HLA allele difference quantification method and application thereof

Abstract

The invention provides an HLA allele difference quantification method and application thereof. The HLA allele difference quantification method comprises the following steps: obtaining typing results of HLA alleles of a recipient and a donor; combining the typing results of the recipient and the donor in pairs to obtain four groups of combined typing results; respectively decoding typing results of the four groups of combinations into amino acid sequences; respectively calculating the HED value of the typing result of each group of combination; calculating the sum of the HED values of the typing results of the four groups of combinations to obtain HEDHLA allele values of the recipient and the donor; and according to the HEDHLA allele value, quantifying the difference between the recipient and the donor in the HLA allele. The HLA allele difference quantification method is used for predicting the chronic graft versus host disease risk, the acute graft versus host disease risk, the recurrence risk, the cytomegalovirus infection risk and the like of hematopoietic stem cell transplantation, and has important guiding significance on selection of prognosis treatment schemes of target objects.

Description

Technical Field

[0001] The present disclosure relates to the technical field related to medical care informatics, and in particular to a method for quantifying HLA allele differences and uses thereof. Background Art

[0002] Hematopoietic stem cell transplantation (HSCT) refers to a treatment method in which hematopoietic stem cells are transplanted into patients after high-dose chemotherapy and radiotherapy have been used to eliminate abnormal (tumor, immune) cells in the patient's body, thereby restoring the patient's normal hematopoietic function.

[0003] Among them, the degree of matching of human leukocyte antigen (HLA) genes determines the success rate of hematopoietic liver cell transplantation and organ survival rate. However, there is currently a lack of quantitative description of the differences in the physical and chemical properties between recipient and donor HLA alleles. Therefore, it is necessary to find a method to quantify the differences in HLA alleles. Summary of the invention

[0004] In view of this, the present disclosure provides a method for quantifying HLA allele differences and uses thereof.

[0005] In a first aspect of the present disclosure, the present disclosure provides a method for quantifying HLA allele differences, the method comprising the following steps:

[0006] Step S101, obtaining the typing results of the HLA alleles of the recipient and the donor; wherein the typing result of the recipient is recorded as allele1 / allele2, and the typing result of the donor is recorded as allele3 / allele4;

[0007] Step S102, combining the typing results allele1 / allele2 of the recipient and the typing results allele3 / allele4 of the donor in pairs, to obtain four groups of typing results which are recorded as allele1 / allele3, allele1 / allele4, allele2 / allele3, and allele2 / allele4 respectively;

[0008] Step S103, decoding the typing results of the four groups of combinations allele1 / allele3, allele1 / allele4, allele2 / allele3, and allele2 / allele4 into amino acid sequences respectively;

[0009] Step S104, according to the amino acid sequences decoded from the typing results of the four groups of combinations, respectively calculating the HED value of the typing results of each group of combinations in the exon region corresponding to the HLA allele;

[0010] Among them, the HED value of the combined typing result allele1 / allele3 is recorded as HED 1 / 3 value;

[0011] The HED value of the combined typing result allele1 / allele4 is recorded as HED 1 / 4 value;

[0012] The HED value of the combined typing result allele2 / allele3 is recorded as HED 2 / 3 value;

[0013] The HED value of the combined typing result allele2 / allele4 is recorded as HED 2 / 4 value;

[0014] Step S105, calculate the sum of the HED values ​​of the typing results of the four groups of combinations in the third exon region of the HLA allele, and obtain the HED values ​​of the recipient and the donor in the exon region corresponding to the HLA allele. HLA等位基因 value;

[0015] HED HLA等位基因 =HED 1 / 3 +HED 1 / 4 +HED 2 / 3 +HED 2 / 4

[0016] Step S106: According to HED HLA等位基因 Value, quantifying the difference between the recipient and the donor at this HLA allele; where HED HLA等位基因 The larger the value, the greater the difference between the recipient and the donor in this HLA allele; HLA等位基因 The smaller the value, the smaller the difference between the recipient and the donor in this HLA allele.

