CN101847181A - Tissue-specific gene and regulatory factor data storage method - Google Patents
Tissue-specific gene and regulatory factor data storage method Download PDFInfo
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Abstract
The invention discloses a tissue-specific gene and regulatory factor data storage method. In the method, data storage is realized by establishing a tissue-specific gene and regulatory factor database comprising a tissue bank, a gene bank, a gene reference name bank, a tissue-specific gene bank and the tissue bank of tissue-specific genes. The method comprises the following steps of: extracting the tissue-specific genes from a Pubmed bibliographic database in a literature mining form; adding extracted tissue information into the tissue bank; retrieving information about the genes in the European Molecular Biology Laboratory (EMBL), Genebank and NCBI by utilizing names of the genes, and adding the information into corresponding items of the gene bank; and generating regulatory factor XML files by utilizing the information of regulating the searching of the genes from Transfac, an Eukaryotic Promoter Database (EPD) and a compel database. Compared with the prior art, the method has the advantages of bringing convenience to researchers utilizing modern computing technology to detect gene expression and regulate an inherent mechanism of network tissue specificity to acquire data on sequences of the tissue-specific genes and corresponding regulatory factors, fully utilizing tissue-specific gene analysis tools and improving research quality and efficiency.
Description
Technical field
The present invention relates to field of bioinformatics, particularly relate to the database technology that concerns between the specific expressed and regulatory factor of tissue-specific gene in this field.
Background technology
The development with calculation biology finished along with the Human Genome Project has accumulated a large amount of gene expression and the data of regulation relationship thereof, for the tissue specificity of research gene expression and regulation relationship thereof provides abundant information resources.
Utilize modern computing technique to excavate gene expression and the tissue-specific inherent mechanism of regulated and control network, become one of the most challenging task of current bioinformatics.Yet, present stage is owing to tissue-specific gene and the regulatory factor data are disperseed, biomolecule information database mixes, present situations such as the complex relationship of the multi-to-multi between tissue and gene and gene and the regulatory factor, mark and expression standard disunity, make the researcher of tissue-specific gene expression and regulation mechanism have to take much time and at first study the content of each database, collect again and verify the tissue-specific gene related data, greatly reduce the quality and the efficient of research.
Summary of the invention
Based on above-mentioned prior art, the present invention proposes a kind of tissue-specific gene and regulatory factor data storage method, this storage means has proposed a kind of new tissue-specific gene and the architecture of regulatory factor database thereof; Integrated tissue-specific gene control region domain model feature and regulatory mechanism information; Tissue-specific gene analysis tool collection is provided, has made things convenient for data mining and fast query.
The present invention proposes a kind of tissue-specific gene and regulatory factor data storage method, the tissue bank tissue-specific gene and the regulatory factor database that comprise tissue bank, gene pool, gene another name storehouse, tissue-specific gene storehouse and tissue specificity base by foundation carry out data storage, and this method may further comprise the steps:
The form of utilizing document to excavate extracts tissue-specific gene at medical literature database;
The organizational information of finding is added in the tissue bank;
Utilize the name of gene in DNA database, nucleic acid and protein sequence, gene order, protein sequence functional data storehouse, to retrieve the information of gene, and this information is added in the clauses and subclauses of gene pool correspondence;
Gene is searched in utilization from database, promoter in eukaryote database and the composite component database of transcription factor, their binding sites on genome and the profiles that combines with DNA regulation and controlling of information generates the gene regulation factor XML files;
Wherein, tissue bank comprises all organizational informations in the database, and content comprises from what increase the type variable uniquely organizes the name of code, tissue, the classification of tissue and the description of tissue; Gene pool comprises all tissue-specific gene informations in the database, and content comprises from the name of the unique genetic code, the gene that increase the type variable, regulatory factor xml file that gene pairs is answered and the nucleotide sequence of gene; Storage is about all or part of another name of each gene in the gene pool in the gene another name storehouse; There is specific expressed gene-correlation connection in the tissue-specific gene storehouse the tissue in the tissue bank with to this tissue, and what content comprised tissue gene increases the unique unique genetic code that increases the type variable certainly in code, the corresponding gene pool, the description of incidence relation, the code pmd_idhe that verifies this incidence relation article in pmd and the expression of corresponding this gene in this tissue organized that increases the type variable certainly in unique incidence relation code of type variable, the corresponding tissue bank certainly; Each clauses and subclauses in the tissue-specific gene storehouse are all distinguished corresponding gene regulation factor XML files, the access path of this document is stored in the gene pool, this document is used for describing gene all regulatory factor information at tissue, comprise the type of transcripting start point and the position in this gene nucleic acid sequence, the transcription factor binding position of site in this nucleotide sequence, the functional description of transcription factor, all of this tissue-specific gene expression of specific regulation and control add the position of hadron (enhancer) in this nucleic acid series, length and functional description, the position of all silencers (sliencer) in this nucleic acid series that this tissue-specific gene of specific regulation and control is expressed, length and functional description, genetic transcription control area pattern feature, transcription factor is to the regulatory mechanism of genetic transcription.
