CN112397174A - Chronic disease medication guidance device and method - Google Patents

Chronic disease medication guidance device and method Download PDF

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CN112397174A
CN112397174A CN202011196713.1A CN202011196713A CN112397174A CN 112397174 A CN112397174 A CN 112397174A CN 202011196713 A CN202011196713 A CN 202011196713A CN 112397174 A CN112397174 A CN 112397174A
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马旭
陈翠霞
曹宗富
王小龙
李乾
喻浴飞
蔡瑞琨
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Abstract

The application relates to a chronic disease medication guidance device and a method. The method comprises the following steps: acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed; carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene locus, mutant gene locus information, a first base type before mutation and a second base type after mutation; generating a target base type according to the mutated second base type and the mutated gene site information; acquiring a preset genotype functional library and a preset drug genotype functional library; inquiring a preset genotype function library in an association manner according to the mutant gene locus, the first base type before mutation and the target base type to obtain the target drug metabolism function of the target haplotype; and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target drug administration scheme. By adopting the method, the accuracy and the efficiency of the medicine for the chronic disease of the doctor can be improved.

Description

Chronic disease medication guidance device and method
Technical Field
The application relates to the technical field of biological computing, in particular to a chronic disease medication guidance method, a device, computer equipment and a storage medium.
Background
Pharmacogenomics studies the effect of genetic polymorphisms (genetically referred to as mutant, homozygous, heterozygous) on drug metabolism (e.g., the CYP family) and drug efficacy. Pharmacogenomics is a research hotspot at home and abroad in recent years. Many genes have been found to interact with drugs and diseases, and information related to drug and disease interaction, such as chronic genetic diseases, can be determined by mutating the genes.
At present, a relatively comprehensive database does not exist in China, and meanwhile, the medicine taking guidance aiming at the chronic genetic disease caused by certain genetic variation is provided, however, doctors usually need to manually inquire matched medicine taking schemes according to specific conditions of patients to be treated when treating the chronic genetic disease, and the mode is time-consuming and labor-consuming, so that the medicine taking of the doctors is not timely.
Disclosure of Invention
Based on this, it is necessary to provide a chronic disease medication guidance method, apparatus, computer device and storage medium for improving the accuracy and efficiency of chronic disease medication by a doctor by establishing a comprehensive genotype function library and a drug genotype function library, and performing an associated query on a target medication guidance corresponding to a mutant gene without manual operation by the doctor.
A medication guidance device, the device comprising:
the patient data acquisition module is used for acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed;
the patient data analysis module is used for carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site, mutant gene site information, a first base type before mutation and a second base type after mutation corresponding to a patient to be analyzed;
the base type determining module is used for generating a target base type according to the mutated second base type and the mutated gene locus information;
the function library acquisition module is used for acquiring a preset genotype function library and a preset drug genotype function library;
the drug metabolism function matching module is used for inquiring a preset genotype function library according to the association of the mutation gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, and the target haplotype is the haplotype matched with the mutation gene locus, the first base type before mutation and the target base type and the genotype formed by the haplotype;
and the medication scheme matching module is used for inquiring a preset drug genotype function library according to the target drug metabolic function association corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
In one embodiment, the medication guidance device further comprises: the candidate clinical annotation information acquisition module is used for screening out clinical annotation information corresponding to gene mutation sites related to various chronic diseases based on a drug genome research public database and a related literature database of the chronic diseases, wherein the clinical annotation information comprises a drug metabolism function; the preset genotype functional library establishing module is used for establishing a preset genotype functional library according to clinical annotation information corresponding to gene mutation sites related to various chronic diseases, wherein the preset genotype functional library comprises a chronic disease haplotype corresponding to the chronic diseases, a drug metabolism function corresponding to the chronic disease haplotype, a mutation gene site corresponding to the chronic disease haplotype, a base type before mutation and a base type after mutation.
In one embodiment, the medication guidance device further comprises: the candidate medication scheme acquisition module is used for screening out medication schemes corresponding to gene mutation sites related to various chronic diseases based on public personalized medication related drugs, metabolic functions and gene databases, wherein the medication schemes comprise drug dosage and drug interaction information; the preset drug genotype functional library establishing module is used for establishing a preset drug genotype functional library according to the medication schemes corresponding to the gene mutation sites related to various chronic diseases and the clinical annotation information corresponding to the gene mutation sites related to various chronic diseases, and the preset drug genotype functional library comprises medication information corresponding to the chronic diseases, medication schemes, haplotypes corresponding to the chronic diseases and drug metabolism functional types.
In one embodiment, the drug metabolism function matching module further comprises: the candidate haplotype determining unit is used for inquiring a preset genotype function library according to the association of the mutant gene locus, the first base type before mutation and the target base type to determine a candidate haplotype set; the target haplotype determining unit is used for calculating the similarity between each candidate haplotype in the candidate haplotype set and the corresponding mutant gene locus of the patient to be analyzed and determining the target haplotype according to the similarity; and the target drug metabolism function determining unit is used for acquiring the target drug metabolism function corresponding to the target haplotype from the preset genotype function library.
In one embodiment, the target haplotype determining unit is further configured to obtain similarities corresponding to the candidate haplotypes, perform descending order according to the similarities corresponding to the candidate haplotypes, obtain a first candidate haplotype with the largest similarity, obtain a preset haplotype score table, obtain a second candidate haplotype with the largest score value according to the candidate haplotypes and the preset haplotype score table, and determine the target haplotype according to the first candidate haplotype and the second candidate haplotype.
In one embodiment, the medication scheme matching module is further configured to obtain a candidate haplotype and a candidate drug metabolic function corresponding to each candidate medication scheme, search for a matched target candidate haplotype and a target candidate drug metabolic function according to the target haplotype and the target drug metabolic function, and determine the medication scheme corresponding to the target candidate haplotype and the target candidate drug metabolic function as the target medication scheme.
