CN108647496B - The method, apparatus and computer readable storage medium of News Search mutant gene - Google Patents
The method, apparatus and computer readable storage medium of News Search mutant gene Download PDFInfo
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Abstract
The present invention relates to genescreen technical fields, and in particular to a kind of method, apparatus and computer readable storage medium of News Search mutant gene, this method include obtaining several patient's gene data collection；Each gene is counted with the presence or absence of variation situation；Calculate the variation frequency of each gene；The highest gene of variation frequency is added in mutant gene list for screening, deletes the gene and has made a variation patient's gene data collection of situation comprising the gene；Calculate the variation frequency that remaining each gene is concentrated in remaining patient's gene data, screened again until several patient's gene data collection deletion finish, then export mutant gene list.The efficiency that this method searches for mutant gene is very high, about 3.5% overall variability gene in average only reservation original database, and there is maximum patient's coverage rate therefore to have very high representativeness, the gene filtered out has significant clinical meaning, it is not only able to instruct medical diagnosis on disease, additionally it is possible to as disease treatment target spot.
Description
Technical field
The present invention relates to genescreen technical fields, and in particular to a kind of method, apparatus of News Search mutant gene and
Computer readable storage medium.
Background technique
With the rapid development of sequencing technologies, current considerable human cancer disease has all had accumulated high pass abundant
Sequencing data storehouse is measured, such as oncogene map plan (The Cancer Genome Atlas, TCGA) etc..In these databases
In, every one kind cancer all incorporates cancerous tissue/health tissues sequencing result of thousands of name patients, can therefrom learn every
The genetic mutation situation of one patient.
Based on high-flux sequence database, there are quite a lot of pharmaceuticals, gene sequencing company to filter out at present
Respective cancer mutant gene list carries out cancer early screening, accurate medication by the cancer related gene in detection list
Deng.
Current all kinds of cancer gene lists are the biggest problems are that due to algorithm difference between different company, the cancer filtered out
Disease list of genes is overlapped very little, and leading to the result analyzed, there are quite a lot of repugnances.At present also lack one it is more outstanding
Search plan, the minimal amount of cancer mutant gene with clinical value is able to use, to cover the maximum amount of cancer patient.
It is how fast in the high-flux sequence database of certain disease (such as all kinds of cancers, diabetes, obesity) patient
Speed filters out a collection of mutant gene, and the mutant gene that this batch filters out has clinical meaning with the representativeness to this disease
Justice, while it is current urgent problem to be solved that quantity is as small as possible.
Summary of the invention
In view of this, the application provides the method, apparatus and computer-readable storage medium of a kind of News Search mutant gene
Matter solves the problems, such as above-mentioned.
In order to solve the above technical problems, technical solution provided by the invention is a kind of method of News Search mutant gene,
The described method includes:
S1: several patient's gene data collection of certain disease type are obtained；
S2: each gene that each patient's gene data of statistics is concentrated is with the presence or absence of variation situation；
S3: the variation frequency that each gene is concentrated in several described patient's gene datas is calculated；
S4: the screening highest gene of variation frequency is added in mutant gene list, deletes the gene and deletes
Except having made a variation patient's gene data collection of situation comprising the gene；
S5: judge whether several described patient's gene data collection are deleted and finish, if it is not, then calculating remaining each gene
In the variation frequency that remaining patient's gene data is concentrated, S4 is returned；If so, into S6；
S6: the mutant gene list is exported.
Preferably, the method for several patient's gene data collection for obtaining certain disease type, comprising:
Several patient's gene data collection of certain disease type are obtained from gene database, the gene database uses
Exon sequencing technologies.
Preferably, the method that each gene that each patient's gene data of statistics is concentrated whether there is variation situation,
Include:
A line number is constructed equal to gene total number, columns is equal to the matrix of patient's gene data collection total number, every a line
The variation situation that a gene is concentrated in each patient's gene data is represented, each column represent patient's gene data and concentrate respectively
The variation situation of a gene；
Successively judge that each gene that each patient's gene data is concentrated whether there is variation situation, it, will if having made a variation
Patient's gene data collection and the matrix value of the gene intersection location are set as the first preset value, if not making a variation, it is pre- to be set as second
If value；
Each gene that the patient's gene data for having counted all is concentrated terminates after whether there is variation situation.