Knit specific controlling to gene region mode feature and regulatory mechanism.Native system excavates by document and two kinds of approach of analysis and research of a large amount of tissue-specific gene regulatory factor data in the system of being stored in is obtained the regulatory mechanism information of tissue-specific gene sequence pattern feature and transcription factor, for the specific expressed research of tissue-specific gene regulation and control provides reference.
Described tissue-specific gene and regulatory factor database also comprise knits specific gene analysis tool collection, and this tool set specifically comprises:
Inquiry service, the user inquires about according to organization name, gene name, and system returns the Query Result of tissue-specific gene sequence and regulatory factor information according to the ontology describing of tissue, tissue-specific gene and regulatory factor thereof;
The identification service, level Bayes mixture model clustering algorithm based on constraint, prioris such as the known promoter region pattern feature of fusion target gene and tissue-specific regulatory factor information offer user Hk (Housekeepinggenes) and TS (Tissue Specific genes);
The discovery service of tissue-specific sequence pattern (motif), utilize statistical model, on the basis that a large amount of HK genes and TS gene Promoter regional sequence pattern and tissue-specific transcription's factor binding pattern are analyzed in to system, by Bayes's factorial analysis, set up the mathematical model of the pattern conspicuousness evaluation of merging priori.
Compared with prior art, the present invention can make the researcher who utilizes modern computing technology excavation gene expression and regulated and control network to knit the group-specific inherent mechanism, conveniently obtain the data of tissue-specific gene sequence and corresponding regulatory factor, make full use of the tissue-specific gene analysis tool, improve the quality and the efficient of research.
Description of drawings
Fig. 1 is tissue-specific gene and regulatory factor Basis of Database framework E-R figure thereof.
Embodiment
Tissue bank tissue comprises organizational informations all in the database, in have tissue_id, tissue_name, category, description.Wherein, tissue_id is from the variable that increases type, unique definite tissue in tissue bank; The name of the corresponding tissue of tissue_name; The classification (consistent) of the corresponding tissue of category with the criteria for classification among the EMBL; The description of corresponding this tissue of description.
Gene pool gene comprises all tissue-specific gene informations in the database, in have gene_id, gene_name, tr_factor_url, sequence_link.Wherein, gene_id is from increasing type, uniquely in gene pool determines a gene; The name of the corresponding gene of gene_name (gene has a plurality of names, gene_name correspondence herein be gene name among the EMBL); Tr_factor_url points to the regulatory factor xml file that this gene pairs is answered; The nucleotide sequence of corresponding this gene of sequence_link.
Storage is about all or part of another name of each gene in the gene storehouse among the gene another name storehouse gene_ref_name.There is specific expressed gene-correlation connection in tissue-specific gene storehouse (tissue_gene) the tissue in the tissue bank with to this tissue, and content comprises id, tissue_id, gene_id, description, pmd_id, gene_express_value.Wherein each id determines the incidence relation of a tissue gene, and this id is from increasing type; Tissue_id in the corresponding tissue bank of tissue_id; Gene gene_id in the corresponding gene of the gene_id storehouse; Description describes this incidence relation; Pmd_id is id number of this incidence relation of checking article in pmd; The expression of corresponding this gene of gene_express_value in this tissue.
