Fault tolerance method of sample tag, computer equipment and computer readable storage medium

Abstract

The invention provides a fault tolerance method for sample tags, computer equipment and a computer readable storage medium, and the method comprises the steps: generating candidate fault tolerance sets corresponding to the sample tags of a plurality of to-be-sequenced samples based on the sample tags of the plurality of to-be-sequenced samples; the candidate fault-tolerant set comprises at least one fault-tolerant label which has fault tolerance with a sample label; each of the sample tag and the fault-tolerant tag is a group of base sequences; sequencing whether fault-tolerant label conflicts exist between candidate fault-tolerant sets corresponding to the sample labels of the to-be-sequenced samples or not; under the condition that fault-tolerant label conflicts exist, candidate fault-tolerant sets corresponding to the sample labels of the to-be-sequenced samples respectively are subjected to conflict removal processing, and then a new candidate fault-tolerant set subjected to conflict removal processing is used for conducting conflict detection again; and under the condition that fault-tolerant label conflicts do not exist, determining the candidate fault-tolerant sets corresponding to the sample labels of the plurality of to-be-sequenced samples at the moment as target fault-tolerant sets.

Description

Technical Field

[0001] The present disclosure relates to the technical field of gene sequencing, and in particular to a fault-tolerant method for sample labels, a computer device, and a computer-readable storage medium. Background Art

[0002] In gene sequencing, after the gene sequences of multiple samples are mixed and sequenced, the gene sequencing results will be fuzzy matched according to the labels set for each sample, so as to determine the specific sample to which the gene sequencing results belong. In order to achieve fuzzy matching, a fault tolerance set will be set for each label. If the fault tolerance sets corresponding to different labels include the same base sequence, that is, the two fault tolerance sets conflict, it may be possible that a certain base sequence recognition result can be successfully matched with two samples, resulting in the problem of being unable to determine the specific sample to which the base sequence recognition result belongs. Summary of the invention

[0003] The disclosed embodiment at least provides a sample label fault tolerance method, comprising: based on sample labels of multiple samples to be sequenced, generating candidate fault tolerance sets corresponding to the sample labels of the multiple samples to be sequenced respectively; the candidate fault tolerance sets include at least one fault tolerance label that is fault-tolerant with the sample label; the sample label and the fault tolerance label are both a group of base sequences; detecting whether there is a fault tolerance label conflict between the candidate fault tolerance sets corresponding to the sample labels of the multiple samples to be sequenced respectively; if there is a fault tolerance label conflict, performing conflict resolution processing on the candidate fault tolerance sets corresponding to the sample labels of the multiple samples to be sequenced respectively, and then re-performing conflict detection on the new candidate fault tolerance sets after the conflict resolution processing; if there is no fault tolerance label conflict, determining the candidate fault tolerance sets corresponding to the sample labels of the multiple samples to be sequenced respectively at this time as the target fault tolerance set.

[0004] In a possible implementation, the method further includes: obtaining sequencing results obtained by performing gene sequencing on multiple objects to be sequenced; the sequencing results corresponding to each of the objects to be sequenced include: a label sequencing sequence, and a gene sequencing sequence; matching the label sequencing sequence with a target fault tolerance set corresponding to sample labels of the multiple samples to be sequenced, and determining the sample source corresponding to each sequencing object based on the result of the matching process.

[0005] In a possible implementation, the method of generating candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced based on the sample labels of the multiple samples to be sequenced includes: for any sample to be sequenced among the multiple samples to be sequenced, replacing the bases in the original base sequence of the sample label of the sample to be sequenced based on a target fault-tolerant parameter to obtain at least one group of fault-tolerant labels, and constructing a candidate fault-tolerant set corresponding to the sample label of the sample to be sequenced based on the at least one group of fault-tolerant labels obtained, wherein the target fault-tolerant parameter indicates the number of bases and / or base types to be replaced in the base sequence of the sample label.

[0006] In a possible implementation, the sample label of the sample to be sequenced includes: a first sample label and a second sample label.

[0007] In a possible implementation, the target fault tolerance parameters include a first target fault tolerance parameter corresponding to the first sample label, and a second target fault tolerance parameter corresponding to the second sample label; the replacing processing of at least one base in the original base sequence of the sample label of the sample to be sequenced based on the target fault tolerance parameters to obtain at least one group of fault tolerance labels includes: based on the first target fault tolerance parameter, replacing the bases in the original base sequence of the first sample label to obtain at least one group of first fault tolerance labels; and, based on the second target fault tolerance parameter, replacing the bases in the original base sequence of the second sample label to obtain at least one group of second fault tolerance labels; any one of the at least one group of first fault tolerance labels and any one of the at least one group of second fault tolerance labels are combined in pairs to form a candidate fault tolerance set of the sample labels of the sample to be sequenced.

[0008] In a possible implementation, the conflict resolution processing of the candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced includes: in each processing cycle in at least one processing cycle, executing the following conflict resolution process: determining the candidate samples to be sequenced having conflicting fault-tolerant labels in the current processing cycle; determining the degree of conflict between the candidate samples to be sequenced, and selecting the target sample to be sequenced for conflict resolution processing in the current processing cycle according to the degree of conflict; replacing the original target fault-tolerant parameters of the target sample to be sequenced to obtain new target fault-tolerant parameters, and based on the new target fault-tolerant parameters, replacing at least one base in the original base sequence of the sample label of the target sample to be sequenced to obtain a new candidate fault-tolerant set of the target sample to be sequenced.

[0009] In a possible implementation, after determining the candidate samples to be sequenced that have fault-tolerant label conflicts in the current processing cycle, the method further includes: determining the difference samples to be sequenced between the candidate samples to be sequenced that have fault-tolerant label conflicts in the current processing cycle and the candidate samples to be sequenced that have fault-tolerant label conflicts in the previous processing cycle; and determining the candidate fault-tolerant set corresponding to the difference samples to be sequenced as the target fault-tolerant set corresponding to the difference samples to be sequenced.

[0010] In one possible implementation, the degree of conflict is determined based on at least one of the following indication information: whether a fault-tolerant label conflict occurs between different candidate samples to be sequenced, the number of fault-tolerant labels that conflict between different candidate samples to be sequenced, and the probability of misidentifying the sample labels corresponding to the candidate samples to be sequenced as conflicting fault-tolerant labels.

[0011] In a possible implementation, determining the degree of conflict between the candidate samples to be sequenced includes: constructing a conflict matrix according to the indication information; the rows of the conflict matrix correspond to the candidate samples to be sequenced one-to-one, and / or the columns of the conflict matrix correspond to the candidate samples to be sequenced one-to-one; the element value of each element in the conflict matrix represents the number of conflicts between the candidate samples to be sequenced corresponding to the row where the element is located and the candidate samples to be sequenced corresponding to the column where the element is located; accumulating the element values ​​of the matrix elements in the conflict matrix by row or by column, and determining the degree of conflict between the candidate samples to be sequenced based on the accumulation result; wherein the number of conflicts between the candidate samples to be sequenced satisfies any of the following:

[0012] The number of conflicts is positively correlated with whether a fault-tolerant label conflict occurs between the candidate samples to be sequenced; the number of conflicts is positively correlated with the number of fault-tolerant labels in which there are fault-tolerant label conflicts between the candidate samples to be sequenced; the number of conflicts is positively correlated with the probability of misidentification of sample labels corresponding to the candidate samples to be sequenced as fault-tolerant labels in which there are conflicts between the candidate samples to be sequenced.

[0013] In a possible implementation, determining the degree of conflict between the candidate samples to be sequenced based on the accumulated results includes: based on the weighting coefficients corresponding to the candidate samples to be sequenced, weighting the accumulated results corresponding to the candidate samples to be sequenced to obtain the degree of conflict corresponding to the candidate samples to be sequenced; wherein the weighting coefficients corresponding to the candidate samples to be sequenced are determined based on the sequencing concentrations of the candidate samples to be sequenced.

[0014] In a possible implementation manner, the conflict resolution processing of the candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced includes: determining the conflicting fault-tolerant labels from the candidate fault-tolerant sets corresponding to the two samples to be sequenced having the conflicting fault-tolerant labels; determining, based on the conflicting fault-tolerant labels, the fault-tolerant labels to be deleted corresponding to the two samples to be sequenced having the conflicting fault-tolerant labels from the candidate fault-tolerant sets corresponding to the two samples to be sequenced having the conflicting fault-tolerant labels; and deleting the fault-tolerant labels to be deleted corresponding to the two samples to be sequenced having the conflicting fault-tolerant labels from the candidate fault-tolerant sets corresponding to the two samples to be sequenced having the conflicting fault-tolerant labels.

[0015] In a possible implementation, the method of determining the fault-tolerant labels to be deleted corresponding to the two samples to be sequenced that have the conflicting fault-tolerant labels from the candidate fault-tolerant sets corresponding to the two samples to be sequenced that have the conflicting fault-tolerant labels respectively according to the conflicting fault-tolerant labels includes: determining whether there is a base sequence consistent with the sample label of the sample to be sequenced in the conflicting base sequence; if so, deleting the base sequence consistent with the sample label of the sample to be sequenced from the conflicting base sequence to obtain the base sequence to be deleted; if not, determining the conflicting base sequences as the base sequences to be deleted.

[0016] In a possible implementation, the conflict resolution processing of the candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced includes: determining, from the candidate fault-tolerant sets corresponding to the samples to be sequenced that have fault-tolerant sample conflicts with other samples to be detected, a first target fault-tolerant label that is the same as the sample label of the samples to be sequenced that have fault-tolerant sample conflicts with other samples to be detected; and constructing, based on the first target fault-tolerant label, a target fault-tolerant set corresponding to the samples to be sequenced that have fault-tolerant sample conflicts with other samples to be detected.

[0017] In a second aspect, an optional implementation of the present disclosure further provides a computer device, a processor, and a memory, wherein the memory stores machine-readable instructions executable by the processor, and the processor is used to execute the machine-readable instructions stored in the memory, and when the machine-readable instructions are executed by the processor, the machine-readable instructions perform the steps in the above-mentioned first aspect, or any possible implementation of the first aspect.

[0018] In a third aspect, an optional implementation of the present disclosure further provides a computer-readable storage medium, on which a computer program is stored, and when the computer program is executed, the steps of the above-mentioned first aspect, or any possible implementation of the first aspect are executed.

[0019] In the embodiment of the present disclosure, when constructing fault-tolerant sets corresponding to sample labels of multiple samples to be sequenced, candidate fault-tolerant sets corresponding to sample labels of multiple samples to be sequenced are first generated according to sample labels corresponding to multiple samples to be sequenced, and then, when there is a conflict of fault-tolerant labels among the candidate fault-tolerant sets corresponding to sample labels of multiple samples to be sequenced, conflict resolution is performed on the candidate fault-tolerant sets corresponding to sample labels of the multiple samples to be sequenced; conflict detection is then performed again using the new candidate fault-tolerant sets after conflict resolution; when there is no conflict of fault-tolerant labels, the candidate fault-tolerant sets corresponding to sample labels of multiple samples to be sequenced are determined as target fault-tolerant sets. In this way, while eliminating the conflict of fault-tolerant labels among different fault-tolerant sets, each fault-tolerant set can be guaranteed as much as possible, thereby maximizing the splitting flux while ensuring the quality of sample data.

[0020] In order to make the above-mentioned objectives, features and advantages of the present disclosure more obvious and easy to understand, preferred embodiments are specifically cited below and described in detail with reference to the attached drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the following is a brief introduction to the drawings required for use in the embodiments. The drawings herein are incorporated into the specification and constitute a part of the specification. These drawings illustrate embodiments consistent with the present disclosure and are used together with the specification to illustrate the technical solutions of the present disclosure. It should be understood that the following drawings only illustrate certain embodiments of the present disclosure and should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can also be obtained based on these drawings without creative work.

