CN108491685A - A kind of genetic engineering algorithm based on cyto-mechanics matrix model - Google Patents
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Abstract
The present invention proposes a kind of genetic engineering algorithm based on cyto-mechanics matrix model, specifically comprises the following steps：1) setting cyto-mechanics is theoretical, 2) theoretical system derived from selection classical mechanics establishes the complicated calculations of cell；3) combine Hamilton's principle, its characteristic is described by Lagrangian, 4) according to 3) being derived from cyto-mechanics equation group；5) according in 4), cyto-mechanics equation group can be written as matrix form of equal value：H|X>=| X'>；The invention enables genetic engineerings to be designed with theoretical foundation, and computer forecast, assessment are carried out to the product of genetic engineering in the design phase；The present invention can be by biological theory mathematicization, to the achievement to human research, it is applied in Robot Design, fast-developing artificial intelligence, since human genome is best operating system, the present invention can design the design method of human genome operating system for computer operating system.
Description
Technical field
The present invention relates to gene engineering technology fields, are concretely related to a kind of gene based on cyto-mechanics matrix model
Engineering Algorithm.
Background technology
Genetic engineering (genetic engineering) is also known as gene splicing technology and DNA recombinant techniques, is lost with molecule
It passes to learn and be pressed the gene of separate sources advance using molecular biology and microbiological modernism as means for theoretical foundation
The blueprint of design builds hybrid DNA molecule, is then introduced into living cells in vitro, to change the original hereditary capacity of biology, obtain
Obtain new varieties, production new product.Technique for gene engineering provides strong means for the research of the structure and function of gene.
In the prior art, be essentially all how to realize the technological means of transgenosis, for transgene how and it is former
Come how biological possessed gene interacts, which kind of mechanism transgene takes regulate and control its expression side in original biology
The problems such as formula, the transgene influence whole to complicated biology nearly all without reference to.The public is for transgenic product at present
Opposition, just reflect the worry of safety of the public to the transgenic product that do not further investigate, because so far, very
To neither one, really rational theoretical and practical method is studied and is designed to these problems.
In the prior art, the most possible method for being studied the complexity of genetic engineering is to be based on nerve net
The biological model of network theory；The paper of nineteen eighty-two, American physicist Hopfield neural networks excite modern neuro net
Network research boom, Stuart A.Kauffman propose the biology mould based on neural network theory according to neural network theory
Type, 1993, he《Order originates from》It is detailed in one book to discuss this theoretical application in biomedicine, it is so far
Most popular biological neural network model.
Patent based on neural network theory is thousands of, we repeat no more herein, however neural network theory
It reasonably can not explain and predict the regulatory mechanism that cell interior is dominated by gene.
Invention content
Therefore the present invention proposes a kind of genetic engineering algorithm based on cyto-mechanics matrix model, for solving transgene
With the complexity problems such as the intrinsic gene interaction of protozoa, expression regulation, entire effect.
The technical proposal of the invention is realized in this way：A kind of genetic engineering algorithm based on cyto-mechanics matrix model,
Specifically comprise the following steps：
1) setting cyto-mechanics is theoretical, and wherein each in prokaryotic cell includes n kinds molecule and ion, each molecule into the cell
Or the quantity of ion is qi, then the state of prokaryotic cell be expressed as with vector：(q1,q2,…,qn)；
Each organelle is expressed as with vector in eukaryocyte：(q1,q2,…,qs)；The state vector of eukaryocyte is each
The combination of a organelle, cytoplasm, nucleus vector；
2) theoretical system derived from classical mechanics is selected to establish the complicated calculations differential equation of cell and matrix norm of equal value
Type；
3) Hamilton's principle is combined, its cell characteristics is described by Lagrangian：
4) according to 3) being derived from, cyto-mechanics equation group is
HereIt is the Lagrangian of cell；qiIt is mole of i-th of component of cell
Concentration,It is that the molar concentration of i-th of component of cell changes with time rate；
5) according in 4), cyto-mechanics equation group-Lagrange's equation group can be written as matrix form of equal value
H|X>=| X'>
Here H is Differential operator Matrix：
Vector | X>For cell state vector：
Wherein, XiFor the molar concentration of i-th of gene outcome in cellular genome, the component h of matrix HijFor cell state
Vector | X>Function, i.e.,
hij=hij(X1,X2,...Xn)
Here it is only a few really to participate in the gene of regulation and control, i.e. hij(X1,X2,...Xn) in parameter XiMost of is zero.