A method for guiding medication for chronic diseases, the method comprising:
acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed;
carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to a patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation;
generating a target base type according to the mutated second base type and the mutated gene site information;
acquiring a preset genotype functional library and a preset drug genotype functional library;
inquiring a preset genotype function library in a correlation manner according to the mutant gene locus, the first base type before mutation and the target base type to obtain a target drug metabolic function corresponding to a target haplotype, wherein the target haplotype is the haplotype matched with the mutant gene locus, the first base type before mutation and the target base type and the genotype formed by the haplotype;
and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
A computer device comprising a memory, a processor and a computer program stored on the memory and executable on the processor, the processor implementing the following steps when executing the computer program:
acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed;
carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to a patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation;
generating a target base type according to the mutated second base type and the mutated gene site information;
acquiring a preset genotype functional library and a preset drug genotype functional library;
inquiring a preset genotype function library in a correlation manner according to the mutant gene locus, the first base type before mutation and the target base type to obtain a target drug metabolic function corresponding to a target haplotype, wherein the target haplotype is the haplotype matched with the mutant gene locus, the first base type before mutation and the target base type and the genotype formed by the haplotype;
and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
A computer-readable storage medium, on which a computer program is stored which, when executed by a processor, carries out the steps of:
acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed;
carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to a patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation;
generating a target base type according to the mutated second base type and the mutated gene site information;
acquiring a preset genotype functional library and a preset drug genotype functional library;
inquiring a preset genotype function library in a correlation manner according to the mutant gene locus, the first base type before mutation and the target base type to obtain a target drug metabolic function corresponding to a target haplotype, wherein the target haplotype is the haplotype matched with the mutant gene locus, the first base type before mutation and the target base type and the genotype formed by the haplotype;
and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
The chronic disease medication guidance method, the device, the computer equipment and the storage medium obtain high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed; carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to a patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation; generating a target base type according to the mutated second base type and the mutated gene site information; acquiring a preset genotype functional library and a preset drug genotype functional library; inquiring a preset genotype function library in a correlation manner according to the mutant gene locus, the first base type before mutation and the target base type to obtain a target drug metabolic function corresponding to a target haplotype, wherein the target haplotype is the haplotype matched with the mutant gene locus, the first base type before mutation and the target base type and the genotype formed by the haplotype; and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
The method realizes automatic judgment of the allele (such as allel 1/allel 2) corresponding to the allele and the related function of drug metabolism in a preset genotype functional library, and then matches and recommends a medication guidance scheme of the chronic disease caused by genome mutation in the preset drug genotype functional library according to the obtained information, wherein the medication guidance scheme can be used for doctors to take medication.
Drawings
FIG. 1 is a diagram of an exemplary application environment for a chronic disease medication guidance method;
FIG. 2 is a block diagram showing the construction of a chronic disease medication guidance apparatus according to an embodiment;
FIG. 3 is a schematic flow chart diagram of a chronic disease medication guidance method in one embodiment;
FIG. 4 is a diagram illustrating an internal structure of a computer device according to an embodiment;
FIG. 5 is a diagram illustrating an internal structure of a computer device according to an embodiment.
Detailed Description
In order to make the objects, technical solutions and advantages of the present application more apparent, the present application is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present application and are not intended to limit the present application.
The chronic disease medication guidance method provided by the application can be applied to the application environment shown in figure 1. Wherein the terminal 102 communicates with the server 104 via a network. The terminal 102 may be, but not limited to, various personal computers, notebook computers, smart phones, tablet computers, and portable wearable devices, and the server 104 may be implemented by an independent server or a server cluster formed by a plurality of servers.
Specifically, the terminal 102 acquires high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed, and sends the high-throughput sequencing data to the server 104, and the server 104 performs mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site, mutant gene site information, a first base type before mutation and a second base type after mutation corresponding to the patient to be analyzed; generating a target base type according to the mutated second base type and the mutated gene site information; acquiring a preset genotype functional library and a preset drug genotype functional library; inquiring a preset genotype function library in a correlation manner according to the mutation gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, wherein the target haplotype is a genotype matched with the mutation gene locus, the first base type before mutation and the target base type; and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed. Further, the server 104 may send the target medication schedule corresponding to the patient to be analyzed to the terminal 102 for the terminal 102 user to view.
In one embodiment, as shown in fig. 2, there is provided a chronic disease medication guidance apparatus 200 comprising a patient data acquisition module 202, a patient data analysis module 204, a base type determination module 206, a function library acquisition module 208, a drug metabolism function matching module 210, and a medication regimen matching module 212, wherein:
a patient data obtaining module 202, configured to obtain high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed.
And the patient data analysis module 204 is configured to perform mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site, mutant gene site information, a first base type before mutation, and a second base type after mutation corresponding to the patient to be analyzed.
Specifically, the vcf file of the high-throughput sequencing data of the gene sequence to be detected of the patient to be analyzed can be used for extracting the gene sequence to be detected of the patient to be analyzed, the mutant gene site corresponding to the patient to be analyzed, the gene point information of the mutant gene site, the first base type before mutation and the second base type after mutation. Wherein, the first base type before mutation can be called the base type of normal population (Reference, i.e. before mutation), and the second base type after mutation can be called the base type after mutation (ALT). Wherein, the mutant gene site refers to the position of the mutant gene, the mutant gene site can be understood as the mark of the position of the mutant gene, the first base type before the mutation refers to the base type before the mutant gene is mutated, namely the base type corresponding to the normal population, and the second base type after the mutation refers to the base type after the mutant gene is mutated.
The vcf format of the high-throughput sequencing data result file of the high-throughput sequencing data of the gene sequence to be analyzed of the patient is a universal format, and a mutant gene site (rsid, such as rs12769205 and the like) corresponding to the patient to be analyzed of the file, a first base type before mutation, such as a normal population base type (Reference, i.e., before mutation), a second base type after mutation, such as all base types after mutation (ALT), and mutant gene site information (GT, such as 0/1, 1/2, 1/3 and the like) corresponding to the mutant gene site corresponding to the patient to be analyzed are extracted.
And a base type determining module 206 for generating a target base type according to the mutated second base type and the mutated gene locus information.
Specifically, the target base type can be generated according to the mutated second base type and the mutated gene site information, that is, the target base type can be obtained according to the conditions of the normal population base type (ALT) and the mutated gene site information (GT).
Specifically, the target base type (SNP) is determined according to the ALT and GT conditions, and the process is as follows: a normal population base type (Reference, i.e., no mutation) if GT is "0/0" (no mutation site) and "/" (missing site); if GT is 0/1, SNP is ALT; if GT is 1/1 (or/2 or/3 or/4), then the SNP takes the corresponding 1 st, 2 nd, 3 th or 4 th variation type of ALT set, and then the target base type (SNP) is obtained.
Wherein, if the genotype is "0/1", it means that the locus is a "wild heterozygous" mutation, there are two genotypes of wild type and mutant type, part of the bases are the same as the wild type bases, and part of the bases are the same as the mutant bases. The "1/1" value indicates that the site is a "homozygous for variation" mutation, and that the overall mutation pattern is identical to the mutant base pattern. "1/2" (or "1/3" etc.) indicates that the site is a "mutation heterozygous for a mutation, and has two genotypes of mutant 1 and mutant 2 (or mutant 3), part of which is identical to the base type of mutant 1, and part of which is identical to the base type of mutant 2 (or mutant 3).