[0017] In some optional implementations of the present disclosure, in step S104, the calculation formula of the HED value is:

[0018] HED=∑D ij =∑[α(c i -c j ) 2 +β(p i -p j ) 2 +γ(v i -v j ) 2 ] 1 / 2

[0019] Among them, α, β, and γ represent inverse mean weight factors;

[0020] i and j represent two amino acids at the same position in the recipient and donor in this HLA allele, respectively;

[0021] c represents the amino acid composition;

[0022] p represents the polarity of amino acid;

[0023] v represents the volume of amino acid molecule.

[0024] In some optional embodiments of the present disclosure, the calculation formulas of α, β, and γ are respectively as follows:

[0025]

[0026] Where n represents the number of amino acid species in the encoded amino acid sequence;

[0027] |c g -c h | represents the difference between the two amino acid compositions after n amino acids are combined in pairs;

[0028] |p g -p h | represents the difference in polarity between two amino acids after n amino acids are combined in pairs;

[0029] |v g -v h | represents the difference in molecular volume between two amino acids after n amino acids are combined in pairs.

[0030] In some optional embodiments of the present disclosure, the HLA allele is selected from at least one of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1.

[0031] In some specific embodiments of the present disclosure, the HLA alleles include HLA-A and HLA-B.

[0032] In the second aspect of the present disclosure, the present disclosure provides a method for quantifying HLA allele differences as described in the first aspect of the present disclosure for predicting the risk of chronic graft-versus-host disease, or the risk of acute graft-versus-host disease, or the risk of relapse, or the risk of cytomegalovirus infection. Exemplarily, by quantifying the difference between HLA-A alleles and HLA-B alleles, the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation can be predicted.

[0033] In a third aspect of the present disclosure, the present disclosure provides a method for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation, the prediction method comprising the following steps:

[0034] Step S201: Calculate the HED of the recipient and the donor in the third exon region of the HLA-A allele based on the HLA allele difference quantification method described in the first aspect of the present disclosure. HLA-A等位基因 value;

[0035] Step S202: Calculate the HED of the recipient and the donor in the third exon region of the HLA-B allele based on the HLA allele difference quantification method described in the first aspect of the present disclosure. HLA-B等位基因 value;

[0036] Step S203: According to HED HLA-A等位基因 Value and HED HLA-B等位基因 The HED values ​​of the recipient and donor in the third exon region corresponding to the HLA-A allele and HLA-B allele were calculated. 受者 / 供者 value;

[0037] HED HLA-A等位基因 +HED HLA-B等位基因 =HED 受者 / 供者

[0038] Step S204: According to HED 受者 / 供者 The HED value predicts the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The larger the value, the lower the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The smaller the value, the higher the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation.

[0039] In some optional implementations of the present disclosure, in step S204, HED 受者 / 供者 The value was compared with the preset threshold to predict the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation.

[0040] If HED 受者 / 供者 If the value is greater than or equal to the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be low;

[0041] If HED 受者 / 供者 If the value is less than the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be high.

[0042] In some optional embodiments of the present disclosure, the preset threshold is selected from any number between 60 and 70; for example, 60, 61, 62, 63, 63.10, 63.20, 63.30, 63.31, 63.32, 63.33, 63.34, 63.35, 63.36, 63.37, 63.38, 63.39, 63.40, 63.50, 63.60, 63.70, 63.80, 63.90, 64, 65, 66, 67, 68, 69 or 70, etc.

[0043] In some optional implementations of the present disclosure, the preset threshold is selected from 63.36.

[0044] In a fourth aspect of the present disclosure, the present disclosure provides a prediction system for the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation, the prediction system being based on the prediction method described in the third aspect of the present disclosure; the prediction system comprising:

[0045] HED HLA-A等位基因 Value calculation module, used to calculate the HED of recipient and donor in the third exon region of HLA-A allele HLA-A等位基因 value;

[0046] HED HLA-B等位基因 Value calculation module, used to calculate the HED of recipient and donor in the third exon region of HLA-B allele HLA-A等位基因 value;

[0047] HED 受者 / 供者 Value calculation module for HED HLA-A等位基因 Value and HED HLA-B等位基因 The HED values ​​of the recipient and donor in the third exon region corresponding to the HLA-A allele and HLA-B allele were calculated. 受者 / 供者 value;

[0048] Prediction module, used to 受者 / 供者 Value, predict the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation.

