device for checking the pairing of cancer surgical tissue and postoperative blood, the device comprising a germline variation union construction unit, a calculation unit, and a judgment unit.

[0072] The germline variation union unit is configured to execute the following steps:

[0073] The mutation detection results of cancer surgical tissues and postoperative blood samples are obtained, and the mutation sites with mutation abundance not less than a threshold (the threshold value can be 25% to 38%) in the mutation detection results are selected as the germline mutation union. Based on the genomic coordinates of the mutation sites in the germline mutation union, the original mutation abundance at each mutation site in the cancer surgical tissues and postoperative blood samples is obtained.

[0074] The computing unit is configured to perform the following operations:

[0075] The Pearson correlation coefficient of the cancer surgical tissue and the postoperative blood sample is calculated based on the original mutation abundance, which is the mutation abundance correlation; the germline variation and each mutation site are judged as pure heterozygous based on the original mutation abundance, and the proportion of the cancer surgical tissue and the postoperative blood sample with the same pure heterozygous judgment in the germline variation and the concentration is calculated, which is the pure heterozygous consistency.

[0076] The judgment unit is configured to perform the following steps:

[0077] Substitute the values ​​of the mutation abundance correlation and pure heterozygous consistency into formula (1). If formula (1) is satisfied, the cancer surgical tissue and the postoperative blood sample are determined to be paired; otherwise, they are not paired.

[0078] 5×mutation abundance correlation + 4×homozygous consistency ≥ 7.6 formula (1).

[0079] Preferably, the method for calculating the mutation abundance correlation includes:

[0080] Where X represents the original mutation abundance of cancer surgical tissue, represents the mean of X; Y represents the original mutation abundance of postoperative blood, represents the mean value of Y, and the correlation r between the mutation abundances is calculated by the following formula:

[0081]

[0082] Preferably, the method for calculating the pure heterozygous consistency includes:

[0083] X represents the original mutation abundance of cancer surgical tissue. If X < 0.05, the mutation is marked as "homozygous wild type" in the cancer surgical tissue; if 0.05 ≤ X < 0.95, the mutation is marked as "heterozygous" in the cancer surgical tissue; if X ≥ 0.95, the mutation is marked as "homozygous mutant" in the cancer surgical tissue.

[0084] Y represents the original mutation abundance in postoperative blood. If Y≤0.05, the mutation is marked as "homozygous wild type" in postoperative blood; if 0.05<Y≤0.95, the mutation is marked as "heterozygous" in postoperative blood; if Y>0.95, the mutation is marked as "homozygous mutant type" in postoperative blood.

[0085] For a mutation, the marker comparison between two samples was performed and the homozygous consistency was calculated as follows:

[0086] Homozygous consistency = number of mutations with the same marker ÷ total number of mutations (Formula (3)).

[0087] Preferably, the method for obtaining the variation detection result includes:

[0088] Variation detection is performed on sequencing data of cancer surgical tissue and postoperative blood samples to obtain the variation detection results.

[0089] Preferably, the variation detection software includes any one of in-house software, GATK, samtools, varScan, varDict or TNscope.

[0090] Preferably, the method for obtaining sequencing data includes:

[0091] Cancer surgical tissues and postoperative blood samples were sequenced to obtain raw data, which were preprocessed and the mutation abundance was calculated based on the SNP site information in the preprocessed data.

[0092] Preferably, the preprocessing includes data splitting, data pasting, sorting and deduplication.