A function library obtaining module 208, configured to obtain a preset genotype function library and a preset drug genotype function library.
Specifically, associated field information is prepared in a preset genotype function library obtained from the 216 function module and a drug genotype function library obtained from the 218 function module, the information includes related site annotation information for genetic detection of the slow drug genomics, such as drug dose, drug interaction and site clinical annotation information prompted by drugs, genes and gene related sites, for example, warfarin (warfarin) related sites and other information, and is arranged into a standard format, such as clinical medication guidance, population frequency, physical location and other information of drug genome related sites on the CYP2D6 gene, which is the most important standard considering east asian population frequency. On the basis, the information standard of a chronic disease-drug-gene-mutation site-drug metabolism function database is provided, the fields, the information types and the information sources which are required to be contained in the database are preliminarily drawn up, and two pharmacogenomics reference databases are constructed according to the information standard of the chronic disease-drug-gene-mutation site-drug metabolism function database: presetting a genotype function library and a preset drug genotype function library, and respectively acquiring corresponding information from the two preset databases.
In one embodiment, the chronic medication guidance device 200 further comprises: a candidate clinical annotation information obtaining module 214, configured to screen out clinical annotation information corresponding to gene mutation sites related to various chronic diseases based on a drug genome research public database and a related literature database of the chronic diseases, where the clinical annotation information includes drug metabolism functions, and a preset genotype function library establishing module 216, configured to establish a preset genotype function library according to clinical annotation information corresponding to gene mutation sites related to various chronic diseases, where the preset genotype function library includes a chronic disease haplotype corresponding to the chronic diseases and a drug metabolism function corresponding to the chronic disease haplotype, and a mutation gene site corresponding to the chronic disease haplotype, a base type before mutation, and a base type after mutation.
Specifically, a public database and a related literature database are researched from the medicine genome of the chronic disease, wherein the public database and the related literature database comprise clinical annotation information corresponding to all gene mutation sites involved in the chronic disease, and the clinical annotation information comprises medicine metabolism functions corresponding to various chronic diseases.
Further, screening public databases and relevant literature databases of pharmacogenomic research based on chronic diseases results in annotation information of clinical functions of known chronic diseases and gene mutation sites related to the chronic diseases. And establishing a mutant allele identification and function annotation database of the gene according to the known information of disease names, gene names, mutant gene loci, variation loci on chromosomes, wild alleles, variant alleles, metabolic function classification and the like. Wherein the pre-established genotype functional library comprises: genes (Gene), haplotypes (the genotype of the allele is two haplotypes in pairs 1/2), the drug metabolism function (metabolizer _ function) of the haplotypes, all the variant site ids (rsid, e.g., rs 127696205) contained by each haplotype, the normal population base type (Reference, i.e., pre-mutation), all the post-mutation base types (SNPs), i.e., the predetermined genotype functional library includes the chronic disease haplotype corresponding to the chronic disease, and the drug metabolism function corresponding to the chronic disease haplotype, and the mutant Gene site, the base type before mutation, and the base type after mutation corresponding to the chronic disease haplotype.
In one embodiment, the chronic medication guidance device 200 further comprises: a candidate medication scheme obtaining module 218, configured to screen out medication schemes corresponding to gene mutation sites related to various chronic diseases based on public personalized medication-related drugs, metabolic functions, and a gene database, where the medication schemes include drug dose and drug interaction information, and the preset drug genotype function library establishing module 220 is configured to establish a preset drug genotype function library according to medication schemes corresponding to gene mutation sites related to various chronic diseases and clinical annotation information corresponding to gene mutation sites related to various chronic diseases, where the preset drug genotype function library includes medication information corresponding to chronic diseases, medication schemes, haplotypes corresponding to chronic diseases, and drug metabolic function types.
Specifically, based on public personalized medicine related medicines, metabolic functions and gene databases, the medicine dose and medicine interaction information prompted by the pathogenic mutant genes are screened out. Wherein, the information based on screening is as follows: and constructing a personalized medicine related medicine functional gene database by using information such as gene names, allele variation related metabolic functions, function classification, medicine guide recommendation and description and the like.
For example, the public database is PharmGKB, FDAbiomarker, MedGen database, the literature database is PubMed database, and the literature database comprises gene-related mutant gene sites, suggested drug dose, drug interaction, site clinical annotation related information, for example, a certain drug exerts the anticoagulant and antithrombotic effect of the drug in the treatment of cardiovascular and cerebrovascular diseases through enzymes acting on related genes, and other genes strictly regulate the activities of the enzymes. Related mutant gene sites can be rapidly screened out according to diseases and medicines. The established mutant gene leads to identification and function annotation database of chronic disease related allele and a drug function gene database related to personalized medication, namely a preset drug genotype function database.
The preset drug genotype function library comprises 27000 genes, 3500 genotypes and 3900 drug data, wherein 579 haplotypes/genotypes related to chronic diseases caused by gene mutation are associated with the drug use recommendation of 60 drugs, and public database data and literature database data which are latest in the research direction of chronic diseases caused by gene mutation are included.
And the drug metabolism function matching module 210 is configured to query a preset genotype function library according to the association among the mutant gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, where the target haplotype is a haplotype matched with the mutant gene locus, the first base type before mutation and the target base type, and a genotype composed of the haplotype.
Specifically, after obtaining a mutant Gene locus, a first base type before mutation and a target base type, all mutant Gene loci (rsid) of the same field corresponding to a preset genotype functional library and the first base type before mutation, such as a normal population base type (Reference) and a target base type (SNP), are related and inquired, and as a result, all possible haplotypes (allels) in a certain Gene (Gene) in a Gene sequence to be detected of the patient to be analyzed are obtained. All mutation sites contained in each allele in the genotype functional library are related by a mutation gene site (rsid), that is, the possible haplotype allee contains the allele mutation site in the genotype functional library, and is probably the allele, which is called as the suspected allele, and the suspected alleles are candidate haplotypes.
Further, by further filtering all possible haplotype allels through the Jaccard distance algorithm and the mutation site contribution degree scoring table, the haplotype allel which is most similar to the sample variant genotype (i.e. the Jaccard distance is the smallest) and the mutation site of the sample has the largest contribution degree to all possible haplotypes is reserved, so that the haplotypes most likely to occur (such as allel 1, allel 2) and the genotypes of the haplotype component alleles (such as allel 1/allel 2) can be automatically recommended, and the respective drug metabolism functions (such as allel 1_ function and allel 2_ function) of the haplotypes can be further obtained.