Each clauses and subclauses is corresponding with unique XML file, and the access path of this file is stored in the tr_factor_url row of gene pool.Regulation and controlling of information for tissue, tissue-specific gene and gene, system developer utilizes the form of document excavation at Pubmed (medical literature database of u.s. national library of medicine) data in literature library lookup tissue-specific gene, and finding to such an extent that organizational information adds in the tissue table; The name of utilizing gene is at the EMBL (EMBL of European Molecular Biology Laboratory (TheEuropean Molecular Biology Laboratory), added by 14 countries in Europe that the Israel in Asia initiated to set up the DNA database jointly in 1974), Genebank (the geneseq database that NIH safeguards, compile and note all disclosed nucleic acid and protein sequences), NCBI (U.S.'s state-run commune hospital construction about biomedical website, document is provided, gene order, the functional data storehouse of protein sequence etc.) information of retrieval gene in, and this information is added in the clauses and subclauses of gene table correspondence; At last, utilization is from (Transfac is about transcription factor, their binding sites on genome and the database of the profiles that combines with DNA), EPD (promoter in eukaryote database (Eukaryotic Promoter Database, EPD), can retrieve Eukaryotic promoter sequence information therein) and compel (composite component database) database in search gene regulation and controlling of information generate the gene regulation factor XML files;
Each clauses and subclauses in the tissue-specific gene storehouse are all distinguished corresponding gene regulation factor XML files, this gene of this file description all regulatory factor information in this tissue, comprise transcripting start point (corresponding promoter of each transcripting start point, the inquiry can extract according to the needs of research from transcribing the nucleic acid fragment of starting point upstream and downstream random length as promoter region) type (single, multiple, region) position and in this gene nucleic acid sequence, the position of transcription factor (TFBS) binding site (the corresponding a plurality of transcription factor binding of each transcripting start point site) in this nucleotide sequence, transcription factor (each transcription factor is bound a site-specific corresponding transcription factor), the functional description of transcription factor, all of this tissue-specific gene expression of specific regulation and control add the position of hadron (enhancer) in this nucleic acid series, length and functional description, the position of all silencers (sliencer) in this nucleic acid series that this tissue-specific gene of specific regulation and control is expressed, length and functional description, genetic transcription control area pattern feature, transcription factor is to the regulatory mechanism of genetic transcription.
Knit specific controlling to gene region mode feature and regulatory mechanism.Native system excavates by document and two kinds of approach of analysis and research of a large amount of tissue-specific gene regulatory factor data in the system of being stored in is obtained the regulatory mechanism information of tissue-specific gene sequence pattern feature and transcription factor, for the specific expressed research of tissue-specific gene regulation and control provides reference.
Tissue-specific gene analysis tool collection.The service that tissue-specific gene analysis tool collection provides is as follows:
Inquiry service;
The service of Hk (Housekeeping genes) and TS (Tissue Specific genes) identification;
The service that tissue-specific sequence pattern (motif) is found.
The present invention will be further described below in conjunction with the accompanying drawing example.
At first utilize Database Systems (Mysql), foundation comprises tissue bank (tissue), gene pool (gene), tissue-specific gene storehouse (tissue_gene), gene another name storehouse (gene_ref_name) is at the interior tissue-specific gene of the present invention and the architecture synoptic diagram of regulatory factor database thereof, as shown in Figure 1.