Preferably, described to calculate variation frequency that each gene is concentrated in several described patient's gene datas
Method, comprising:
It calculates each gene and concentrates the variation total number that there is variation situation in several patient's gene datas；
The variation total number of calculated each gene is obtained divided by the total number of patient's gene data collection respectively each
The variation frequency that gene is concentrated in several patient's gene datas.
Preferably, it is described screening the highest gene of variation frequency be added in mutant gene list, delete the gene with
And delete comprising the gene made a variation situation patient's gene data collection method, comprising:
According to the variation frequency of each gene of calculating, all genes are pressed into variation frequency descending sort；
It deletes the gene that ranks the first and deletes and made a variation patient's gene data collection of situation comprising the gene.
Preferably, the highest gene of variation frequency is added to the method in mutant gene list for the screening, comprising:
When the highest gene of variation frequency filtered out is multiple, by the gene and the clinical feasible database of gene
Gene catalogue and/or the gene catalogue of annotation of gene function database be compared；
It will have been deposited in the gene catalogue of the clinical feasible database of gene and/or the gene catalogue of annotation of gene function database
Gene be added in mutant gene list as the highest gene of variation frequency filtered out.
The present invention also provides a kind of device of News Search mutant gene, described device includes:
Module is obtained, for obtaining several patient's gene data collection of certain disease type；
Statistical module whether there is variation situation for counting each gene that each patient's gene data is concentrated；
Computing module: the variation frequency concentrated for calculating each gene in several patient's gene datas；
Screening module is added in mutant gene list for screening the highest gene of variation frequency, deletes the gene
And it deletes and has made a variation patient's gene data collection of situation comprising the gene；
Judgment module is finished for judging whether several patient's gene data collection are deleted, if it is not, then calculating remaining each
The variation frequency that a gene is concentrated in remaining patient's gene data returns to screening module；If so, into output module；
Output module, for exporting mutant gene list.
The present invention also provides a kind of devices of News Search mutant gene, comprising:
Memory, for storing computer program；
Processor realizes the step of the method such as above-mentioned News Search mutant gene for executing the computer program
Suddenly.
The present invention also provides a kind of computer readable storage mediums, which is characterized in that the computer readable storage medium
It is stored with computer program, the method such as above-mentioned News Search mutant gene is realized when the computer program is executed by processor
The step of.
Compared with prior art, detailed description are as follows for its advantages by the application: News Search variation provided by the invention
The method of gene, several patient's gene data collection including obtaining certain disease type；Count each patient's gene data collection
In each gene with the presence or absence of variation situation；Calculate the frequency of variation that each gene is concentrated in several patient's gene datas
Rate；The highest gene of variation frequency is added in mutant gene list for screening, deletes the gene and deletes comprising the gene
The patient's gene data collection for the situation that made a variation；Judge whether several patient's gene data collection are deleted to finish, if it is not, then calculating surplus
Under the variation frequency concentrated in remaining patient's gene data of each gene, carry out screening sequence again until several diseases
The deletion of people's gene data set finishes, then exports mutant gene list.The efficiency that this method searches for mutant gene is very high, average only to protect
In original database about 3.5% overall variability gene is stayed, and there is maximum patient's coverage rate, therefore there is very high representative
Property, the gene filtered out has significant clinical meaning, is not only able to instruct medical diagnosis on disease, additionally it is possible to as disease treatment target spot.
Detailed description of the invention
Fig. 1 is a kind of method flow schematic diagram of News Search mutant gene provided in an embodiment of the present invention；
Fig. 2 is a kind of apparatus structure schematic diagram of News Search mutant gene provided in an embodiment of the present invention；
Fig. 3 is that the method for News Search mutant gene provided in an embodiment of the present invention applies the mutant gene in 12 kinds of cancers
Gene dosage changes comparison sheet after screening.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, rather than whole embodiments.Based on this
Embodiment in invention, those of ordinary skill in the art are without making creative work, obtained every other
Embodiment belongs to the scope of the present invention.