Differential operator Matrix acts on cell vector | X>It is vector to make the variation of its state vector | X'>, when the effect of differential operator makes it
When cell state vector enters an attractor, cell enters a relatively steady state, thin to eukaryon biologically
For born of the same parents, a certain cell differentiation state stablized is represented；
The nonlinear terms for removing equation, are reduced to system of linear equations, i.e., matrix H are reduced to linear positive definite matrix,
It then solves equation and is reduced to ask eigenvalue of matrix problem：
H|X>=ω | X>
Here H is cellular matrices, | X>For cell vector, it reflects the form of cell cycle solution, it indicates that cell is normally numerous
The state grown, for eukaryocyte, it indicates the proper splitting state that do not break up.
Further, the step 3)In, it is assumed that at t=t1 and t=t2 moment cells
In two determining states, the two states are respectively by two groups of generalized coordinates q(1)And q(2)It determines, q is all q here1,
q2... qnSet, qiRepresentative cell in i-th of component molar concentration, referred to as i-th of generalized coordinates；
In this case, state of the cell system two moment, which follows, makes integral
It is developed for the mode of minimum possible value, integral S is the actuating quantity of cell system.
Further, in order to simplify formulation process, it is assumed that system only has one degree of freedom, determines function q (t),
It is assumed that q=q (t) is the function for making S obtain minimum, function is used
q(t)+δq(t)
Replace q (t) when, S increases, and wherein δ q are the function of very little, referred to as function q in the time interval from t1 to t2
(t) variation, since as t=t1 and t=t2, all functions that can be used for comparing should have identical q(1)And q(2), because
This can be released
δ q (dying 1)=δ q (dying 2)=0
The variation of S caused by q is replaced to be represented by with q+ δ q
This difference by δ q andThe expansion of index is originated from level-one item, and it is that S is obtained that these summation, which is equal to 0,
The necessary condition of minimum, this summation is known as integrating the level-one variation of S, therefore Hamilton's principle can be write as
It can be write as after variation
Integration by parts is carried out to Section 2, according to the expression formula to t derivations
It obtains
It is learnt by condition δ q (t1)=δ q (t2)=0, first item is constantly equal to 0, therefore no matter δ q take any value, remaining product
Dividing be equal to 0, and such case only is likely to occur in the case where the expression formula being integrated is equal to 0, therefore, the side of obtaining
Journey：
When cell has s degree of freedom, according to Hamilton's principle, it should independent variation s different function qi
(t), s equation therefore, is obtained：
Further, since chemical reaction changes over time between the component in the cell, this variation will be obeyed
The constraint of chemical equation, therefore each chemical equation provides a constraints, therefore cell system group
The number that the number divided subtracts various chemical equations in cell is only the number that cell freely changes component, i.e. cell
Degree of freedom.
By above disclosure, beneficial effects of the present invention are：The invention enables genetic engineerings to be designed with theoretical base
Plinth carries out computer forecast, assessment in the design phase to the product of genetic engineering；The present invention can be by biological theory mathematics
Change, to the achievement to human research, be applied in Robot Design, fast-developing artificial intelligence, due to human genome
It is best operating system, the design method of human genome operating system can be used for computer operating system by the present invention
Design.
Specific implementation mode
Clear, complete description is carried out below in conjunction with technical solution in the embodiment of the present invention of the embodiment of the present invention,
Obviously, described embodiment is only a part of the embodiment of the present invention, instead of all the embodiments.Based on the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts,
It shall fall within the protection scope of the present invention.
The present invention proposes a kind of genetic engineering algorithm based on cyto-mechanics matrix model.