[0022] Figure 1 A schematic diagram of a nucleic acid sequencing system / instrument provided by some embodiments of the present disclosure is shown;

[0023] Figure 2 A schematic diagram of the structure of an optical sequencing system provided by some embodiments of the present disclosure is shown;

[0024] Figure 3 A flowchart of a sample labeling error tolerance method provided by some embodiments of the present disclosure is shown;

[0025] Figure 4 A flowchart showing a specific method for determining a target fault tolerance set corresponding to a first sample to be sequenced provided in some embodiments of the present disclosure is shown;

[0026] Figure 5 A flowchart showing another specific method for determining a target fault tolerance set corresponding to a first sample to be sequenced provided by some embodiments of the present disclosure is shown;

[0027] Figure 6 Specific examples of several situations in which the fault-tolerant sets corresponding to the first sample M1 to be sequenced and the second sample M2 to be sequenced respectively provided in some embodiments of the present disclosure are shown;

[0028] Figure 7 A specific example of performing a conflict resolution operation on a candidate fault-tolerant set having conflicting fault-tolerant labels provided by some embodiments of the present disclosure is shown;

[0029] Figure 8 A specific example of using a Huffman coding tree to encode different types of bases provided by some embodiments of the present disclosure is shown;

[0030] Fig. 9 A specific example of the error-tolerant method of sample labels provided by some embodiments of the present disclosure is shown;

[0031] Fig.10 A schematic diagram of a computer device provided by some embodiments of the present disclosure is shown. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical scheme and advantages of the embodiments of the present disclosure clearer, the technical scheme in the embodiments of the present disclosure will be clearly and completely described below in conjunction with the drawings in the embodiments of the present disclosure. Obviously, the described embodiments are only part of the embodiments of the present disclosure, rather than all of the embodiments. The components of the embodiments of the present disclosure generally described and shown here can be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present disclosure is not intended to limit the scope of the present disclosure claimed for protection, but merely represents the selected embodiments of the present disclosure. Based on the embodiments of the present disclosure, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present disclosure.

[0033] Figure 1 The structure diagram of a gene sequencing system / instrument provided by the embodiment of the present disclosure is shown in FIG. Figure 1 As shown, the gene sequencing system / instrument (also called a nucleic acid sequencing system) provided by the embodiment of the present disclosure includes: a chip 10, a chip platform 20, a reagent storage container 30, a flow guide system 40, an optical sequencing system 50 and a computer system 60.

[0034] Among them, one or more sequencing objects are attached to the chip 10; the sequencing object here can be a nucleic acid fragment, which includes a base sequence of a certain length, for example, 150 bp in length; the sequencing object can also be a nucleic acid molecule.

[0035] A chip platform 20 configured to fix and support the chip 10;

[0036] The reagent storage container 30 is configured to store one or more reagents; here, the reagents may exemplarily include polymerase chain reaction (PCR) fluorescent reagents.

[0037] The flow guiding system 40 is configured to controllably transport the one or more reagents from the reagent storage container 30 to the chip 10 so as to contact and chemically react with the sequencing object, so that the sequencing object is fluorescently labeled;

[0038] An optical sequencing system 50 is configured to excite a fluorescent marker carried on a sequencing object and sequence a fluorescent signal generated by the excited fluorescent marker;

[0039] The computer system 60 is configured to acquire a fluorescent image from the optical sequencing system 50 and identify a nucleic acid sequence of a sequencing object based on the fluorescent image.

[0040] See also Figure 2 As shown, Figure 2 This is a schematic diagram of the structure of an optical sequencing system provided in an embodiment of the present disclosure. The optical sequencing system 50 at least includes a light source component 501 and an imaging component 502.

[0041] The imaging assembly 502 at least includes an aperture plate 5021, a dichroic mirror 5022-1, a microscope 5023 and an image sensor 5024. The aperture plate 5021 is provided with a plurality of light holes 5025. The image sensor 5024 may be an industrial camera.

[0042] The light source component 501 emits scattered excitation light, and the excitation light passes through at least some of the multiple light holes on the aperture plate 5021 to form multiple laser light beams and irradiate the dichroic mirror 5022-1; the dichroic mirror 5022-1 reflects the excitation light beams passing through the light holes to the chip 10 to assist the microscope 5023 in focusing; the microscope 5023 collects the fluorescence signals generated by the sequencing objects on the chip 10 after a chemical reaction; the image sensor 5024 senses the fluorescence signals and generates a fluorescence image.

[0043] Optionally, the dichroic mirror 5022-1 can be fixed at a certain angle, and can be fixed by glue dispensing.

[0044] In a possible implementation, the light source component 501 may be, for example, a light emitting diode, or a semiconductor laser (Laser Diode, LD). The aperture piece 5021 may be made of an opaque material, and may be, for example, a metal sheet. The scattered excitation light emitted by the light source component 501 may only pass through the light-through hole portion, and the non-light-through hole portion of the aperture piece 5021 will block the excitation light.

[0045] In a possible implementation manner, the imaging assembly 502 further includes an attenuation plate 5026, which is disposed in parallel with the aperture plate 5021 and configured to attenuate the intensity of the excitation light beam. Figure 2 As shown, the attenuation plate 5026 can be arranged behind the aperture plate 5021 , and the excitation light beam can directly irradiate the attenuation plate 5026 after passing through the light hole.

[0046] In a possible implementation, the imaging component 502 further includes a convex lens 5027, which is disposed parallel to the attenuation plate 5026 and located between the attenuation plate 5026 and the dichroic mirror 5022-1, and is configured to collimate the excitation light beam into a parallel light beam.

[0047] The microscope 5023 may include an objective lens 50231 and a tube lens 50232 , wherein the objective lens 50231 is located below the dichroic mirror 5022 - 1 , the tube lens 50232 is located above the dichroic mirror 5022 - 1 , and the image sensor 5024 is located above the tube lens 50232 .

[0048] Optionally, a motor is configured on one side of the objective lens 50231, for example, it can be a voice coil motor. Through the motor on the objective lens 50231, the objective lens 50231 can be controlled to move up and down to achieve focusing.

[0049] In the process of sequencing gene samples using an optical sequencing system, in many cases, the gene sequences of multiple samples are segmented and then mixed for sequencing to obtain mixed gene sequencing results of multiple samples. In order to identify the sample to which each gene sequencing result belongs, a label for identifying the corresponding sample will be determined for each sample before sequencing. The label is usually composed of multiple bases in a certain order, so it can also be called a sample label. When performing gene sequencing, the label will be added to the gene sequence fragment corresponding to each sample to form an object to be sequenced; then the object to be sequenced is subjected to gene sequencing, and the obtained gene sequencing results will also include two parts, namely the base sequence recognition result of the sample label (hereinafter referred to as the sequencing sample label, that is, the label sequence obtained by gene sequencing of the sample label) and the base sequence recognition result of the gene fragment. After obtaining the gene sequencing results, the sequencing sample labels are read and identified from each gene sequencing result, and the sequencing sample labels are fuzzy matched with the fault-tolerant sets constructed based on the labels corresponding to each sample. In the fault-tolerant set, multiple fault-tolerant labels are included; if the sequencing sample labels identified from the gene sequencing object are consistent with the fault-tolerant labels in any of the fault-tolerant sets, it is considered that the sequencing sample labels and the fault-tolerant set are successfully matched; the samples corresponding to the successfully matched fault-tolerant sets are used as the samples to which the object to be sequenced belongs. However, if the same fault-tolerant labels are included in the fault-tolerant sets corresponding to different labels, that is, the two fault-tolerant sets have a conflict of fault-tolerant labels, resulting in the possibility that the base sequence recognition results of a certain object to be sequenced can be successfully matched with two samples, resulting in the problem that the specific belonging sample of the object to be sequenced cannot be determined.

[0050] Currently, in order to solve the above problem, when the fault tolerance sets of any two samples conflict, the fault tolerance parameter will be set to 0, that is, the fault tolerance set only includes fault tolerance labels with the same base sequence as the sample label, thereby solving the conflict problem between fault tolerance sets; but this will reduce the splitting flux corresponding to each sample, resulting in poor detection results.

[0051] Based on the above research, the present disclosure provides a fault-tolerant method for sample labels. When constructing fault-tolerant sets corresponding to sample labels of multiple samples to be sequenced, first, candidate fault-tolerant sets corresponding to sample labels of multiple samples to be sequenced are generated according to sample labels corresponding to the multiple samples to be sequenced. Then, when there is a conflict of fault-tolerant labels between the candidate fault-tolerant sets corresponding to sample labels of the multiple samples to be sequenced, conflict-resolving processing is performed on the candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced. Conflict detection is then performed again using the new candidate fault-tolerant sets after conflict-resolving processing. When there is no conflict of fault-tolerant labels, the candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced at this time are determined as target fault-tolerant sets. In this way, while eliminating the conflict of fault-tolerant labels between different fault-tolerant sets, the above method can also maximize the guarantee of each fault-tolerant set as much as possible, thereby maximizing the splitting flux under the premise of ensuring the quality of sample data.

[0052] The defects existing in the above solutions are the results obtained by the inventor after practice and careful research. Therefore, the discovery process of the above problems and the solutions proposed by the present disclosure for the above problems below should be the contributions made by the inventor to the present disclosure during the disclosure process.

[0053] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, further definition and explanation thereof is not required in subsequent drawings.

[0054] To facilitate understanding of this embodiment, a sample labeling fault tolerance method disclosed in the embodiment of the present disclosure is first introduced in detail.

[0055] See also Figure 3 FIG. 1 is a flowchart of a sample label fault tolerance method provided by an embodiment of the present disclosure, wherein the method includes steps S301 to S304, wherein:

[0056] S301: Based on sample labels of multiple samples to be sequenced, generating candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced respectively; the candidate fault-tolerant sets include at least one fault-tolerant label that is fault-tolerant with the sample label; the sample label and the fault-tolerant label are both a group of base sequences;

[0057] S302: Detecting whether there is a conflict of fault-tolerant labels between candidate fault-tolerant sets corresponding to sample labels of the plurality of samples to be sequenced;

[0058] S303: in the case of a conflict in fault-tolerant labels, performing conflict-removal processing on candidate fault-tolerant sets corresponding to the sample labels of the plurality of samples to be sequenced, and then re-performing conflict detection using the new candidate fault-tolerant sets after the conflict-removal processing;

[0059] S304: In the case where there is no conflict in the error-tolerant labels, the candidate error-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced are determined as the target error-tolerant sets.

[0060] The above S301 to S304 are described in detail below.

[0061] In S301 above, the plurality of samples to be sequenced, for example, are objects to which genes to be sequenced belong, which may be any organism having genetic material. The sample to be sequenced may also be a segment of genetic material composed of bases of a certain organism.

[0062] The sample tag of the sample to be sequenced is a specific base sequence determined for the sample to be sequenced before sequencing begins and used to identify the identity of the sample to be sequenced.

[0063] For each sample to be sequenced, one or two sample tags are determined for each sample to be sequenced. The sample tag usually includes a fixed number of bases, and the types of the bases include, for example, adenine (A), guanine (G), cytosine (C), and thymine (T). The bases form a set of base sequences in a specific order, which is also the sample tag.

[0064] For example, for the sample M1 to be sequenced, its corresponding sample label barcode_1 is: CCTGATTG.

[0065] For the sample M2 to be sequenced, its corresponding sample label barcode_2 is: ACTGATTG.

[0066] Specifically, the sample label corresponding to each sample to be sequenced can be set according to actual needs, and the above sample labels are only examples.

[0067] The sample to be sequenced corresponds to the genetic material to be sequenced (hereinafter referred to as gene). The genetic material will be divided into multiple gene fragments during sequencing. Before the gene fragments of multiple samples to be sequenced are mixed and sequenced, the sample label corresponding to each sample to be sequenced will be added to the head and / or tail of the gene fragment of each sample to be sequenced to form the object to be sequenced.

[0068] For example, if the gene fragment "XXXXXXXXX" corresponding to the sample M1 to be sequenced is added with barcode_1 at its head, a new gene fragment is formed, that is, the object to be sequenced corresponding to M1:

[0069] "CCTGATTGXXXXXXXXX".

[0070] For the gene fragment "YYYYYYYYYY" corresponding to the sample M2 to be sequenced, after adding barcode_2 at its head and tail respectively, a new gene fragment is formed, that is, the object to be sequenced corresponding to the sample M2 to be sequenced:

[0071] "ACTGATTGYYYYYYYYYACTGATTG".

[0072] In addition, the sample labels added at the beginning and end of the gene fragment corresponding to the sample to be sequenced may be different; for example, for the sample M3 to be sequenced, there are two corresponding sample labels, namely: index_1: CCTGATTG, index_2: ACTGATTG.