It is with reference to the accompanying drawing and specific real in order to make those skilled in the art more fully understand technical solution of the present invention
Applying example, the present invention is described in further detail.
As shown in Figure 1, the embodiment of the present invention provides a kind of method of News Search mutant gene, this method comprises:
S1: several patient's gene data collection of certain disease type are obtained；
S2: counting each gene that each patient's gene data is concentrated whether there is variation situation；
S3: the variation frequency that each gene is concentrated in several patient's gene datas is calculated；
S4: the highest gene of variation frequency is added in mutant gene list for screening, deletes the gene and deletes packet
It has made a variation patient's gene data collection of situation containing the gene；
S5: judging whether several patient's gene data collection are deleted and finish, if it is not, then calculating remaining each gene surplus
Under patient's gene data concentrate variation frequency, return S4；If so, into S6；
S6: output mutant gene list.
It should be noted that the method for obtaining several gene data collection of certain disease type in step S1, comprising:
Several patient's gene data collection of certain disease type are obtained from gene database, the gene database is using outer
Show sub- sequencing technologies.Skill is sequenced using the state-of-the-art exon in the current world in the cancer gene database that this algorithm uses
Art is included in thousands of cases, has fully ensured that the authority of data source.
The cBioPortal of cancer gene group is most early in Memorial Sloan Kettering Cancer center (MSK)
The database of exploitation is sponsored by MSK molecular weight tumor center.Currently, it is the most comprehensive data of cancer gene group data
Source, including cancer gene group map (TCGA).TCGA is a kind of publicly available data source, the synthesis comprising 33 seed type cancers
Genome variation.Patient's gene data collection that the present invention uses, can from cBioPortal (http: //
The highest 12 kinds of cancer types of new case and the death rate www.cbioportal.org/) (LGG, BRCA, COAD, HNSC,
KIRC, LIHC, LUAD, OV, PRAD, SKCM, STAD, THCA) patient data collect collect.It is sequenced and is detected by exon
These variations only relate to exon or the expression region of DNA.The sequencing cost that this technology compares entire human genome is wanted
It is much lower.
It should be noted that counting each gene that each patient's gene data is concentrated in step S2 whether there is variation feelings
The method of condition, comprising:
A line number is constructed equal to gene total number, columns is equal to the matrix of patient's gene data collection total number, every a line
The variation situation that a gene is concentrated in each patient's gene data is represented, each column represent patient's gene data and concentrate respectively
The variation situation of a gene；
Successively judge that each gene that each patient's gene data is concentrated whether there is variation situation, it, will if having made a variation
Patient's gene data collection and the matrix value of the gene intersection location are set as the first preset value, if not making a variation, it is pre- to be set as second
If value；
Each gene that the patient's gene data for having counted all is concentrated terminates after whether there is variation situation.
It should be noted that calculating the variation frequency that each gene is concentrated in several patient's gene datas in step S3
Method, comprising:
It calculates each gene and concentrates the variation total number that there is variation situation in several patient's gene datas；
The variation total number of calculated each gene is obtained divided by the total number of patient's gene data collection respectively each
The variation frequency that gene is concentrated in several patient's gene datas.
It is added in mutant gene list it should be noted that screening the highest gene of variation frequency in step S4, deletes
Except the gene and delete comprising the gene made a variation situation patient's gene data collection method, comprising:
According to the variation frequency of each gene of calculating, all genes are pressed into variation frequency descending sort；
It deletes the gene that ranks the first and deletes and made a variation the gene data collection of situation comprising the gene.