The present invention is directed to export a cell number scientific principle based on mathematics, physics and molecular biology basic assumption
By according to the custom of physics, mechanics is the mathematical theory of physics, so setting this theory is known as cyto-mechanics, this is thin
Born of the same parents' mechanics is the mathematical theory of a research life cells.
Basic assumption
The theory for recognizing all generally acknowledged basic mathematicals and physics at present first introduces a vacation substantially for cell
Fixed, i.e., the state of cell can be by forming the state description of the molecule, ion of cell.
For prokaryotic cell, if one includes n kinds molecule and ion into the cell, the quantity of each molecule or ion is
qi, then the state of this cell can use vector (q1,q2,…,qn) describe, have ignored here each molecule position,
Size, shape, direction；Because the research of molecular biology finds that statistically these are changed over time, and can not be tracked
The information such as position are relatively inessential；Molecule displays and effect due to the molecule in portion in the cell and on cell membrane very not phase
Together, therefore the molecule on cell membrane and intracellular molecule should be distinguished in theory.
For eukaryocyte, model will consider various organelles, to each organelle vector (q1,q2,…,qs) come
Description, and entire cell is described by forming the organelle, nucleus and cytoplasmic set of vectors of this cell.
It should be pointed out that since the main component part of cell is water, so convenient description method is vector
Each component is normalized to molar concentration；Middle component q discussed belowiRepresent the molar concentration of i-th of component, point of vector
It measures us and is known as coordinate according to custom,Refer to that the molar concentration of i-th of component in cell changes with time rate, coordinate qi
It is considered as the generalized coordinates of the phase space of description cell state.
For simple prokaryotic cell, although cell can exchange substance, δ q with ambient enviromentiWith cell itself phase
Than the amount of substance of exchange is less, and cell is regarded as an isolated blob, cell is exchanged with external substance then and is regarded as
With the interaction of other systems.
Select classical mechanics
Which type of for physical system, first have to determine us using theoretical body when determining the method for research system
System, is classical mechanics system, quantum mechanics system or Relativistic Mechanics system.
As life, movement is clearly low-speed motion, therefore the theory of relativity can exclude, and then compare quantum mechanics and still pass through
Allusion quotation mechanics is write with reference to Ai Erwen Schrodinger《What life is》This monument directly uses quantum-mechanical sight
Point explains the phenomenon that life, so the scholar of most of class origin physics starts with from quantum mechanics, it is intended to use quantum mechanics solution
Release biological phenomena；However, research finds quantum mechanics in two intermolecular interactions in understanding life in the present embodiment,
It is a useful tool, but the statistic processes of cell interior and intercellular interaction is macro in understanding life
It is unnecessary, the statistic processes of cell interior when seeing result：Such as point between the synthesis of DNA replication dna, protein, organelle
Work, etc. more like a factory production process, and be it is quite deterministic, rather than problems of quantum mechanics like that not really
Fixed probability behavior, and the success of molecular biology shows that this viewpoint is correct.
The experimental result for studying the molecular biology method offer of cell-intrinsic process is all statistical data, the life studied
Object macromolecular has also reached the scale that can be handled using classical mechanics on scale, and therefore, the present embodiment is using warp herein
The method of allusion quotation mechanics theorizes, and avoid quantum mechanics in this way causes when handling the life cells structure of complexity in this way
Imponderable problem, be specific using theoretical system derived from classical mechanics and can calculate.
Hamilton's principle
The most basic principle of classical mechanics is Hamilton's principle, the most common rule of any one mechanical system can be with
It is provided by Hamilton's principle, cell is regarded as a mechanical system by the present embodiment, according to Hamilton's principle, this mechanics
System can be described its characteristic by Lagrangian：
For convenience, this Lagrangian is abbreviated as below
Meet following condition with the cell system that this Lagrangian represents.
It is assumed that being in two determining states in t=t1 and t=t2 moment cells, the two states are respectively by two groups of broad sense
Coordinate q(1)And q(2)It determines.(q is all q1, q2... qnSet, qiRepresentative cell in i-th of component molar concentration,
We are referred to as i-th of generalized coordinates)
In this case, state of the cell system two moment, which follows, makes integral
It is developed for the mode of minimum possible value, integral S is known as the actuating quantity of cell system, this principle is referred to as Ha Mier
Principle or least action principle solve the mathematical method for the differential equation for making integral S obtain minimum, are referred to as functional
Extreme-value problem.
