CN106529213A - Method and device for acquiring gene mutation site corresponding to five sense organs - Google Patents

Method and device for acquiring gene mutation site corresponding to five sense organs Download PDF

Info

Publication number
CN106529213A
CN106529213A CN201610973345.4A CN201610973345A CN106529213A CN 106529213 A CN106529213 A CN 106529213A CN 201610973345 A CN201610973345 A CN 201610973345A CN 106529213 A CN106529213 A CN 106529213A
Authority
CN
China
Prior art keywords
gene
variant sites
face
site
information
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201610973345.4A
Other languages
Chinese (zh)
Inventor
范振鑫
郭涛
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chengdu Xin Yun Decoding Technology Co Ltd
Original Assignee
Chengdu Xin Yun Decoding Technology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chengdu Xin Yun Decoding Technology Co Ltd filed Critical Chengdu Xin Yun Decoding Technology Co Ltd
Priority to CN201610973345.4A priority Critical patent/CN106529213A/en
Publication of CN106529213A publication Critical patent/CN106529213A/en
Pending legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B30/00ICT specially adapted for sequence analysis involving nucleotides or amino acids
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16BBIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B50/00ICT programming tools or database systems specially adapted for bioinformatics

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medical Informatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Biotechnology (AREA)
  • Evolutionary Biology (AREA)
  • Theoretical Computer Science (AREA)
  • Bioethics (AREA)
  • Databases & Information Systems (AREA)
  • Data Mining & Analysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Artificial Intelligence (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Evolutionary Computation (AREA)
  • Public Health (AREA)
  • Software Systems (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

The invention provides a method and device for acquiring a gene mutation site corresponding to five sense organs, and relates to the technical field of biological information. The method comprises: performing data comparison on multiple short sequences of a to-be-tested gene and a reference genome, thereby acquiring initial mutation site information of the to-be-tested gene; according to the initial mutation site information, canceling mutation sites, which do not meet preset preservation conditions, in multiple initial mutation sites, and using a mutation site, which is obtained after canceling, of the to-be-tested gene as a to-be-tested site; comparing the to-be-tested site with the multiple mutation sites of the gene corresponding to the five sense organs in a five sense organs gene pool; and when the to-be-tested site has a mutation site having the same position in the five sense organs gene pool and the same mutant base, acquiring the mutation situation of a gene site corresponding to the five sense organs in the to-be-tested gene. According to the method and device for acquiring the gene mutation site corresponding to the five sense organs, the mutation situation of the multiple mutation sites corresponding to the five sense organs in the mutation sites of the to-be-tested gene can be obtained.