[0073] Add index_1 to the head of the gene fragment "ZZZZZZZZZZ" corresponding to the sample to be sequenced, and add index_2 to the end of the gene fragment to form a new gene fragment, that is, the object to be sequenced corresponding to the sample M3 to be sequenced: "CCTGATTG ZZZZZZZZZ ACTGATTG".

[0074] The locations and quantities of the sample labels are not limited in the embodiments of the present disclosure, and the specific adding method can be determined according to actual needs.

[0075] In addition, for each sample label corresponding to the sample to be sequenced, a fault tolerance set corresponding to the sample label of each sample to be sequenced is also generated. In the fault tolerance set corresponding to each sample label, at least one fault tolerance label that is fault-tolerant with the sample label is included. Each fault tolerance label also includes a set of base sequences. The base types of the bases in the fault tolerance label include, for example, one or more of adenine (A), guanine (G), cytosine (C), thymine (T), and an unknown base (N).

[0076] Specifically, the embodiment of the present disclosure provides a specific method for generating candidate fault-tolerant sets corresponding to the sample labels of multiple samples to be sequenced based on the sample labels of the multiple samples to be sequenced, including:

[0077] For any sample to be sequenced among the multiple samples to be sequenced, at least one base in the original base sequence of the sample label of any sample to be sequenced is replaced based on the target fault tolerance parameter to obtain at least one group of fault tolerance labels, and a candidate fault tolerance set corresponding to the sample label of the sample to be sequenced is constructed based on the at least one group of fault tolerance labels obtained, wherein the target fault tolerance parameter indicates the number of bases and / or base types to be replaced in the base sequence of the sample label.

[0078] The target fault tolerance parameter indicates the number of bases to be replaced in the base sequence of the sample label, for example, which refers to the maximum number of different bases that can exist in the fault tolerance label and the corresponding sample label.

[0079] When the target fault tolerance parameter is 0, it means that the maximum number of different bases that can exist between the fault tolerance label in the fault tolerance set and the sample label corresponding to the sample to be sequenced is 0, that is, the fault tolerance label and the sample label are the same. For example, if the sample label is: CCTGATTG, the fault tolerance label in the candidate fault tolerance set also includes: CCTGATTG.

[0080] When the target fault tolerance parameter is 1, it means that the maximum number of different bases that can exist in the fault tolerance label in the fault tolerance set and the sample label corresponding to the sample to be sequenced is 1, that is, the fault tolerance label is the same as the sample label, or the number of different bases that exist in the fault tolerance label and the sample label is 1. Then, when the bases in the sample label are replaced based on the target fault tolerance parameter, for example, it includes: not replacing the bases in the sample label, determining the sample label as a fault tolerance label, and for the base at each position in the sample label, sequentially replacing the base type of the base at the position with other base types except the base type corresponding to the base position, and obtaining the fault tolerance label obtained after the base at the position is replaced.

[0081] For example, assuming that the sample label is: CCTGATTG, when the base at the first position is replaced, the "C" at the first position is replaced with: A, G, T and N in sequence, and the error-tolerant labels obtained after the base at the first position is replaced are: ACTGATTG, GCTGATTG, TCTGATTG, NCTGATTG. In this way, 4 error-tolerant labels corresponding to the first position can be obtained.

[0082] When the base at the second position is replaced, the "C" at the second position is replaced with A, G, T and N in sequence, and the error-tolerant labels obtained after the base at the second position is replaced are: CATGATTG, CGTGATTG, CTTGATTG, CNTGATTG. In this way, 4 error-tolerant labels corresponding to the second position can be obtained.

[0083] When the base at the second position is replaced, the "T" at the second position is replaced with A, G, C and N in sequence, and the error-tolerant labels obtained after the base at the second position is replaced are: CCAGATTG, CCGGATTG, CCCGATTG, CCNGATTG. Four error-tolerant labels corresponding to the second position can be obtained.

[0084] In this way, the above process is repeated until the "G" at the eighth position is replaced with A, C, T and N in sequence, completing the replacement of the base at the eighth position, and obtaining 4 fault-tolerant labels after replacing the base at the eighth position: CCTGATTA, CCTGATTC, CCTGATTT, CCTGATTN.

[0085] The final generated fault-tolerant labels include: 4*8+1, a total of 33 fault-tolerant labels.

[0086] When the target fault tolerance parameter is 2, it means that the maximum number of different bases that can exist in the fault-tolerant labels in the fault-tolerant set and the sample labels corresponding to the samples to be sequenced is 2, that is, the fault-tolerant labels and the sample labels are the same, or the number of different bases that exist in the fault-tolerant labels and the sample labels is 1, or the number of different bases that exist in the fault-tolerant labels and the sample labels is 2. The specific process of performing base replacement processing on the sample labels corresponding to each of the samples to be sequenced based on the target fault-tolerant parameters to obtain multiple fault-tolerant labels is similar to the above process and will not be repeated here.

[0087] In addition, in the case where there are two sample labels corresponding to a sample to be sequenced, the two sample labels can be added to the head of the gene fragment, or added to the tail of the gene fragment, or added to the head and tail of the gene fragment respectively. In this case, the sample label corresponding to the sample to be sequenced includes, for example: a first sample label and a second sample label; the target fault tolerance parameter includes a first target fault tolerance parameter corresponding to the first sample label, and a second target fault tolerance parameter corresponding to the second sample label;

[0088] The replacing process of at least one base in the original base sequence of the sample label of the sample to be sequenced based on the target fault tolerance parameter to obtain at least one set of fault tolerance labels includes:

[0089] Based on the first target fault tolerance parameter, bases in the original base sequence of the first sample label are replaced to obtain at least one set of first fault tolerance labels; and based on the second target fault tolerance parameter, bases in the original base sequence of the second sample label are replaced to obtain at least one set of second fault tolerance labels;

[0090] Any one of the at least one set of first error-tolerant labels is combined with any one of the at least one set of second error-tolerant labels in pairs to form a candidate error-tolerant set of sample labels of the sample to be sequenced.

[0091] Exemplarily, it is assumed that the first sample label and the second sample label at both ends of the gene fragment corresponding to the sample M3 to be sequenced are represented as index_1 and index_2 respectively.

[0092] For index_1, a corresponding first target fault tolerance parameter index1Mismatch is set; for index_2, a corresponding second target fault tolerance parameter index2Mismatch is set. Among them, index1Mismatch and index2Mismatch can be the same or different, for example, index1Mismatch is set to 1 and index2Mismatch is set to 0; or, index1Mismatch is set to 1 and index2Mismatch is also set to 1. index1Mismatch and index2Mismatch can also be other values, such as 2, 3, etc., which can be set according to actual sequencing needs.

[0093] Assume that index1Mismatch and index2Mismatch are both greater than 0.

[0094] Using index1Mismatch, replace the bases in the original base sequence of index_1 to obtain at least one group of first labels to be combined corresponding to index_1. The at least one group of first labels to be combined constitutes a fault-tolerant set A1, which includes: barcode_1_1, barcode_1_2, ... barcode_1_n. The above-mentioned fault-tolerant set A1 includes the first labels to be combined whose sequence is consistent with index_1 (when 0 bases in index_1 are replaced).

[0095] And, using index2Mismatch, the bases in the original base sequence of index_2 are replaced to obtain at least one set of second labels to be combined corresponding to index_2, and the at least one set of second labels to be combined constitutes a fault-tolerant set A2, and the set A2 includes: barcode_2_1, barcode_2_2, ... barcode_2_m. The second base sequence to be combined includes the second labels to be combined that are consistent with index_2 (when 0 bases in index_2 are replaced).

[0096] Then, for barcode_1_1, barcode_1_1 and the second label to be combined in the fault-tolerant set A2 are sequentially combined to obtain multiple fault-tolerant labels: barcode_1_1+barcode_2_1, barcode_1_1+barcode_2_2, ..., barcode_1_1+barcode_2_m;

[0097] For barcode_1_2, barcode_1_2 and the second label to be combined in the fault-tolerant set A2 are combined in sequence to obtain multiple fault-tolerant labels: barcode_1_2+barcode_2_1, barcode_1_2+barcode_2_2, ..., barcode_1_2+barcode_2_m;

[0098] …

[0099] For barcode_1_n, combine barcode_1_n and the second label to be combined in the fault-tolerant set A2 in sequence to obtain multiple fault-tolerant labels: barcode_1_n+barcode_2_1, barcode_1_n+barcode_2_2, ..., barcode_1_n+barcode_2_m;

[0100] All the above-mentioned fault-tolerant labels are combined into a set to form a candidate fault-tolerant set of sample labels corresponding to the sample M3 to be sequenced.

[0101] For example, for the combination of index_1 and index_2: GTACGCAA+ATCCGCAC, and the first target fault tolerance parameter and the second target fault tolerance parameter are both 1, the fault tolerance set result of index_1 is as follows:

[0102] GTACGCAA fault-tolerant set =

[0103] {GTACGCAA, ATACGCAA, TTACGCAA, CTACGCAA, NTACGCAA, GAACGCAA, GCACGCAA, GGACGCAA, GNACGCAA, GTTCGCAA, GTCCGCAA, GTGCGCAA, GTNCGCAA, GTAAGCAA, GTATGCAA, GTAGGCAA, GTAN GCAA, GTACACAA, GTACTCAA, GTACCCAA, GTACCNCAA, GTACGAAA, GTACGTAA, GTACGGAA, GTACGNAA, GTACGCTA, GTACGCCA, GTACGCGA, GTACGCNA, GTACGCAT, GTACGCAC, GTACGCAG, GTACGCAN}

[0104] The fault tolerance set results for index_2 are as follows:

[0105] ATCCGCAC fault tolerance collection =

[0106] {ATCCGCAC,CTCCGCAC,TTCCGCAC,GTCCGCAC,NTCCGCAC,AACCGCAC,A CCCGCAC,AGCCGCAC,ANCCGCAC,ATACGCAC,ATTCGCAC,ATGCGCAC,ATNCGC AC,ATCAGCAC,ATCTGCAC,ATCGGCAC,ATCNGCAC,ATCCACAC,ATCCTCAC,ATCC CCAC,ATCCNCAC,ATCCGAAC,ATCCGTAC,ATCCGGAC,ATCCGNAC,ATCCGCTC,AT CCGCCC,ATCCGCGC,ATCCGCNC,ATCCGCAA,TCCGCAT,ATCCGCAG,ATCCGCAN},

[0107] Then the fault-tolerant sets of index_1 and index_2 are combined to obtain the GTACGCAA+GTCCGCAC fault-tolerant set of {GTACGCAA+ATCCGCAC, GTACGCAA+CTCCGCAC, GTACGCAA+TTCCGCAC, GTACGCAA+GTCCGCAC…}, with a total of 1089 (33X33) fault-tolerant labels.

[0108] By adopting the above method, a candidate fault-tolerant set of sample labels corresponding to a plurality of samples to be sequenced can be generated.

[0109] Regarding the above S302:

[0110] The existence of fault-tolerant label conflicts in the candidate fault-tolerant sets means that there are fault-tolerant labels with the same base sequences in the candidate fault-tolerant sets corresponding to the two samples to be sequenced.

[0111] Take the above sample label barcode_1: CCTGATTG and sample label barcode_2: ACTGATTG as examples. The candidate tolerance sets corresponding to the two include the tolerance label: GCTGATTG. If the identified marker sequence index is GCTGATTG when identifying gene fragment K1, since the marker sequence can successfully match the candidate tolerance sets corresponding to barcode_1 and barcode_2, it is impossible to determine the specific sample to be sequenced to which the gene fragment K1 belongs.

[0112] Furthermore, in the embodiment of the present disclosure, for each sample to be sequenced among multiple samples to be sequenced, if there is a fault-tolerant label conflict between the candidate fault-tolerant set corresponding to the sample to be sequenced and the initial set corresponding to any other sample to be sequenced, it is necessary to perform conflict resolution processing on the candidate fault-tolerant set with the fault-tolerant label conflict to obtain the target fault-tolerant set corresponding to the sample to be sequenced.

[0113] If there is no fault tolerance label conflict between the candidate fault tolerance set corresponding to a certain sample to be sequenced among multiple samples to be sequenced and the candidate fault tolerance set corresponding to any other sample to be sequenced, the candidate fault tolerance set corresponding to the sample to be sequenced can be determined as the target fault tolerance set corresponding to the second sample to be sequenced.

[0114] In this way, the conflict problem between the fault-tolerant sets corresponding to the samples to be sequenced is solved, and the splitting throughput can be maximized while ensuring the quality of sample data.