It is following to derive the differential equation for making integral S meet Hamilton's principle, even if integral S obtains the differential side of minimum value
Journey.In order to simplify formulation process, first assume that system only has one degree of freedom, it is thus necessary to determine that only there are one function q (t).
It is assumed that q=q (t) is the function for making S obtain minimum, that is to say, that use function
q(t)+δq(t) (3.2)
When replacement q (t), S just will increase.Wherein δ q are the function of very little, referred to as letter in the time interval from t1 to t2
The variation of number q (t).Since as t=t1 and t=t2, all functions (3.2) that can be used for comparing should have identical q(1)
And q(2), therefore obtain：
δ q (t1)=δ q (t2)=0 (3.3)
The variation of S caused by q is replaced to be represented by with q+ δ q
This difference by δ q andThe expansion of index is originated from level-one item, and it is that S is obtained that these summation, which is equal to 0,
The necessary condition of minimum.This summation is known as integrating the level-one variation of S.Therefore Hamilton's principle can be write as
It can be write as after variation
Integration by parts is carried out to Section 2, according to our expression formulas to t derivations
We obtain
It is learnt by condition (3.3), first item is constantly equal to 0, therefore no matter δ q take any value, remaining integral that should be equal to 0.
Such case only is likely to occur in the case where the expression formula being integrated is equal to 0.Therefore, equation is obtained
When cell has s degree of freedom, according to Hamilton's principle, it should independent variation s different function qi
(t).Therefore, s equation is obtained
Here it is cell differentials equation groups.This is the well known Lagrange's equation in mechanics, when we select classical power
Processing cell problem is learned, the most common Lagrange's equation of mechanics is obtained.
It is to be noted that：Here coordinate is being not coordinate in mechanics, but the molar concentration of cellular component.
Cyto-mechanics equation-Lagrange's equation
From the above discussion, cyto-mechanics equation group is
Here
It is the Lagrangian of cell, qiIt is the molar concentration of i-th of component of cell,It is rubbing for i-th of component of cell
Your concentration changes with time rate.
The degree of freedom of cell
Since chemical reaction changes over time between component in cell, this variation will obey chemical equation
Constraint.Therefore each chemical equation provides a constraints.Therefore the number of cell system component subtracts cell
In the numbers of various chemical equations be only the number that cell freely changes component, the i.e. degree of freedom of cell.
Cell degree of freedom=cellular component number-chemical equation number (corresponding above-mentioned 3.2)
The gene of cell
The genome that component is most importantly encoded by cell DNA in cell, the product by the genome of DNA encoding include
MRNA, tRNA, protein, various enzymes and other derivative products, these constitute the most basic component of cell, and other components are
The nutrient and energy and the relevant equation structure of cellular genome of exotic and its decomposition product, wherein pith composition cell
At cell equation meat and potatoes.
Lagrange's equation solves
The Lagrange's equation group of cell is extremely complex, is substantially a Nonlinear System of Equations.In the present embodiment
The Lagrange's equation group of cell is simplified, removes its nonlinear part, only considers its linear part, one can be obtained
Simplified equation, the equation group simplified from this, can obtain a cycle solution, this periodic solution it will be appreciated that cell week
The basic variation of phase.
From the general aspects of nonlinear equation, the attractor of these non-linear cell equation groups can be speculated, it may be possible to thin
The common form of born of the same parents represents the different differentiation form of cell for eukaryocyte.
The matrix model of cyto-mechanics
Cyto-mechanics equation group-Lagrange's equation group can be written as matrix form of equal value
H|X>=| X'> (8.1)
Here H is Differential operator Matrix
Vector | X>For cell state vector.