[0049] In some optional embodiments of the present disclosure, the HED HLA-A等位基因 The value calculation module includes:

[0050] Typing result acquisition module 1, used to obtain the typing results of recipient and donor HLA-A alleles;

[0051] The typing result combination module 1 is used to combine the typing results of the recipient and donor HLA-A alleles in pairs and obtain four groups of combined typing results;

[0052] Decoding module 1 is used to decode the typing results of the four groups of combinations of recipient and donor HLA-A alleles into amino acid sequences respectively;

[0053] The first level calculation module is used to calculate the HED value of each combination of typing results in the third exon region of the HLA-A allele according to the amino acid sequences decoded from the typing results of the four combinations of the recipient and the donor HLA-A alleles;

[0054] Secondary calculation module 1 is used to calculate the HED of the recipient and the donor in the third exon region of the HLA-A allele according to the HED value of the third exon region of the HLA-A allele of the four groups of combined typing results of the recipient and the donor HLA-A alleles. HLA*A等位基因 value.

[0055] In some optional embodiments of the present disclosure, the HED HLA-B等位基因 The value calculation module includes:

[0056] Typing result acquisition module 2 is used to obtain the typing results of recipient and donor HLA-B alleles;

[0057] The second typing result combination module is used to combine the typing results of the recipient and the donor in pairs and obtain four groups of combined typing results;

[0058] Decoding module 2 is used to decode the typing results of the four groups of combinations of recipient and donor HLA-B alleles into amino acid sequences respectively;

[0059] The first-level calculation module 2 is used to calculate the HED value of each combination of typing results in the third exon region of the HLA-B allele according to the amino acid sequences decoded from the typing results of the four combinations of the recipient and donor HLA-B alleles;

[0060] Secondary calculation module 2 is used to calculate the HED of the recipient and the donor in the third exon region of the HLA-B allele according to the HED value of the typing results of the four groups of combinations of the recipient and the donor HLA-B allele in the third exon region of the HLA-B allele. HLA-B等位基因 value.

[0061] In the fifth aspect of the present disclosure, the present disclosure provides a prediction device for the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation, the prediction device comprising a memory and a processor; wherein the memory is used to store program instructions; the processor is used to call the program instructions, and when the program instructions are executed, the steps of the prediction method described in the third aspect of the present disclosure are implemented.

[0062] In a sixth aspect of the present disclosure, the present disclosure provides a computer-readable storage medium having a computer program stored thereon, and when the computer program is executed by a processor, the steps of the prediction method described in the third aspect of the present disclosure are performed.

[0063] It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present disclosure and, together with the description, serve to explain the principles of the present disclosure.

[0065] Figure 1 is a flow chart showing a method for quantifying HLA allele differences according to an exemplary embodiment.

[0066] Figure 2 A method for combining the recipient's typing result allele1 / allele2 and the donor's typing result allele3 / allele4 according to an exemplary embodiment

[0067] Figure 3 The present invention is a flowchart of a method for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation according to an exemplary embodiment.

[0068] Figure 4 The cumulative incidence curve of cGVHD in the target subjects who received haploid hematopoietic stem cell transplantation and did not receive MSC treatment was predicted to be low-risk and high-risk groups when the preset threshold was selected as 63.36.

[0069] Figure 5 The present invention is a flowchart of a system for predicting the risk of chronic graft-versus-host disease after haploid hematopoietic stem cell transplantation according to an exemplary embodiment. DETAILED DESCRIPTION

[0070] The present disclosure discloses a method for quantifying HLA allele differences and its use. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present disclosure. The methods and applications of the present disclosure have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present disclosure to implement and apply the technology of the present disclosure.

[0071] Terminology explanation:

[0072] The term "hematopoietic stem cell transplantation" used in this disclosure can be divided into: autologous transplantation, allogeneic transplantation and syngeneic transplantation according to the source of the donor. Among them, "allogeneic transplantation" is further divided into sibling donor transplantation and non-blood donor transplantation. "Syngeneic transplantation" is a transplantation in which the recipient and the donor are exactly the same gene. In humans, it only refers to the transplantation between identical twins.

[0073] The term "allogeneic hematopoietic stem cell transplantation" used in the present disclosure is divided into fully matched and incompatible according to the degree of matching of the ten sites of the human leukocyte antigen (HLA) gene, wherein fully matched means that the ten sites of the HLA gene of the recipient and the donor are the same, and incompatible means that at least one site of the HLA gene of the recipient and the donor is different. Among them, "haploidentical hematopoietic stem cell transplantation (haplo-HSCT)" is a type of allogeneic hematopoietic stem cell transplantation.