Description

The acquisition methods and device in the mutational site of the corresponding gene of face
Technical field
The application is related to technical field of biological information, in particular to a kind of mutational site of the corresponding gene of face Acquisition methods and device.
Background technology
With development and the maturation of medical science, genomics and high throughput sequencing technologies, accurate medical treatment (Precision Medicine) also apply in countries in the world, become new medical model.Precisely medical treatment is by individual people's gene, environment and life The disease prevention that custom difference is taken into account and the therapy disposed, according to everyone hereditary information, personalized, precision Go formulate medical treatment and health management scheme.
And everyone genetic background be it is distinguishing, in the process, it is necessary to determine everyone genome or The catastrophe of some genes being associated with corresponding organ or position, it is further according to the base mutation situation to allow to Analysis contrast, it is determined that final ill probability, to specify corresponding medical treatment and health management scheme.
Face include eye, mouth, ear, nose, larynx, are the important organ of organism.If there are pathological changes in face, can the life of opposite life birth Affect.Then, certain preventive measure is done to facial disease, it is to reduce incidence probability, of crucial importance.
As the incidence of facial disease is contacted with certain with gene, the site alkali of the corresponding gene of face Base catastrophe is different, and the incidence and incidence probability of the different facial diseases of face may be made different.Thus it is possible to utilize Precisely medical model, sends out to facial disease according to the combination of the base mutation situation and other information of the corresponding gene of face State of an illness condition and probability are predicted, and are a kind of effective precautionary approach to carry out prevention to facial disease.
The existing determination to face gene point mutation situation, typically by chemical mode obtain testing gene certain The base mutation situation of the gene locis of one specified location, the limited amount in the mutational site that the acquisition modes are obtained, generally only The catastrophe of some or certain several bases can be obtained, it is impossible to while determining using up for gene corresponding with face in testing gene The catastrophe of the multiple variant sites more than possible, makes subsequently to combine prediction knot of the other information to the disease condition of facial disease Fruit is likely to occur relatively large deviation.
The content of the invention
In view of this, the embodiment of the present application provides a kind of acquisition methods and dress in the mutational site of the corresponding gene of face Put, by multiple variant sites of the gene variant sites of testing gene corresponding with the face in face gene bank are compared Compared with, it is hereby achieved that the base mutation situation of multiple variant sites of the corresponding gene of face in testing gene, to improve The problems referred to above.
To achieve these goals, the technical scheme that the application is adopted is as follows:
A kind of acquisition methods in the mutational site of the corresponding gene of face, methods described include:By the multiple of testing gene Short sequence carries out comparing with reference gene group, obtains the preliminary variant sites information of testing gene, the preliminary change dystopy Point information includes the mutating alkali yl of multiple preliminary variant sites and the positional information of each preliminary variant sites;According to described Preliminary variant sites information, the variant sites for being unsatisfactory for default reserve in the plurality of preliminary variant sites are deleted, will Variant sites in the testing gene obtained after deletion are used as site to be checked;By in the site to be checked and face gene bank Multiple variant sites of the corresponding gene of face be compared, the face gene bank includes the every of the corresponding gene of face The mutating alkali yl of individual variant sites and each variant sites position;When existing in the site to be checked and the face base Because in storehouse position is identical and mutating alkali yl identical variant sites, the site of the corresponding gene of face in the testing gene is obtained Catastrophe.
A kind of acquisition device in the mutational site of the corresponding gene of face, described device include:Comparing module, for treating The multiple short sequence of cls gene carries out comparing with reference gene group, obtains the preliminary variant sites information of testing gene, institute Stating preliminary variant sites information includes the mutating alkali yl of multiple preliminary variant sites and the position of each preliminary variant sites Information;Filtering module, for according to the preliminary variant sites information, will be unsatisfactory for presetting in the plurality of preliminary variant sites The variant sites of reserve are deleted, using the variant sites in the testing gene obtained after deletion as site to be checked;Than Compared with module, for multiple variant sites of the gene site to be checked corresponding with the face in face gene bank are compared Compared with the face gene bank includes the mutating alkali yl of each variant sites of the corresponding gene of face and each variant sites Position;Mutation acquisition module, when exist in the site to be checked it is identical with position in the face gene bank and be mutated alkali Base identical variant sites, for obtaining the site mutation situation of the corresponding gene of face in the testing gene.
The acquisition methods and device in the mutational site of the corresponding gene of face that the embodiment of the present application is provided, it is to be measured obtaining In the case of the variant sites of gene, by the variant sites of testing gene gene corresponding with face in face gene bank it is many Individual variant sites are compared, face gene bank include the mutating alkali yl of each variant sites of the corresponding gene of face and Each variant sites position.Become when there is and mutating alkali yl identical identical with position in face gene bank in testing gene Ectopic sites, it may be determined that there is the corresponding gene mutation of face in the testing gene.
As face gene bank includes the multiple variant sites related to face, then this programme can determine testing gene In multiple variant sites related to face, and the concrete base mutation situation of the plurality of variant sites.
For enabling the above-mentioned purpose of the application, feature and advantage to become apparent, preferred embodiment cited below particularly, and coordinate Appended accompanying drawing, is described in detail below.
Description of the drawings
For making the purpose, technical scheme and advantage of the embodiment of the present application clearer, below in conjunction with the embodiment of the present application In accompanying drawing, the technical scheme in the embodiment of the present application is clearly and completely described, it is clear that described embodiment is Some embodiments of the present application, rather than the embodiment of whole.Based on the embodiment in the application, those of ordinary skill in the art The every other embodiment obtained under the premise of creative work is not made, belongs to the scope of the application protection.
Fig. 1 shows the structural representation of the computer that the embodiment of the present application is provided;
Fig. 2 shows the one of the acquisition methods in the mutational site of the corresponding gene of face that the application first embodiment is provided Plant flow chart;
Fig. 3 shows the portion of the acquisition methods in the mutational site of the corresponding gene of face that the application first embodiment is provided Flow chart step by step;
Fig. 4 shows the work(of the acquisition device in the mutational site of the corresponding gene of face that the application second embodiment is provided Can module map;
Fig. 5 shows the base of the acquisition device in the mutational site of the corresponding gene of face that the application second embodiment is provided Yin Ku sets up the functional block diagram of module;
Fig. 6 shows the mistake of the acquisition device in the mutational site of the corresponding gene of face that the application second embodiment is provided The functional block diagram of filter module;
Fig. 7 shows the ratio of the acquisition device in the mutational site of the corresponding gene of face that the application second embodiment is provided Functional block diagram to module.
Specific embodiment
Below in conjunction with accompanying drawing in the embodiment of the present application, the technical scheme in the embodiment of the present application is carried out clear, complete Ground description, it is clear that described embodiment is only some embodiments of the present application, rather than the embodiment of whole.Generally exist The component of the embodiment of the present application described and illustrated in accompanying drawing can be arranged and be designed with a variety of configurations herein.Cause This, the detailed description of the embodiments herein to providing in the accompanying drawings is not intended to limit claimed the application's below Scope, but it is merely representative of the selected embodiment of the application.Based on embodiments herein, those skilled in the art are not doing The every other embodiment obtained on the premise of going out creative work, belongs to the scope of the application protection.