Each clauses and subclauses in the gene pool are corresponding with unique XML file, and the access path of this file is stored in the tr_factor_url row of gene pool.For the regulation and controlling of information of tissue, tissue-specific gene and gene, system developer utilizes the form of document excavation at Pubmed data in literature library lookup tissue-specific gene, and finding to such an extent that organizational information adds in the tissue table; Utilize the name of gene in EMBL, Genebank, NCBI, to retrieve the information of gene, and this information is added in the clauses and subclauses of gene table correspondence; At last, utilize the regulation and controlling of information of from Transfac, EPD and compel database, searching gene to generate the gene regulation factor XML files:
<？xml?version＝″1.0″encoding＝″GB2312″standalone＝″yes″？>
<gene>
<sequence>
</sequence>
<！--transcription?type＝″singal、multiple、regoin″-->
<ts_type?value＝″>
<！--if?s_type?value＝′singal′，there?is?only?one?ts_position；if?ts_type＝′multiple′there?are?many
ts_position-->
<ts?position＝″>
<！--if?there?are?more?than?one?transcription?factors?binding?sites，there?will?be?a?couple
of?tags-->
<tfbs?position＝″>
<tf>″</tf>
<function_description>″</function_description>
</tfbs>
</ts>
<！--if?ts_position＝′region′-->
<ts_start_position>″</ts_start_position>
<ts_length>″</ts_length>
</ts_type>
<trans_control_motif>″</trans_control_motif>
<！--if?there?are?more?than?one?transcription?control?motifs，there?will?be?a?couple?of?tags-->
<enhancer>
<！--if?there?are?more?than?one?enhancer，there?will?be?a?couple?of?tags-->
<position>″</position>
<sequence>″</sequence>
<description>″</description>
</enhancer>
<sliencer>
<！--if?there?are?more?than?one?sliencer，there?will?be?a?couple?of?tags-->
<position>″</position>
<sequence>″</sequence>
<description>″</description>
</sliencer>
</gene>
Secondly native system excavates by document and two kinds of approach of analysis and research of a large amount of tissue-specific gene regulatory factor data in the system of being stored in is obtained the regulatory mechanism information of tissue-specific gene sequence pattern feature and transcription factor, and this information with tissue-specific gene regulatory factor XML file description.For the specific expressed research of tissue-specific gene regulation and control provides reference.
Subsystem provides tissue-specific gene analysis tool collection again, and the service that provides has: inquiry service; The identification service of Hk (Housekeepinggenes) and TS (Tissue Specific genes); The discovery service of tissue-specific sequence pattern (motif).
The inventor utilizes existing web development technique jsp to realize search function, after system accepts user's input key word, takes different bottom operations according to the type (gene name, organization name, PMD_ID) of key word.When key word type is " gene name ", gene another name storehouse table is at first searched by system, search gene clauses and subclauses of the same name therewith, take out the gene_id row, and search the gene storehouse according to this column information and show, in the result who finds, take out except that " tr_factor_url " is listed as and return to the user, when if the user selects " checking the details of gene ", system reads the content of gene regulation information XML file according to " tr_factor_url " indicated path, when if the user selects to check the organizational information of gene-correlation therewith, system is by gene_id parameter query tissue storehouse, and Query Result is shown to the user, and can be shown to the user according to the display mode that the user formulates.When key word type is " organization name ", tissue bank is at first searched by system, search and organize clauses and subclauses of the same name therewith, take out all information of these clauses and subclauses, simultaneity factor is extracted " tissue_id " row of finding clauses and subclauses, and foundation " tissue_id " is searched the tissue_gene storehouse, after finding all genes that tissue is relevant therewith, utilizing " gene_id " retrieval gene storehouse, search gene clauses and subclauses of the same name therewith, take out these clauses and subclauses and return to the user except that " tr_factor_url " row, when if the user selects " checking the details of gene ", system reads the content of gene regulation information XML file according to " tr_factor_url " indicated path, and can be shown to the user according to the display mode that the user formulates.When key word type was " PMD_ID ", after system received parameter, retrieval gene_tissue storehouse table was listed as identical clauses and subclauses therewith according to " PMD_ID " in this table number retrieval.System utilization retrieval obtains the gene_id information searching gene table in the clauses and subclauses, returns to user all sequence information and regulation and controlling of information of gene-correlation therewith; System's utilization retrieve the tissue_id information searching tissue table in the clauses and subclauses, return to the relevant information of this tissue of user.