[0074] The term "chronic graft-versus-host disease (cGVHD)" used in this disclosure refers to a clinical pathological syndrome (including classic cGVHD and overlap syndrome) caused by lymphocytes from the donor attacking the recipient's organs during the process of the recipient's reconstruction of the donor's immunity. It is one of the major complications after transplantation.

[0075] The term "risk" as used in the present disclosure refers to the possibility that a certain event will occur within a specific period of time, such as the occurrence of non-relapse mortality after incompatible allogeneic hematopoietic stem cell transplantation.

[0076] The term "risk prediction" as used in this disclosure includes predicting the probability, odds ratio, or likelihood risk prediction of an event that may occur.

[0077] The term "threshold" used in the present disclosure is used to evaluate the sensitivity of an influencing factor to the effector response of an organism. In the prediction of the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation, the reasonable setting of the threshold is of great guiding significance for the prognosis evaluation of the target subject receiving chronic haploid hematopoietic stem cell transplantation and the selection of the prognosis treatment plan for the target subject.

[0078] Methods for quantifying HLA allele differences:

[0079] In one embodiment, a method for quantifying HLA allele differences is provided. Figure 1 FIG. 1 is a flow chart of a method for quantifying HLA allele differences according to an exemplary embodiment. The method for quantifying HLA allele differences comprises the following steps:

[0080] In step S101, the typing results of the HLA alleles of the recipient and the donor are obtained; wherein the typing result of the recipient is recorded as allele1 / allele2, and the typing result of the donor is recorded as allele3 / allele4.

[0081] In step S102, the typing results allele1 / allele2 of the recipient and allele3 / allele4 of the donor are combined in pairs to obtain four groups of typing results which are recorded as allele1 / allele3, allele1 / allele4, allele2 / allele3, and allele2 / allele4. Figure 2 A method for combining the typing result allele1 / allele2 of the recipient and the typing result allele3 / allele4 of the donor is shown according to an exemplary embodiment.

[0082] In step S103, the typing results of the four combinations allele1 / allele3, allele1 / allele4, allele2 / allele3, and allele2 / allele4 are decoded into amino acid sequences respectively.

[0083] In step S104, based on the amino acid sequences decoded from the typing results of the four groups, the HED value of the typing results of each group in the exon region corresponding to the HLA allele is calculated respectively.

[0084] The calculation formula of HED value is:

[0085] HED=∑D ij =∑[α(c i -c j ) 2 +β(p i -p j ) 2 +γ(v i -v j ) 2 ] 1 / 2

[0086] In the formula, i and j represent the two amino acids at the same position of the allele; c represents the amino acid composition; p represents the polarity of the amino acid; and v represents the volume of the amino acid molecule.

[0087] The amino acid composition uses the AAindex database to represent GRAR740101 composition; the amino acid polarity uses the AAindex database to represent GRAR740102 polarity; the amino acid molecular volume uses the AAindex database to represent GRAR740103 molecular volume. D1 / A1 Value, HED D1 / A2 Value, HED D2 / A1 Value and HED D2 / A2 The values ​​are calculated based on Grantham's physicochemical distances between amino acids for three physicochemical characteristics: GRAR740101 composition, GRAR740102 polarity, and GRAR740103 molecular volume, which quantify the differences in the physicochemical properties of amino acid sequences between HLA typing alleles.

[0088] Where α, β, and γ represent the inverse mean weight factors.

[0089] The calculation formulas for α, β, and γ are as follows:

[0090]

[0091] Where n represents the number of amino acid species in the encoded amino acid sequence;

[0092] |c g -c h | represents the difference between the two amino acid compositions after n amino acids are combined in pairs;

[0093] |p g -p h | represents the difference in polarity between two amino acids after n amino acids are combined in pairs;

[0094] |v g -v h | represents the difference in molecular volume between two amino acids after n amino acids are combined in pairs.