It should be noted that:Similar label and letter represent similar terms in following accompanying drawing, therefore, once a certain Xiang Yi It is defined in individual accompanying drawing, then in subsequent accompanying drawing which further need not be defined and is explained.Meanwhile, the application's In description, term " first ", " second " etc. are only used for distinguishing description, and it is not intended that indicating or implying relative importance.
As shown in figure 1, being the block diagram of the application computer 100.The computer 100 includes the corresponding base of face The acquisition device 200 in the mutational site of cause, memorizer 101, storage control 102, processor 103, Peripheral Interface 104, input Output unit 105 and other.
The memorizer 101, storage control 102, processor 103, Peripheral Interface 104 and input-output unit 105 Each element is directly or indirectly electrically connected with each other, to realize the transmission or interaction of data.For example, these elements mutually it Between can pass through one or more communication bus or holding wire and realize being electrically connected with.The mutational site of the corresponding gene of the face Acquisition device 200 include at least one can be stored in the memorizer 101 in the form of software or firmware (firmware) in or The software function module being solidificated in the operating system (operating system, OS) of the computer 100.The processor 103 be used for performing memorizer 101 in the executable module that stores, such as the acquisition in the mutational site of the corresponding gene of described face Software function module or computer program that device 200 includes.
Wherein, memorizer 101 may be, but not limited to, random access memory (Random Access Memory, RAM), read only memory (Read Only Memory, ROM), programmable read only memory (Programmable Read-Only Memory, PROM), erasable read-only memory (Erasable Programmable Read-Only Memory, EPROM), Electricallyerasable ROM (EEROM) (Electric Erasable Programmable Read-Only Memory, EEPROM) etc.. Wherein, memorizer 101 is used for storage program, and the processor 103 performs described program after execute instruction is received, aforementioned Method performed by the computer 100 of the stream process definition that the embodiment of the present application any embodiment is disclosed can apply to processor In 103, or realized by processor 103.
A kind of possibly IC chip of processor 103, the disposal ability with signal.Above-mentioned processor 103 can To be general processor, including central processing unit (Central Processing Unit, abbreviation CPU), network processing unit (Network Processor, abbreviation NP) etc.;Can also be digital signal processor (DSP), special IC (ASIC), It is ready-made programmable gate array (FPGA) or other PLDs, discrete gate or transistor logic, discrete hard Part component.Can realize or perform disclosed each method in the embodiment of the present application, step and logic diagram.General processor Can be microprocessor or the processor 103 can also be any conventional processor etc..
Various input/output devices are coupled to processor 103 and memorizer 101 by the Peripheral Interface 104.At some In embodiment, Peripheral Interface 104, processor 103 and storage control 102 can be realized in one single chip.Other one In a little examples, they can be realized by independent chip respectively.
Input-output unit 105 is used for being supplied to user input data to realize interacting for user and the computer.It is described Input-output unit may be, but not limited to, digital independent device, mouse and keyboard etc..
It should be understood that structure shown in Fig. 1 is only illustrated, computer 100 can also include it is more more than shown in Fig. 1 or Less component, or with the configuration different from shown in Fig. 1.Each component shown in Fig. 1 can using hardware, software or its Combination is realized.
First embodiment
The embodiment of the present application provides a kind of acquisition methods in the mutational site of the corresponding gene of face, to be measured for obtaining The base mutation situation of the variant sites of the gene related to face in gene.Fig. 2 is referred to, the method includes:
Step S110:The multiple short sequence of testing gene and reference gene group are carried out into comparing, testing gene is obtained Preliminary variant sites information, the preliminary variant sites information includes the mutating alkali yl of multiple preliminary variant sites and every The positional information of individual preliminary variant sites.
First, the multiple short sequence of testing gene is obtained, the short sequence can be exported by second filial generation microarray dataset.Will The short sequence of testing gene is compared with reference gene group.Such as, if testing gene is human gene, the reference gene group is then Mankind's reference gene group.
Certainly, the comparison process can include repeatedly comparing and the process such as duplicate removal, after being compared including multiple changes The preliminary variant sites information of ectopic sites.
Specifically, as shown in figure 3, in the present embodiment, the comparing in this step is believed with obtaining preliminary variant sites The process of breath can include:
Step S111:The multiple short sequence of the testing gene and reference gene group are compared first, SAM lattice are obtained The comparison result of formula.
The short sequence of testing gene and reference gene group are carried out into comparing, the comparison process can utilize existing ratio Software is carried out, such as Bowtie2, it is possible to obtain the comparison result of SAM forms, be stored with the comparison result of the SAM forms ratio Comparison information to rear acquisition.It should be understood that in the comparison result of the SAM forms, including each alkali in testing gene The information of base, such as positional information.
Certainly, the representation of specifically used comparison software and comparison result is not intended as limit in the present embodiment System, can compare the multiple short sequence of testing gene and reference gene group and obtain the comparison information for representing comparison result It is advisable.
Step S112:Duplicate removal is carried out to the comparison result, contrast is made to the short sequence of a position of reference gene group Number is less than or equal to 1.
In the comparison result that step S111 is obtained, there are a certain proportion of repetitive sequence and result, for example, contrast to referring to base Because the same position organized there may be multiple short sequences, then, in this step, comparison result is carried out into duplicate removal.
In the present embodiment, it is possible to use software Picard carries out duplicate removal work.Specifically, that what is utilized can be Picard MarkDuplicate instrument duplicate removals, obtain bam forms duplicate removal result.
Step S113:Local anharmonic ratio is carried out to the comparing result after duplicate removal to (local multiple alignment).
It is difficult accurately to compare highly similar repetition to the short sequence that reference gene group is compared due to what is obtained Region, then the repeat region in genome be readily available false-positive variant sites, such as false-positive SNPs.It is appreciated that , false-positive variant sites are the variant sites of comparison result mistake.In order to reduce false positive variant sites quantity and Ratio, in the present embodiment, carries out local anharmonic ratio pair to the comparing result after duplicate removal.
Specifically, the local anharmonic ratio can be using in GATK to (local multiple alignment) IndelRealigner is carried out, and obtains comparison result of the anharmonic ratio of bam forms to after.The comparison process typically has three steps, A. detect suspicious, need to carry out the region of anharmonic ratio pair;B. anharmonic ratio pair is carried out to these suspicious regions;C. repair in anharmonic ratio The mate pairing information lost to during.
Step S114:Recalculate the base mass fraction in comparison result of the local anharmonic ratio to after.
In the step of during aforementioned processing S111, each single base can be endowed in data processing One mass fraction (Quality scores), for reflecting the credibility of nucleotide that corresponding base is observed.
As the mass fraction obtained during aforementioned processing does not have preferably to contact with the genotyping result probability of mistake Get up, while the mass fraction of single base, the contact of no and other specification phase example, the different surveys such as in same sample Sequence platform, different sequencing circulations, different libraries etc. are contacted.
Therefore, in this step in S114, the mass fraction of each base is connected with each factor in sequencing procedure System, recalculates to the mass fraction of each base, generates new mass fraction, for judging that each base whether may be used Letter.