System is based on the level Bayes mixture model clustering algorithm of constraint, prioris such as the known promoter region pattern feature of fusion target gene and tissue-specific regulatory factor information offer the identification service of user Hk (Housekeeping genes) and TS (Tissue Specific genes);
Utilize statistical model, on the basis that a large amount of HK genes and TS gene Promoter regional sequence pattern and tissue-specific transcription's factor binding pattern are analyzed in to system, by Bayes's factorial analysis, set up the mathematical model of the pattern conspicuousness evaluation of merging priori, the service of finding tissue-specific sequence pattern (motif) is provided.
Claims (2)
1. tissue-specific gene and regulatory factor data storage method, the tissue-specific gene and the regulatory factor database that comprise the tissue bank of tissue bank, gene pool, gene another name storehouse, tissue-specific gene storehouse and tissue specificity base by foundation are realized data storage, and this method may further comprise the steps:
The form of utilizing document to excavate extracts tissue-specific gene at medical literature database;
The organizational information of finding is added in the tissue bank;
Utilize the name of gene in DNA database, nucleic acid and protein sequence, gene order, protein sequence functional data storehouse, to retrieve the information of gene, and this information is added in the clauses and subclauses of gene pool correspondence;
Gene is searched in utilization from database, promoter in eukaryote database and the composite component database of transcription factor, their binding sites on genome and the profiles that combines with DNA regulation and controlling of information generates the gene regulation factor XML files;
Wherein, tissue bank comprises all organizational informations in the database, and content comprises from what increase the type variable uniquely organizes the name of code, tissue, the classification of tissue and the description of tissue; Gene pool comprises all tissue-specific gene informations in the database, and content comprises from the name of the unique genetic code, the gene that increase the type variable, regulatory factor xml file that gene pairs is answered and the nucleotide sequence of gene; Storage is about all or part of another name of each gene in the gene pool in the gene another name storehouse; There is specific expressed gene-correlation connection in the tissue-specific gene storehouse the tissue in the tissue bank with to this tissue, and what content comprised tissue gene increases the unique unique genetic code that increases the type variable certainly in code, the corresponding gene pool, the description of incidence relation, the code pmd_idhe that verifies this incidence relation article in pmd and the expression of corresponding this gene in this tissue organized that increases the type variable certainly in unique incidence relation code of type variable, the corresponding tissue bank certainly; Each clauses and subclauses in the tissue-specific gene storehouse are all distinguished corresponding gene regulation factor XML files, the path is stored in the gene pool between the visit of this document, this document is used for describing gene all regulatory factor information at tissue, comprise the type of transcripting start point and the position in this gene nucleic acid sequence, the transcription factor binding position of site in this nucleotide sequence, the functional description of transcription factor, all of this tissue-specific gene expression of specific regulation and control add the position of hadron (enhancer) in this nucleic acid series, length and functional description, the position of all silencers (sliencer) in this nucleic acid series that this tissue-specific gene of specific regulation and control is expressed, length and functional description, genetic transcription control area pattern feature, transcription factor is to the regulatory mechanism of genetic transcription.
2. tissue-specific gene as claimed in claim 1 and regulatory factor data storage method is characterized in that, described tissue-specific gene and regulatory factor database also comprise knits specific gene analysis tool collection, and this tool set specifically comprises:
Inquiry service, the user inquires about according to organization name, gene name, and system returns the Query Result of tissue-specific gene sequence and regulatory factor information according to the ontology describing of tissue, tissue-specific gene and regulatory factor thereof;
The identification service, level Bayes mixture model clustering algorithm based on constraint, prioris such as the known promoter region pattern feature of fusion target gene and tissue-specific regulatory factor information offer the service of user Housekeepinggenes and Tissue Specific genes identification;
The discovery service of tissue-specific sequence pattern motif, utilize statistical model, on the basis that a large amount of HK genes and TS gene Promoter regional sequence pattern and tissue-specific transcription's factor binding pattern are analyzed in to system, by Bayes's factorial analysis, set up the mathematical model of the pattern conspicuousness evaluation of merging priori
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