[0095] For example, if n=20, ∑|c g -c h | is the sum of the differences between the two amino acid compositions of the 20 amino acids after pairwise combination (excluding self-combinations, a total of 380 groups); ∑|p g -p h | is the sum of the polarity differences of the two amino acids after the 20 amino acids are combined in pairs (excluding their own combinations, a total of 380 groups); ∑|v g -v h | is the sum of the differences in the molecular volumes of two amino acids after the 20 amino acids are combined in pairs (excluding their own combinations, a total of 380 groups).

[0096] Among them, the HED value of the combined typing result allele1 / allele3 is recorded as HED 1 / 3 The HED value of the combined typing result allele1 / allele4 is recorded as HED 1 / 4 The HED value of the combined typing result allele2 / allele3 is recorded as HED 2 / 3 The HED value of the combined typing result allele2 / allele4 is recorded as HED 2 / 4 value.

[0097] In step S105, the sum of the HED values ​​of the typing results of the four groups in the exon region corresponding to the HLA allele is calculated to obtain the HED values ​​of the recipient and the donor in the exon region corresponding to the HLA allele. HLA等位基因 value.

[0098] Among them, HED HLA等位基因 =HED 1 / 3 +HED 1 / 4 +HED 2 / 3 +HED 2 / 4 .

[0099] In step S106, according to HED HLA等位基因 Value, quantifying the difference between the recipient and the donor at this HLA allele; where HED HLA等位基因 The larger the value, the greater the difference between the recipient and the donor in this HLA allele; HLA等位基因 The smaller the value, the smaller the difference between the recipient and the donor in this HLA allele.

[0100] The HLA allele difference visualization and quantification method provided by the present disclosure can be used to predict the risk of chronic graft-versus-host disease in hematopoietic stem cell transplantation, or the risk of acute graft-versus-host disease, or the risk of relapse, or the risk of cytomegalovirus infection. Exemplarily, by quantifying the difference between HLA-A alleles and HLA-B alleles, the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation can be predicted.

[0101] Methods for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation:

[0102] In one embodiment, a method for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation is provided. Figure 3 The present invention is a flowchart of a method for predicting the risk of chronic graft-versus-host disease after haploid hematopoietic stem cell transplantation according to an exemplary embodiment. The method comprises the following steps:

[0103] In step S201, based on a method for quantifying HLA allele differences provided in an embodiment of the present disclosure, the HED of the recipient and the donor in the third exon region of the HLA-A allele is calculated. HLA-A等位基因 value.

[0104] In step S202, based on a method for quantifying HLA allele differences provided in an embodiment of the present disclosure, the HED of the recipient and the donor in the third exon region of the HLA-B allele is calculated. HLA-B等位基因 value.

[0105] In step S203, HED is calculated HLA-A等位基因 Value and HED HLA-B等位基因 The sum of the values ​​is used to obtain the HED of the recipient and donor in the third exon region corresponding to the HLA-A allele and HLA-B allele. 受者 / 供者 value.

[0106] Among them, HED HLA-A等位基因 +HED HLA-B等位基因 =HED 受者 / 供者 .

[0107] In step S204, according to HED 受者 / 供者 The HED value predicts the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The larger the value, the lower the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The smaller the value, the higher the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation.

[0108] In one embodiment, the HED 受者 / 供者 The HED value was compared with the preset threshold to predict the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 If HED is greater than or equal to the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be low; 受者 / 供者 If the value is less than the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be high.

[0109] Exemplarily, the preset threshold is 63.36. Figure 4The cumulative incidence curve of cGVHD in the target subjects who received haploid hematopoietic stem cell transplantation and did not receive MSC treatment was predicted to be low-risk and high-risk groups when the preset threshold was selected as 63.36. Among them, the incidence of chronic graft-versus-host disease in recipients in the low-risk group within 18 months after haploid hematopoietic stem cell transplantation was predicted to be 17%; the incidence of chronic graft-versus-host disease in recipients in the high-risk group within 18 months after haploid hematopoietic stem cell transplantation was predicted to be 37%. There was a significant difference in the incidence of cGVHD between the low-risk group and the high-risk group, with a p value of 0.0041.

[0110] The method for predicting the risk of chronic graft-versus-host disease after haploid hematopoietic stem cell transplantation disclosed in the present invention has important guiding significance for the selection of prognostic treatment plans for target subjects.