For convenience of understanding, the present embodiment thinks XiFor the molar concentration of i-th of gene outcome in cellular genome, due to base
The expression of cause is controlled by the state of cell, therefore Differential operator Matrix H depends on cell state vector, that is to say, that matrix H
Component hijFor cell state vector | X>Function, i.e.,
hij=hij(X1,X2,...Xn) (8.2)
Certainly, the gene for really participating in regulation and control here is only a few, i.e. hij(X1,X2,...Xn) in parameter XiIt is most of
It is zero.These parameters can be determined by experiment.
By equation (8.1) it is found that Differential operator Matrix acts on cell vector | X>It is vector to make the variation of its state vector |
X'>, when the effect of differential operator makes its cell state vector enter an attractor, cell is metastable into one
State, biologically, it is these attractors that we are interested.For eukaryocyte, it represents the thin of a certain stabilization
Born of the same parents' differentiation state.
If removing the nonlinear terms of equation, it is reduced to system of linear equations, i.e., matrix H is reduced to linear positive definite square
Battle array, then solve equation and be reduced to ask eigenvalue of matrix problem
H|X>=ω | X> (8.3)
Here H is cellular matrices, | X>For cell vector；It reflects the form of cell cycle solution, indicates that cell is normally bred
State, for eukaryocyte, it indicates the proper splitting state do not broken up.
For eukaryocyte, the present embodiment is the solution of corresponding non-linear H, it is anticipated that some different attractors, it is right
It should be in the different differentiation form of cell.
The biochemical process of cell interior is under genome manipulation by the orderly progress of the intrinsic rule of cell, these controls
The gene expression of cell physiological, biochemical process constitutes the operating system of cellular gene expression.
Genetic engineering algorithm
The matrix model of cyto-mechanics, which can allow, is readily appreciated that cellular gene expression operating system, establishes the thin of certain biology
The matrix model of born of the same parents, has just understood the gene operating system of this biology, this model can help to carry out genetic engineering
Design.
Such as：We introduce a foreign gene X to certain plantn+1。
The introducing of this foreign gene makes protozoa cell state vector become
Corresponding H-matrix becomes
According to matrix multiplication rule | X'>=H | X>
xi'=∑ hn+1kxk
The matrix multiplication regular targets are to make xi' expressed in plant stem cell, and do not expressed in fruit cell, therefore
Design hn+1k(k=1,2 ... .n+1) meet demand, as a result, it has been found that gene xmAnd expressed in stalk cell, and fruit cell
In the gene do not expressed, therefore gene x can be chosenmManipulation scheme, that is, take the component of following H
hN+1k=hlk(k=1,2 ..., n)
Take hN+1n+1=0
Above-mentioned mathematical operations are equivalent to genetic manipulation below
(1) interception foreign gene Xn+1
5’XXX----------------------------------YYY3‘
(2) interception endogenous gene XmPromoter sections
5’PPP---------------PPP3’
-45-1
(3) it prepares and is inserted into gene Xn+1
5‘PPP---------------PPPXXX----------------------------YYY3‘
(4) it is inserted into recombination Xn+1To endogenous gene XmThe chromosome at place is close to gene XmRegion
5’GGG-----Xm---Xn+1---------------3‘
The foreign gene X that aforesaid operations basic guarantee is newly inserted inton+1Expression manipulation and endogenous gene XmUnanimously.
Finally illustrate, the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although with reference to compared with
Good embodiment describes the invention in detail, it will be understood by those of ordinary skill in the art that, it can be to the skill of the present invention
Art scheme is modified or replaced equivalently, and without departing from the objective and range of technical solution of the present invention, should all be covered at this
In the right of invention.