For example, A represents the set of all mutant gene sites of the gene sequence to be tested of the patient to be analyzed, B represents the set of all "suspected" haplotype allels in the "predetermined genotype functional library", which includes n subsets Bi(i＝1，2，3，…n)，BiRepresents the mutant site collection related to the ith "suspected" allele in the B collection. Introducing Jaccard distance algorithm, and calculating each subset B of the A set and the B setiJaccard distance of (a):
Figure BDA0002754229570000111
wherein
Figure BDA0002754229570000112
| A | represents the number of mutation sites in the mutation site set A in the gene sequence to be analyzed of the patient, | BiI representsThe i th suspected allele related mutation site set B in the preset genotype functional libraryiThe number of the convex points, | A ≦ BiI represents a mutation site set A in a sample vcf file and a mutation site set B related to the ith ' suspected ' allele inquired in a ' genotype function libraryiThe number of abrupt change points in the intersection, | A ≧ U ^ BiI represents a mutation site set A in a sample vcf file and a mutation site set B related to the ith ' suspected ' allele inquired in a ' genotype function libraryiThe number of mutation sites in the union. Smaller Jaccard distances indicate more similarity between the two sets, i.e., more similarity between the mutation in the sample and the ith "suspected" allele mutation queried in the "genotype library".
Thus, by adopting a statistical jaccard distance algorithm, calculating a set A of all mutation sites (rsid) in a gene sequence to be tested of a patient to be analyzed and each subset B of all alleles (set B) inquired in a' preset genotype functional libraryi(the set of all mutation sites rsid involved in the ith allele), sorting the jaccard distances between the two sets in ascending order, wherein the smallest distance represents the largest similarity between the two sets, so that the target haplotype can be obtained. Wherein the target haplotype comprises the target haplotype and a genotype consisting of the target haplotype.
And finally, after the target haplotype is screened out, searching and matching the preset genotype function library to obtain the target drug function corresponding to the target haplotype.
In one embodiment, the drug metabolism function matching module 210 further includes: the haplotype analysis device comprises a candidate haplotype determining unit 210a for querying a preset haplotype function library in association with a mutant gene locus, a first base type before mutation and a target base type to determine a candidate haplotype set, a target haplotype determining unit 210b for calculating the similarity between each candidate haplotype in the candidate haplotype set and the mutant gene locus corresponding to a patient to be analyzed and determining a target haplotype according to the similarity, and a target drug metabolism function determining unit 210c for obtaining a target drug metabolism function corresponding to the target haplotype from the preset haplotype function library.
Specifically, after obtaining a mutant Gene locus, a first base type before mutation and a target base type, all mutant Gene loci (rsid) of the same field corresponding to a preset genotype functional library and the first base type before mutation, such as a normal population base type (Reference) and a target base type (SNP), are related and inquired, and as a result, all possible haplotypes (allels) in a certain Gene (Gene) in a Gene sequence to be detected of the patient to be analyzed are obtained. All mutation sites contained in each allele in the genotype functional library are related by a mutation gene site (rsid), that is, the possible haplotype allele contains the allele mutation site in the genotype functional library, and the allele is probably the allele, which is called the suspected allele.
Further, by further filtering all possible haplotype allels through the Jaccard distance algorithm and the mutation site contribution degree scoring table, the haplotype allel which is most similar to the sample variant genotype (i.e. the Jaccard distance is the smallest) and the mutation site of the sample has the largest contribution degree to all possible haplotypes is reserved, so that the haplotypes most likely to occur (such as allel 1, allel 2) and the genotypes of the haplotype component alleles (such as allel 1/allel 2) can be automatically recommended, and the respective drug metabolism functions (such as allel 1_ function and allel 2_ function) of the haplotypes can be further obtained.
For example, A represents the set of all mutant gene sites of the gene sequence to be tested of the patient to be analyzed, B represents the set of all "suspected" haplotype allels in the "predetermined genotype functional library", which includes n subsets Bi(i＝1，2，3，…n)，BiRepresents the mutant site collection related to the ith "suspected" allele in the B collection. Introducing Jaccard distance algorithm, and calculating each subset B of the A set and the B setiJaccard distance of (a):
Figure BDA0002754229570000131
wherein
Figure BDA0002754229570000132
| A | represents the number of mutation sites in the mutation site set A in the gene sequence to be analyzed of the patient, | BiI represents the mutant site set B related to the ith ' suspected ' allele in the ' preset genotype functional libraryiThe number of the convex points, | A ≦ BiI represents a mutation site set A in a sample vcf file and a mutation site set B related to the ith ' suspected ' allele inquired in a ' genotype function libraryiThe number of abrupt change points in the intersection, | A ≧ U ^ BiI represents a mutation site set A in a sample vcf file and a mutation site set B related to the ith ' suspected ' allele inquired in a ' genotype function libraryiThe number of mutation sites in the union. Smaller Jaccard distances indicate more similarity between the two sets, i.e., more similarity between the mutation in the sample and the ith "suspected" allele mutation queried in the "genotype library".
Thus, by adopting a statistical jaccard distance algorithm, calculating a set A of all mutation sites (rsid) in a gene sequence to be tested of a patient to be analyzed and each subset B of all alleles (set B) inquired in a' preset genotype functional libraryi(the set of all mutation sites rsid involved in the ith allele), sorting the jaccard distances between the two sets in ascending order, wherein the smallest distance represents the largest similarity between the two sets, so that the target haplotype can be obtained.
In one embodiment, the target haplotype determining unit 210b is further configured to obtain similarities corresponding to the candidate haplotypes, perform descending order according to the similarities corresponding to the candidate haplotypes, obtain a first candidate haplotype with the smallest similarity, obtain a preset haplotype score table, obtain a second candidate haplotype with the largest score value according to the candidate haplotypes and the preset haplotype score table, and determine the target haplotype according to the first candidate haplotype and the second candidate haplotype.
Specifically, after obtaining the similarity corresponding to each candidate haplotype, constructing a single of the mutant site of the sets A and B to a certain gene of the sampleThe contribution degree scoring table of the interpretation and genotype construction of body type allele: the contribution degree of the mutation sites refers to a mutation site A set, and all subsets B of a B set are related and inquired based on the inquiry conditions that rsid is equaliThe mutation site set and the haplotype constructed by the same are based on the related definitions of medical genetics about genotypes and haplotypes, aiming at the following four statistical scoring indexes: intersection of the 1-A set and the Bi set, genotype of the 2-A set, base type after mutation of the 3-A set and base type after mutation of the Bi set are compared, intersection of all subsets of the 4-B set is calculated pairwise, and a rating table is constructed as follows:
Figure BDA0002754229570000141
Figure BDA0002754229570000151
wherein GT-0/1 indicates that one of the alleles is mutation-free and the other allele is mutation-heterozygous for the wild type; GT 1/1 indicates that both positions of the allele are mutated and identical, i.e. homozygous variant; GT 1/2(/2/3/4) indicates that both positions of the allele are mutated and not identical, i.e. heterozygous variants.