[0111] Prediction system for the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation:

[0112] In one embodiment, a system for predicting the risk of chronic graft-versus-host disease after haploid hematopoietic stem cell transplantation is provided. The prediction system is based on a method for predicting the risk of chronic graft-versus-host disease after haploid hematopoietic stem cell transplantation provided in an embodiment of the present disclosure. Figure 5 is a flowchart of a prediction system for the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation according to an exemplary embodiment. The prediction system includes HED HLA-A等位基因 Value calculation module, HED HLA-B等位基因 Value calculation module, HED 受者 / 供者 Value calculation module and prediction module.

[0113] HED HLA-A等位基因 Value calculation module, used to calculate the HED of recipient and donor in the third exon region of HLA-A allele HLA*A等位基因 The HED HLA-A等位基因 The value calculation module includes a typing result acquisition module 1, a typing result combination module 1, a decoding module 1, a primary calculation module 1 and a secondary calculation module 1.

[0114] The typing result acquisition module 1 is used to obtain the typing results of the recipient and donor HLA-A alleles.

[0115] The typing result combination module 1 is used to combine the typing results of the recipient and donor HLA-A alleles in pairs and obtain four groups of combined typing results.

[0116] The decoding module 1 is used to decode the typing results of the four groups of combinations of recipient and donor HLA-A alleles into amino acid sequences respectively.

[0117] The first level calculation module is used to calculate the HED value of each combination of typing results in the third exon region of the HLA-A allele according to the amino acid sequences decoded from the typing results of the four combinations of the recipient and donor HLA-A alleles.

[0118] Secondary calculation module 1 is used to calculate the HED of the recipient and the donor in the third exon region of the HLA-A allele according to the HED value of the third exon region of the HLA-A allele of the four groups of combined typing results of the recipient and the donor HLA-A alleles. HLA-A等位基因 value.

[0119] HED HLA-B等位基因 Value calculation module, used to calculate the HED of recipient and donor in the third exon region of HLA-B allele HLA-A等位基因 The HED HLA-B等位基因 The value calculation module includes the HED HLA-B等位基因 The value calculation module includes a typing result acquisition module 2, a typing result combination module 2, a decoding module 2, a primary calculation module 2 and a secondary calculation module 2.

[0120] The typing result acquisition module 2 is used to obtain the typing results of the recipient and donor HLA-B alleles.

[0121] The typing result combination module 2 is used to combine the typing results of the recipient and the donor in pairs and obtain four groups of combined typing results.

[0122] The decoding module 2 is used to decode the typing results of the four groups of combinations of recipient and donor HLA-B alleles into amino acid sequences respectively.

[0123] The first-level calculation module 2 is used to calculate the HED value of each combination of typing results in the third exon region of the HLA-B allele according to the amino acid sequences decoded from the typing results of the four combinations of the recipient and donor HLA-B alleles.

[0124] Secondary calculation module 2 is used to calculate the HED of the recipient and the donor in the third exon region of the HLA-B allele according to the HED value of the typing results of the four groups of combinations of the recipient and the donor HLA-B allele in the third exon region of the HLA-B allele. HLA*B等位基因 value.

[0125] HED 受者 / 供者 Value calculation module for HED HLA-A等位基因 Value and HED HLA-B等位基因 The HED values ​​of the recipient and donor in the third exon region corresponding to the HLA-A allele and HLA-B allele were calculated. 受者 / 供者 value.

[0126] Prediction module, used to 受者 / 供者 The HED value predicts the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The larger the value, the lower the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The smaller the value, the higher the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation. 受者 / 供者 The HED value was compared with the preset threshold to predict the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者和供者 If the HED value is greater than or equal to the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be low; if 受者 / 供者 If the value is less than the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be high.

[0127] Predictors of chronic graft-versus-host disease risk in haploid hematopoietic stem cell transplantation:

[0128] In one embodiment, a device for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation is provided, and the prediction device includes a memory and a processor; wherein the memory is used to store program instructions; the processor is used to call the program instructions, and when the program instructions are executed, the steps of a method for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation provided in an embodiment of the present disclosure are implemented.

[0129] Computer readable storage medium:

[0130] In one embodiment, a computer-readable storage medium is provided, on which a computer program is stored. When the computer program is executed by a processor, the steps of a method for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation provided in an embodiment of the present disclosure are performed.