Specifically, in the present embodiment, it is possible to use GATK carries out empirical quality score Recalibration, obtains the result of bam forms.
Step S115:According to the base mass fraction, SNP and indel is carried out to comparing result of the local anharmonic ratio to after Analysis, obtains preliminary variant sites information.
According to the base mass fraction for recalculating acquisition, local anharmonic ratio is carried out to the comparison result for obtaining SNP and The preliminary interpretation of indel, carries out SNP and indel typings to which, to obtain the variant sites information for including multiple variant sites, , used as preliminary variant sites information, multiple variant sites that this includes are used as preliminary variant sites for the variant sites information.Can be with Understand, in the preliminary variant sites information, include the mutating alkali yl of multiple preliminary variant sites, and each becomes dystopy Point position.In the present embodiment, variant sites are SNP and indel, it is preferred that in the present embodiment, variant sites are only SNP。
Specifically, in this step, can be analyzed using the Unified Genotyper of GATK.Because complete Into after the typing of SNPs, many data filtering parameter logistics are employed according to being filtered again, with further control data quality, So standard minimum confidence thresholds are both configured to zero in this step.It should be understood that SNPs represents the plural form of SNP.
Certainly, the preliminary interpretation process of the SNP and indel can also be carried out in other ways, in the present embodiment not As limit, or other, the such as HaplotypeCaller of GATK is carried out.
In this step, it is possible to obtain including the vcf files of preliminary variant sites information, the preliminary change in the vcf files Ectopic sites information includes each variant sites for obtaining in step s 110 and the corresponding positional information of each variant sites, Certainly, also including other, here is not added with repeating.
Step S120:According to the preliminary variant sites information, will be unsatisfactory for presetting in the plurality of preliminary variant sites The variant sites of reserve are deleted, using the variant sites in the testing gene obtained after deletion as site to be checked.
In step s 110, in the preliminary variant sites in the preliminary variant sites information of acquisition, it would still be possible to there is false sun Property variant sites, then, this step is further filtered to preliminary variant sites, delete wherein false positive probability it is higher Variant sites, using the variant sites in the result after deletion as the testing gene in variant sites, make last acquisition Variant sites are more accurate.It should be understood that delete after result in further comprises each variant sites positional information and Other information, will not be described here.
Specifically, in this step, the variation for being unsatisfactory for default reserve can be deleted including following one or more The mode in site:
Mode one:Remove in the plurality of preliminary variant sites, the number of allele is more than the change dystopy of predetermined threshold value Point.
Allele is that the probability of false positive variant sites is higher, which is carried out more than the variant sites of predetermined threshold value Remove.In the present embodiment, the predetermined threshold value can value according to actual needs, due to comprising more than more than 1 allele Site just have higher gene type mistake, it is preferred that the value of the predetermined threshold value can be 1.
When predetermined threshold value value is 1, that is, there is more than 1 allele in removing the multiple preliminary variant sites of acquisition Variant sites.
Mode two:Delete in the plurality of preliminary variant sites, positioned at each insertion and deletion (indel) upstream span or All variant sites in person's span downstream, the base number that the upstream span and span downstream include are predetermined number.
As the short sequence for comparing is often exported by secondary direction finding platform, and the short sequence of secondary microarray dataset exists The comparison of mistake is more prone near the region of insertion and deletion (indel), and the local anharmonic ratio in above-mentioned processing procedure is not to This mistake can be completely eliminated.Then, all variant sites in insertion and deletion upstream span or span downstream are deleted, with Reduce the probability of false positive results.
The base number that the upstream span and span downstream include be predetermined number, the predetermined number can by user according to Actual demand determines, is not restricted in the present embodiment, also, the predetermined number of upstream span and span downstream can phase It is same or different.
In the present embodiment, the base number that scope includes above is preferably 5, the base number that span downstream includes is excellent Elect 5 as.That is, it is determined that all indel in preliminary variant sites, for each indel, by its upstream 5bp (5 bases) Within all variant sites delete, or all variant sites within 5bp downstream are deleted.
Certainly, in the present embodiment, only can delete in variant sites or the span downstream in the upstream span of indel Variant sites, it is also possible to the variant sites in the upstream span of indel and the variant sites in span downstream are all deleted.
Preferably, in the present embodiment, in the upstream span or span downstream for insertion and deletion (indel) of deletion All SNPs.
Mode three:By in the plurality of preliminary variant sites, the variant sites for being spaced default base number each other are deleted Remove.
In this step, variant sites close to each other are deleted, will variation of the distance less than certain value each other Delete in site.
In the present embodiment, the default base number is not intended as limiting, and can set according to actual needs.
Preferably, the default base number is 4, if variation of the base number being spaced between existing less than 4 Site, is deleted.That is, deleting the variant sites within upstream each other or downstream 5bp.
Preferably, in the step, the SNPs for being spaced default base number each other of deletion.
Mode four:By in the plurality of preliminary variant sites, corresponding GQ (Genotype quality) value is less than default The variant sites of GQ threshold values are deleted.
GQ (Genotype quality) is a posterior probability (the phred-scaled probabilities) value, For each site, GQ values are not possible of truth to represent the site in the genotypic results of current acquisition Property, that is, represent the probability existed in the site genotype for obtaining.Calculation is:
GQ values=- 10*log10 (P [error]), wherein, P [error] represents that corresponding site is not the general of truth Rate.
Preferably, in the present embodiment, it is 20 to preset GQ threshold values.Empirical tests, when GQ threshold values are 20, theoretic mistake Rate is 1%.
Mode five:By in the plurality of preliminary variant sites, corresponding MQ (Mapping quality) value is less than default MQ The variant sites of threshold value are deleted.
MQ represents the specificity (uniqueness) in aligned sequences.When same short sequence can compare it is same During genome zones of different, the alignment score of first best comparison area (the first best alignment) The alignment score of (alignment's score) and second best comparison area (the second best alignment), two Person's difference is bigger, shows that the specificity for comparing is better, and the value of MQ is higher.
In this embodiment it is believed that it is false sun that MQ values have higher probability less than the variant sites of default MQ threshold values Property, it is deleted.
Preferably, in the present embodiment, it is 30 to preset MQ threshold values value.Empirical tests, when MQ values are 30, P [error]= 0.001, i.e., relative to current location is compared, the probability for comparing another position is up to 0.1%.
In embodiments of the present invention, mode one is optional executive mode to mode five, i.e., in this step, can adopt which In a certain mode, certain several ways or all of mode.When carrying out being unsatisfactory for the change of reservation conditions using various ways During the deletion of ectopic sites, the execution sequence between the various ways is not intended as limiting.Certainly, the various ways can also be parallel Perform.
In addition, in the step 120, when there is various ways to be performed serially, follow-up step can be in preceding step On the basis of perform.For example, if the number of the plurality of preliminary variant sites allelic of removal of executive mode one is more than pre- If in the variant sites of threshold value, and mode three, default base will be spaced in the plurality of preliminary variant sites each other The variant sites of number are deleted, and first carry out mode one, then executive mode three.Then in mode three, deletion can be mode It is spaced the variant sites of default base number in variant sites after one process each other.
Step S120 is carried out to preliminary variant sites after deletion filtration, and the variant sites in the final result of acquisition are used as treating The site to be checked of cls gene, can be represented with vcf formatted files.