Claims (4)
1. a kind of genetic engineering algorithm based on cyto-mechanics matrix model, it is characterised in that：Specifically comprise the following steps：
1) setting cyto-mechanics is theoretical, and wherein each in prokaryotic cell includes n kinds molecule and ion into the cell, each molecule or from
The quantity of son is qi, then the state of prokaryotic cell be expressed as with vector：(q1,q2,…,qn)；
The state of each organelle is expressed as with vector in eukaryocyte：(q1,q2,…,qs)；The state vector of cell is cell
The combination of device, cytoplasm and nucleus state vector；
2) theoretical system derived from classical mechanics is selected to establish the complicated calculations of cell；
3) Hamilton's principle is combined, its characteristic is described by Lagrangian：
4) according to 3) being derived from, cyto-mechanics equation group is
HereIt is the Lagrangian of cell；qiIt is the molar concentration of i-th of component of cell,It is that the molar concentration of i-th of component of cell changes with time rate；
5) according in 4), cyto-mechanics equation group-Lagrange's equation group can be written as matrix form of equal value
H|X>=| X'>
Here H is Differential operator Matrix：
Vector | X>For cell state vector：
Wherein, XiFor the molar concentration of i-th of gene outcome in cellular genome, the component h of matrix HijFor cell state vector |
X>Function, i.e.,
hij=hij(X1,X2,...Xn)
Here it is only a few really to participate in the gene of regulation and control, i.e. hij(X1,X2,...Xn) in parameter XiMost of is zero, differential
Operator matrix acts on cell vector | X>It is vector to make the variation of its state vector | X'>, when the effect of differential operator makes its cell
When state vector enters an attractor, cell enters a relatively steady state, biologically, comes to eukaryocyte
It says, represents a certain cell differentiation state stablized；
If removing the nonlinear terms of equation, it is reduced to system of linear equations, i.e., matrix H is reduced to linear positive definite matrix,
It then solves equation and is reduced to ask eigenvalue of matrix problem：
H|X>=ω | X>
Here H is cellular matrices, | X>For cell vector, it reflects the form of cell cycle solution, it indicates what cell was normally bred
State, for eukaryocyte, it indicates the proper splitting state that do not break up.
2. a kind of genetic engineering algorithm based on cyto-mechanics matrix model according to claim 1, it is characterised in that：Institute
State step 3)In, it is assumed that two determining states are in t=t1 and t=t2 moment cells, this
Two states are respectively by two groups of generalized coordinates q(1)And q(2)It determines, q is all q here1, q2... qnSet, qiRepresentative it is thin
The molar concentration of i-th of component in born of the same parents, referred to as i-th of generalized coordinates；
In this case, state of the cell system two moment, which follows, makes integral
It is developed for the mode of minimum possible value, integral S is the actuating quantity of cell system.
3. a kind of genetic engineering algorithm based on cyto-mechanics matrix model according to claim 2, it is characterised in that：For
Simplified formulation process, it is assumed that system only has one degree of freedom, determine function q (t), it is assumed that q=q (t) is that S is made to obtain pole
The function of small value, uses function
q(t)+δq(t)
Replace q (t) when, S increases, and wherein δ q are functions of very little in the time interval from t1 to t2, referred to as function q's (t)
Variation, since as t=t1 and t=t2, all functions that can be used for comparing should have identical q(1)And q(2), therefore can be with
It releases
δ q (t1)=δ q (t2)=0
The variation of S caused by q is replaced to be represented by with q+ δ q
This difference by the expansion of δ q and δ q indexes is originated from level-one item, and it is that S acquirements are minimum that these summation, which is equal to 0,
The necessary condition of value, this summation is known as integrating the level-one variation of S, therefore Hamilton's principle can be write as
It can be write as after variation
Integration by parts is carried out to Section 2, according to the expression formula to t derivations
It obtains
It is learnt by condition δ q (t1)=δ q (t2)=0, first item is constantly equal to 0, therefore no matter δ q take any value, remaining integral to answer
0 should be equal to, such case only is likely to occur in the case where the expression formula being integrated is equal to 0, therefore, obtains equation：
When cell has s degree of freedom, according to Hamilton's principle, it should independent variation s different function qi(t), because
This, obtains s equation：
4. a kind of genetic engineering algorithm based on cyto-mechanics matrix model according to claim 3, it is characterised in that：Institute
It states since chemical reaction changes over time between the component in cell, this variation will obey the constraint of chemical equation,
Therefore each chemical equation provide a constraints, therefore the number of cell system component subtract it is various in cell
The number of chemical equation is only the number that cell freely changes component, the i.e. degree of freedom of cell.
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| CN115547412B (en) * | 2022-11-09 | 2024-02-02 | 内蒙古大学 | Method and device for evaluating cell differentiation potential based on Hopfield network |
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