阅读说明：本技术 一种人类白细胞抗原分型方法及装置 (Human leukocyte antigen typing method and device ) 是由 徐银银 常玉俊 张智 于 2020-07-07 设计创作，主要内容包括：本发明公开了一种人类白细胞抗原分型方法及装置,所述方法包括：基于预构建的人类白细胞抗原错误分型数据库,获得候选错误分型样本,所述人类白细胞抗原错误分型数据库包括基因和基因分型结果；对所述候选错误分型样本的比对结果进行覆盖度深度分析,得到候选组合型别列表信息；对所述候选组合型别列表信息进行组合型别分析,得到候选组合型别。本发明通过构建常见错误分型数据库和参考序列外显子特征数据库,针对候选错误分型样本,设计组合型别分析算法,提供候选组合型别,可以大幅提升样本分型准确性,满足实际应用需求。(The invention discloses a human leukocyte antigen typing method and a device, wherein the method comprises the following steps: obtaining a candidate mistyping sample based on a pre-constructed human leukocyte antigen mistyping database, wherein the human leukocyte antigen mistyping database comprises genes and a genotyping result; performing coverage depth analysis on the comparison result of the candidate error typing samples to obtain candidate combination type list information; and performing combined type analysis on the candidate combined type list information to obtain a candidate combined type. According to the method, a common error typing database and a reference sequence exon characteristic database are constructed, a combined type analysis algorithm is designed aiming at candidate error typing samples, candidate combined types are provided, the sample typing accuracy can be greatly improved, and the actual application requirements are met.)

1. A method of human leukocyte antigen typing, said method comprising:

obtaining a candidate mistyping sample based on a pre-constructed human leukocyte antigen mistyping database, wherein the human leukocyte antigen mistyping database comprises genes and a genotyping result;

performing coverage depth analysis on the comparison result of the candidate error typing samples to obtain candidate combination type list information;

and performing combined type analysis on the candidate combined type list information to obtain a candidate combined type.

2. The method of claim 1, wherein obtaining a candidate mis-typing sample based on a pre-constructed human leukocyte antigen mis-typing database comprises:

obtaining a sample typing result;

screening the genotyping results appearing in the human leukocyte antigen mispyping database from the sample genotyping results, and determining the screening results as candidate mispyping samples.

3. The method of claim 1, wherein the performing a depth-of-coverage analysis on the comparison result of the candidate mis-typing samples to obtain candidate combination type list information comprises:

performing coverage depth analysis on the comparison result of the candidate error typing sample to obtain initial information, wherein the initial information comprises depth information of the sample on each exon, each position, average depth information of the exons, coverage information of the exons and site proportion information of all possible typing samples;

detecting whether the coverage and average depth information of the core exons reach corresponding thresholds or not based on the initial information, and determining a candidate typing set based on the detection result;

and filtering the candidate typing sets, and combining the filtered candidate typing sets to obtain candidate combination type list information.

4. The method of claim 1, further comprising:

carrying out credibility sorting on the candidate combination type to obtain a sorting result;

and determining the target combination type according to the sorting result.

5. The method of claim 3, wherein the filtering the candidate typing set comprises:

calling a reference sequence exon characteristic database to obtain exon characteristics;

and filtering the candidate typing set based on the exon characteristics to obtain a filtered candidate typing set.

6. A human leukocyte antigen typing device, said device comprising:

the system comprises an acquisition unit, a classification unit and a classification unit, wherein the acquisition unit is used for acquiring a candidate error typing sample based on a pre-constructed human leukocyte antigen error typing database, and the human leukocyte antigen error typing database comprises genes and a genotyping result;

the first analysis unit is used for carrying out coverage depth analysis on the comparison result of the candidate error typing samples to obtain candidate combination type list information;

and the second analysis unit is used for carrying out combined type analysis on the candidate combined type list information to obtain a candidate combined type.

7. The apparatus of claim 6, wherein the obtaining unit comprises:

the first obtaining subunit is used for obtaining a sample typing result;

and the first screening subunit is used for screening the genotyping results appearing in the human leukocyte antigen mispyping database from the sample typing results and determining the screening results as candidate mispyping samples.

8. The apparatus of claim 6, wherein the first analysis unit comprises:

a first analysis subunit, configured to perform coverage depth analysis on the comparison result of the candidate incorrect typing sample to obtain initial information, where the initial information includes depth information of each exon, each position, average depth information of exons, coverage information of exons, and site proportion information of the sample in all possible typing;

a detecting subunit, configured to detect whether coverage and average depth information of the core exons reach corresponding thresholds based on the initial information, and determine a candidate typing set based on a detection result;

and the filtering subunit is used for filtering the candidate typing sets and combining the filtered candidate typing sets to obtain candidate combination type list information.

9. The apparatus of claim 6, further comprising:

the sorting unit is used for sorting the credibility of the candidate combination type to obtain a sorting result;

and the determining unit is used for determining the target combination type according to the sorting result.

10. The device according to claim 8, wherein the filtering subunit comprises:

calling a reference sequence exon characteristic database to obtain exon characteristics;

and filtering the candidate typing set based on the exon characteristics to obtain a filtered candidate typing set.

Technical Field

The invention relates to the technical field of information processing, in particular to a human leukocyte antigen typing method and a human leukocyte antigen typing device.