[0131] The above is a detailed introduction to a method for quantifying HLA allele differences and its uses provided by the present disclosure. This article uses specific examples to illustrate the principles and implementation methods of the present disclosure. The description of the above embodiments is only used to help understand the method and its core ideas of the present disclosure. It should be pointed out that for those skilled in the art, without departing from the principles of the present disclosure, several improvements and modifications can be made to the present disclosure, and these improvements and modifications also fall within the scope of protection of the claims of the present disclosure.

Claims

1. A method for quantifying HLA allele differences, characterized in that: The HLA gene difference quantification method comprises the following steps: Step S101, obtaining the typing results of the HLA alleles of the recipient and the donor; wherein the typing result of the recipient is recorded as allele1 / allele2, and the typing result of the donor is recorded as allele3 / allele4; Step S102, combining the typing results allele1 / allele2 of the recipient and the typing results allele3 / allele4 of the donor in pairs, to obtain four groups of typing results which are recorded as allele1 / allele3, allele1 / allele4, allele2 / allele3, and allele2 / allele4 respectively; Step S103, decoding the typing results of the four groups of combinations allele1 / allele3, allele1 / allele4, allele2 / allele3, and allele2 / allele4 into amino acid sequences respectively; Step S104, according to the amino acid sequences decoded from the typing results of the four groups of combinations, respectively calculating the HED value of the typing results of each group of combinations in the exon region corresponding to the HLA allele; Among them, the HED value of the combined typing result allele1 / allele3 is recorded as HED 1 / 3 value; The HED value of the combined typing result allele1 / allele4 is recorded as HED 1 / 4 value; The HED value of the combined typing result allele2 / allele3 is recorded as HED 2 / 3 value; The HED value of the combined typing result allele2 / allele4 is recorded as HED 2 / 4 value; Step S105, calculate the sum of the HED values ​​of the typing results of the four groups of combinations in the exon region corresponding to the allele, and obtain the HED values ​​of the recipient and the donor in the exon region corresponding to the HLA allele. HLA等位基因 value; HOT HLA等位基因 =HOT 1 / 3 +HED 1 / 4 +HED 2 / 3 +HED 2 / 4 Step S106: According to the HED HLA等位基因 Value, quantifying the difference between the recipient and the donor at this HLA allele; where HED HLA 等位基因 The larger the value, the greater the difference between the recipient and the donor in this HLA allele; HLA等位基因 The smaller the value, the smaller the difference between the recipient and the donor in this HLA allele.

2. The method for quantifying HLA allele differences according to claim 1, characterized in that: In step S104, the calculation formula of the HED value is: HED=ΣD ij =Σ[α(c i -c j ) 2 +β(p i -p j ) 2 +γ(v i -v j ) 2 ] 1 / 2 Among them, α, β, and γ represent inverse mean weight factors; i and j represent two amino acids at the same position in the recipient and donor in this HLA allele, respectively; c represents the amino acid composition; p represents the polarity of amino acid; v represents the volume of amino acid molecule.

3. The method for quantifying HLA allele differences according to claim 2, characterized in that: The calculation formulas for α, β, and γ are as follows: Where n represents the number of amino acid species in the encoded amino acid sequence; |c g -c h | represents the difference between the two amino acid compositions after n amino acids are combined in pairs; |p g -p h | represents the difference in polarity between two amino acids after n amino acids are combined in pairs; |v g -v h | represents the difference in molecular volume between two amino acids after n amino acids are combined in pairs.

4. The method for quantifying HLA allele differences according to claim 1, characterized in that: The HLA allele is selected from at least one of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1.

5. Use of the HLA allele difference quantification method as described in any one of claims 1 to 4 in predicting the risk of chronic graft-versus-host disease, or the risk of acute graft-versus-host disease, or the risk of relapse, or the risk of cytomegalovirus infection in hematopoietic stem cell transplantation.