[0115] Specifically, the following method may be used to detect whether there is a conflict of fault-tolerant labels between the candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced:

[0116] For each sample to be sequenced among the multiple samples to be sequenced, traverse other samples to be sequenced except each sample to be sequenced, and determine whether the candidate fault tolerance set corresponding to each sample to be sequenced and the candidate fault tolerance sets corresponding to other traversed samples to be sequenced have the same fault tolerance label;

[0117] If the candidate fault-tolerant set corresponding to each sample to be sequenced and the candidate fault-tolerant sets corresponding to all other samples to be sequenced do not have the same tolerance base sequence, then there is no fault-tolerant label conflict between the candidate fault-tolerant sets corresponding to the sample labels of multiple samples to be sequenced;

[0118] If the candidate fault-tolerant set corresponding to any sample to be sequenced has the same fault-tolerant label as the candidate fault-tolerant set corresponding to at least one other sample to be sequenced, there is a fault-tolerant label conflict between the candidate fault-tolerant sets corresponding to the sample labels of multiple samples to be sequenced.

[0119] Exemplarily, it is assumed that there are N samples to be sequenced, and the sample labels corresponding to the N samples to be sequenced are: barcode_1, barcode_2, barcode_3..., barcode_N.

[0120] For barcode_1, determine in turn whether there are the same fault-tolerant labels between the candidate fault-tolerant sets corresponding to barcode_2, barcode_3, ..., barcode_N and the candidate fault-tolerant set corresponding to barcode_1. If there are no same fault-tolerant labels between the candidate fault-tolerant sets corresponding to barcode_2, barcode_3, ..., barcode_N and the candidate fault-tolerant set corresponding to barcode_1, it is considered that there is no fault-tolerant label conflict between the candidate fault-tolerant sets corresponding to barcode_1 and other sample labels.

[0123] For barcode_2, determine in turn whether there are the same fault-tolerant labels between the candidate fault-tolerant sets corresponding to barcode_3, ..., barcode_N and the candidate fault-tolerant set corresponding to barcode_2 (in the above process, it has been determined whether there are the same fault-tolerant labels between the candidate fault-tolerant sets corresponding to barcode_1 and barcode_2, so it will not be determined again here). If there are the same fault-tolerant labels between the candidate fault-tolerant sets corresponding to barcode_i and the candidate fault-tolerant sets corresponding to barcode_2 (where i is an integer greater than 2 and less than N+1), it can be considered that there is a conflict of fault-tolerant labels between the candidate fault-tolerant sets corresponding to the samples to be sequenced corresponding to barcode_2 and barcode_i, and the candidate fault-tolerant sets corresponding to barcode_2 and barcode_i can be subsequently processed for conflict resolution.

[0124] When determining whether there are the same fault-tolerant labels between the candidate fault-tolerant sets corresponding to the two samples to be sequenced, the intersection of the candidate fault-tolerant sets corresponding to the two sequencing samples can be performed; if the intersection is empty, it is considered that there are no identical fault-tolerant labels between the two; if the intersection is empty, it is considered that there are identical fault-tolerant labels between the two. When finding the intersection, a consistency matching method can be used, for example, in the future, the fault-tolerant labels from two different candidate fault-tolerant sets will be matched in sequence for consistency; if the consistency matching passes, it is considered that there is a conflict of fault-tolerant labels between the two different candidate fault-tolerant sets; if the consistency matching fails, it is considered that there is no conflict of fault-tolerant labels between the two different candidate fault-tolerant sets.

[0125] In addition, it is also possible to determine whether there is a fault-tolerant label conflict between two candidate fault-tolerant sets based on the Hamming distance between the sample labels corresponding to the two samples to be sequenced.

[0126] Here, the Hamming distance is used to describe the number of base positions where different bases exist in two sample labels. For example, there are two sample labels: barcode_1: ATTCGCAG and barcode_2: ATTCGCTC. In the two fault-tolerant labels, the base positions where different bases exist include: the 7th and 8th positions, and the Hamming distance between the two is 2.

[0127] The necessary and sufficient condition for judging that there is no fault-tolerant label conflict between the fault-tolerant sets corresponding to two sample labels is that the Hamming distance between the two sample labels is greater than the sum of the target fault-tolerant parameters corresponding to the two sample labels.

[0128] Assume that the corresponding fault tolerance parameters of barcode_A and barcode_B are mismatch_A and mismatch_B respectively, and the Hamming distance between barcode_A and barcode_B is Dis_AB. Then the necessary and sufficient conditions for there to be no fault tolerance label conflict between barcode_A and barcode_B, and between barcode_A and barcode_B are:

[0129] Dis_AB>(mismatch_A+mismatch_B).

[0130] In the above embodiment, when determining whether the candidate fault-tolerant set corresponding to each sample to be sequenced and the candidate fault-tolerant sets corresponding to other traversed samples to be sequenced have the same fault-tolerant label, for example, the following method may be used:

[0131] Determine the Hamming distance between the sample label corresponding to each sample to be sequenced and the sample labels corresponding to other traversed samples to be sequenced;

[0132] And, summing the target fault tolerance parameter of the sample label corresponding to each sample to be sequenced and the target fault tolerance parameters of the sample labels corresponding to other traversed samples to be sequenced to obtain the fault tolerance parameter and value;

[0133] If the Hamming distance is greater than the fault tolerance parameter and value, the candidate fault tolerance set corresponding to each sample to be sequenced and the candidate fault tolerance sets corresponding to other samples to be sequenced that have been traversed do not have the same fault tolerance label;

[0134] If the Hamming distance is less than or equal to the fault tolerance parameter and value, the candidate fault tolerance set corresponding to each sample to be sequenced and the candidate fault tolerance sets corresponding to other traversed samples to be sequenced have the same fault tolerance label.

[0135] By adopting the above method, it is possible to quickly determine whether there is a conflict of fault-tolerant labels between the candidate fault-tolerant sets of sample labels corresponding to two samples to be sequenced.

[0136] In addition, for two samples to be sequenced with two sample labels respectively, only when there is a fault-tolerant label conflict in both fault-tolerant set A1 and fault-tolerant set A2, there will be a fault-tolerant label conflict between the candidate fault-tolerant sets corresponding to the two samples to be sequenced.

[0137] For example, for samples sample_A and sample_B to be sequenced:

[0138] Among them, the two sample labels of sample_A are: barcode_A1 and barcode_A2; the first target error tolerance parameters corresponding to barcode_A1 are: mismatch_A1 and mismatch_A2.

[0139] The two sample labels of sample_B are: barcode_B1 and barcode_B2; the first target error tolerance parameters corresponding to barcode_B1 are: mismatch_B1 and mismatch_B2.

[0140] Among them, the Hamming distance between barcode_A1 and barcode_B1 is Dis_AB1; the Hamming distance between barcode_A2 and barcode_B2 is Dis_AB2.

[0141] Then it satisfies: Dis_AB1>(mismatch_A1+mismatch_B1), or, Dis_AB2>(mismatch_A2+mismatch_B2), which means that there is no fault-tolerant label conflict between the fault-tolerant sets corresponding to sample_A and sample_B respectively, that is, there will be no fault-tolerant label conflict between the two samples to be sequenced as long as there is no fault-tolerant label conflict between the fault-tolerant sets corresponding to the sample labels on either side.

[0142] If Dis_AB1≤(mismatch_A1+mismatch_B1) and Dis_AB2≤(mismatch_A2+mismatch_B2), it means that there is a fault-tolerant label conflict in the fault-tolerant sets corresponding to sample_A and sample_B respectively. That is, there is a fault-tolerant label conflict between the fault-tolerant sets corresponding to the sample labels on both sides of the two samples to be sequenced, and there is a fault-tolerant label conflict between the two samples to be sequenced.

[0143] By adopting the above-mentioned conflict sequencing process, it is possible to determine the samples to be sequenced that have conflicts in fault-tolerant labels between candidate fault-tolerant sets.

[0144] Regarding the above S303:

[0145] When performing conflict resolution processing on the candidate fault-tolerant set corresponding to the first sample to be sequenced that has a conflict in fault-tolerant labels, for example, any one of the following methods A to C may be used.

[0146] A: See Figure 4 As shown, a specific method for performing conflict resolution processing on candidate fault-tolerant sets corresponding to sample labels of the plurality of samples to be sequenced is provided in an embodiment of the present disclosure, comprising:

[0147] In each processing cycle of at least one processing cycle, the following de-confliction process is performed:

[0148] S401: Determine candidate samples to be sequenced that have fault-tolerant label conflicts in the current processing cycle.

[0149] Here, if the current processing cycle is the first processing cycle, the corresponding candidate samples to be sequenced include all samples to be sequenced that have fault-tolerant label conflicts between the candidate fault-tolerant sets of the corresponding sample labels determined in S102; if the current processing cycle is not the first processing cycle, then since past conflict processing has been performed on the previously determined candidate samples to be sequenced in at least one historical processing cycle, there may be a situation where some of the samples to be sequenced no longer have fault-tolerant label conflicts with other samples to be sequenced. In this case, these samples to be sequenced that no longer have fault-tolerant label conflicts will no longer be used as candidate samples to be sequenced in the current processing cycle. After the historical processing cycle processing, the samples to be sequenced that still have fault-tolerant label conflicts are used as candidate samples to be sequenced in the current processing cycle.

[0150] When the above situation exists, after determining the candidate samples to be sequenced corresponding to the current processing cycle, the following may also be included:

[0151] Determine the difference samples to be sequenced between the candidate samples to be sequenced having fault-tolerant label conflicts in the current processing cycle and the candidate samples to be sequenced having fault-tolerant label conflicts in the previous processing cycle;

[0152] The candidate fault tolerance set corresponding to the difference sample to be sequenced is determined as the target fault tolerance set corresponding to the difference sample to be sequenced.

[0153] Exemplarily, assuming that the candidate samples to be sequenced determined in the previous processing cycle include: sample1, sample2, sample3, and sample4, wherein, after the conflict resolution processing is performed in the previous processing cycle, the fault-tolerant label conflict between sample3 and other candidate samples to be sequenced is eliminated, while the fault-tolerant label conflict problem still exists between sample1, sample2, and sample3, then in the current processing cycle, sample1, sample2, and sample3 are used as candidate samples to be sequenced.

[0154] Sample3 is the difference sample to be sequenced between the previous processing cycle and the current processing cycle, and the candidate fault tolerance set corresponding to the sample label of sample3 is determined as the target fault tolerance set corresponding to the sample label of sample3.

[0155] Here, the candidate fault tolerance set corresponding to the sample label of sample3 may be the original candidate fault tolerance set generated for sample3 in the above S101, or may be a new candidate fault tolerance set obtained after deconflicting the candidate fault tolerance set of sample3 during the conflict processing process of a certain historical processing cycle.

[0156] In this embodiment, when determining the candidate samples to be sequenced corresponding to the current processing cycle, for example, conflict sequencing processing can be performed on the candidate samples to be sequenced in the previous processing cycle, and samples to be sequenced that still have fault-tolerant label conflicts can be screened out as candidate samples to be sequenced in the current processing cycle. The manner of performing conflict sequencing processing can be referred to the specific description of the above embodiment, which will not be repeated here.

[0157] S402: Determine the conflict degree between the candidate samples to be sequenced, and select the target sample to be sequenced for which conflict removal processing is to be performed in the current processing cycle according to the conflict degree.

[0158] The degree of conflict is determined based on any one of the following indication information a1 to a3:

[0159] a1: Whether there is a conflict of fault-tolerant labels between different candidate samples to be sequenced.

[0160] Here, for a candidate sample to be sequenced, the more other candidate samples to be sequenced that have fault-tolerant label conflicts with the candidate sample to be sequenced, the higher the conflict degree is considered to be.

[0161] For example: for candidate samples M1 to M5 to be sequenced, M1 has fault-tolerant label conflicts with M2, M3, and M5 respectively. In addition to having a fault-tolerant label conflict with M1, M2 also has a fault-tolerant label conflict with M4. M4 has a fault-tolerant label conflict with M5; M3 only has a fault-tolerant label conflict with M1.

[0162] Then the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M1 is 3; the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M2 is 2; the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M3 is 1; the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M4 is 2; the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M5 is 1. When the degree of conflict is determined based on this number, M1 has the highest degree of conflict.

[0163] a2: The number of conflicting error-tolerant labels between different candidate samples to be sequenced.