Wherein, in order to make the set A correlate the total interpretation scores (X) of all the 'suspected' allels queried in the set B1，X2，X3…, Xn), it is necessary to perform extreme value normalization on these scores, map all data between 0 and 1,
Figure BDA0002754229570000152
Xscalethe set is the normalized calibrated contribution score value. The set is sorted in reverse order, and the largest score is the most contributing, i.e., the mutation involved in the haplotype allele is most likely to occur.
To this end, the allel that most closely resembles the sample mutant genotype calculated from the jaccard distance (the jaccard distance is the smallest) is selected, and the haplotype allel that most closely matches the sample mutant genotype (the contribution score is the largest) is selected according to the scoring table.
If 1 allel meeting the two conditions is considered to be allel 1, judging that the mutant genotype of the sample is reference/allel 1, and the corresponding drug metabolism function is reference _ function and allel 1_ function;
if 2, the number is allole 1 and allole 2, the genotype of the mutation of the sample is judged to be allole 1/allole 2, and the corresponding drug metabolism function is allole 1_ function and allole 2_ function;
if there are 3, the genotype is judged to be allole 1, allole 2 and allole 3.. the genotype of the mutant of the sample is reference/allole 1, reference/allole 2 and reference/allole 3.. the corresponding metabolic function of the drug is allole 1_ function, allole 2_ function and allole 3_ function;
thus, the two most likely haplotypes (e.g., allel 1, allel 2) and the genotypes of the haplotype-constituting alleles (e.g., allel 1/allel 2) are automatically proposed, and the respective drug metabolism functions (e.g., allel 1_ function and allel 2_ function) of these haplotypes are derived.
And the medication scheme matching module 212 is configured to query a preset drug genotype function library according to the target drug metabolic function association corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
In one embodiment, the medication scheme matching module 212 is further configured to obtain a candidate haplotype and a candidate drug metabolic function corresponding to each candidate medication scheme, search for a matched target candidate haplotype and a target candidate drug metabolic function according to the target haplotype and the target drug metabolic function, and determine the medication scheme corresponding to the target candidate haplotype and the target candidate drug metabolic function as the target medication scheme.
Specifically, after a target drug metabolism function corresponding to the target haplotype is obtained, the same corresponding fields in the drug genotype function library are related and inquired, so that a corresponding target medication scheme is obtained. For example, the target haplotype is the drug metabolism function (such as the allele1_ function and the allele2_ function) involved in the allele1/allele2, the same corresponding fields in the "drug genotype library" are queried in association with the drug metabolism function (allele2_ function) of the allele1, the drug metabolism function (allele1_ function) of the allele2, and the medication guidance plan (such as the drug name (Chemical _ CN), the drug metabolism function type (metabolism _ type), the treatment recommendation (Therapeutic _ details), the evidence intensity Classification (Level _ of _ evidence), the medication Classification recommendation (Classification _ of _ recommendation), the chinese medication Classification recommendation (recommendation _ CN)) and the like of the chronic disease caused by the genomic mutation are precisely matched to realize the personalized medication guidance information, thereby realizing the medication guidance plan of the chronic disease caused by the genomic mutation. The medication guidance scheme is not a reference scheme for obtaining a diagnosis result or a health condition but a medication guidance for a doctor, and is not necessarily directly related to the diagnosis or the health condition of a disease.
In the chronic disease medication guiding device, the device acquires high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed; carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to a patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation; generating a target base type according to the mutated second base type and the mutated gene site information; acquiring a preset genotype functional library and a preset drug genotype functional library; inquiring a preset genotype function library in a correlation manner according to the mutation gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, wherein the target haplotype is a genotype matched with the mutation gene locus, the first base type before mutation and the target base type; and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
The method realizes automatic judgment of the allele (such as allel 1/allel 2) corresponding to the allele and the related function of drug metabolism in a preset genotype functional library, and then matches and recommends a medication guidance scheme of the chronic disease caused by genome mutation in the preset drug genotype functional library according to the obtained information, wherein the medication guidance scheme can be used for medication reference of doctors, and the target medication guidance corresponding to the mutant gene is related and inquired by establishing a comprehensive genotype functional library and a drug genotype functional library without manual operation of the doctors, so that the accuracy and the medication efficiency of the doctors for the chronic disease are improved.
In a specific application scenario, a chronic disease medication guidance method applied to a chronic disease medication guidance device is provided, and specifically includes the following steps:
1. clinical drug genome research public database and relevant literature database based on chronic diseases screens out clinical annotation information of mutation sites related to various chronic diseases, and establishes a mutant allele identification and function annotation database of genes.
2. Based on public personalized medicine related drugs, metabolic functions and gene databases, drug dose and drug interaction information prompted by the pathogenic mutant genes are screened out, and personalized medicine related drug function gene databases are constructed.
3. Genomic mutations in vcf files for high throughput sequencing of a sample and genotype status of the mutation site.
4. And automatically matching out the allele corresponding to the gene and the related function of drug metabolism in the allele identification and function database of the gene through statistics of the jaccart distance, the contribution degree scoring table of the mutation sites and normalization calibration.
5. Then, the obtained information is matched in a medicine functional gene database to recommend a medication guide scheme of chronic diseases caused by genome mutation. The system comprises the method provided by the technical scheme.
With the development of high-throughput sequencing technology, a large amount of data generated by new genetic detection technology is to be further interpreted and guided to clinical diagnosis and treatment. The embodiment can realize genome variation obtained from sequencing, find the corresponding gene and the haplotype of the variant gene, then match the corresponding enzyme metabolic function type according to the haplotype function, and finally obtain the corresponding medication name and the medication dosage recommendation guidance.
In the personalized medication method for chronic diseases caused by genome mutation provided by this embodiment, because the mutation allele identification of genes, the function annotation database and the drug function gene database related to personalized medication are established based on massive gene mutation, metabolic function annotation and drug function gene data in public databases and literature databases, it can be ensured that the database can cover all currently known chronic diseases and corresponding gene mutation data and function information, and further the matching accuracy is ensured.