6. A method for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation, characterized in that: The prediction method comprises the following steps: Step S201: Calculate the HED of the recipient and the donor in the third exon region of the HLA-A allele based on the HLA allele difference quantification method according to any one of claims 1 to 4. HLA-A等位基因 value; Step S202: Calculate the HED of the recipient and the donor in the third exon region of the HLA-B allele based on the HLA allele difference quantification method according to any one of claims 1 to 4. HLA-B等位基因 value; Step S203: According to HED HLA*A等位基因 Value and HED HLA-B等位基因 The HED values ​​of the recipient and donor in the third exon region corresponding to the HLA-A allele and HLA-B allele were calculated. 受者 / 供者 value; HOT HLA-A等位基因 +HED HLA-B等位基因 =HOT 受者 / 供者 Step S204: According to HED 受者 / 供者 The HED value predicts the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The larger the value, the lower the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. 受者 / 供者 The smaller the value, the higher the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation.

7. The prediction method according to claim 6, characterized in that: In step S204, HED 受者 / 供者 The value was compared with the preset threshold to predict the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation. If HED 受者 / 供者 If the value is greater than or equal to the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be low; If HED 受者 / 供者 If the value is less than the preset threshold, the risk of chronic graft-versus-host disease in the recipient of haploid hematopoietic stem cell transplantation is predicted to be high.

8. The prediction method according to claim 7, characterized in that: The preset threshold is selected from any number between 60 and 70.

9. A prediction system for the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation, characterized in that: The prediction system is based on the prediction method according to any one of claims 6 to 8; the prediction system comprises: HED HLA*A等位基因 Value calculation module, used to calculate the HED of recipient and donor in the third exon region of HLA-A allele HLA-A等位基因 value; HED HLA-B等位基因 Value calculation module, used to calculate the HED of recipient and donor in the third exon region of HLA-B allele HLA-A等位基因 value; HED 受者 / 供者 Value calculation module for HED HLA-A等位基因 Value and HED HLA-B等位基因 The HED values ​​of the recipient and donor in the third exon region corresponding to the HLA-A allele and HLA-B allele were calculated. 受者 / 供者 value; Prediction module, used to 受者 / 供者 Value, predict the risk of chronic graft-versus-host disease in recipients of haploid hematopoietic stem cell transplantation.

10. The prediction system according to claim 9, characterized in that The HED HLA-A等位基因 The value calculation module includes: Typing result acquisition module 1, used to obtain the typing results of recipient and donor HLA-A alleles; The typing result combination module 1 is used to combine the typing results of the recipient and donor HLA-A alleles in pairs and obtain four groups of combined typing results; Decoding module 1 is used to decode the typing results of the four groups of combinations of recipient and donor HLA-A alleles into amino acid sequences respectively; The first level calculation module is used to calculate the HED value of each combination of typing results in the third exon region of the HLA-A allele according to the amino acid sequences decoded by the typing results of the four combinations of recipient and donor HLA-A alleles; Secondary calculation module 1 is used to calculate the HED of the recipient and the donor in the third exon region of the HLA-A allele according to the HED value of the third exon region of the HLA-A allele of the four groups of combinations of the recipient and the donor HLA-A allele. HLA-A等位基因 value.

11. The prediction system according to claim 9, characterized in that The HED HLA-B等位基因 The value calculation module includes: Typing result acquisition module 2 is used to obtain the typing results of recipient and donor HLA-B alleles; Typing result combination module 2 is used to combine the typing results of recipient and donor HLA-B alleles in pairs and obtain four groups of combined typing results; Decoding module 2 is used to decode the typing results of the four combinations of recipient and donor HLA-B alleles into amino acid sequences respectively; The first-level calculation module 2 is used to calculate the HED value of each combination of typing results in the third exon region of the HLA-B allele according to the amino acid sequences decoded from the typing results of the four combinations of the recipient and donor HLA-B alleles; Secondary calculation module 2 is used to calculate the HED values ​​of the recipient and donor in the third exon region of the HLA-B allele based on the HED values ​​of the typing results of the four groups of combinations in the third exon region of the HLA-B allele HLA-B等位基因 value.

12. A device for predicting the risk of chronic graft-versus-host disease in haploid hematopoietic stem cell transplantation, characterized in that: The prediction device includes a memory and a processor; wherein the memory is used to store program instructions; the processor is used to call the program instructions, and when the program instructions are executed, the steps of the prediction method according to any one of claims 6 to 8 are implemented.

13. A computer-readable storage medium having a computer program stored thereon, characterized in that: The computer program is executed by a processor to perform the steps of the prediction method according to any one of claims 6 to 8.

Images