Upload
thomasanung
View
168
Download
1
Tags:
Embed Size (px)
DESCRIPTION
My Presentation in MECBIC 2009
Citation preview
Modelling Cell Cycle at DifferentLevels of Representation
Thomas Anung Basuki, Antonio Cerone and Rafael V. Carvalho
Bologna, September 5, 2009
Modelling Cell Cycle at Different Levels of Representation – p. 1/32
Motivation
Many formalisms and tools have been produced to helpbiologists for in silico experiments (P Systems, Biocham,Virtual Cell)
are based on deterministic approach, while biologicalsystems are stochastic
use text/plot to express result is often inadequate=⇒ needs visualisation/animation
Our approach
is stochastic
supports simulation and visualisation of the model
supports model-checking
Modelling Cell Cycle at Different Levels of Representation – p. 2/32
Architecture of Our Approach
Levels of Representation
Visual�
Molecular�
6
� : horizontal rules
6 : vertical rules
State of the system is represented as Spatial CLS terms
Horizontal rules:
• control behaviour at one level
• Spatial CLS rewrite rules
with rate constant
PLk7→ PR
Vertical rules:
• link behaviour between levels
• Instantaneous rewrite rules
PL∞7→ PR
Modelling Cell Cycle at Different Levels of Representation – p. 3/32
Using Spatial CLS for Visualisation
Two-level modelling, using positional terms at visuallevel and non positional terms at molecular level
A visual state describes three kinds of information:spatial information;a stage of the system evolution, which we call visualstage;information on whether that stage has beenvisualised.
Two kinds of rewrite rule:horizontal rules to define behaviour in one levelvertical rules to link the behaviour in the differentlevels
Modelling Cell Cycle at Different Levels of Representation – p. 4/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)big cell after growth (end of phase G1)replicated chromosomes inside the nucleus (end ofphase S)cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)big cell after growth (end of phase G1)replicated chromosomes inside the nucleus (end ofphase S)cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)
big cell after growth (end of phase G1)replicated chromosomes inside the nucleus (end ofphase S)cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)big cell after growth (end of phase G1)
replicated chromosomes inside the nucleus (end ofphase S)cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)big cell after growth (end of phase G1)replicated chromosomes inside the nucleus (end ofphase S)
cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)big cell after growth (end of phase G1)replicated chromosomes inside the nucleus (end ofphase S)cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)big cell after growth (end of phase G1)replicated chromosomes inside the nucleus (end ofphase S)cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual State for Cell Cycle
Spatial information: mp, 3r4
4 phases (G1 - S - G2 - M) =⇒ 4 visual stages:
small cell before growth (beginning of phase G1)big cell after growth (end of phase G1)replicated chromosomes inside the nucleus (end ofphase S)cell with two nuclei (phase M before cytokinesis)
described by symbol stagei, with i = 1, ..., 4
Visual rules introduce symbol visualisedi, whichactivates vertical rules to change from stagei tostage(i+1)mod4
Modelling Cell Cycle at Different Levels of Representation – p. 5/32
Visual Level/Cellular Level
Horizontal rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
R2 :(
m)L
p,r c ((n)Lu c (cr.x | cr.y) | stage2)
0.0337−→
(m)Lp,r c ((n)L
u c (2cr.x | 2cr.y) | stage2 | visualised2)
R3 :(
n)L(0,0,0), 2r
5c (2cr.x | 2cr.y) | stage3
0.047−→
(n)L(− r
2 ,0,0), 2r5c(cr.x | cr.y) |
(
n)L( r
2 ,0,0), 2r5c (cr.x | cr.y) | stage3 | visualised3
R4 :(
m)L
p,r c ((
n)L
u c X |(
n)L
v c Y | stage4)0.27−→
(
m)L
p, 3r4c (
(
n)L
u c X | stage4 | visualised4) |(
m)L
getpos, 3r4c (
(
n)L
u c Y | stage4 | visualised4)
Initial state:
(b)L.,R c (m)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |molecules)
Modelling Cell Cycle at Different Levels of Representation – p. 6/32
Molecular Level
Reaction rates at molecular level are classified into 4categories:
very fast, with rate constant 20
fast, with rate constant 5
slow, with rate constant 1
very slow, with rate constant 0.25
Reactions at molecular level are much faster than reactionsat cellular level.We define a speeding factor s, and multiply it by thereaction rates to control reaction speed at molecular level.