[0164] Here, for a candidate sample to be sequenced, the greater the number of conflicting fault-tolerant labels between other candidate samples to be sequenced that have a fault-tolerant label conflict with the candidate sample to be sequenced, the higher the degree of conflict is considered to be.

[0165] Exemplarily, for candidate samples to be sequenced M1 to M7, the number of fault-tolerant labels that conflict between M1 and M2 is 8, the number of fault-tolerant labels that conflict between M1 and M3 is 12, the number of fault-tolerant labels that conflict between M1 and M4 is 12, the number of fault-tolerant labels that conflict between M1 and M5 is 12, the number of fault-tolerant labels that conflict between M1 and M6 is 16, and the number of fault-tolerant labels that conflict between M1 and M7 is 12. Then, the number of fault-tolerant labels that conflict with M1 and other candidate samples to be sequenced that have fault-tolerant label conflicts is: 8+12+12+12+16+12=72.

[0166] a3: the probability of misidentifying the sample label corresponding to the candidate sample to be sequenced as a conflicting fault-tolerant label.

[0167] Here, in the process of two-color fluorescence second-generation sequencing, the probability of misidentification between different bases is different; that is, for the four bases A, G, C, and T, the probability of identifying A as G, identifying A as C, and identifying A as T will be different; at the same time, the probability of identifying G as A and identifying A as G will also be different. Based on the existence of this situation, in the embodiment of the present disclosure, when determining the degree of conflict of each candidate sample to be sequenced, for a candidate sample to be sequenced M1, it is assumed that the candidate sample to be sequenced M1 and another candidate sample to be sequenced M2 have a fault-tolerant label conflict, and the sample labels corresponding to M1 and M2 are: barcode_1 and barcode_2 respectively; and the conflicting fault-tolerant labels between the two are x1, x2, and x3, then the degree of conflict corresponding to M1 can be determined according to the probability of misidentifying the sample label barcode_1 corresponding to M1 as x1, x2, and x3 respectively, and the degree of conflict corresponding to M2 can be determined according to the probability of misidentifying the sample label barcode_2 corresponding to M2 as x1, x2, and x3 respectively.

[0168] The present disclosure also provides a specific method for determining the degree of conflict between the candidate samples to be sequenced, including:

[0169] According to the indication information, a conflict matrix is ​​constructed; the rows of the conflict matrix correspond to the candidate samples to be sequenced one by one, and / or the columns of the conflict matrix correspond to the candidate samples to be sequenced one by one; the element value of each element in the conflict matrix represents the number of conflicts between the candidate samples to be sequenced corresponding to the row where the element is located and the candidate samples to be sequenced corresponding to the column where the element is located;

[0170] Accumulating the element values ​​of the matrix elements in the conflict matrix by row or by column, and determining the degree of conflict between the candidate samples to be sequenced based on the accumulation result;

[0171] The number of conflicts between the candidate samples to be sequenced satisfies any of the following conditions:

[0172] The number of conflicts is positively correlated with whether a fault-tolerant tag conflict occurs between the candidate samples to be sequenced;

[0173] There is a positive correlation between the number of error-tolerant labels with conflicting error-tolerant labels among the candidate samples to be sequenced;

[0174] The sample labels corresponding to the candidate samples to be sequenced are identified as having a positive correlation with the probability of misidentification of conflicting fault-tolerant labels among the candidate samples to be sequenced.

[0175] The following is a detailed description of the methods of constructing the conflict matrix for the above three situations a1 to a3:

[0176] In a1 above, the conflict degree corresponding to each candidate sample to be sequenced is determined according to whether a fault-tolerant label conflict occurs between different candidate samples to be sequenced. For example, the candidate samples to be sequenced that directly or indirectly have a fault-tolerant label conflict include: M1 to M5, wherein M1 has a fault-tolerant label conflict with M2, M3, and M5, respectively; M2 has a fault-tolerant label conflict with M4 in addition to a fault-tolerant label conflict with M1; M4 has a fault-tolerant label conflict with M5; and M3 has a fault-tolerant label conflict only with M1.

[0177] The conflict matrix formed according to whether there is a conflict between different candidate samples to be sequenced is as follows:

[0178]

[0179] Among them, the rows in the conflict matrix correspond to M1~M5 one-to-one, and the columns correspond to M1~M5 one-to-one. The conflict matrix formed is a symmetric matrix. Based on the positive correlation between the number of conflicts and whether a fault-tolerant label conflict occurs between the candidate samples to be sequenced, in this embodiment, when there is a conflict between the first candidate sample to be sequenced corresponding to the row where each element in the conflict matrix is ​​located and the second candidate sample to be sequenced corresponding to the column, the value of the element is 1; when there is no conflict between the first candidate sample to be sequenced corresponding to the row where each element in the conflict matrix is ​​located and the second candidate sample to be sequenced corresponding to the column, the value of the element is 0. Then, the conflict matrix is ​​accumulated row by row or column by column, and the conflict degree corresponding to M1 is 3, that is, the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M1 is 3; the conflict degree corresponding to M2 is 2, that is, the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M2 is 2; the conflict degree corresponding to M3 is 1, that is, the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M3 is 1; the conflict degree corresponding to M4 is 2, that is, the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M4 is 2; the conflict degree corresponding to M5 is 2, that is, the number of other candidate samples to be sequenced that have fault-tolerant label conflicts with M5 is 2.

[0180] In this example, the conflict degree corresponding to M1 is the highest. At this time, M1 can be determined as the target sample to be sequenced, and conflict resolution processing is performed on M1.

[0181] Regarding the situation in a2 above, the conflict degree corresponding to each candidate sample to be sequenced is determined based on the number of conflicting fault-tolerant labels between different candidate samples to be sequenced:

[0182] For example, the candidate samples to be sequenced that directly or indirectly have conflicts in fault-tolerant labels include: M1 to M7, among which the number of fault-tolerant labels that conflict between M1 and M7 is 8, the number of fault-tolerant labels that conflict between M1 and M3 is 12, the number of fault-tolerant labels that conflict between M1 and M4 is 12, the number of fault-tolerant labels that conflict between M1 and M5 is 12, the number of fault-tolerant labels that conflict between M1 and M6 is 16, and the number of fault-tolerant labels that conflict between M1 and M7 is 12.

[0183] In addition to 8 conflicting fault-tolerant labels between M2 and M1, there are 4 conflicting fault-tolerant labels between M2 and M6.

[0184] In addition to the 12 conflicting fault-tolerant labels between M6 and M1, there are also 12 conflicting fault-tolerant labels between M6 and M7.

[0185] The conflict matrix formed according to whether there is a conflict between different candidate samples to be sequenced is as follows:

[0186]

[0187] The above conflict matrix is ​​accumulated row by row or column by column, where the conflict degree corresponding to M1 is: 8+12+12+12+16+12=72; the conflict degree corresponding to M2 is: 8+4=12; the conflict degree corresponding to M3 is: 12; the conflict degree corresponding to M4 is: 12; the conflict degree corresponding to M5 is: 12; the conflict degree corresponding to M6 is: 16+4+12=32; the conflict degree corresponding to M7 is: 12+12=24; in the above example, the conflict degree corresponding to M1 is the highest. At this time, M1 can be determined as the target sample to be sequenced, and conflict removal processing is performed on M1.

[0188] In a3 above, the error recognition probability of misidentifying the sample label corresponding to the candidate sample to be sequenced as a conflicting fault-tolerant label is used to determine the degree of conflict corresponding to each candidate sample to be sequenced. For example, the error rate from base A to base G is different from the error rate from base G to base T, which is related to the signal acquisition method, basecall algorithm, and signal noise. Therefore, the probability of each fault-tolerant label in the fault-tolerant set is different, which will also affect the elements in the fault-tolerant matrix. For example, a sample label barcode_0 is:

[0189] GACAACTGAA+AGTGGTCAGG (double sample labels); the fault-tolerant set has fault-tolerant labels:

[0190] GACGACTGAA+AGTGATCAGG (misidentification probability is 0.5, there are two mismatches in total), GACAACTGAT+AGTGGTCAGG (misidentification probability is 0.9, the probability of A mismatching to T is higher), GACAACTGAA+AGTGGTCAGA (misidentification probability is 0.8, the probability of G mismatching to A is higher).

[0191] Assume that the candidate samples to be sequenced include: M1~M3, where the sample labels corresponding to M1~M3 are barcode_1~barcode_3 respectively;

[0192] Among them, the conflicting fault-tolerant labels between barcode_1 and barcode_2 are x1, x2, and x3, and it can be known that the probabilities of misidentifying the sample label barcode_1 corresponding to M1 as x1, x2, and x3 are 0.11, 0.1, and 0.21, respectively; the probabilities of misidentifying the sample label barcode_2 corresponding to M2 as x1, x2, and x3 are 0.12, 0.11, and 0.22, respectively.

[0193] The conflicting fault-tolerant labels between barcode_2 and barcode_3 are y1 and y2. It can be seen that the probability of misidentifying the sample label barcode_2 corresponding to M2 as y1 and y2 is 0.21 and 0.3 respectively; the probability of misidentifying the sample label barcode_3 corresponding to M3 as y1 and y2 is 0.2 and 0.23 respectively.

[0194] Then, the error recognition probabilities of the sample labels corresponding to M1 being incorrectly identified as x1, x2, and x3 are accumulated, and the error recognition probability corresponding to M1 is: 0.11+0.1+0.21=0.42;

[0195] The error recognition probabilities of the sample labels corresponding to M2 being incorrectly identified as x1, x2, and x3 are accumulated, and the error recognition probability corresponding to M2 is: 0.12+0.11+0.22=0.45;

[0196] The probability of misidentification of the sample label corresponding to M3 as y1 and y2 is accumulated, and the probability of misidentification corresponding to M2 is: 0.21+0.3=0.52;

[0197] The error recognition probabilities of the sample labels corresponding to M3 being mistakenly identified as y1 and y2 are accumulated, and the error recognition probability corresponding to M3 is obtained as: 0.2+0.23=0.43.

[0198] The conflict matrix is ​​expressed as:

[0199]

[0200] Then, the above conflict matrix is ​​accumulated row by row, and the conflict degree of M1 is obtained as follows: 0.42; the conflict degree of M2 is obtained as follows: 0.97; and the conflict degree of M3 is obtained as follows: 0.43.

[0201] Since the conflict degree of M2 is the highest, M2 is taken as the target sample to be sequenced and conflict removal processing is performed on M2.

[0202] In the case of a3 above, the probability of misidentification of the sample label corresponding to the candidate sample to be sequenced as the conflicting fault-tolerant label can be obtained by, for example, statistically analyzing the detection results in the historical gene sequencing work in advance; for each base, the probability of misidentification of it as each of the other three bases can be statistically analyzed. Then, based on the above probability, a table of misidentification probabilities between different bases can be pre-constructed; in this table, not only the probability of identifying one base as another base can be included, but also the probability of identifying any combination of two bases as another two arbitrary combinations of two bases, or the probability of identifying any combination of three bases as another three arbitrary combinations of three bases. In this way, when using the above misidentification probability to determine the degree of conflict corresponding to each candidate sample to be sequenced, the required misidentification probability can be obtained directly through this table.

[0203] In addition, when the gene fragment corresponding to the candidate sample to be sequenced includes two sample labels, when determining the probability that the sample label is mistakenly identified as a conflicting fault-tolerant label, for example, an error recognition probability can be determined for each sample label, and then the error recognition probabilities corresponding to the two sample labels are multiplied to obtain the error recognition probability corresponding to the sample to be sequenced.

[0204] For example, for a sample M1 to be sequenced, it includes two sample labels index1 and index2. Based on the first target fault tolerance parameter index1Mismatch corresponding to index1, the bases in index1 are replaced, and the obtained fault tolerance set A1 includes multiple first base sequences to be combined; and based on the first target fault tolerance parameter index2Mismatch corresponding to index2, the bases in index2 are replaced, and the obtained fault tolerance set A2 includes multiple second base sequences to be combined; after the first base sequence Q1 to be combined and the second base sequence Q2 to be combined are combined to obtain the fault tolerance label Q1-Q2, if a certain fault tolerance label is determined to be a fault tolerance label that conflicts with another sample M2 to be sequenced, the error recognition probability of misidentifying index1 as Q1 is p1; the error recognition probability of misidentifying index2 as Q2 is p2, and the error recognition probability of misidentifying the sample labels index1 and index2 corresponding to M1 as the fault tolerance labels Q1-Q2 is p1*p2.