[0093] Compared with the prior art, the present invention has the following beneficial effects:

[0094] The present invention designs a new method for paired examination of cancer surgical tissue and postoperative blood, and develops a minimal residual disease detection device. Based on sequencing data, the union of germline variations of the two samples is obtained, and the two-sample paired examination is combined with mutation abundance correlation and pure heterozygous consistency. A specific construction and judgment scheme is designed, and the results are directly analyzed based on sequencing technology (such as second-generation sequencing technology), eliminating the need for additional SNP array testing, and the accuracy is higher than SNP array testing. BRIEF DESCRIPTION OF THE DRAWINGS

[0095] Figure 1 A schematic diagram comparing the implementation of the minimal residual lesion detection device of the present invention with the existing method;

[0096] Figure 2 Schematic diagram of the process of paired examination of cancer surgical tissue and postoperative blood for dynamic monitoring;

[0097] Figure 3 This is a diagram showing the results of paired examinations of cancer surgery tissue and postoperative blood. DETAILED DESCRIPTION

[0098] To further illustrate the technical means and effects of the present invention, the present invention is further described below with reference to the embodiments and drawings. It should be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention.

[0099] If no specific techniques or conditions are specified in the examples, the experiments were carried out according to the techniques or conditions described in the literature in the field or according to the product instructions. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0100] Example 1

[0101] The present invention designs a method for pairing blood and surgical tissue examination after cancer surgery based on dynamic monitoring. The flow chart is as follows: Figure 2 shown.

[0102] (1) Illumina sequencer data was split using the public software bcl2fastq to generate fastq files;

[0103] (2) Use the public software bwa to map the fastq to the genome and generate a bam file, which is then sorted and deduplicated;

[0104] (3) Use samtools to calculate mutation abundance based on SNP site information;

[0105] (4) Use in-house software for variant detection;

[0106] (5) For the variants obtained in step 4, the variants with mutation abundance of not less than 25% are regarded as candidate germline variants, and the candidate germline variants of the two samples are obtained. Based on the genomic coordinates of this variant union, regardless of whether it passes the various filters, the original mutation abundances of the two samples at these sites are obtained;

[0107] (6) Calculate the mutation abundance correlation and pure heterozygosity consistency between the two samples in the germline variation set of step (5), and calculate the Pearson correlation coefficient of the original mutation abundance of the two samples in the germline variation set. This value is the "mutation abundance correlation" and is recorded as x; based on the original mutation abundance, perform pure heterozygosity judgment on each mutation in the germline variation set: (1) sites with mutation abundance <0.05 are judged as wild type, (2) sites with 0.05≤mutation abundance <0.95 are judged as heterozygous mutant type, (3) sites with mutation abundance ≥0.95 are judged as homozygous mutant type, and based on this judgment result, calculate the proportion of the two samples with the same pure heterozygosity judgment in the germline variation set. This value is the "pure heterozygous consistency" and is recorded as y;

[0108] (7) Determine whether the sample pairing is correct based on whether the value calculated in step (6) satisfies formula (1);

[0109] 5x+4y≥7.6 formula (1).

[0110] Based on the above method flow, a cancer surgical tissue and postoperative blood pairing inspection device, as well as corresponding electronic equipment, computer-readable storage media, etc. can be further designed and constructed to quickly and standardizedly implement and complete the above method.

[0111] Example 2

[0112] This example retrospectively reviewed the collection process of two samples (postoperative blood and surgical tissue) from 112 patients and determined their pairing. Among them, the two samples from 8 patients were incorrectly paired (the error rate was 8 / 112*100%=7.14%).

[0113] Using the pure heterozygous concordance of next-generation sequencing to simulate the performance of the SNP array method will result in higher accuracy than the SNP array method and can be considered the upper limit of the SNP array method's performance. Generally, the SNP array will identify a pure heterozygous concordance of ≤ 0.9 as a mispairing.

[0114] According to the steps described in Example 1, the raw mutation abundance was used to determine homozygous mutations for each mutation in the germline variation set as follows:

[0115] (1) Sites with mutation abundance < 0.05 were considered wild type;

[0116] (2) Sites with mutation abundances of 0.05 ≤ < 0.95 were determined to be heterozygous mutants;

[0117] (3) Sites with mutation abundance ≥ 0.95 were determined to be homozygous mutants.