Specifically, after the VCF file is obtained from the high-throughput data file of the patient sample, the information of the mutation site, the wild type reference base type, the mutant base type, the variant genotype and the like is extracted, the mutant allele identification and function annotation database is searched, through statistics of a jaccart distance and mutation site contribution degree grading table and normalization calibration, automatically matching out the corresponding allele and the related function of drug metabolism in the allele identification and function database of the gene, and then, a drug function gene database related to the individualized medication of the chronic disease is inquired according to the information association, and the inquiry result is obtained and includes information such as the allele type of the sample a and the gene name related to the metabolic function annotation information, the metabolic function related to allele variation, the function classification, the medication guide recommendation, the variation description and the like. Thereby completing the recommendation of personalized medication guiding scheme of chronic diseases caused by genome mutation.
The application shows that the personalized medicine application method for the chronic diseases caused by the genome mutation can realize one-stop automation from high-throughput genome sequencing data results to diagnosis and treatment and medicine application guidance, further provides theoretical support for clinical differential diagnosis and medicine application amount of rare diseases of the genetic diseases, shortens diagnosis and treatment time and can improve the diagnosis and treatment rate and treatment effect of the genetic diseases; in addition, the method provided by the application is not limited by the type of a high-throughput sequencing test, and only a vcf standard file can be input into the system, so that the method has a better application scene and a wide application range.
Therefore, the method for personalized medicine application of the chronic disease caused by the genome mutation can realize the guidance from high-throughput genome sequencing data result one-stop automation to diagnosis and treatment and medicine application, can extract information of vcf file data based on the high-throughput genetic gene detection result of a patient, can quickly and automatically match the information of the haplotype, the genotype, the metabolic function information, the related genes, the medicine application dosage recommendation and the like of a patient sample, can improve the diagnosis rate, the medicine application dosage and the treatment effect of the chronic disease caused by the gene mutation while shortening the diagnosis and treatment time, and further provides theoretical support for clinical diagnosis, identification and treatment of the chronic disease caused by the gene mutation, and can improve the personalized diagnosis and treatment accuracy and cure rate of the gene mutation pathogenicity while shortening the diagnosis and treatment time; in addition, the method provided by the application is not limited by the type of the high-throughput sequencing platform, and supports the input of the universal format vcf file, so that the method has a better application scene and a wide application range.
Specifically, step 1 in the above embodiment includes:
the public database and the related literature database are researched from the pharmacogenomic research of the chronic diseases, and the clinical function annotation information of the known chronic diseases and the mutation sites related to the chronic diseases is obtained through screening. And establishing a mutant allele identification and function annotation database of the gene according to known information such as disease name, gene name, mutation number rsid, mutation site on chromosome, wild allele, mutant allele, metabolic function classification and the like.
Specifically, step 2 provided in the above embodiment includes:
based on public personalized medicine related medicines, metabolic functions and gene databases, the medicine dose and medicine interaction information prompted by the pathogenic mutant genes are screened out. Based on the screened information such as: and constructing a personalized medicine related medicine functional gene database by using information such as gene names, allele variation related metabolic functions, function classification, medicine guide recommendation and description and the like.
Illustratively, the public database is PharmGKB, FDAbiomarker, MedGen database, and the literature database is PubMed database, which includes gene-related sites, suggested drug dose, drug interaction, site clinical annotation related information, for example, a drug exerts its anticoagulant and antithrombotic effects in the treatment of cardiovascular and cerebrovascular diseases by enzymes acting on the related genes, and other genes strictly regulate the activities of these enzymes. The relevant sites can be rapidly screened out according to diseases and drugs. The established mutant genes lead to identification of chronic disease related alleles and identification of function annotation database and personalized medicine related medicine function gene database, wherein 27000 genes, 3500 genotypes and 3900 medicine data are included, wherein 579 haplotypes/genotypes related to chronic diseases caused by gene mutation are associated with the medicine recommendation of 60 medicines, and public database data and literature database data which lead to the latest research direction of chronic diseases caused by gene mutation are included.
Specifically, step 3 provided in the above embodiment includes:
extracting genome mutation and genotype information of the mutation site from a vcf file of high-throughput sequencing data of a certain sample, and judging the base type (SNP) after mutation.
Mutation and genotype information were extracted: high throughput sequencing data for samples the vcf format of the result file is a universal format, extracting all variant site ids (rsid, e.g., rs 127696205, etc.), normal population base types (Reference, i.e., pre-mutation), all post-mutation base types (ALT), and genotype information for all mutant sites (GT, e.g., 0/1, 1/2, 1/3, etc.) of the file.
Judging the type of the mutated base: the base type (SNP) after mutation is judged according to the ALT and GT conditions, and the process is as follows: GT is considered Reference, i.e. no mutation, if it is "0/0" (no mutation site) and "/" (missing site); if GT is 0/1, SNP is ALT; if GT is 1/1 (or/2 or/3 or/4), then SNP takes the value of the corresponding 1 st, 2 nd, 3 th or 4 th variation type of ALT set, and further obtains the base type (SNP) after mutation, and executes step 4.
Further, step 4 provided in the above embodiment includes:
and automatically matching out the allele corresponding to the gene and the related function of drug metabolism in the allele identification and function database of the gene through statistics of the jaccart distance, the contribution degree scoring table of the mutation sites and normalization calibration.
And (3) performing correlation query on all mutation sites id (rsid), normal population base types (Reference) and all mutated base types (SNP) of the corresponding same field in the genotype functional library through the rsid, Reference and SNP information obtained in the step (3), and obtaining a plurality of all possible haplotypes (allele) in a certain Gene (Gene) in the sample. Note that all mutation sites contained in the "genotype functional library" of each allele in the query result are correlated by the rsid of step S3, that is, the case where the sample possible haplotype allele contains the allele mutation site in the "genotype functional library" is likely to be the allele, which is called "suspected allele".
Automatically matching out the allele corresponding to the allele and the related function of drug metabolism in the allele identification and function database of the gene through statistics of a jaccart distance and a contribution degree scoring table of mutation sites and normalization calibration, and executing the step 5;
finally, step 5 provided by the above embodiment includes:
the results obtained in step 4 are used to sample the drug metabolism function (such as all 1_ function and all 2_ function) involved in the genotype all 1/all 2 of a certain Gene (Gene) allele, and to query the corresponding same fields Gene, the drug metabolism function (all 1_ function) of the haplotype all 1 and the drug metabolism function (all 2_ function) of the haplotype all 2 in the "drug genotype functional library" in association, so as to precisely match the medication guidance scheme of the chronic disease caused by the genome mutation (such as drug name (Chemical _ CN), drug metabolism function type (metabolism _ type), treatment recommendation (Therapeutic _ references), evidence intensity Classification (Level _ of _ evidence english), Classification medication recommendation (Classification _ of _ drug), and thus the medication guidance scheme of the chronic disease caused by the genome mutation.
