CN107133492A - A kind of method that gene pathway is recognized based on PAGIS - Google Patents
A kind of method that gene pathway is recognized based on PAGIS Download PDFInfo
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Abstract
The embodiment of the invention discloses a kind of method that gene pathway is recognized based on PAGIS, including sample is obtained, and determine the signal path and gene of sample, and further obtain the gene frequency and gene out-degree of each gene；According to the gene frequency and gene out-degree of each gene, maximum gene frequency, minimum basis are counted because frequency, maximum gene out-degree and minimum basis are because of out-degree, and obtain the gene frequency weight and gene out-degree weight of each gene；According to the gene frequency weight of each gene and gene out-degree weight, calculate the comprehensive weight of each gene, and obtain the weight of each signal path, and be further ranked up the weight of each signal path, determine that the maximum probability changed occurs in the signal path corresponding to peak signal path weight.Implement the embodiment of the present invention, recognize path with reference to the importance and specificity of gene, improve the accuracy of identification of path.
Description
Technical field
The present invention relates to systems biology studying technological domain, more particularly to a kind of gene pathway is recognized based on PAGIS
Method.
Background technology
High-throughput techniques based on microarray generate substantial amounts of gene expression data, how from these magnanimity gene expressions
The understanding for the property seen clearly is obtained in data, and then the mechanism for understanding biological phenomena is still one of pendulum in face of world scientists from all over the world
Individual stern challenge.Biological pathway is the interaction relationship between the gene of one group of completion specific function, mainly there is signal biography
Guiding path and metabolic pathway.In signal transduction pathway, node on behalf gene (or gene outcome), Bian is represented to be turned from a gene
Lead the signal of another gene.In metabolic pathway, node on behalf biochemical compound, side represents the compound encoded by enzyme
Between biochemical reaction, enzyme is for gene code.Conventional pathway database has KEGG and Reactome databases, it
Provide gene interphase interaction visual pattern.
From the angle of systems biology, interaction and its dynamic (dynamical) change between gene be cause various diseases and
The main cause that cancer occurs, because the topological features of path have reacted position of the gene in path, importance and
Interaction between gene, therefore the identification of path should consider the various information for including gene in path, such as base as far as possible
Interactively between the upstream and downstream position of cause, the quantity of controlling gene, gene etc. factor.
2005, the paper of two important path analysis methods is delivered on PNAS, one is that Tian et al. is proposed
Notable path analysis method based on function, this method has considered gene expression and the outer base of set in a gene sets
Because of the conspicuousness (line replacement) of differential expression, and the gene set gene expression and the conspicuousness (column permutation) of phenotype correlation.
Another is that Subramanian et al. proposes famous gene set enrichment analysis method GSEA methods, and its main thought is basis
Correlation in path between expression conditions and given phenotype is ranked up to all genes, it is then determined that given path P
Kolmogorov-Smirnov (Vladimir Smirnov) statistic in sorted lists close to extreme place's degree score.This method
In, the conspicuousness of Kolmogorov-Smirnov statistics is determined according to the column permutation of sample.2006, Zahn et al. was used
Van der Waerden (model obtains Walden) statistic replaces Kolmogorov-Smirnov statistics and replaced with bootstrapping sampling
Permutation test method this method considers in path the correlation of two gene expression doses and the correlation with other factors.
The same year, EFRON et al. substitutes Kolmogorov-Smirnov statistics to calculate path fraction with maximum-Valued Statistics, so
The fraction is standardized by line replacement method afterwards, the conspicuousness of path score value is finally examined using column permutation, this is just
It is famous GSA methods.
On the basis of said gene collection enrichment analysis method GSEA and gene set analysis method GSA, also scholar proposes
Signal path impact analysis method SPIA and overlapping genes drop power method PADOG.In signal path impact analysis method SPIA
In, the influence of the upstream and downstream position of gene to the propagation of disturbing signal is only considered, but have ignored and regulate and control lots of genes in path
Gene should be more even more important than only regulating and controlling the gene of a small amount of gene, their difference has bigger influence to the function of path
Property, and in overlapping genes drop power method PADOG, though on the basis of combining GSA methods, reduction frequently occurs on many paths
In " public gene " influence, but also do not consider path in regulation and control lots of genes gene should be than only regulating and controlling a small amount of gene
Gene it is even more important, their difference has bigger influence to the function of path.