[0205] In this way, it is achieved that the conflict degree of each candidate sample to be sequenced is determined based on any one of the three indication information, and based on the conflict degree, a target sample to be sequenced is determined from multiple candidate samples to be sequenced.

[0206] In another embodiment of the present disclosure, when determining the conflict degree corresponding to each candidate sample to be sequenced based on the accumulated result, the accumulated result corresponding to each candidate sample to be sequenced may be weighted based on the weight coefficient corresponding to each candidate sample to be sequenced to obtain the conflict degree corresponding to each candidate sample to be sequenced;

[0207] The weight coefficient corresponding to each candidate sample to be sequenced is determined based on the sequencing concentration of each candidate sample to be sequenced.

[0208] Here, the sequencing concentration corresponding to the candidate sample to be sequenced is, for example, the ratio of the gene fragment corresponding to a sample to be sequenced to all the gene fragments when the gene fragments corresponding to multiple samples to be sequenced are mixed during a gene sequencing operation.

[0209] According to different sample sequencing strategies, the conflict removal process may be preferentially performed on candidate samples to be sequenced with lower sequencing concentrations, or preferentially performed on candidate samples to be sequenced with higher sequencing concentrations.

[0210] Exemplarily, the lower the sequencing concentration, the smaller the number of gene fragments corresponding to the sample to be sequenced, which means that in general, the detection flux of the sample to be sequenced is lower. Therefore, when the sample sequencing strategy is to try to ensure that all samples to be sequenced have a certain detection flux, in order to ensure the sequencing flux of samples to be sequenced with a lower sequencing concentration, the candidate samples to be sequenced with a higher sequencing concentration can be preferentially de-conflicted. The higher the sequencing concentration of a sample to be sequenced, the more fault-tolerant labels are reserved for it, which means that the results of sequencing all samples to be sequenced will retain more detection flux. Therefore, when the sample sequencing strategy is to ensure the overall detection flux of all samples to be sequenced, the candidate samples to be sequenced with a lower sequencing concentration can be preferentially de-conflicted. At this time, a higher weighting coefficient can be set for the candidate samples to be sequenced with a lower sequencing concentration.

[0211] In addition, selection conditions for the above two situations can also be set. For example, when the difference between the sequencing concentrations of two candidate samples to be sequenced is less than a certain threshold, priority is given to ensuring the overall detection flux of all candidate samples to be sequenced. At this time, priority can be given to de-conflicting the candidate samples to be sequenced with a smaller sequencing concentration; when the difference between the sample concentrations of two candidate samples to be sequenced is greater than or equal to the threshold, priority is given to ensuring the detection flux of the candidate samples to be sequenced with a smaller sequencing concentration. At this time, priority can be given to de-conflicting the candidate samples to be sequenced with a larger sequencing concentration. At this time, a higher weighting coefficient can be set for the candidate samples to be sequenced with a higher sequencing concentration.

[0212] In this way, the sequencing concentration of each candidate sample to be sequenced can be used to achieve more refined screening of the target sample to be sequenced, thereby improving the effect of conflict resolution processing.

[0213] Based on the above method, a target sample to be sequenced can be determined from multiple candidate samples to be sequenced.

[0214] Exemplary:

[0215] Assume that sample i and sample j have k intersections (indexMismatch = 1index2Mismatch = 1), calculate the element a in the conflict matrix _ij The method is that the barcode of sample i is GACAACTGAA+AGTGGTCAGG, and the barcode of sample j is GACAACTGTA+AGTGGTCAGG. Then the intersection of sample i and sample j is {GACAACTGCA+AGTGGTCAGG, GACAACTGGA+AGTGGACAGG, GACAACTGGA+AGTGGTCAGG...}. First, the sum of the fault tolerance weights corresponding to the above k intersection elements is calculated according to the historical statistical probability (that is, the probability of false recognition):

[0216] GACAACTGCA+AGTGGTCAGG(0.9);

[0217] GACAACTGGA+AGTGGACAGG(0.5);

[0218] GACAACTGGA+AGTGGTCAGG(0.8);

[0219] …

[0221] Then multiply it by the coefficient K_i, which is inversely proportional to the sequencing concentration of sample i. In this way, a conflict matrix related to the current sample tolerance value can be obtained, which is not a symmetric matrix. That is, B = KA, where B is the conflict matrix after the sequencing concentration coefficient is optimized (n*n matrix, n is the number of samples), A is the conflict matrix before the concentration coefficient is optimized (n*n matrix, n is the number of samples), and K is the weighted coefficient matrix, which is expressed as:

[0222]

[0223] Based on the above method, the conflict degree corresponding to each candidate sample to be sequenced can be obtained, and then the target sample to be sequenced is determined according to the conflict degree.

[0224] Following the above S402, after the target sample to be sequenced is determined, in the conflict resolution method provided by the embodiment of the present disclosure, each processing cycle further includes:

[0225] S403: Replace the original target fault tolerance parameters of the target sample to be sequenced to obtain new target fault tolerance parameters, and based on the new target fault tolerance parameters, replace at least one base in the original base sequence of the sample label of the target sample to be sequenced to obtain a new candidate fault tolerance set of the target sample to be sequenced.

[0226] Here, when replacing the original target fault tolerance parameters corresponding to the target sample to be sequenced, for example, the candidate fault tolerance set of the sample labels corresponding to the target sample to be sequenced can be reduced by reducing the target fault tolerance parameters, so that the conflicting fault tolerance labels between the fault tolerance sets of sample labels corresponding to different samples to be sequenced are reduced or disappear.

[0227] Then, new target fault tolerance parameters corresponding to the target sample to be sequenced are regenerated based on the new target fault tolerance parameters, and a new candidate fault tolerance set of the target sample to be sequenced is constructed.

[0228] Specifically, in the case where the sample to be sequenced includes a sample label located at the beginning or end of the corresponding gene fragment, the target fault tolerance parameter can be reduced according to the preset step size; for example, if the original target fault tolerance parameter is 2 and the preset step size of the replacement processing is 1, then the new target fault tolerance parameter is 1.

[0229] In the case where each sample to be sequenced includes a first sample tag and a second sample tag located at both ends of a gene fragment corresponding to the target sample to be sequenced, the target fault tolerance parameter of the target sample to be sequenced may be replaced in the following manner to obtain a new target fault tolerance parameter corresponding to the target sample to be sequenced:

[0230] Determining a first conflict degree corresponding to the first sample label, and determining a second conflict degree corresponding to the second sample label;

[0231] Determining a target sample label from the first sample label and the second sample label according to a magnitude relationship between the first conflict degree and the second conflict degree;

[0232] The target fault tolerance parameter corresponding to the target sample label is replaced to obtain a new target fault tolerance parameter corresponding to the target sample to be sequenced.

[0233] Here, the method of determining the first conflict degree of the first sample label and the method of determining the second conflict degree corresponding to the second sample label are similar to the method of determining the conflict degrees corresponding to each candidate sample to be sequenced in S402 above, and will not be repeated here.

[0234] Then, according to the first conflict degree and the second conflict degree, the sample label with a higher conflict degree is determined from the first sample label and the second sample label as the target sample label, and then the target fault tolerance parameter corresponding to the target sample label is reduced according to the preset step length to obtain a new target fault tolerance parameter corresponding to the target sample label. Then, according to the new target fault tolerance parameter corresponding to the target sample label and the original target fault tolerance parameter corresponding to another sample label, a new candidate fault tolerance set corresponding to the target sample to be sequenced is generated.

[0235] S404: re-detecting conflicts using the new candidate fault-tolerant set after the conflict removal process to detect whether there are candidate samples to be sequenced with fault-tolerant label conflicts; if yes, jump to S401 and enter the next processing cycle; if no, jump to S405;

[0236] S405: construct a target fault tolerance set for the non-target samples to be sequenced based on the candidate fault tolerance sets corresponding to the non-target samples to be sequenced; and construct a target fault tolerance set for the target samples to be sequenced based on the new candidate fault tolerance sets corresponding to the target samples to be sequenced. End the iterative process.

[0237] By adopting the above method, it is possible to implement conflict resolution processing for the candidate fault-tolerant sets corresponding to the samples to be sequenced that have conflicting fault-tolerant labels.

[0238] B: See Figure 5 As shown, another specific method provided by the embodiment of the present disclosure for performing conflict resolution processing on the candidate fault-tolerant set corresponding to the first sample to be sequenced having a conflicting fault-tolerant label to obtain a target fault-tolerant set corresponding to the first sample to be sequenced includes:

[0239] S501: determining conflicting fault-tolerant labels from candidate fault-tolerant sets corresponding to two samples to be sequenced that have conflicting fault-tolerant labels;

[0240] S502: According to the conflicting fault-tolerant labels, respectively from the candidate fault-tolerant sets corresponding to the two samples to be sequenced that have the conflicting fault-tolerant labels, determine the fault-tolerant labels to be deleted that correspond to the two samples to be sequenced that have the conflicting fault-tolerant labels;

[0241] S503: Deleting the to-be-deleted fault-tolerant labels corresponding to the two samples to be sequenced with the fault-tolerant label conflict from the candidate fault-tolerant sets corresponding to the two samples to be sequenced with the fault-tolerant label conflict.

[0242] In a specific implementation, the conflict resolution process may be continuous with the process of detecting whether there is a conflict of fault-tolerant labels between the candidate fault-tolerant sets corresponding to the sample labels of the plurality of samples to be sequenced in S102 above.

[0243] When it is determined based on the above process that there is a conflict in fault-tolerant labels between candidate fault-tolerant sets corresponding to two samples to be sequenced, that is, the intersection of the initial tolerance sets corresponding to the two samples to be sequenced is not empty, the fault-tolerant labels included in the intersection are called conflicting fault-tolerant labels.

[0244] For samples to be sequenced, when determining the error-tolerant labels to be deleted corresponding to the two samples to be sequenced with conflicting error-tolerant labels from the conflicting error-tolerant labels, the following method may be specifically used:

[0245] Determining whether there is a base sequence in the conflicting base sequence that is consistent with the sample label of the sample to be sequenced;

[0246] If so, the base sequence consistent with the sample tag of the sample to be sequenced is deleted from the conflicting base sequence to obtain the base sequence to be deleted;

[0247] If not, the conflicting base sequences are all determined as the base sequences to be deleted.

[0248] Specifically, assuming that there are two samples M1 and M2 to be sequenced with conflicting fault tolerance labels between candidate fault tolerance sets, the candidate fault tolerance set K_1 of sample label barcode_1 corresponding to sample M1 to be sequenced = {k_11, k_12, ... k_1M}. The candidate fault tolerance set K_2 of sample label barcode_2 corresponding to sample M2 to be sequenced = {k_21, k_22, ... k_2M}.

[0249] If there is an intersection P = {p_1, p_2, ... p_f} between the initial fault-tolerant set K_1 and the candidate fault-tolerant set K_2, where f < M.

[0250] For the sample M1 to be sequenced, determine whether there is a conflicting fault-tolerant label that is the same as barcode_1 in P = {p_1, p_2, ... p_f}. If it is determined that p_j is the same as barcode_1, p_j is determined as the target fault-tolerant label, and p_j is deleted from P = {p_1, p_2, ... p_f}. The remaining conflicting fault-tolerant labels: p_1, ..., p_j-1, p_j+1, ..., p_f, are deleted from K_1 as the fault-tolerant labels to be deleted, and the target fault-tolerant set corresponding to the sample M1 to be sequenced is obtained.

[0251] For the sample M2 to be sequenced, determine whether there is a conflicting fault-tolerant label that is the same as barcode_2 in P = {p_1, p_2, ... p_f}. If it is determined that there is no conflicting fault-tolerant label that is the same as barcode_2 in P = {p_1, p_2, ... p_f}, then p_1, p_2, ... p_f are all taken as fault-tolerant labels to be deleted and deleted from K_2 to obtain the target fault-tolerant set corresponding to the sample M2 to be sequenced.

[0252] like Figure 6 In the example shown, specific examples of several situations in which the fault-tolerant sets corresponding to the sample to be sequenced M1 and the sample to be sequenced M2 respectively exist are shown.