Modelling Cell Cycle at Different Levels of Representation – p. 7/32
Rule Application
The state of the system:
(b)L.,R c ((m|GFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
iSBF|iMBF|Sic1|Net1|Cdc14)|GF)
Molecular rewrite rules:
S1 : (Y | GFR)LcX | GF 20·s7−→ (Y | iGFR)Lc(Cln3 | X)
S2 : Cln3 | iSBF | iMBF 1·s7−→ Cln3 | SBF | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 8/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|iSBF|iMBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S1 : (Y | GFR)LcX | GF 20·s7−→ (Y | iGFR)Lc(Cln3 | X)
S2 : Cln3 | iSBF | iMBF 1·s7−→ Cln3 | SBF | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 9/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|iSBF|iMBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S1 : (Y | GFR)LcX | GF 20·s7−→ (Y | iGFR)Lc(X | Cln3)
S2 : Cln3 | iSBF | iMBF 1·s7−→ Cln3 | SBF | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 10/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|SBF|MBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S1 : (Y | GFR)LcX | GF 20·s7−→ (Y | iGFR)Lc(X | Cln3)
S2 : Cln3 | iSBF | iMBF 1·s7−→Cln3 | SBF | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 11/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|SBF|MBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S3 : (n)Lc(y.gN2.x |Y) | SBF0.25·s7−→ (n)Lc(y.gN2.x |Y) | Cln2 | SBF
S4 : (n)Lc(y.gB5.x |Y) | MBF 0.25·s7−→ (n)Lc(y.gB5.x |Y) | Clb5 | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 12/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|MBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S3 : (n)Lc(y.gN2.x |Y) | SBF 0.25·s7−→ (n)Lc(y.gN2.x |Y) | Cln2 | SBF
S4 : (n)Lc(y.gB5.x |Y) | MBF 0.25·s7−→ (n)Lc(y.gB5.x |Y) | Clb5 | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 13/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|MBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S3 : (n)Lc(y.gN2.x |Y) | SBF 0.25·s7−→ (n)Lc(y.gN2.x |Y) | Cln2 | SBF
S4 : (n)Lc(y.gB5.x |Y) | MBF0.25·s7−→ (n)Lc(y.gB5.x |Y) | Clb5 | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 14/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|Clb5|MBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S3 : (n)Lc(y.gN2.x |Y) | SBF 0.25·s7−→ (n)Lc(y.gN2.x |Y) | Cln2 | SBF
S4 : (n)Lc(y.gB5.x |Y) | MBF 0.25·s7−→ (n)Lc(y.gB5.x |Y) | Clb5 | MBF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 15/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|Clb5|MBF|Sic1|Net1|Cdc14))
Molecular rewrite rules:
S5 : Clb5| Sic1 5·s7−→ Sic1 − Clb5
S9 : Cln2 | Sic1 − Clb5 5·s7−→ Cln2 | pSic1 | Clb5
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 16/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|MBF|Sic1−Clb5|Net1|Cdc14))
Molecular rewrite rules:
S5 : Clb5| Sic1 5·s7−→Sic1 − Clb5
S9 : Cln2 | Sic1 − Clb5 5·s7−→ Cln2 | pSic1 | Clb5
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 17/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|MBF|Sic1−Clb5|Net1|Cdc14))
Molecular rewrite rules:
S5 : Sic1 | Clb5 5·s7−→ Sic1 − Clb5
S9 : Cln2 | Sic1 − Clb5 5·s7−→ Cln2 | pSic1 | Clb5
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 18/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|MBF|pSic1|Clb5|Net1|Cdc14))
Molecular rewrite rules:
S5 : Sic1 | Clb5 5·s7−→ Sic1 − Clb5
S9 : Cln2 | Sic1 − Clb5 5·s7−→Cln2 | pSic1 | Clb5
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,r c (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 19/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
Cln3|Cln2|SBF|MBF|pSic1|Clb5|Net1|Cdc14))
Molecular rewrite rules:
S10 : pSic1 | SCF 1·s7−→ SCF
S11 : Cln2 | SCF 1·s7−→ SCF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,rc (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 20/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0), 3r4c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
visualised1|Cln3|Cln2|SBF|MBF|pSic1|Clb5|Net1|Cdc14))
Molecular rewrite rules:
S10 : pSic1 | SCF 1·s7−→ SCF
S11 : Cln2 | SCF 1·s7−→ SCF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→ Cln2mc(Cln2,2)|stage2
Visual rewrite rules:
R1 :(
m)L
p, 3r4c (X | stage1)
0.0257−→
(
m)L
p,rc (X | stage1 | visualised1)
Modelling Cell Cycle at Different Levels of Representation – p. 21/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0),r c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage1 |
visualised1|Cln3|Cln2|SBF|MBF|pSic1|Clb5|Net1|Cdc14))
Molecular rewrite rules:
S10 : pSic1 | SCF 1·s7−→ SCF
S11 : Cln2 | SCF 1·s7−→ SCF
Vertical rewrite rules:
T1 : stage1|visualised1|Cln2mc(Cln2,2) ∞7−→ stage2|Cln2mc(Cln2,2)
Visual rewrite rules:
R2 :(
m)L
p,r c ((n)Lu c (cr.x | cr.y) | stage2)
0.0337−→
(m)Lp,r c ((n)L
u c (2cr.x | 2cr.y) | stage2 | visualised2)
Modelling Cell Cycle at Different Levels of Representation – p. 22/32
Rule Application
The state of the system:
(b)L.,R c ((m|iGFR)L
(0,0,0),r c ((n)L c (cr.gN2.gB5 | cr.gB2.gC20)|stage2 |
Cln3|Cln2|SBF|MBF|pSic1|Clb5|Net1|Cdc14))
Molecular rewrite rules:
S10 : pSic1 | SCF 1·s7−→ SCF
S11 : Cln2 | SCF 1·s7−→ SCF
Vertical rewrite rules:
T1 : visualised1|Cln2mc(Cln2,2)|stage1∞
7−→stage2|Cln2mc(Cln2,2)
Visual rewrite rules:
R2 :(
m)L
p,r c ((n)Lu c (cr.x | cr.y) | stage2)
0.0337−→
(m)Lp,r c ((n)L
u c (2cr.x | 2cr.y) | stage2 | visualised2)
Modelling Cell Cycle at Different Levels of Representation – p. 23/32
Propensity
Propensity aµ
measures the probability of reaction Rµ to be chosen asnext reaction
aµ = kµ × hµ
where hµ = number of possible combinations ofreactants
Based on assumption that molecules arehomogeneously distributed in the system
Ex: X1 molecules of A and X2 molecules of B
R1 : A + B → 2Aa1 = k1(
X11 )(X2
1 ) = k1X1X2
Modelling Cell Cycle at Different Levels of Representation – p. 24/32
Compartments and Propensity
compartments make molecules not homogeneouslydistributed in the system
molecules are contained in compartments and arehomogeneously distributed within each compartment
each reaction can only involves reactants from onecompartment
aσµ measures the probability of reaction Rµ to be chosen
as next reaction and occurs at compartment σ
aσµ = kµ × hσ
µ
where hσµ = number of possible combinations of
reactants at compartment σ
Modelling Cell Cycle at Different Levels of Representation – p. 25/32
Modified Gillespie’s Direct Method
Given reactions {R1, . . . , RM} and molecular populationX1, . . . , XN and C compartments, where Xi = ∑
Cv=1 Xv
i
Step 0 Initialise time variable t to 0. Calculate a1, . . . aM.Calculate ∑
Mv=1 ∑
Cw=1 aw
v .