Therefore, it is necessary to which the quantity that a gene regulates and controls downstream gene in path is set into gene out-degree and base is defined as
The importance of cause, is set to gene frequency by the number of times that a gene occurs in path and is defined as the specificity of gene, so that
The accuracy of identification of path is improved with reference to the importance and specificity that gene is defined.
The content of the invention
The purpose of the embodiment of the present invention is to provide a kind of method for recognizing gene pathway based on PAGIS, with reference to gene
Importance and specificity recognize path, improve the accuracy of identification of path.
In order to solve the above-mentioned technical problem, the embodiments of the invention provide a kind of side that gene pathway is recognized based on PAGIS
Method, methods described includes：
A, sample is obtained, and determine gene contained by the signal path and each signal path of the sample, and according to
Each gene and correlation between phenotype are ranked up to contained gene in all signal paths, further according to the sequence after
Gene, determine the gene frequency and gene out-degree of each gene；Wherein, the gene frequency is gene in the determination
The total degree occurred in signal path, the gene out-degree is that gene regulates and controls downstream gene in the signal path of the determination
Quantity；
B, the gene frequency of each gene got according to and gene out-degree, count maximum gene frequency,
Minimum basis is because frequency, maximum gene out-degree and minimum basis are because of out-degree, and according to the maximum gene frequency counted and minimum
Gene frequency, obtains the gene frequency weight of each gene, and according to the maximum gene out-degree and minimum counted
Gene out-degree, obtains the gene out-degree weight of each gene；
C, the correction fraction for determining each gene after gene number amount contained by each signal path and sequence, and according to
The correction fraction and its correspondingly of gene number amount contained by each signal path of the determination and each gene after sequence
Gene frequency weight, calculate the path fraction of each signal path；
D, each gene obtained according to gene frequency weight and its corresponding gene out-degree weight, are calculated
The comprehensive weight of each gene, and according to the comprehensive weight of each gene calculated, to the letter accordingly calculated
The path fraction of number path is revised, and is further arranged the path fraction of each revised signal path
Sequence, it is determined that the maximum probability changed occurs in the signal path after sequence corresponding to maximum access fraction.
Wherein, the step b is specifically included：
According to formulaObtain the gene frequency weight of each gene；Wherein,
f(gj) it is gene g after sequencejGene frequency；wf(gj) it is gene g after sequencejGene frequency weight；
According to formulaObtain the gene out-degree weight of each gene；Wherein,
d(gj) it is gene g after sequencejGene out-degree；wd(gj) it is gene g after sequencejGene out-degree weight.
Wherein, the span of the gene frequency weight of each gene is [1,2].
Wherein, the span of the gene out-degree weight of each gene is [1,2].
Wherein, " comprehensive weight of each gene " passes through formula in the step d
To realize；Wherein, w (gj) it is gene g after sequencejComprehensive weight.
Wherein, the span of the comprehensive weight of each gene is [1,2].
Wherein, in the step d " the path fraction of the signal path to accordingly calculating is revised " by formulaTo realize；Wherein, ES0(S) it is gene g after sequencejPlace signal path S path point
Number；M is gene g after sequencejContained gene number amount in the signal path S of place；T(gj) it is gene g after sequencejCorrection fraction.
Implement the embodiment of the present invention, have the advantages that：
In embodiments of the present invention, the gene frequency weight (i.e. the specificity of gene) and gene out-degree weight of gene are counted
(i.e. the importance of gene), and combine to calculate the comprehensive weight of gene by the two, so that it is determined that the weight of signal path
And the importance of path is recognized with the weight of signal path, reach the purpose for the accuracy of identification for improving path.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
There is the accompanying drawing used required in technology description to be briefly described, it should be apparent that, drawings in the following description are only this
Some embodiments of invention, for those of ordinary skill in the art, without having to pay creative labor, according to
These accompanying drawings obtain other accompanying drawings and still fall within scope of the invention.
Fig. 1 is the flow chart of the method provided in an embodiment of the present invention that gene pathway is recognized based on PAGIS.
Embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, it is right below in conjunction with drawings and Examples
The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and
It is not used in the restriction present invention.