[0253] like Figure 6 As shown in a, K_1 and K_2 have an intersection P. However, there are no conflicting fault-tolerant labels in the intersection P that are the same as those of barcode_1 and barcode_2. Therefore, the target fault-tolerant set corresponding to barcode_1 is: K_1-(K_1∩K_2). The target fault-tolerant set corresponding to barcode_2 is: K_2-(K_1∩K_2).

[0254] like Figure 6 As shown in b, K_1 and K_2 have an intersection P. In the intersection P, there are conflicting fault-tolerant labels that are the same as barcode_1, but there are no conflicting fault-tolerant labels that are the same as barcode_2. Then the target fault-tolerant set corresponding to barcode_1 is: K_1-(K_1∩K_2)+barcode_1. The target fault-tolerant set corresponding to barcode_2 is: K_2-(K_1∩K_2).

[0255] like Figure 6 As shown in c, K_1 and K_2 have an intersection P. In the intersection P, there is no conflicting fault-tolerant label that is the same as barcode_1, but there is a conflicting fault-tolerant label that is the same as barcode_2. Then the target fault-tolerant set corresponding to barcode_1 is: K_1-(K_1∩K_2). The target fault-tolerant set corresponding to barcode_2 is: K_2-(K_1∩K_2)+barcode_2.

[0256] like Figure 6 As shown in d, K_1 and K_2 have an intersection P. If there are conflicting fault-tolerant labels in the intersection P that are the same as those of barcode_1 and barcode_2, then the target fault-tolerant set corresponding to barcode_1 is: K_1-(K_1∩K_2)+barcode_1. The target fault-tolerant set corresponding to barcode_2 is: K_2-(K_1∩K_2)+barcode_2.

[0257] Specifically, the present disclosure also provides a Figure 6 A specific example with the same situation as in a:

[0258] For the two sample labels barcode_1: GTACGCAA and barcode_2: GTCCGCAC, the initial fault tolerance sets are:

[0259] barcode_1: Candidate fault tolerance set corresponding to GTACGCAA = {GTACGCAA, ATACGCAA, TTACGCAA, CTACGCAA, NTACGCAA, GAACGCAA, GCACGCAA, GGACGCAA, GNACGCAA, GTTCGCAA, GTCCGCAA, GTGCGCAA, GTNCGCAA, GTAAGCAA, GTATGCAA ,GTAGGCAA,GTANGCAA,GTACACAA,GTACTCAA,GTACCCAA,GTACCNCAA,GTACGAAA,GTACGTAA,GTACGGAA,GTACGNAA,GTACGCTA,GTACGCCA,GTACGCGA,GTACGCNA,GTACGCAT,GTACGCAC,GTACGCAG,GTACGCAN}

[0260] barcode_2: Candidate fault tolerance set corresponding to GTCCGCAC = {GTCCGCAC, ATCCGCAC, TTCCGCAC, CTCCGCAC, NTCCGCAC, GACCGCAC, GCCCGCAC, GGCCGCAC, GNCCGCAC, GTACGCAC, GTTCGCAC, GTGCGCAC, GTNCGCAC, GTCAGCAC, GTCTGCAC , GTCGGCAC, GTCNGCAC, GTCCACAC, GTCCTCAC, GTCCCAC, GTCCNCAC, GTCCGAAC, GTCCGTAC, GTCCGGAC, GTCCGNAC, GTCCGCTC, GTCCGCCC, GTCCGCGC, GTCCGCNC, GTCCGCAA, GTCCGCAT, GTCCGCAG, GTCCGCAN}

[0261] The intersection of the candidate fault-tolerant set corresponding to GTACGCAA and the candidate fault-tolerant set corresponding to GTCCGCAC is {GTCCGCAA, GTACGCAC}.

[0262] This means that the two fault-tolerant labels in the intersection {GTCCGCAA, GTACGCAC} are conflicting fault-tolerant labels. And the two fault-tolerant labels are different from barcode_1 and barcode_2. Therefore, the two conflicting fault-tolerant labels are deleted from the candidate fault-tolerant set corresponding to GTACGCAA. Then:

[0263] barcode_1: Target fault tolerance set corresponding to GTACGCAA = {GTACGCAA, ATACGCAA, TTACGCAA, CTACGCAA, NTACGCAA, GAACGCAA, GCACGCAA, GGACGCAA, GNACGCAA, GTTCGCAA, GTGCGCAA, GTNCGCAA, GTAAGCAA, GTATGCAA ,GTAGGCAA,GTANGCAA,GTACACAA,GTACTCAA,GTACCCAA,GTACCNCAA,GTACGAAA,GTACGTAA,GTACGGAA,GTACGNAA,GTACGCTA,GTACGCCA,GTACGCGA,GTACGCNA,GTACGCAT,GTACGCAG,GTACGCAN}

[0264] Delete the two conflicting fault-tolerant labels from the candidate fault-tolerant set corresponding to GTCCGCAC, then:

[0265] barcode_1: Target fault tolerance set corresponding to GTCCGCAC = {GTCCGCAC, ATCCGCAC, TTCCGCAC, CTCCGCAC, NTCCGCAC, GACCGCAC, GCCCGCAC, GGCCGCAC, GNCCGCAC, GTTCGCAC, GTGCGCAC, GTNCGCAC, GTCAGCAC, GTCTGCAC ,GTCGGCAC,GTCNGCAC,GTCCACAC,GTCCTCAC,GTCCCCAC,GTCCNCAC,GTCCGAAC,GTCCGTAC,GTCCGGAC,GTCCGNAC,GTCCGCTC,GTCCGCCC,GTCCGCGC,GTCCGCNC,GTCCGCAT,GTCCGCAG,GTCCGCAN}

[0266] In addition, in a specific implementation, in a possible situation, a sample to be sequenced has an intersection with only one other sample to be sequenced. In this case, during traversal, only one other sample to be sequenced that has a fault-tolerant label conflict with the sample to be sequenced will be traversed. For the sample to be sequenced, only one conflict resolution process needs to be performed on the candidate fault-tolerant set corresponding to the sample to be sequenced.

[0267] In another possible situation, there is an intersection between a sample to be sequenced and at least two other samples to be sequenced. In this case, during traversal, at least two other samples to be sequenced that have fault-tolerant label conflicts with the sample to be sequenced will be traversed. In this case, multiple conflict resolution processes need to be performed on the candidate fault-tolerant set corresponding to the sample to be sequenced.

[0268] Among them, when multiple conflict resolution processes are performed on the candidate fault tolerance set corresponding to the sample to be sequenced, the fault tolerance set for the first conflict resolution process is the candidate fault tolerance set corresponding to the sample to be sequenced. The fault tolerance set used in the i-th (i>1) conflict resolution process may be the fault tolerance set obtained after the i-1th conflict resolution process. After multiple conflict resolution processes are performed, the target fault tolerance set corresponding to the sample to be sequenced is obtained.

[0269] For example, if the candidate fault-tolerant set K_1 corresponding to the sample M1 to be sequenced has fault-tolerant label conflicts with the candidate fault-tolerant set K_2 corresponding to the sample M2 to be sequenced and the candidate fault-tolerant set K_3 corresponding to the sample M3 to be sequenced, the candidate fault-tolerant set K_1 and the candidate fault-tolerant set K_2 may be first deconflicted to obtain the fault-tolerant set K_1_1 corresponding to the sample M1 to be sequenced; then, the fault-tolerant set K_1_1 and the candidate fault-tolerant set K_3 may be deconflicted to obtain the fault-tolerant set K_1_2 corresponding to the sample M1 to be sequenced, and K_1_2 may be determined as the target fault-tolerant set corresponding to the sample M1 to be sequenced.

[0270] In addition, the candidate fault-tolerant set corresponding to the sample to be sequenced can be de-conflicted with the candidate fault-tolerant sets corresponding to multiple other samples to be sequenced that have fault-tolerant label conflicts, and then the intersection of the fault-tolerant sets after base processing of the candidate fault-tolerant set corresponding to the sample to be sequenced is calculated to obtain the target fault-tolerant set corresponding to the sample to be sequenced.

[0271] For example, the candidate fault-tolerant set K_1 corresponding to the sample M1 to be sequenced has fault-tolerant label conflicts with the candidate fault-tolerant set K_2 corresponding to the sample M2 to be sequenced and the candidate fault-tolerant set K_3 corresponding to the sample M3 to be sequenced, then the candidate fault-tolerant set K_1 and the candidate fault-tolerant set K_2 are de-conflicted to obtain the fault-tolerant set K_1_1 corresponding to the sample M1 to be sequenced; and the candidate fault-tolerant set K_1 and the candidate fault-tolerant set K_3 are de-conflicted to obtain the fault-tolerant set K_1_2 corresponding to the sample M1 to be sequenced, and then the intersection between K_1_1 and K_1_2 is determined to obtain the target fault-tolerant set corresponding to the sample M1 to be sequenced.

[0272] C: In the embodiment of the present disclosure, another specific method for performing conflict resolution processing on the candidate fault-tolerant set corresponding to the sample to be sequenced that has a fault-tolerant sample conflict with other samples to be detected to obtain the target fault-tolerant set corresponding to the sample to be sequenced that has a fault-tolerant sample conflict with other samples to be detected, including:

[0273] From the candidate fault-tolerant set corresponding to the sample to be sequenced that has a fault-tolerant sample conflict with other samples to be detected, determine a first target fault-tolerant label that is the same as the sample label of the sample to be sequenced that has a fault-tolerant sample conflict with other samples to be detected; based on the first target fault-tolerant label, construct a target fault-tolerant set corresponding to the sample to be sequenced that has a fault-tolerant sample conflict with other samples to be detected.

[0274] In the specific implementation, Figure 7 In the example shown, a specific example of performing a conflict elimination operation on a candidate fault-tolerant set having a conflicting fault-tolerant label is shown. In this example, Figure 7 As shown in a, the first sample M1 to be sequenced corresponds to the candidate fault-tolerant set K_1, the sample M2 to be sequenced corresponds to the candidate fault-tolerant set K_2, and the sample M3 to be sequenced corresponds to the candidate fault-tolerant set K_3. Among them, there is a fault-tolerant label conflict between the candidate fault-tolerant set K_1 and the candidate fault-tolerant set K_2, that is, the intersection between the candidate fault-tolerant set K_1 and the candidate fault-tolerant set K_2 is not empty. There is no fault-tolerant label conflict among the candidate fault-tolerant set K_1, the candidate fault-tolerant set K_2, and the candidate fault-tolerant set K_3, that is, the intersection of the candidate fault-tolerant set K_1 and the candidate fault-tolerant set K_3 is empty, and the intersection of the candidate fault-tolerant set K_2 and the candidate fault-tolerant set K_3 is empty.

[0275] At this time, the above method is used to perform conflict resolution on the candidate fault-tolerant set K_1 and the candidate fault-tolerant set K_2. Figure 7 As shown in b, the target fault tolerance set corresponding to the first sample to be sequenced M1 only includes the same fault tolerance label as the sample label barcode_1 corresponding to the candidate fault tolerance set K_1, and the target fault tolerance set corresponding to the sample to be sequenced M2 only includes the same fault tolerance label as the sample label barcode_2 corresponding to the candidate fault tolerance set K_2. The target fault tolerance set corresponding to the sample to be sequenced M3 is the same as K_3.

[0276] In this way, by adopting the above method, target fault tolerance sets corresponding to multiple samples to be sequenced can be obtained.

[0277] In another embodiment of the present disclosure, in the fault tolerance method provided in the embodiment of the present disclosure, after obtaining the target fault tolerance set, the method may further include:

[0278] Acquire sequencing results obtained by performing gene sequencing on a plurality of objects to be sequenced; the sequencing results corresponding to each of the objects to be sequenced include: a tag sequencing sequence and a gene sequencing sequence;

[0279] The tag sequencing sequence is matched with a target fault tolerance set corresponding to the sample tags of the plurality of samples to be sequenced, and the sample source corresponding to each sequencing object is determined according to the result of the matching process.

[0280] Specifically, in the process of mixed sequencing of gene fragments of multiple samples to be sequenced, a base sequence corresponding to the sample label will be added to each gene fragment to form an object to be sequenced corresponding to each sample to be sequenced. During the sequencing process, gene sequencing will be performed on the object to be sequenced to obtain the sequencing results of each object to be sequenced. The sequencing results corresponding to each object to be sequenced include: a label sequencing sequence and a gene sequencing sequence.