Specifically, the highest gene of variation frequency is added to the method in mutant gene list for screening, further includes:
When the highest gene of variation frequency filtered out is multiple, by the gene and the clinical feasible database of gene
Gene catalogue and/or the gene catalogue of annotation of gene function database be compared；
It will have been deposited in the gene catalogue of the clinical feasible database of gene and/or the gene catalogue of annotation of gene function database
Gene be added in mutant gene list as the highest gene of variation frequency filtered out.
It should be noted that for every kind of cancer types multiple patient's gene data collection can be collected, due to patient's gene
Data set is downloaded from separate sources, it is therefore necessary to which carrying out processing could further analyze.For every kind of cancer types, by institute
There is sample (several patient's gene data collection) to be merged into sample file, and by all assortments of genes at gene document, the two
Realized by using Linux command " cat ".In order to prepare to analyze data, by the perl script of customization from each patient's base
Because of data set generation (0,1) matrix, i.e., the information that genetic mutation is concentrated in patient's gene data is collected from lane database, use Perl
Programming language is organized into variation in the information of patient's gene data collection the form of matrix, and every a line represents a gene, each
Column represent a patient.If this gene is concentrated in this patient's gene data and made a variation, it is 1 that program, which just fills out matrix, is not had
Variation just fills out 0.0 in matrix indicates that genetic mutation is not present in sample, and 1 indicates that there are genetic mutations in sample.In addition, wound
The character matrix of original document is built.Character matrix indicates the merging that genetic mutation occurs between the sample of all original documents
Number.Having the sample of variation to fill out is 1, and no filling out is 0, therefore for each gene, adds up and just obtain the total of genetic mutation
Number.
In order to design the list of genes of the patient of cover-most quantity and the mutant gene of minimum number, use R and
Perl programming language is for analyzing and carrying out algorithm realization.Aim at the dynamic gene searching algorithm (Dynamic of this target
Gene Search, dynamic gene retrieval) it is applied to various disease types.
Firstly, for the variation of each gene, by with the sample size of genetic mutation divided by the quantity of total number of samples come
Calculate variation frequency, formula are as follows: total number of samples/total number of samples of genetic mutation frequency=have variation.According still further to calculated change
After the descending permutation matrix of alien frequencies rate, selects the gene with maximum patient coverage rate and be added in mutant gene list.Its
It is secondary, matrix is updated by deleting the mutant gene selected and deleting the sample that the mutant gene is covered.Third repeats
The process, until all samples with variation are capped.If occur a choice relation in any step, apply
One tiebreak rule: when a choice relation occurs, preferential selection has clinical feasible or functional annotation variation.Face
Bed it is feasible mean that show the gene be it is pharmaceutical, according to drug-gene interaction database (DGIdb, http: //
Www.dgidb.org/search_interactions).Meaning that for functional annotation shows that the gene is to represent cancer gene
The gene planned in census data library, the database are comprising the catalogue with Cancer-causing mutation gene.Cancer gene population
Census data library (Cancer Gene Census) includes catalogue and functional annotation-database second best plan with carcinogenic mutant gene
The gene drawn.Up to the present, it includes about 600 genes.By applying all these conditions, the list of genes of program output
It is considered the best list of genes with highest patient coverage and minimum variation quantity.
As shown in Fig. 2, the present invention also provides a kind of device of News Search mutant gene, which includes:
Module is obtained, for obtaining several patient's gene data collection of certain disease type；
Statistical module whether there is variation situation for counting each gene that each patient's gene data is concentrated；
Computing module: the variation frequency concentrated for calculating each gene in several patient's gene datas；
Screening module is added in mutant gene list for screening the highest gene of variation frequency, deletes the gene
And it deletes and has made a variation patient's gene data collection of situation comprising the gene；
Judgment module is finished for judging whether several patient's gene data collection are deleted, if it is not, then calculating remaining each
The variation frequency that a gene is concentrated in remaining patient's gene data returns to screening module；If so, into output module；
Output module, for exporting mutant gene list.
The explanation of feature may refer to the related description of embodiment corresponding to Fig. 1 in embodiment corresponding to Fig. 2, here no longer
It repeats one by one.