As shown in figure 1, in the embodiment of the present invention, a kind of method that gene pathway is recognized based on PAGIS of proposition is described
Method includes：
Step S1, acquisition sample, and gene contained by the signal path and each signal path of the sample is determined, and
Contained gene in all signal paths is ranked up with correlation between phenotype according to each gene, further according to the row
Gene after sequence, determines the gene frequency and gene out-degree of each gene；Wherein, the gene frequency is gene described true
The total degree occurred in fixed signal path, the gene out-degree is that gene regulates and controls downstream base in the signal path of the determination
The quantity of cause；
Detailed process is, obtains sample, determine the signal path and each signal path of sample contained by gene, go forward side by side one
Step determines gene channel zapping and the distribution of gene out-degree of gene.The frequency (i.e. gene frequency) that gene occurs in path is actual
On reflect the specificity of a gene, frequently occur on the gene in many paths and belong to " public gene ", they are right
The influence of path is relatively small, and its specificity of the gene only occurred in one or several path is high, their differential expression
Influence gene to path is just big.Similarly, what gene out-degree was represented is the quantity of the downstream gene of a gene regulation, therefore goes out
The bigger gene of degree, the influence to path is bigger.
Meanwhile, contained gene in all signal paths is ranked up with correlation between phenotype according further to each gene,
In order to count the correction fraction between gene.It is assumed that all gene numbers are N, a signal path S is given, the signal leads to
Gene number is M in the S of road, according to each gene g and correlation r between phenotype (or t statistics) to N number of gene order L=
[g1,...,gj,...gN]。
Step S2, the gene frequency of each gene got according to and gene out-degree, count maximum gene
Frequency, minimum basis because frequency, maximum gene out-degree and minimum basis are because of out-degree, and according to the maximum gene frequency counted and
Minimum basis obtains the gene frequency weight of each gene because of frequency, and according to the maximum gene out-degree counted and
Minimum basis obtains the gene out-degree weight of each gene because of out-degree；
Detailed process is, according to the gene frequency and gene out-degree of each gene got, to count maximum gene
Frequency max (f), minimum basis are because frequency min (f), maximum gene out-degree max (d) and minimum basis are because of out-degree min (d)；
According to formulaObtain the gene frequency weight of each gene；Wherein,
f(gj) it is gene g after sequencejGene frequency；wf(gj) it is gene g after sequencejGene frequency weight, the value reflection gene exist
Specific degree in path, and the more big then gene specific degree in path of the value is higher, it is on the contrary then specific degree is lower, wf(gj)
Span between [1,2], i.e., the span of the gene frequency weight of each gene be [1,2]；
According to formulaObtain the gene out-degree weight of each gene；Wherein,
d(gj) it is gene g after sequencejGene out-degree；wd(gj) it is gene g after sequencejGene out-degree weight, the value reflection gene exist
Importance in path, the more big then gene significance level in path of the value is higher；On the contrary then gene significance level in path
It is lower, wd(gj) span between [1,2], i.e., the span of the out-degree weight of each gene is [1,2].
Step S3, the correction fraction for determining each gene after gene number amount contained by each signal path and sequence,
And according to contained by each signal path of the determination gene number amount and sequence after each gene correction fraction and
Its corresponding gene frequency weight, calculates the path fraction of each signal path；
Detailed process is that the average using the weighting definitely correction fraction sum of all genes in signal path is each to calculate
The path fraction of individual signal path, you can pass through formulaTo realize that each signal leads to
The calculating of the path fraction on road；Wherein, ES0(S) it is gene g after sequencejPlace signal path S path fraction；After M is sequence
Gene gjContained gene number amount in the signal path S of place；T(gj) it is gene g after sequencejCorrection fraction.
Step S4, each gene obtained according to gene frequency weight and its corresponding gene out-degree weight,
The comprehensive weight of each gene is calculated, and according to the comprehensive weight of each gene calculated, to corresponding calculating
The path fraction of the signal path gone out is revised, and further by the path fraction of each revised signal path
It is ranked up, it is determined that the maximum probability changed occurs in the signal path after sequence corresponding to maximum access fraction.
Detailed process is to merge gene frequency weight and gene out-degree weight, pass through formula
Calculate the comprehensive weight w (g of each genej)；Wherein, w (gj) it is gene g after sequencejComprehensive weight, the value reflection base
Because of the importance and specific degree in path, the more high then value of gene significance level and specific degree in path is more
Greatly, it is on the contrary then the significance level of gene or specific degree are lower, w (gj) span between [1,2], i.e. each gene
Comprehensive weight span be [1,2].