Step S130:Multiple variant sites of the gene site to be checked corresponding with the face in face gene bank are entered Row compares, and the face gene bank includes the mutating alkali yl of each variant sites of the corresponding gene of face and each variation Site position.
In embodiments of the present invention, face gene bank is initially set up, the face gene bank includes the corresponding gene of face Each variant sites mutating alkali yl and each variant sites position.
The face gene bank step S130 relatively before set up.Specifically, this sets up process can be, obtain COSMIC gene databases, the clivar data bases of NCBI, other international and domestic each big authoritative academic journal magazine, gene tests In the gene database that company and relevant government department announce, the gene locis information related to face.Mainly acquisition is Described in base mutation situation and each variant sites position including each variant sites of the corresponding gene of face Gene locis information.
Certainly, the Data Source for obtaining gene locis information can also be other, be not intended as in the present embodiment limiting.
Further, each variant sites of the corresponding gene of face can also be included in the gene locis information of acquisition Impact of every kind of mutating alkali yl to protein function, that is, get the base of certain variant sites by normal base mutation to current Mutating alkali yl, the function of corresponding protein can be produced which kind of impact.
Certainly, in the present embodiment, can also include in the gene locis information of acquisition:The corresponding base in each mutational site Write a Chinese character in simplified form because of name, the coordinate of gene name full name, this site in human genome, corresponding histoorgan type, gene are dashed forward Change type, normal gene are in the base in this site, whether this kind of mutation in this site of clinical research causes a disease, original mutation finds In the source that crowd, the sex of original mutation carrier patient, the age of original mutation carrier patient, original mutation are recorded One or more.
Again will be with a low credibility in preset standard and mistake gene locis information deletion in the gene locis information, The gene locis information of acquisition forms the face gene bank.
In the present embodiment, include following at least one less than the gene locis information of preset standard:
1) the gene locis information got from the very poor periodical of non-SCI periodicals or reputation in the field of business, reputation is very in the industry for this Poor periodical can be factor of influence less than the periodical for being unsatisfactory for requiring under the periodical of certain value or other judgment criteria;2) record In the original of the gene locis information, sample size used is less than certain value so that being not enough to draw the conclusion of science 's;3) in the original for recording the gene locis, the gene locis are not the most important gene locis found in document, The most important gene locis can be in the result for getting front 10% site.
The gene locis information of mistake includes following at least one:1) the gene locis information described in the data base for obtaining Original substantially do not have been reported that this site;2) record in the original of the gene locis, the gene locis As a result it is statistically non-significant.
Certainly, the criterion of preset standard and gene locis information errors, is not intended as limiting in the present embodiment, Can be determined according to practical situation.
Further, as the gene studiess related to face are constantly carried out, the variant sites of the gene related to face Catastrophe in updating, and can might not there is the related gene of all face in current face gene bank Variant sites catastrophe, then, in embodiments of the present invention, also includes entering the face data base every preset time period Row updates.
Specific renewal process can be, every preset time period, acquisition is newest to be published in internal authority scholarly journal, such as The research paper related to face delivered on Nature, Nature Genetics etc., it is newest in the research paper that will be obtained The gene locis information related to face, deletes wherein with a low credibility in preset standard and mistake gene locis information, It is added in face data base to realize updating.
After obtaining face gene bank, by multiple change dystopys of gene site to be checked corresponding with the face in face data base Point is compared.
In the present embodiment, the comparison procedure can directly be carried out behind the acquisition site to be checked of step S120, also may be used Be by user triggering carry out.I.e. after the inquiry request for receiving user's triggering, the comparison in step S130 is performed.
Alternatively, it is also possible to be, one or more in the site to be checked obtained in user input step S120, step S130 Multiple variant sites of the middle site to be checked by user input gene corresponding with the face in face gene bank are compared.
Alternatively, it is also possible to be, user directly obtains the variant sites of face correlation from face gene bank.Specifically, use Family by input-output unit be input into gene name, site genome the information such as coordinate.Receiving the letter of user input After breath, made a look up in face gene bank according to the information of user input, by lookup result, such as gene name, site coordinate, The various information such as base mutation type are shown.If finding the information of user input in face gene bank, prove that this is defeated Enter the corresponding gene locis of information related to face, and there is base mutation.It should be understood that site in the coordinate of genome is For the position in site.
Step S140:When existing in the site to be checked with the face gene bank, position is identical and mutating alkali yl is identical Variant sites, obtain the site mutation situation of the corresponding gene of face in the testing gene.
When comparative result is, exist in site to be checked and identical variant sites in face data base, then can be according to five In official data base, the identical variant sites have the site mutation of the corresponding gene of face in determining the testing gene, and are mutated feelings Condition is consistent with the identical variant sites in face data base.Thus it is possible to which have related to face in obtaining testing gene Gene variant sites and the concrete catastrophe of each variant sites related to face, which the catastrophe is included in Which base mutation of individual position is which base.
It should be understood that identical variant sites refer to that the position of variant sites is identical and base mutation situation is identical, that is, exist Same position has identical mutating alkali yl, it is believed that be in site to be checked with identical variant sites in face data base.Five I.e. related to the face gene of the corresponding gene of official.
Then, related personnel can according to obtain testing gene in the corresponding gene of face site mutation situation, with And other information, such as possible disease condition under every kind of catastrophe of face related gene, determine that the testing gene is corresponding The face disease condition of object.
Further, in the present embodiment, can be with prominent according to the site of the corresponding gene of face in the testing gene In change situation, and face data base, every kind of mutating alkali yl of each variant sites of the corresponding gene of face is to protein function Impact, determine the impact of the mutations on protein function of each variant sites in the testing gene, may thereby determine that and treat Which protein function related to face of the corresponding object of cls gene (such as corresponding people) is affected, and which receives Affect.So that skilled addressee can according to the impact of protein function, with reference to other information, such as protein function change with Interactively of organ concrete function etc., judges the facial disease illness probability of the corresponding object of the testing gene and may suffer from Which facial disease.
Certainly, include the catastrophe of every kind of variant sites to face disease in embodiments of the present invention, or directly The impact of the pathogenic situation of disease, such as certain ocular disease potentially include it is pathogenic, may cause a disease, risk factor, not know, have conflict Result of study, benign, wherein the pathogenic situation of certain certain mutating alkali yl of position is risk factor, shows that the position has this kind to dash forward The probability that the object for becoming base suffers from this kind of ocular disease is very high, should be noted prevention.
Second embodiment
A kind of acquisition device 200 in the mutational site of the corresponding gene of face is present embodiments provided, Fig. 4 is referred to, should Device 200 includes:
Comparing module 210, for the multiple short sequence of testing gene and reference gene group are carried out comparing, is treated The preliminary variant sites information of cls gene, the preliminary variant sites information include the mutating alkali yl of multiple preliminary variant sites And the positional information of each preliminary variant sites.
Filtering module 220, for according to the preliminary variant sites information, will be unsatisfactory in multiple preliminary variant sites pre- If the variant sites of reserve are deleted, using the variant sites in the testing gene obtained after deletion as site to be checked.