Background

Human leukocyte antigen, hla (human leukocyte antigen), is the major genetic system regulating the human specific immune response and determining individual differences in disease susceptibility, and is closely associated with rejection in allogeneic organ transplantation. The HLA system plays an important role in antigen recognition, antigen presentation, immune response and regulation, destruction of foreign antigen target cells and the like, and is the main material basis for causing immunological rejection. Both class I and class II antigens on the cell surface of the graft are strong graft antigens, and both humoral and cellular immunity are involved in rejection of the graft, and it is critical that HLA matching between recipients be successful, whether allogeneic organ, tissue or cell transplantation.

HLA typing is a highly polymorphic complex composed of a series of closely linked loci that characterize the most abundant genetic system of human polymorphisms. The HLA typing method based on NGS sequencing has the genotyping accuracy which is difficult to reach 99%. From the sample level, each sample contains a plurality of HLA-associated genes, and the sample can be classified accurately only if all the gene analysis results are correct. As a result, currently NGS-based HLA sample typing is less accurate. In practical applications, however, clinicians and related medical tests are more concerned about sample typing accuracy. Therefore, how to improve the typing accuracy of the HLA sample becomes the focus of the current research.

Disclosure of Invention

Aiming at the problems, the invention provides a human leukocyte antigen typing method and a human leukocyte antigen typing device, which achieve the purposes of obtaining a candidate combination type, improving the typing accuracy of a sample and meeting the actual requirements.

In order to achieve the purpose, the invention provides the following technical scheme:

a method of human leukocyte antigen typing, the method comprising:

obtaining a candidate mistyping sample based on a pre-constructed human leukocyte antigen mistyping database, wherein the human leukocyte antigen mistyping database comprises genes and a genotyping result;

performing coverage depth analysis on the comparison result of the candidate error typing samples to obtain candidate combination type list information;

and performing combined type analysis on the candidate combined type list information to obtain a candidate combined type.

Optionally, the obtaining a candidate mis-typing sample based on a pre-constructed human leukocyte antigen mis-typing database comprises:

obtaining a sample typing result;

screening the genotyping results appearing in the human leukocyte antigen mispyping database from the sample genotyping results, and determining the screening results as candidate mispyping samples.

Optionally, the performing coverage depth analysis on the comparison result of the candidate error typing sample to obtain candidate combination type list information includes:

performing coverage depth analysis on the comparison result of the candidate error typing sample to obtain initial information, wherein the initial information comprises depth information of the sample on each exon, each position, average depth information of the exons, coverage information of the exons and site proportion information of all possible typing samples;

detecting whether the coverage and average depth information of the core exons reach corresponding thresholds or not based on the initial information, and determining a candidate typing set based on the detection result;

and filtering the candidate typing sets, and combining the filtered candidate typing sets to obtain candidate combination type list information.

Optionally, the method further comprises:

carrying out credibility sorting on the candidate combination type to obtain a sorting result;

and determining the target combination type according to the sorting result.

Optionally, the filtering the candidate typing set includes:

calling a reference sequence exon characteristic database to obtain exon characteristics;

and filtering the candidate typing set based on the exon characteristics to obtain a filtered candidate typing set.

A human leukocyte antigen typing device, the device comprising:

the system comprises an acquisition unit, a classification unit and a classification unit, wherein the acquisition unit is used for acquiring a candidate error typing sample based on a pre-constructed human leukocyte antigen error typing database, and the human leukocyte antigen error typing database comprises genes and a genotyping result;

the first analysis unit is used for carrying out coverage depth analysis on the comparison result of the candidate error typing samples to obtain candidate combination type list information;

and the second analysis unit is used for carrying out combined type analysis on the candidate combined type list information to obtain a candidate combined type.

Optionally, the obtaining unit includes:

the first obtaining subunit is used for obtaining a sample typing result;

and the first screening subunit is used for screening the genotyping results appearing in the human leukocyte antigen mispyping database from the sample typing results and determining the screening results as candidate mispyping samples.

Optionally, the first analysis unit comprises:

a first analysis subunit, configured to perform coverage depth analysis on the comparison result of the candidate incorrect typing sample to obtain initial information, where the initial information includes depth information of each exon, each position, average depth information of exons, coverage information of exons, and site proportion information of the sample in all possible typing;

a detecting subunit, configured to detect whether coverage and average depth information of the core exons reach corresponding thresholds based on the initial information, and determine a candidate typing set based on a detection result;

and the filtering subunit is used for filtering the candidate typing sets and combining the filtered candidate typing sets to obtain candidate combination type list information.

Optionally, the apparatus further comprises:

the sorting unit is used for sorting the credibility of the candidate combination type to obtain a sorting result;

and the determining unit is used for determining the target combination type according to the sorting result.

Optionally, the filtering subunit specifically includes:

calling a reference sequence exon characteristic database to obtain exon characteristics;

and filtering the candidate typing set based on the exon characteristics to obtain a filtered candidate typing set.

Compared with the prior art, the invention provides a method and a device for typing human leukocyte antigens, wherein the method comprises the following steps: obtaining a candidate mistyping sample based on a pre-constructed human leukocyte antigen mistyping database, wherein the human leukocyte antigen mistyping database comprises genes and a genotyping result; performing coverage depth analysis on the comparison result of the candidate error typing samples to obtain candidate combination type list information; and performing combined type analysis on the candidate combined type list information to obtain a candidate combined type. According to the method, a common error typing database and a reference sequence exon characteristic database are constructed, a combined type analysis algorithm is designed aiming at candidate error typing samples, candidate combined types are provided, the sample typing accuracy can be greatly improved, and the actual application requirements are met.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 is a schematic flow chart of a method for typing human leukocyte antigens according to an embodiment of the present invention;

FIG. 2 is a schematic structural diagram of a human leukocyte antigen typing device according to an embodiment of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.