It is illustrated in figure 3 and the method for News Search mutant gene is applied into the gene after the mutant gene screening of 12 kinds of cancers
Quantity changes comparison sheet.Wherein, abscissa respectively corresponds the name of 12 kinds of cancers, and ordinate is gene dosage, each cancer
In corresponding two pillars, the left side is all gene dosages before screening, and the right is the gene column obtained after being screened by algorithm
The sum of table.Pass through comparison, it can be seen that the overall cancer mutant gene of original database there are thousands of, after algorithm, is added
Cancer mutant gene in list only has tens or so, and about 3.5% overall cancer becomes in average only reservation original database
Allogene, the gene number after screening only account for the minimum ratio of original gene number, embody the validity of the filtering algorithm, simultaneously
The gene filtered out also has very high representativeness.
The present invention also provides a kind of devices of News Search mutant gene, comprising: memory, for storing computer journey
Sequence；Processor, the step of method of above-mentioned News Search mutant gene is realized for executing the computer program.
The present invention also provides a kind of computer readable storage medium, the computer-readable recording medium storage has computer
Program, when the computer program is executed by processor the step of the realization such as method of above-mentioned News Search mutant gene.
It is provided for the embodiments of the invention the method, apparatus of a kind of News Search mutant gene and computer-readable above
Storage medium is described in detail.Each embodiment is described in a progressive manner in specification, and each embodiment emphasis is said
Bright is the difference from other embodiments, and the same or similar parts in each embodiment may refer to each other.For reality
For applying device disclosed in example, since it is corresponded to the methods disclosed in the examples, so being described relatively simple, related place
Referring to method part illustration.It should be pointed out that for those skilled in the art, not departing from the present invention
, can be with several improvements and modifications are made to the present invention under the premise of principle, these improvement and modification also fall into right of the present invention
It is required that protection scope in.
Professional further appreciates that, unit described in conjunction with the examples disclosed in the embodiments of the present disclosure
And algorithm steps, can be realized with electronic hardware, computer software, or a combination of the two, in order to clearly demonstrate hardware and
The interchangeability of software generally describes each exemplary composition and step according to function in the above description.These
Function is implemented in hardware or software actually, the specific application and design constraint depending on technical solution.Profession
Technical staff can use different methods to achieve the described function each specific application, but this realization is not answered
Think beyond the scope of this invention.
The step of method described in conjunction with the examples disclosed in this document or algorithm, can directly be held with hardware, processor
The combination of capable software module or the two is implemented.Software module can be placed in random access memory (RAM), memory, read-only deposit
Reservoir (ROM), electrically programmable ROM, electrically erasable ROM, register, hard disk, moveable magnetic disc, CD-ROM or technology
In any other form of storage medium well known in field.
Claims (6)
1. a kind of method of News Search mutant gene, which is characterized in that the described method includes:
S1: several patient's gene data collection of certain disease type are obtained；
S2: each gene that each patient's gene data of statistics is concentrated is with the presence or absence of variation situation；Wherein, a row is constructed
Number is equal to gene total number, and columns is equal to the matrix of patient's gene data collection total number, and every a line represents a gene each
The variation situation that patient's gene data is concentrated, each column represent the variation situation that patient's gene data concentrates each gene；
Successively judge that each gene that each patient's gene data is concentrated whether there is variation situation, if having made a variation, by patient's base
Because the matrix value of data set and the gene intersection location is set as the first preset value, if not making a variation, it is set as the second preset value；Statistics
Each gene that complete all patient's gene datas are concentrated terminates after whether there is variation situation；
S3: the variation frequency that each gene is concentrated in several described patient's gene datas is calculated；Wherein, it calculates each
Gene concentrates the variation total number that there is variation situation in several patient's gene datas；By the variation of calculated each gene
Total number obtains each gene divided by the total number of patient's gene data collection respectively and concentrates in several patient's gene datas
Variation frequency；
S4: the screening highest gene of variation frequency is added in mutant gene list, deletes the gene and deletes packet
It has made a variation patient's gene data collection of situation containing the gene；Wherein, according to the variation frequency of each gene of calculating, will own
Gene presses variation frequency descending sort；It deletes the gene row that ranks the first and deletes and made a variation the disease of situation comprising the gene
People's gene data set column；
S5: judge whether several described patient's gene data collection are deleted and finish, if it is not, then calculating remaining each gene surplus
Under patient's gene data concentrate variation frequency, return S4；If so, into S6；
S6: the mutant gene list is exported.