[0118] X represents the original mutation abundance of cancer surgical tissue. If X is less than 0.05, the mutation is marked as “homozygous wild type” in the cancer surgical tissue; if 0.05≤X<0.95, the mutation is marked as “heterozygous” in the cancer surgical tissue; if X≥0.95, the mutation is marked as “homozygous mutant type” in the cancer surgical tissue; Y represents the original mutation abundance of postoperative blood. If Y≤0.05, the mutation is marked as “homozygous wild type” in the postoperative blood; if 0.05<Y≤0.95, the mutation is marked as “heterozygous” in the postoperative blood; if Y>0.95, the mutation is marked as “homozygous mutant type” in the postoperative blood; for a mutation, the labeling comparison between two samples is performed, and the homozygous and heterozygous consistency is calculated according to formula (3):

[0119] Homozygous consistency = number of mutations with the same marker ÷ total number of mutations (Formula (3)).

[0120] Based on this judgment result, the proportion of the two samples with the same pure heterozygous judgment in the germline mutation set is compared. This value is the "pure heterozygous consistency" and is calculated as y.

[0121] The Pearson correlation coefficient was calculated for the raw mutation abundances of the two samples in the germline variant pool. This value is the "mutation abundance correlation" and is denoted as r.

[0122] Where X represents the original mutation abundance of cancer surgical tissue, represents the mean of X; Y represents the original mutation abundance of postoperative blood, represents the mean value of Y, and the correlation r between the mutation abundances of the two is calculated by formula (2):

[0123]

[0124] When the values ​​of the two satisfy the formula 5r+4y≥7.6, the pairing of the two samples is considered correct.

[0125] Under these conditions, the performance comparison of the two methods is shown in Table 1, where the TP (True Positive, true positive) of the simulated SNP array method is 5, the FN (False Negative, false negative) is 3, the FP (False Positive, false positive) is 1, and the TN (True Negative, true negative) is 103; the TP of the method of the present invention is 8, the FN is 0, the FP is 0, and the TN is 104. The specific values ​​are as follows Figure 3 As shown in the figure, according to the threshold value of the method of the present invention, 8 cases of incorrect pairing can be accurately judged, while according to the threshold value of the SNP array method, there are some misjudgments. It can be seen that the sensitivity and accuracy of the pairing detection method designed by the present invention are better than the existing SNP array method.

[0126] Table 1

[0127] Sensitivity TP / (TP+FN) Accuracy TP / (TP+FP) Simulated SNP array 62.50％ 83.33％ The present invention 100.00％ 100.00％

[0128] In summary, the present invention adopts a novel approach, first obtaining the union of germline variants of two samples, then pairing the samples based on mutation abundance correlation and pure heterozygosity, and designing a specific construction and judgment scheme. This eliminates the need for additional SNP array testing, thus achieving a simple and highly accurate paired examination of blood and surgical tissue after cancer surgery.

[0129] The applicant states that the present invention is intended to illustrate the detailed methods of the present invention through the above-described embodiments, but the present invention is not limited to the above-described detailed methods, that is, it does not mean that the present invention must rely on the above-described detailed methods in order to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions for various raw materials in the products of the present invention, addition of auxiliary ingredients, and selection of specific methods, etc., are all within the scope of protection and disclosure of the present invention.

Claims

1. A minimal residual lesion detection device, characterized in that: The detection device is used to perform the following steps: (1) Obtain mutation detection results from cancer surgical tissues and postoperative blood samples; (2) Determine whether the two samples are paired based on the mutation detection results of the two samples; if the two samples are paired correctly, dynamic monitoring is performed; otherwise, the detection is terminated, or, Perform dynamic monitoring and determine whether the two samples are paired based on the mutation detection results of the two samples. If the two samples are paired correctly, output the dynamic monitoring results, otherwise end the detection.