Step 1 Execute any applicable vertical rules.
Step 2 If the space is fully occupied then stop simulation.Otherwise generate r1 and calculate τ. Increment t byτ.
Step 3 Generate r2 and calculate (µ, σ).
Step 4 Execute Rµ. Update X1, . . . , XN and a1, . . . , aN.
Step 5 Calculate ∑Mv=1 av. Return to Step 2.
Modelling Cell Cycle at Different Levels of Representation – p. 26/32
Computing τ, µ and σ
If awv is the propensity of reaction Ri in compartment w and
a0 = ∑Mv=1 ∑
Cw=1 aw
v then
τ =1a0
ln(1r1
) (1)
(µ, σ) = the integers for whichµ
∑v=1
σ−1
∑w=1
awv < r2a0 ≤
µ
∑v=1
σ
∑w=1
awv (2)
where r1, r2 ∈ [0, 1] are two real values generated by a random
number generator.
Modelling Cell Cycle at Different Levels of Representation – p. 27/32
Conclusion
defined an approach to model biological systems atdifferent levels of representation
molecular level and one or more visual levelscase study budding yeast cell cycle
defined a modified Gillespie’s algorithm to deal withcompartmentalisation and spatial information
implemented a tool for visualisation
Modelling Cell Cycle at Different Levels of Representation – p. 28/32
Spatial CLS Terms
We assume an alphabet E . Terms T, Branes B and
Sequences S are given by the following grammar:
T ::= λ∣
∣ (S)d∣
∣
(
Bd)L
c T∣
∣ T | T
B ::= λ∣
∣ (S)d∣
∣ B | B
S ::= ε∣
∣ a∣
∣ S · S
where a is an element of E , ε is the empty sequence,
and d ∈ D = ((Rn) ∪ {.})× R
+.
Two kinds of term: positional terms, has position and size,
and non positional terms, only has size
Modelling Cell Cycle at Different Levels of Representation – p. 29/32
Brane and Sequence Patterns
Left Brane Patterns BPL, Sequence Patterns SP and
Right Brane Patterns BPR are given by the following grammar:
BPL ::= (SP)u∣
∣ BPL | BPL
BPR ::= (SP)g∣
∣ BPR | BPR
SP ::= ε∣
∣ a∣
∣ SP.SP∣
∣ x∣
∣ x
where u ∈ PV, x ∈ X , x ∈ SV and g ∈ T
Modelling Cell Cycle at Different Levels of Representation – p. 30/32
Left and Right Patterns
Left Patterns PL and Right Patterns PR
are given by the following grammar:
PL ::= (SP)u∣
∣
(
BPLX)L
u c PLX∣
∣ PL | PL
BPLX ::= BPL∣
∣ BPL | X∣
∣ X
PLX ::= PL∣
∣ PL | X
PR ::= ε∣
∣ (SP)g∣
∣
(
BPRX)L
g c PR∣
∣ PR | PR∣
∣ X∣
∣ X
BPRX ::= BPR∣
∣ BPR | X∣
∣ X
where u ∈ PV, x ∈ X , x ∈ SV and g ∈ T.
Modelling Cell Cycle at Different Levels of Representation – p. 31/32
Rewrite Rules
A rewrite rule is a 4-tuple ( fc, PL, PR, k), usually written as
[ fc]PLk7→ PR
where fc : T → {tt, f f }, k ∈ R+, Var(PR) ⊆ Var(PL),
and each function g appearing in PR
refers only to position variables in Var(PL).
Modelling Cell Cycle at Different Levels of Representation – p. 32/32