By the comprehensive weight w (g of each resulting genej) replace gene frequency weight wf(gj), revised with this every
The path fraction of one gene, that is, pass through formulaTo realize repairing for gene pathway fraction
Order, and further revised path fraction sorts according to order from big to small, it is determined that maximum access fraction institute after sequence
There is the more forward then signal path tendency of the maximum probability changed, i.e. path fraction ranking as research in corresponding signal path
Value it is higher.
Implement the embodiment of the present invention, have the advantages that：
In embodiments of the present invention, the gene frequency weight (i.e. the specificity of gene) and gene out-degree weight of gene are counted
(i.e. the importance of gene), and combine to calculate the comprehensive weight of gene by the two, so that it is determined that the weight of signal path
And the importance of path is recognized with the weight of signal path, reach the purpose for the accuracy of identification for improving path.
Can be with one of ordinary skill in the art will appreciate that realizing that all or part of step in above-described embodiment method is
The hardware of correlation is instructed to complete by program, described program can be stored in a computer read/write memory medium,
Described storage medium, such as ROM/RAM, disk, CD.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
Any modifications, equivalent substitutions and improvements made within refreshing and principle etc., should be included in the scope of the protection.
Claims (7)
1. a kind of method that gene pathway is recognized based on PAGIS, it is characterised in that methods described includes：
A, acquisition sample, and gene contained by the signal path and each signal path of the sample is determined, and according to each
Individual gene is ranked up with correlation between phenotype to contained gene in all signal paths, further according to the base after the sequence
Cause, determines the gene frequency and gene out-degree of each gene；Wherein, the gene frequency is signal of the gene in the determination
The total degree occurred in path, the gene out-degree is the number that gene regulates and controls downstream gene in the signal path of the determination
Amount；
B, the gene frequency of each gene got according to and gene out-degree, count maximum gene frequency, minimum
Gene frequency, maximum gene out-degree and minimum basis because of out-degree, and according to the maximum gene frequency counted and minimum basis because
Frequency, obtains the gene frequency weight of each gene, and according to the maximum gene out-degree counted and minimum basis because
Out-degree, obtains the gene out-degree weight of each gene；
C, the correction fraction for determining each gene after gene number amount contained by each signal path and sequence, and according to described
The correction fraction and its corresponding base of gene number amount contained by each signal path determined and each gene after sequence
Because of frequency weight, the path fraction of each signal path is calculated；
D, each gene obtained according to gene frequency weight and its corresponding gene out-degree weight, are calculated each
The comprehensive weight of individual gene, and according to the comprehensive weight of each gene calculated, the signal accordingly calculated is led to
The path fraction on road is revised, and is further ranked up the path fraction of each revised signal path,
It is determined that there is the maximum probability changed in the signal path after sequence corresponding to maximum access fraction.
2. the method as described in claim 1, it is characterised in that the step b is specifically included：
According to the gene frequency and gene out-degree of each gene got, count maximum gene frequency max (f),
Minimum basis is because frequency min (f), maximum gene out-degree max (d) and minimum basis are because of out-degree min (d)；
According to formulaObtain the gene frequency weight of each gene；Wherein, f
(gj) it is gene g after sequencejGene frequency；wf(gj) it is gene g after sequencejGene frequency weight；
According to formulaObtain the gene out-degree weight of each gene；Wherein, d (gj)
For gene g after sequencejGene out-degree；wd(gj) it is gene g after sequencejGene out-degree weight.
3. method as claimed in claim 2, it is characterised in that the span of the gene frequency weight of each gene
For [1,2].
4. method as claimed in claim 2, it is characterised in that the span of the gene out-degree weight of each gene
For [1,2].
5. method as claimed in claim 2, it is characterised in that " comprehensive weight of each gene " leads in the step d
Cross formulaTo realize；Wherein, w (gj) it is gene g after sequencejComprehensive weight.
6. method as claimed in claim 5, it is characterised in that the span of the comprehensive weight of each gene is
[1,2].
7. method as claimed in claim 2, it is characterised in that " to the logical of the signal path that accordingly calculates in the step d
Road fraction is revised " by formulaTo realize；Wherein, ES0(S) it is base after sequence
Because of gjPlace signal path S path fraction；M is gene g after sequencejContained gene number amount in the signal path S of place；T(gj)
For gene g after sequencejCorrection fraction.
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| CN109817337A (en) * | 2019-01-30 | 2019-05-28 | 中南大学 | A kind of appraisal procedure and similar disorder differentiating method of single disease sample Pathway Activation degree |
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