For specific limitations of the chronic disease medication guidance device, reference may be made to the limitations of the chronic disease medication guidance method described above, and further description thereof will be omitted. The modules in the chronic disease medication guide device can be wholly or partially realized by software, hardware and a combination thereof. The modules can be embedded in a hardware form or independent from a processor in the computer device, and can also be stored in a memory in the computer device in a software form, so that the processor can call and execute operations corresponding to the modules.
In one embodiment, as shown in fig. 3, a chronic disease medication guidance method is provided, comprising the steps of:
step 302, obtaining high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed.
And 304, carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to the patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation.
And step 306, generating a target base type according to the mutated second base type and the mutated gene site information.
And 308, acquiring a preset genotype function library and a preset drug genotype function library.
And 310, inquiring a preset genotype function library according to the association of the mutation gene locus, the first base type before mutation and the target base type to obtain the target drug metabolism function corresponding to the target haplotype, wherein the target haplotype is the genotype matched with the mutation gene locus, the first base type before mutation and the target base type.
And step 312, inquiring a preset drug genotype function library according to the target drug metabolic function association corresponding to the target haplotype to obtain a target drug administration scheme corresponding to the patient to be analyzed.
In one embodiment, a preset genotype function library is inquired in an associated manner according to a mutant gene locus, a first base type before mutation and a target base type to obtain a drug metabolism function corresponding to the target genotype, and a candidate haplotype set is determined by inquiring the preset genotype function library in an associated manner according to the mutant gene locus, the first base type before mutation and the target base type; calculating the similarity of each candidate haplotype in the candidate haplotype set and the corresponding mutant gene locus of the patient to be analyzed, and determining a target haplotype according to the similarity; and acquiring the target drug metabolism function corresponding to the target haplotype from the preset genotype function library.
It should be understood that, although the steps in the above-described flowcharts are shown in order as indicated by the arrows, the steps are not necessarily performed in order as indicated by the arrows. The steps are not performed in the exact order shown and described, and may be performed in other orders, unless explicitly stated otherwise. Moreover, at least a portion of the steps in the above-described flowcharts may include multiple sub-steps or multiple stages, which are not necessarily performed at the same time, but may be performed at different times, and the order of performing the sub-steps or the stages is not necessarily sequential, but may be performed alternately or alternatingly with other steps or at least a portion of the sub-steps or stages of other steps.
In one embodiment, a computer device is provided, which may be a server, the internal structure of which may be as shown in fig. 4. The computer device includes a processor, a memory, a network interface, and a database connected by a system bus. Wherein the processor of the computer device is configured to provide computing and control capabilities. The memory of the computer device comprises a nonvolatile storage medium and an internal memory. The non-volatile storage medium stores an operating system, a computer program, and a database. The internal memory provides an environment for the operation of an operating system and computer programs in the non-volatile storage medium. The database of the computer device is used for storing high-throughput sequencing data of a gene sequence to be tested of a patient to be analyzed. The network interface of the computer device is used for communicating with an external terminal through a network connection. The computer program is executed by a processor to implement a chronic disease medication guidance method.
In one embodiment, a computer device is provided, which may be a terminal, and its internal structure diagram may be as shown in fig. 5. The computer device includes a processor, a memory, a network interface, a display screen, and an input device connected by a system bus. Wherein the processor of the computer device is configured to provide computing and control capabilities. The memory of the computer device comprises a nonvolatile storage medium and an internal memory. The non-volatile storage medium stores an operating system and a computer program. The internal memory provides an environment for the operation of an operating system and computer programs in the non-volatile storage medium. The network interface of the computer device is used for communicating with an external terminal through a network connection. The computer program is executed by a processor to implement a chronic disease medication guidance method. The display screen of the computer equipment can be a liquid crystal display screen or an electronic ink display screen, and the input device of the computer equipment can be a touch layer covered on the display screen, a key, a track ball or a touch pad arranged on the shell of the computer equipment, an external keyboard, a touch pad or a mouse and the like.
Those skilled in the art will appreciate that the configurations shown in fig. 4 or 5 are merely block diagrams of some configurations relevant to the present disclosure, and do not constitute a limitation on the computing devices to which the present disclosure may be applied, and that a particular computing device may include more or less components than those shown, or may combine certain components, or have a different arrangement of components.
In one embodiment, a computer device is provided, comprising a memory, a processor, and a computer program stored on the memory and executable on the processor, the processor implementing the following steps when executing the computer program: acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed; carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to a patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation; generating a target base type according to the mutated second base type and the mutated gene site information; acquiring a preset genotype functional library and a preset drug genotype functional library; inquiring a preset genotype function library in a correlation manner according to the mutation gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, wherein the target haplotype is a genotype matched with the mutation gene locus, the first base type before mutation and the target base type; and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
In one embodiment, the processor, when executing the computer program, further performs the steps of: inquiring a preset genotype function library in a correlation manner according to the mutant gene locus, the first base type before mutation and the target base type, and determining a candidate haplotype set; calculating the similarity of each candidate haplotype in the candidate haplotype set and the corresponding mutant gene locus of the patient to be analyzed, and determining a target haplotype according to the similarity; and acquiring the target drug metabolism function corresponding to the target haplotype from the preset genotype function library.
In one embodiment, a computer-readable storage medium is provided, having a computer program stored thereon, which when executed by a processor, performs the steps of: acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed; carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site corresponding to a patient to be analyzed, mutant gene site information, a first base type before mutation and a second base type after mutation; generating a target base type according to the mutated second base type and the mutated gene site information; acquiring a preset genotype functional library and a preset drug genotype functional library; inquiring a preset genotype function library in a correlation manner according to the mutation gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, wherein the target haplotype is a genotype matched with the mutation gene locus, the first base type before mutation and the target base type; and inquiring a preset drug genotype function library according to the target drug metabolic function correlation corresponding to the target haplotype to obtain a target medication scheme corresponding to the patient to be analyzed.
In one embodiment, the processor, when executing the computer program, further performs the steps of: inquiring a preset genotype function library in a correlation manner according to the mutant gene locus, the first base type before mutation and the target base type, and determining a candidate haplotype set; calculating the similarity of each candidate haplotype in the candidate haplotype set and the corresponding mutant gene locus of the patient to be analyzed, and determining a target haplotype according to the similarity; and acquiring the target drug metabolism function corresponding to the target haplotype from the preset genotype function library.