2. The detection device according to claim 1, characterized in that Determining whether two samples are paired includes: Select the union of germline variants in the variant detection results; Obtain germline variants and centralize the raw mutation abundance at each variant site; Calculating the Pearson correlation coefficient between cancer surgical tissue and postoperative blood samples based on the raw mutation abundance, i.e., the mutation abundance correlation; Performing pure heterozygous determination on the germline variation and each variation site in the set according to the original mutation abundance, and calculating the proportion of the same pure heterozygous determination in the germline variation and set between the cancer surgical tissue and the postoperative blood sample, which is pure heterozygous consistency; The pairing of cancer surgical tissue and postoperative blood samples was determined based on mutation abundance correlation and pure heterozygosity consistency.

3. The detection device according to claim 2, characterized in that The method for determining whether a cancer surgical tissue and a postoperative blood sample are paired comprises: Substitute the values ​​of the mutation abundance correlation and pure heterozygous consistency into formula (1). If formula (1) is satisfied, the cancer surgical tissue and the postoperative blood sample are determined to be paired; otherwise, they are not paired. 5×mutation abundance correlation + 4×homozygous consistency ≥ 7.6 formula (1).

4. The detection device according to claim 2 or 3, characterized in that: The method for selecting the germline variation union includes: The mutation detection results of cancer surgical tissues and postoperative blood samples are obtained, and the mutation sites with mutation abundance not less than a threshold in the mutation detection results are selected as the germline mutation union, and the threshold is 25% to 38%.

5. The detection device according to any one of claims 2 to 4, characterized in that: The criteria for determining pure heterozygosity include: original mutation abundance ≥ 0.95; Preferably, the method for calculating the mutation abundance correlation includes: Where X represents the original mutation abundance of cancer surgical tissue, represents the mean of X; Y represents the original mutation abundance of postoperative blood, represents the mean value of Y, and the correlation r between the mutation abundances of the two is calculated by formula (2):

6. The detection device according to any one of claims 2 to 5, characterized in that: The calculation method of the homozygous consistency includes: X represents the original mutation abundance in cancer surgical tissues. If X < 0.05, the mutation is marked as "homozygous wild type" in cancer surgical tissues; if 0.05 ≤ X < 0.95, the mutation is marked as "heterozygous" in cancer surgical tissues; if X ≥ 0.95, the mutation is marked as "homozygous mutant" in cancer surgical tissues. Y represents the original mutation abundance in postoperative blood. If Y≤0.05, the mutation is marked as "homozygous wild type" in postoperative blood; if 0.05<Y≤0.95, the mutation is marked as "heterozygous" in postoperative blood; if Y>0.95, the mutation is marked as "homozygous mutant" in postoperative blood. For a mutation, the markers of two samples were compared and the homozygous consistency was calculated according to formula (3): Homozygous consistency = number of mutations with the same marker ÷ total number of mutations (Formula (3)).

7. The detection device according to any one of claims 1 to 6, characterized in that: The detection device is also used to perform the steps of obtaining cancer surgical tissue and postoperative blood samples and performing sequencing.

8. The detection device according to any one of claims 1 to 7, characterized in that: The method for obtaining the variation detection result includes: performing mutation detection on sequencing data of cancer surgical tissue and postoperative blood samples to obtain the mutation detection results; Preferably, the variation detection software includes any one of in-house software, GATK, samtools, varScan, varDict or TNscope; Preferably, the method for obtaining sequencing data includes: Sequencing cancer surgical tissues and postoperative blood samples to obtain raw data, preprocessing the raw data, and calculating mutation abundance based on SNP site information in the preprocessed data; Preferably, the preprocessing includes data splitting, data pasting, sorting and deduplication.

9. An electronic device comprising one or more processors and a memory for storing executable instructions, characterized in that: The one or more processors are configured to call the executable instructions stored in the memory to implement the functions of the minimal residual lesion detection device according to any one of claims 1-8.

10. A computer-readable storage medium having computer program instructions stored thereon, characterized in that: When the computer program instructions are executed by a processor, the functions of the minimal residual lesion detection device according to any one of claims 1 to 8 are realized.

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