[0281] The tag sequencing sequence includes the base sequence obtained by sequencing the sample tags included in the object to be sequenced, and the gene sequencing sequence includes the base sequence obtained by sequencing the gene fragments included in the object to be tested.

[0282] Then, the tag sequencing sequence is matched with the target fault tolerance sets corresponding to the sample tags of the multiple samples to be sequenced. If the tag sequencing sequence is the same as the fault tolerance tag in a target fault tolerance set, it is considered that the tag sequencing sequence and the target fault tolerance set are successfully matched, and the sample to be sequenced corresponding to the target fault tolerance set is used as the sample source corresponding to the object to be sequenced.

[0283] Exemplarily, assume that the target fault tolerance set of the sample M1 to be sequenced is represented as L_1, the target fault tolerance set corresponding to the sample M2 to be sequenced is represented as L_2, and the target fault tolerance set corresponding to the sample M3 to be sequenced is represented as L_3. After obtaining the label sequencing sequence index_1 of the sequencing result G1 of a certain object to be sequenced, match index_1 with the fault tolerance labels in L_1, L_2, and L_3. If the match with a certain fault tolerance label in L_2 is successful, that is, index_1 is the same as a certain fault tolerance label in L_2, then the classification result of G1 is determined as: sample M2 to be sequenced.

[0284] In the above embodiment, in order to match the tag sequencing sequence with the fault-tolerant tags in the target fault-tolerant set, a hash table can also be constructed based on the target fault-tolerant sets corresponding to the multiple samples to be sequenced; the hash table includes the first encoding value of the fault-tolerant tag included in the target fault-tolerant set.

[0285] The step of matching the tag sequencing sequence with the fault-tolerant tags in the target fault-tolerant set includes:

[0286] Encoding the tag sequencing sequence to obtain a second encoding value corresponding to the tag sequencing sequence;

[0287] Querying the hash table whether there is a target first code value that is the same as the second code value;

[0288] If the target first encoding value exists in the hash table, the match is successful;

[0289] If the target first encoding value does not exist in the hash table, the match fails.

[0290] In a specific implementation, in the hash table, the key value is the first encoding value of the fault-tolerant tag. The value is the sample identification number, such as sample No. 1 or sample No. 2, etc. Each sample can correspond to a sample tag, which is used to distinguish different samples to be sequenced.

[0291] Among them, when encoding the tag sequencing sequence and the error-tolerant tag, it can be determined by constructing a Huffman coding tree.

[0292] like Figure 8 As shown, a specific example of using the Huffman coding tree to encode different types of bases is shown. Among them: adenine (A), its code is: 11;

[0293] Guanine (G), its code is: 00;

[0294] Cytosine (C), its code is: 01;

[0295] Thymine (T), its code is: 101;

[0296] Unknown base (N), its code is: 100.

[0297] Each time mixed sequencing is performed, a hash table is formed. For the multiple samples to be sequenced, the corresponding hash table is queried to determine the sample to be sequenced to which the identification result of each object to be sequenced belongs. Fig. 9 As shown, the embodiment of the present disclosure also provides a specific example of a sample label fault tolerance method, including:

[0298] For n samples M1 to Mn to be sequenced, according to the sample labels barcode_1 to barcode_n corresponding to M1 to Mn respectively, the candidate fault-tolerant sets K_1 to K_n corresponding to barcode_1 to barcode_n are constructed respectively.

[0299] The generated candidate fault-tolerant sets K_1~K_n are intersected in pairs, and the candidate fault-tolerant sets whose intersections are not empty are de-conflicted to obtain the target fault-tolerant sets L_1~L_n corresponding to barcode_1~barcode_n respectively.

[0300] The target fault-tolerant sets L_1~L_n are combined to form a hash table.

[0301] For the sequencing result of each object to be sequenced, the tag sequencing sequence index is read and encoded to obtain a second encoding value.

[0302] Look up the hash table based on the second encoded value.

[0303] Determine whether the search was successful.

[0304] If the search is successful, the sample to be sequenced to which the object to be sequenced belongs is output.

[0305] If the search fails, the identification result of the object to be sequenced is determined to be unknown.

[0306] Those skilled in the art will appreciate that, in the above method of specific implementation, the order in which the steps are written does not imply a strict execution order and does not constitute any limitation on the implementation process. The specific execution order of the steps should be determined by their functions and possible internal logic.

[0307] The present disclosure also provides a computer device, such as Fig.10 FIG. 1 is a schematic diagram of a computer device structure provided in an embodiment of the present disclosure, including:

[0308] A processor 11 and a memory 12; the memory 12 stores machine-readable instructions executable by the processor 11, and the processor 11 is used to execute the machine-readable instructions stored in the memory 12. When the machine-readable instructions are executed by the processor 11, the processor 11 performs the following steps:

[0309] Based on sample labels of multiple samples to be sequenced, generating candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced respectively; the candidate fault-tolerant sets include at least one fault-tolerant label that is fault-tolerant with the sample label; the sample label and the fault-tolerant label are both a group of base sequences;

[0310] Detecting whether there is a conflict of fault-tolerant labels between candidate fault-tolerant sets corresponding to sample labels of the plurality of samples to be sequenced;

[0311] In the case of a conflict of fault-tolerant labels, performing conflict-removal processing on candidate fault-tolerant sets corresponding to the sample labels of the plurality of samples to be sequenced, and then re-performing conflict detection using the new candidate fault-tolerant sets after the conflict-removal processing;

[0312] In the case where there is no conflict in the error-tolerant labels, the candidate error-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced are determined as the target error-tolerant sets.

[0313] The above-mentioned memory 12 includes internal memory 121 and external memory 122; the memory 121 here is also called internal memory, which is used to temporarily store the calculation data in the processor 11, as well as the data exchanged with the external memory 122 such as the hard disk. The processor 11 exchanges data with the external memory 122 through the internal memory 121.

[0314] The specific execution process of the above instructions can refer to the steps of the fault-tolerant method of sample labels described in the embodiment of the present disclosure, which will not be repeated here.

[0315] The present disclosure also provides a computer-readable storage medium, on which a computer program is stored, and when the computer program is executed by a processor, the steps of the fault-tolerant method for sample labels described in the above method embodiment are executed. The storage medium may be a volatile or non-volatile computer-readable storage medium.

[0316] The present disclosure also provides a computer program product that carries a program code. The program code includes instructions that can be used to execute the steps of the sample label fault tolerance method described in the above method embodiment. For details, please refer to the above method embodiment, which will not be repeated here.

[0317] The computer program product may be implemented in hardware, software or a combination thereof. In one optional embodiment, the computer program product is implemented as a computer storage medium. In another optional embodiment, the computer program product is implemented as a software product, such as a software development kit (SDK).

[0318] Finally, it should be noted that the above-described embodiments are only specific implementation methods of the present disclosure, which are used to illustrate the technical solutions of the present disclosure, rather than to limit them. The protection scope of the present disclosure is not limited thereto. Although the present disclosure is described in detail with reference to the above-described embodiments, ordinary technicians in the field should understand that any technician familiar with the technical field can still modify the technical solutions recorded in the above-described embodiments within the technical scope disclosed in the present disclosure, or can easily think of changes, or make equivalent replacements for some of the technical features therein; and these modifications, changes or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present disclosure, and should be included in the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be based on the protection scope of the claims.

Claims

1. A fault-tolerant method for sample labels, It is characterized in that include: Based on the sample labels of the multiple samples to be sequenced, generating candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced respectively; The candidate fault-tolerant set includes at least one fault-tolerant label that is fault-tolerant to the sample label; The sample label and the error-tolerant label are both a group of base sequences; Detecting whether there is a conflict of fault-tolerant labels between candidate fault-tolerant sets corresponding to sample labels of the plurality of samples to be sequenced; In the case of a conflict of fault-tolerant labels, performing conflict-removal processing on candidate fault-tolerant sets corresponding to the sample labels of the plurality of samples to be sequenced, and then re-performing conflict detection using the new candidate fault-tolerant sets after the conflict-removal processing; In the case where there is no conflict in the error-tolerant labels, the candidate error-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced are determined as the target error-tolerant sets.

2. The fault-tolerant method according to claim 1, It is characterized in that The method further comprises: Acquire sequencing results obtained by performing gene sequencing on a plurality of objects to be sequenced; the sequencing results corresponding to each of the objects to be sequenced include: a tag sequencing sequence and a gene sequencing sequence; The tag sequencing sequence is matched with a target fault tolerance set corresponding to the sample tags of the plurality of samples to be sequenced, and the sample source corresponding to each sequencing object is determined according to the result of the matching process.

3. The fault-tolerant method according to claim 1 or 2, It is characterized in that The step of generating, based on the sample labels of the multiple samples to be sequenced, candidate fault-tolerant sets corresponding to the sample labels of the multiple samples to be sequenced respectively comprises: For any sample to be sequenced among the multiple samples to be sequenced, bases in the original base sequence of the sample label of the sample to be sequenced are replaced based on the target fault tolerance parameter to obtain at least one group of fault tolerance labels, and a candidate fault tolerance set corresponding to the sample label of the sample to be sequenced is constructed based on the at least one group of fault tolerance labels obtained, wherein the target fault tolerance parameter indicates the number of bases and / or base types to be replaced in the base sequence of the sample label.

4. The fault-tolerant method according to claim 3, It is characterized in that The sample labels of the samples to be sequenced include: a first sample label and a second sample label.

5. The fault-tolerant method according to claim 4, It is characterized in that The target fault tolerance parameter includes a first target fault tolerance parameter corresponding to the first sample label, and a second target fault tolerance parameter corresponding to the second sample label; The replacing process of at least one base in the original base sequence of the sample label of the sample to be sequenced based on the target fault tolerance parameter to obtain at least one set of fault tolerance labels includes: Based on the first target fault tolerance parameter, bases in the original base sequence of the first sample label are replaced to obtain at least one set of first fault tolerance labels; and based on the second target fault tolerance parameter, bases in the original base sequence of the second sample label are replaced to obtain at least one set of second fault tolerance labels; Any one of the at least one group of first error-tolerant labels and any one of the at least one group of second error-tolerant labels are combined in pairs to form a candidate error-tolerant set of sample labels of the sample to be sequenced.

6. The fault-tolerant method according to any one of claims 1 to 5, It is characterized in that The conflict elimination process of the candidate fault-tolerant sets respectively corresponding to the sample labels of the plurality of samples to be sequenced includes: In each processing cycle of at least one processing cycle, the following de-confliction process is performed: Determine candidate samples to be sequenced that have fault-tolerant label conflicts in the current processing cycle; Determining the degree of conflict between the candidate samples to be sequenced, and selecting a target sample to be sequenced for performing conflict resolution processing in the current processing cycle according to the degree of conflict; The original target fault tolerance parameters of the target sample to be sequenced are replaced to obtain new target fault tolerance parameters, and based on the new target fault tolerance parameters, at least one base in the original base sequence of the sample label of the target sample to be sequenced is replaced to obtain a new candidate fault tolerance set of the target sample to be sequenced.

7. The fault-tolerant method according to claim 6, It is characterized in that After determining the candidate samples to be sequenced that have error-tolerant label conflicts in the current processing cycle, the following steps are also included: Determine the difference samples to be sequenced between the candidate samples to be sequenced having fault-tolerant label conflicts in the current processing cycle and the candidate samples to be sequenced having fault-tolerant label conflicts in the previous processing cycle; The candidate fault tolerance set corresponding to the difference sample to be sequenced is determined as the target fault tolerance set corresponding to the difference sample to be sequenced.

8. The fault-tolerant method according to claim 6 or 7, It is characterized in that The degree of conflict is determined based on at least one of the following indication information: whether a fault-tolerant label conflict occurs between different candidate samples to be sequenced, the number of fault-tolerant labels that conflict between different candidate samples to be sequenced, and the probability of misidentifying sample labels corresponding to the candidate samples to be sequenced as conflicting fault-tolerant labels.

9. A computer device, It is characterized in that include: A processor and a memory, wherein the memory stores machine-readable instructions executable by the processor, and the processor is used to execute the machine-readable instructions stored in the memory. When the machine-readable instructions are executed by the processor, the processor executes the steps of the fault-tolerant method according to any one of claims 1 to 8.

10. A computer-readable storage medium, It is characterized in that The computer-readable storage medium stores a computer program. When the computer program is executed by a computer device, the computer device executes the steps of the fault-tolerant method according to any one of claims 1 to 8.

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