2. the method for News Search mutant gene according to claim 1, which is characterized in that described certain disease class of acquisition
The method of several patient's gene data collection of type, comprising:
Several patient's gene data collection of certain disease type are obtained from gene database, the gene database is using outer aobvious
Sub- sequencing technologies.
3. the method for News Search mutant gene according to claim 1, which is characterized in that described to screen variation frequency
Highest gene is added to the method in mutant gene list, comprising:
When the highest gene of variation frequency filtered out is multiple, by the base of the gene and the clinical feasible database of gene
Because the gene catalogue of catalogue and/or annotation of gene function database is compared；
It will be already present in the gene catalogue of the clinical feasible database of gene and/or the gene catalogue of annotation of gene function database
Gene is added in mutant gene list as the highest gene of variation frequency filtered out.
4. a kind of device of News Search mutant gene, which is characterized in that described device includes:
Module is obtained, for obtaining several patient's gene data collection of certain disease type；
Statistical module whether there is variation situation for counting each gene that each patient's gene data is concentrated；Wherein, it constructs
One line number is equal to gene total number, and columns is equal to the matrix of patient's gene data collection total number, and every a line represents a gene
In the variation situation that each patient's gene data is concentrated, each column represent the variation that patient's gene data concentrates each gene
Situation；Successively judge that each gene that each patient's gene data is concentrated whether there is variation situation, if having made a variation, by the disease
People's gene data set and the matrix value of the gene intersection location are set as the first preset value, if not making a variation, are set as the second preset value；
Each gene that the patient's gene data for having counted all is concentrated terminates after whether there is variation situation；
Computing module: the variation frequency concentrated for calculating each gene in several patient's gene datas；Wherein, it calculates each
A gene concentrates the variation total number that there is variation situation in several patient's gene datas；By the change of calculated each gene
Different total number obtains what each gene was concentrated in several patient's gene datas divided by the total number of patient's gene data collection respectively
Variation frequency；
Screening module, for screen the highest gene of variation frequency be added in mutant gene list, delete the gene and
It deletes and has made a variation patient's gene data collection of situation comprising the gene；Wherein, according to the variation frequency of each gene of calculating,
All genes are pressed into variation frequency descending sort；It deletes the gene row that ranks the first and deletes and made a variation feelings comprising the gene
Patient's gene data collection of condition arranges；
Judgment module is finished for judging whether several patient's gene data collection are deleted, if it is not, then calculating remaining each base
Because of the variation frequency concentrated in remaining patient's gene data, screening module is returned；If so, into output module；
Output module, for exporting mutant gene list.
5. a kind of device of News Search mutant gene characterized by comprising
Memory, for storing computer program；
Processor, for executing the computer program, to realize, News Search makes a variation as described in any one of claims 1 to 3
The step of method of gene.
6. a kind of computer readable storage medium, which is characterized in that the computer-readable recording medium storage has computer journey
Sequence realizes the News Search mutant gene as described in any one of claims 1 to 3 when the computer program is executed by processor
Method the step of.
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| CN111540407B (en) * | 2020-04-13 | 2023-06-27 | 中南大学湘雅医院 | Method for screening candidate genes by integrating multiple neurodevelopmental diseases |
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| 肝癌重测序数据整合以及肝癌关键致病基因的研究;张攀;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20161015(第10期);摘要，第15页最后一段至第16页第1段，第19页最后一段 |
| 蛋白激酶基因在不同癌基因组中的变异频率及表达变化;郭冬梅等;《中国现代医学杂志》;20161124;第26卷(第21期);参见第1节 |
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