It will be understood by those skilled in the art that all or part of the processes of the methods of the embodiments described above can be implemented by hardware instructions of a computer program, which can be stored in a non-volatile computer-readable storage medium, and when executed, can include the processes of the embodiments of the methods described above. Any reference to memory, storage, database, or other medium used in the embodiments provided herein may include non-volatile and/or volatile memory, among others. Non-volatile memory can include read-only memory (ROM), Programmable ROM (PROM), Electrically Programmable ROM (EPROM), Electrically Erasable Programmable ROM (EEPROM), or flash memory. Volatile memory can include Random Access Memory (RAM) or external cache memory. By way of illustration and not limitation, RAM is available in a variety of forms such as Static RAM (SRAM), Dynamic RAM (DRAM), Synchronous DRAM (SDRAM), Double Data Rate SDRAM (DDRSDRAM), Enhanced SDRAM (ESDRAM), Synchronous Link DRAM (SLDRAM), Rambus Direct RAM (RDRAM), direct bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM).
The technical features of the above embodiments can be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the above embodiments are not described, but should be considered as the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present application, and the description thereof is more specific and detailed, but not construed as limiting the claims. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the concept of the present application, which falls within the scope of protection of the present application. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (10)

1. A chronic medication guidance device, the device comprising:
the patient data acquisition module is used for acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed;
the patient data analysis module is used for carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site, mutant gene site information, a first base type before mutation and a second base type after mutation corresponding to the patient to be analyzed;
a base type determining module for generating a target base type according to the mutated second base type and the mutated gene locus information;
the function library acquisition module is used for acquiring a preset genotype function library and a preset drug genotype function library;
the drug metabolism function matching module is used for inquiring the preset genotype function library according to the association among the mutant gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, wherein the target haplotype is the haplotype matched with the mutant gene locus, the first base type before mutation and the target base type and the genotype formed by the haplotype;
and the medication scheme matching module is used for inquiring the preset drug genotype function library according to the target drug metabolic function association corresponding to the target haplotype to obtain the target medication scheme corresponding to the patient to be analyzed.
2. The apparatus of claim 1, further comprising:
the candidate clinical annotation information acquisition module is used for screening out clinical annotation information corresponding to gene mutation sites related to various chronic diseases based on a drug genome research public database and a related literature database of the chronic diseases, wherein the clinical annotation information comprises a drug metabolism function;
and the preset genotype function library establishing module is used for establishing the preset genotype function library according to clinical annotation information corresponding to the gene mutation sites related to various chronic diseases, wherein the preset genotype function library comprises a chronic disease haplotype corresponding to the chronic diseases, a drug metabolic function corresponding to the chronic disease haplotype, a mutation gene site corresponding to the chronic disease haplotype, a base type before mutation and a base type after mutation.
3. The apparatus of claim 2, further comprising:
the candidate medication scheme acquisition module is used for screening out medication schemes corresponding to gene mutation sites related to various chronic diseases based on public personalized medication related drugs, metabolic functions and gene databases, wherein the medication schemes comprise drug dosage and drug interaction information;
and the preset drug genotype function library establishing module is used for establishing the preset drug genotype function library according to the medication schemes corresponding to the gene mutation sites related to the various chronic diseases and the clinical annotation information corresponding to the gene mutation sites related to the various chronic diseases, and the preset drug genotype function library comprises the medication information, the medication schemes, the haplotypes corresponding to the chronic diseases and the drug metabolism function types corresponding to the chronic diseases.
4. The apparatus of claim 1, wherein the drug metabolism function matching module further comprises:
the candidate haplotype determining unit is used for inquiring the preset genotype functional library according to the mutant gene locus, the first base type before mutation and the target base type in an associated manner to determine a candidate haplotype set;
the target haplotype determining unit is used for calculating the similarity between each candidate haplotype in the candidate haplotype set and the corresponding mutant gene locus of the patient to be analyzed and determining a target haplotype according to the similarity;
and the target drug metabolism function determining unit is used for acquiring the target drug metabolism function corresponding to the target haplotype from the preset genotype function library.
5. The apparatus according to claim 4, wherein the target haplotype determining unit is further configured to obtain similarities corresponding to the candidate haplotypes, perform descending order sorting according to the similarities corresponding to the candidate haplotypes, obtain a first candidate haplotype with the largest similarity, obtain a preset haplotype score table, obtain a second candidate haplotype with the largest score value from the candidate haplotypes and the preset haplotype score table, and determine the target haplotype according to the first candidate haplotype and the second candidate haplotype.
6. The apparatus of claim 1, wherein the medication scheme matching module is further configured to obtain candidate haplotypes and candidate drug metabolic functions corresponding to the respective candidate medication schemes, search for a matched target candidate haplotype and target candidate drug metabolic function according to the target haplotype and the target drug metabolic function, and determine the medication schemes corresponding to the target candidate haplotype and the target candidate drug metabolic function as the target medication schemes.
7. A method for guiding medication for chronic diseases, comprising:
acquiring high-throughput sequencing data of a gene sequence to be detected of a patient to be analyzed;
carrying out mutation detection analysis on the high-throughput sequencing data to obtain a mutant gene site, mutant gene site information, a first base type before mutation and a second base type after mutation corresponding to the patient to be analyzed;
generating a target base type according to the mutated second base type and the mutated gene locus information;
acquiring a preset genotype functional library and a preset drug genotype functional library;
inquiring the preset genotype function library in a correlation manner according to the mutant gene locus, the first base type before mutation and the target base type to obtain a target drug metabolism function corresponding to a target haplotype, wherein the target haplotype is a genotype matched with the mutant gene locus, the first base type before mutation and the target base type;
and inquiring the preset drug genotype function library according to the target drug metabolic function association corresponding to the target haplotype to obtain a target drug administration scheme corresponding to the patient to be analyzed.
8. The method according to claim 7, wherein the querying the preset genotype functional library according to the association among the mutant gene locus, the first base type before mutation and the target base type to obtain the drug metabolism function corresponding to the target genotype comprises:
inquiring the preset genotype functional library according to the mutant gene locus, the first base type before mutation and the target base type in a correlation manner, and determining a candidate haplotype set;
calculating the similarity of each candidate haplotype in the candidate haplotype set and the corresponding mutant gene locus of the patient to be analyzed, and determining a target haplotype according to the similarity;
and acquiring the target drug metabolism function corresponding to the target haplotype from the preset genotype function library.
9. A computer device comprising a memory, a processor and a computer program stored on the memory and executable on the processor, characterized in that the steps of the method according to any of claims 7 to 8 are implemented when the computer program is executed by the processor.
10. A computer-readable storage medium, on which a computer program is stored, which, when being executed by a processor, carries out the steps of the method of any one of claims 7 to 8.
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