Comparison module 230, for by multiple changes of the gene site to be checked corresponding with the face in face gene bank Ectopic sites are compared, the face gene bank include the mutating alkali yl of each variant sites of the corresponding gene of face and Each variant sites position.
Mutation acquisition module 240, when exist in the site to be checked it is identical with position in the face gene bank and be mutated Base identical variant sites, for obtaining the site mutation situation of the corresponding gene of face in the testing gene.
Further, the every kind of mutating alkali yl in face gene bank also including each variant sites of the corresponding gene of face Impact to protein function, the mutation acquisition module 240 in the present embodiment are additionally operable to according to face pair in the testing gene The site mutation situation of the gene answered, determines the shadow of the mutations on protein function of each variant sites in the testing gene Ring.
Further, in the present embodiment, as shown in figure 4, also module 250 is set up including gene bank, for setting up face base Yin Ku, the gene bank sets up module 250 to be included:Data capture unit 251, for obtaining COSMIC gene databases, NCBI Clivar data bases in the gene locis information related to face, the gene locis information includes the corresponding gene of face Each variant sites mutating alkali yl and each variant sites position.Data deletion unit 252, for by the base Because with a low credibility in preset standard and mistake gene locis information deletion, the gene locis information of acquisition in site information Form the face gene bank.
Further, as shown in figure 5, the gene bank sets up module 250 also includes updating block 253, for every default Time period is updated to the face gene bank.
Further, as shown in fig. 6, in the present embodiment, filtering module 220 includes one or more of:First deletes Except unit 221, for removing in the plurality of preliminary variant sites, the number of allele is more than the change dystopy of predetermined threshold value Point.Second deletes unit 222, for deleting in the plurality of preliminary variant sites, positioned at the upstream span of each insertion and deletion Or all variant sites in span downstream, the base number that the upstream span and span downstream include is predetermined number. 3rd deletes unit 223, for by the plurality of preliminary variant sites, being spaced the change dystopy of default base number each other Point deletion.4th deletes unit 224, for by the plurality of preliminary variant sites, corresponding GQ values are less than default GQ threshold values Variant sites delete.5th deletes unit 225, for by the plurality of preliminary variant sites, corresponding MQ values are less than pre- If the variant sites of MQ threshold values are deleted.
In this example, Fig. 7 is referred to, comparing module 210 can include:Comparing unit 211, for by the base to be measured The multiple short sequence of cause is compared first with reference gene group, obtains the comparison result of SAM forms;Duplicate removal unit 212, is used for Duplicate removal is carried out to the comparison result, makes contrast 1 is less than or equal to the short sequence number of a position of reference gene group;Weight Comparing unit 213, for carrying out local anharmonic ratio pair to the comparing result after duplicate removal;Computing unit 214, it is local for recalculating Base mass fraction in comparison result of the anharmonic ratio to after;Just sentence unit 215, for according to the base mass fraction, to this Ground comparing result of the anharmonic ratio to after carries out SNP and indel analyses, obtains preliminary variant sites information.
In sum, the acquisition methods and device in the mutational site of the corresponding gene of face provided in an embodiment of the present invention, Behind the site to be measured for obtaining testing gene, site to be measured is entered with multiple variant sites of corresponding gene in face gene bank Row compares, it is hereby achieved that the mutation feelings of multiple variant sites related to face in the variant sites in the testing gene Condition, for aiding in the judgement of the possibility disease condition of facial disease.
It should be noted that each embodiment in this specification is described by the way of progressive, each embodiment weight Point explanation is all difference with other embodiment, between each embodiment identical similar part mutually referring to. For device class embodiment, due to itself and embodiment of the method basic simlarity, so description is fairly simple, related part ginseng See the part explanation of embodiment of the method.
In several embodiments provided herein, it should be understood that disclosed apparatus and method, it is also possible to pass through Other modes are realized.Device embodiment described above is only schematically, for example flow chart and block diagram in accompanying drawing Show the device of multiple embodiments according to the application, the architectural framework in the cards of method and computer program product, Function and operation.At this point, each square frame in flow chart or block diagram can represent the one of module, program segment or a code Part, a part for the module, program segment or code are used for realizing holding for the logic function for specifying comprising one or more Row instruction.It should also be noted that at some as in the implementations replaced, the function of being marked in square frame can also be being different from The order marked in accompanying drawing occurs.For example, two continuous square frames can essentially be performed substantially in parallel, and they are sometimes Can perform in the opposite order, this is depending on involved function.It is also noted that every in block diagram and/or flow chart The combination of individual square frame and block diagram and/or the square frame in flow chart, can be with the special base for performing the function or action for specifying Realize in the system of hardware, or can be realized with the combination of specialized hardware and computer instruction.
In addition, each functional module in the application each embodiment can integrate to form an independent portion Divide, or modules individualism, it is also possible to which two or more modules are integrated to form an independent part.
If the function is realized using in the form of software function module and as independent production marketing or when using, can be with It is stored in a computer read/write memory medium.Based on such understanding, the technical scheme of the application is substantially in other words The part contributed to prior art or the part of the technical scheme can be embodied in the form of software product, the meter Calculation machine software product is stored in a storage medium, is used including some instructions so that a computer equipment (can be individual People's computer, server 100, or network equipment etc.) perform all or part of step of the application each embodiment methods described Suddenly.And aforesaid storage medium includes:USB flash disk, portable hard drive, read only memory (ROM, Read-Only Memory), deposit at random Access to memory (RAM, Random Access Memory), magnetic disc or CD etc. are various can be with the medium of store program codes. It should be noted that herein, such as first and second, another or the like relational terms be used merely to an entity or Person is operated and is made a distinction with another entity or operation, and not necessarily requires or imply that presence is appointed between these entities or operation What this actual relation or order.And, term " including ", "comprising" or its any other variant are intended to non-row His property is included, so that a series of process, method, article or equipment including key elements not only include those key elements, and And also include other key elements being not expressly set out, or also include for this process, method, article or equipment institute inherently Key element.In the absence of more restrictions, the key element for being limited by sentence "including a ...", it is not excluded that including institute Also there is other identical element in process, method, article or the equipment of stating key element.
The preferred embodiment of the application is the foregoing is only, the application is not limited to, for the skill of this area For art personnel, the application can have various modifications and variations.It is all within spirit herein and principle, made any repair Change, equivalent, improvement etc., should be included within the protection domain of the application.It should be noted that:Similar label and letter exist Similar terms is represented in figure below, therefore, once being defined in a certain Xiang Yi accompanying drawing, then it is not required in subsequent accompanying drawing Which is further defined and is explained.
The above, the protection domain of the only specific embodiment of the application, but the application is not limited thereto, any Those familiar with the art can readily occur in change or replacement in the technical scope that the application is disclosed, and should all contain Cover within the protection domain of the application.Therefore, the protection domain of the application described should be defined by scope of the claims.

Claims (10)

1. the acquisition methods in the mutational site of the corresponding gene of a kind of face, it is characterised in that methods described includes:
The multiple short sequence of testing gene and reference gene group are carried out into comparing, the preliminary variant sites of testing gene are obtained Information, the preliminary variant sites information include the mutating alkali yl of multiple preliminary variant sites and each preliminary variant sites Positional information;
According to the preliminary variant sites information, the variant sites of default reserve will be unsatisfactory in multiple preliminary variant sites Delete, using the variant sites in the testing gene obtained after deletion as site to be checked;
Multiple variant sites of the gene site to be checked corresponding with the face in face gene bank are compared, described five Official's gene bank includes the mutating alkali yl of each variant sites of the corresponding gene of face and each variant sites position;
When there are and mutating alkali yl identical variant sites identical with position in the face gene bank in the site to be checked, obtain Obtain the site mutation situation of the corresponding gene of face in the testing gene.
2. method according to claim 1, it is characterised in that also include the corresponding gene of face in the face gene bank Each variant sites impact of every kind of mutating alkali yl to protein function, methods described also includes:
According to the site mutation situation of the corresponding gene of face in the testing gene, each variation in the testing gene is determined The impact of the mutations on protein function in site.
3. method according to claim 1, it is characterised in that described by the site to be checked and face gene bank It is before multiple variant sites of the corresponding gene of face are compared, also including face gene bank is set up, described to set up face base Yin Ku includes:
The gene locis information related to face, the base in acquisition COSMIC gene databases, the clivar data bases of NCBI Because site information includes that the mutating alkali yl of each variant sites of the corresponding gene of face and each variant sites institute are in place Put;
Will be with a low credibility in preset standard and mistake gene locis information deletion in the gene locis information, acquisition Gene locis information forms the face gene bank.
4. method according to claim 3, it is characterised in that also include:
The face gene bank is updated every preset time period.
5. method according to claim 1, it is characterised in that described to be unsatisfactory for default guarantor in multiple preliminary variant sites The variant sites deletion of condition is stayed to include one or more of:
Remove in the plurality of preliminary variant sites, the number of allele is more than the variant sites of predetermined threshold value;
Delete in the plurality of preliminary variant sites, it is all in the upstream span or span downstream of each insertion and deletion Variant sites, the base number that the upstream span and span downstream include are predetermined number;
By in the plurality of preliminary variant sites, the variant sites for being spaced default base number each other are deleted;
By in the plurality of preliminary variant sites, corresponding GQ values are deleted less than the variant sites of default GQ threshold values;
By in the plurality of preliminary variant sites, corresponding MQ values are deleted less than the variant sites of default MQ threshold values.
6. method according to claim 1, it is characterised in that the multiple short sequence and reference gene by testing gene Group carries out comparing, and the preliminary variant sites information for obtaining testing gene includes:
The multiple short sequence of the testing gene and reference gene group are compared first, the comparison result of SAM forms is obtained;
Duplicate removal is carried out to the comparison result, contrast is less than or equal to the short sequence number of a position of reference gene group 1;
Local anharmonic ratio pair is carried out to the comparing result after duplicate removal;
Recalculate the base mass fraction in comparison result of the local anharmonic ratio to after;
According to the base mass fraction, SNP and indel analyses are carried out to comparing result of the local anharmonic ratio to after, obtain preliminary Variant sites information.
7. method according to claim 1, it is characterised in that the variant sites are SNP.
8. the acquisition device in the mutational site of the corresponding gene of a kind of face, it is characterised in that described device includes:
Comparing module, for the multiple short sequence of testing gene and reference gene group are carried out comparing, obtains testing gene Preliminary variant sites information, the preliminary variant sites information includes the mutating alkali yl of multiple preliminary variant sites and every The positional information of individual preliminary variant sites;
Filtering module, for according to the preliminary variant sites information, will be unsatisfactory for default reservation in multiple preliminary variant sites The variant sites of condition are deleted, using the variant sites in the testing gene obtained after deletion as site to be checked;
Comparison module, for multiple variant sites of the gene site to be checked corresponding with the face in face gene bank are entered Row compares, and the face gene bank includes the mutating alkali yl of each variant sites of the corresponding gene of face and each variation Site position;
Mutation acquisition module, when existing in the site to be checked with the face gene bank, position is identical and mutating alkali yl is identical Variant sites, for obtaining the site mutation situation of the corresponding gene of face in the testing gene.
9. device according to claim 8, it is characterised in that also set up module including gene bank, for setting up face base Yin Ku, the gene bank sets up module to be included:
Data capture unit, for obtaining base related to face in the clivar data bases of COSMIC gene databases, NCBI Because of site information, the gene locis information includes the mutating alkali yl of each variant sites of the corresponding gene of face and every Individual variant sites position;
Data deletion unit, for will be with a low credibility in preset standard and mistake gene position in the gene locis information Point information deletion, the gene locis information of acquisition form the face gene bank.
10. device according to claim 8, it is characterised in that the filtering module includes one or more of:
First deletes unit, and for removing in the plurality of preliminary variant sites, the number of allele is more than predetermined threshold value Variant sites;
Second delete unit, for deleting in the plurality of preliminary variant sites, positioned at each insertion and deletion upstream span or All variant sites in person's span downstream, the base number that the upstream span and span downstream include are predetermined number;
3rd deletes unit, for by the plurality of preliminary variant sites, being spaced the variation of default base number each other Delete in site;
4th deletes unit, for by the plurality of preliminary variant sites, corresponding GQ values are less than the variation for presetting GQ threshold values Delete in site;
5th deletes unit, for by the plurality of preliminary variant sites, corresponding MQ values are less than the variation for presetting MQ threshold values Delete in site.
CN201610973345.4A 2016-11-04 2016-11-04 Method and device for acquiring gene mutation site corresponding to five sense organs Pending CN106529213A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610973345.4A CN106529213A (en) 2016-11-04 2016-11-04 Method and device for acquiring gene mutation site corresponding to five sense organs

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610973345.4A CN106529213A (en) 2016-11-04 2016-11-04 Method and device for acquiring gene mutation site corresponding to five sense organs

Publications (1)

Publication Number Publication Date
CN106529213A true CN106529213A (en) 2017-03-22

Family

ID=58349761

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610973345.4A Pending CN106529213A (en) 2016-11-04 2016-11-04 Method and device for acquiring gene mutation site corresponding to five sense organs

Country Status (1)

Country Link
CN (1) CN106529213A (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104462869A (en) * 2014-11-28 2015-03-25 天津诺禾致源生物信息科技有限公司 Method and device for detecting somatic cell SNP
CN105740243A (en) * 2014-12-08 2016-07-06 深圳华大基因研究院 Method and device for constructing biological information database
CN106011224A (en) * 2015-12-24 2016-10-12 晶能生物技术(上海)有限公司 Nervous system genetic disease gene united screening method, kit and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104462869A (en) * 2014-11-28 2015-03-25 天津诺禾致源生物信息科技有限公司 Method and device for detecting somatic cell SNP
CN105740243A (en) * 2014-12-08 2016-07-06 深圳华大基因研究院 Method and device for constructing biological information database
CN106011224A (en) * 2015-12-24 2016-10-12 晶能生物技术(上海)有限公司 Nervous system genetic disease gene united screening method, kit and preparation method thereof

Similar Documents

Publication Publication Date Title
CN106407747A (en) Method and device for acquiring mutation sites of genes corresponding to tumors
JP6231654B2 (en) Systems and methods for analysis and reporting of disease-related human genome variants
JP4437050B2 (en) Diagnosis support system, diagnosis support method, and diagnosis support service providing method
US20120310539A1 (en) Predicting gene variant pathogenicity
US20140067813A1 (en) Parallelization of synthetic events with genetic surprisal data representing a genetic sequence of an organism
WO2017072707A1 (en) Methods, systems and processes of determining transmission paths of infectious agents
US20140088942A1 (en) Molecular genetic diagnostic system
Johnston et al. PEMapper and PECaller provide a simplified approach to whole-genome sequencing
KR20170000744A (en) Method and apparatus for analyzing gene
CN106529211A (en) Variable site obtaining method and apparatus
CA2894752A1 (en) System and method for determining relatedness
KR20220069943A (en) Single-cell RNA-SEQ data processing
US20230050513A1 (en) Screening system and method for acquiring and processing genomic information for generating gene variant interpretations
CN106407745A (en) Mutation site acquisition method and device for a gene corresponding to skin
Bobak et al. Assessment of imputation methods for missing gene expression data in meta-analysis of distinct cohorts of tuberculosis patients
CN106503489A (en) The acquisition methods and device in the mutational site of the corresponding gene of cardiovascular system
CN106529208A (en) Method and device for obtaining mutation sites of gene corresponding to nervous system
CN106407746A (en) Method and device for acquiring mutational sites of genes corresponding to respiratory system
CN106529210A (en) Method and device for acquiring gene mutation site corresponding to psychology and spirit
CN106407744A (en) Mutation site acquisition method and device for a gene corresponding to diet and health
Conn et al. Random Forests and Fuzzy Forests in Biomedical Research.
CN106529209A (en) Method and device for acquiring gene mutation site corresponding to immune system
CN106529213A (en) Method and device for acquiring gene mutation site corresponding to five sense organs
CN106503488A (en) The acquisition methods and device in the mutational site of the corresponding gene of digestive system
CN106503490A (en) The acquisition methods and device in the mutational site of urinary system gene corresponding with reproductive system

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20170322