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ABSTRACT
The impulses are one of the sources of fluctuations
which lead to the sharp changes in the biochemical
systems such as the changes in epidemic and
population models. These effects have been
comprehensively studied under deterministic
models, whereas, have not been analyzed in
stochastic models. Hereby, in this study, we
implement these effects in two exact stochastic
simulation algorithms, namely, the direct method
and the first reaction method under different
dimensional systems and impulses scenarios. In the
application, we use real systems and apply impulses
to the biologically meaningful proteins. Then, we
evaluate the performances of both exact methods in
terms of computational demand via distinct criteria.
KEYWORDS
Stochastic simulation, biochemical systems,
impulses, direct method, first reaction method.
1 INTRODUCTION
The biochemical modeling is the mathematical
way to explain the dynamics of biological
systems such as the interaction of proteins and
molecules (Wilkinson, 2006). But, the
vivo/vitro analyses of the biological systems
can be expensive and limited. In this situation,
we can perform the simulation methods under
realistic assumptions so that we can visualize
the behavior of the real biological system
artificially.
Each biological event can be represented by a
reaction. Thus, the biochemical reaction is a
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Proceedings of The Third International Conference on Data Mining, Internet Computing, and Big Data, Konya, Turkey 2016
ii.
iii.
iv.
v.
vi.
2 METHODS
2.1 Stochastic Simulation Algorithms
The gene regulation is generally modeled by
differential equations (DE). Although this
deterministic model is the most widely used
approach and can successfully explain the
steady-state behavior of the system under
discrete time and states, it cannot describe the
randomness of the system as seen in the
transcription and the translation of the proteins.
Thus, the stochastic model is the only choice to
present this randomness in a mathematical way
(Bower and Bolouri, 2001; Purutuolu, 2010).
There are five main exact stochastic simulation
algorithms which enable to generate the actual
randomness in the model. These are the direct
method (Wilkinson, 2006), also called Gillespie
method, the first reaction method (Gillespie
1992; Turner, 2005), the next reaction method
(Gibson and Bruck, 2000; Turner, 2004), also
named as the Gibson-Bruck algorithm, the
optimal direct method (Cao, 2004) and the
sorting direct method (McCollum and Peterson,
2006).
2.1.1 Direct Method
The direct algorithm, also called as the
Gillespie method, is the fastest simulator in the
calculation of time, especially, for small
systems (Wilkinson, 2006, Gillespie, 1977;
Turner, 2004). However, its application is hard
in heterogeneous situation and is not
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Proceedings of The Third International Conference on Data Mining, Internet Computing, and Big Data, Konya, Turkey 2016
ii.
iii.
iv.
v.
vi.
(2)
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Proceedings of The Third International Conference on Data Mining, Internet Computing, and Big Data, Konya, Turkey 2016
(5)
(6)
3 APPLICATION
3.1 Measurement Criteria
In order to assess the performance of different
simulation methods in terms of the
computational demand, certain measures are
suggested. Among alternatives, the most widely
used ones can be listed as the average search
depth, the average weighted degree and the
central processing unit.
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4 CONCLUSION
In this study, we have dealt with the stochastic
simulation of the biochemical systems by
performing two major algorithms in this field.
These are the direct and the first reaction
methods. They are exact algorithms in the sense
that they are based on the chemical master
equation. Here, we have evaluated them under
different dimensional systems and impulsive
scenarios.
From the results, we have observed that there is
no significant difference between the direct and
the first reaction methods in most of the
pathways and simulation times. But a slight
difference is seen when the system gets
complicated. Moreover, we have detected that
the effect of impulses can be observable for
large systems and can be hardly seen under
small or moderate dimensional systems.
Furthermore, if the impulses are put on the
initial species which can trigger whole
activation of the systems, such as the growth
factor or external stimulus, the activations of all
remaining species alter too as expected and the
impulses become visible in the outputs of the
simulations. On the other hand, if the
underlying effects, either in increasing or
decreasing direction in the number of
molecules, are frequently fired, they cannot be
observed clearly. Whereas, such effects have
always caused an increase in CPU and local
time as expected and these differences become
visible while the systems have complex
structures, i.e., higher dimensions.
As a future work, we consider to investigate the
effect of bifurcations in the stochastic modeling
and in these algorithms. Because the impulses
can cause unstable positions for the systems
and the bifurcation is detected under such
instabilities. Finally, we think to extend this
study for the approximate stochastic simulation
algorithms under various conditions of
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2.68
2.69
2.72
2.64
2.66
2.75
First Reaction
Method
Without Impulse
2.07
13511.13
1485.81
First
Reaction
Method
Local Time
SD
WD
t=5
16.20
352.26
5.49
2.78
t=20
6677.65
29867.95
5.68
2.99
t=50
8806532.30
2935560.26
457.51
231.66
t=5
22.88
388.73
5.64
2.78
t=20
11153.05
45008.64
6.70
2.99
t=50
9899785.86
6675700.8
546.5
242.8
2.76
13517.28
1486.68
2.33
2.63
4132.7
30.52
t=50
Direct
Method
CPU
2.20
2.04
11798.44
1441.96
26.42
t=20
3922.02
2.58
2.36
1483.75
13278.22
2.73
2.22
1.95
12095.05
1445.47
22.24
t=5
3651.37
2.38
2.57
1475.25
12961.56
2.55
2.39
2.06
12280.33
1447.36
28.89
t=50
4127.22
2.62
2.33
1485.81
13511.13
2.79
2.20
2.04
11789.94
1440.7
24.69
t=20
3916.6
2.59
2.35
1482.68
13274.68
2.72
2.23
1.97
12089.78
1444.55
20.98
t=5
3648.11
2.37
2.55
1474.64
12959.4
2.59
2.39
SD
Local Time
CPU
SD
Local
Time
CPU
LV
Path
way
CPU
Local
Time
SD
WD
WD
WD
Direct Method
89
t=5
First Reaction
t=20
Method
t=50
24.22
22.34
23.01
23.76
8329.5
9107.82
t=5 1286.39
First Reaction
t=20 1444.1
Method
22.06
SD
8245.74
Local
Time
23.24
1259.2
9.28
9.53
10.24
9.29
9.39
Without Impulse
6299.52
3026.31
1471.29
4730.27
2526.77
10.21
SD
Direct
Method
t=5
851.9
t=50
CPU
323.88
1348.92
Local
Time
Without Impulse
7.11
7.17
7.18
7.03
7.18
7.18
WD
5.70
5.75
5.91
5.72
5.73
5.87
WD
184537.8
185542.4
187302.8
184121.8
185175.6
187167.2
Local Time
10.46
10.50
10.97
10.47
10.47
10.85
SD
Local
Time
SD
2262.23
2028.8
1884.21
21.50
97368.3
23.27
96482.65 22.48
95327.5
CPU
WD
5.85
5.86
5.96
5.85
5.87
5.94
7.00
7.12
7.15
6.99
7.17
7.11
WD
3282.69
3511.34
3848.27
3151.68
3405.7
3807.95
CPU
190665
188761
9.19
9.38
9.94
SD
5.75
5.80
5.87
WD
9.75
9.98
5.76
5.81
Local
Time
SD
CPU
7.25
7.18
7.18
7.28
7.22
7.18
WD
4877.44 191787.9
4201.15 189185.1
4536.39
4073.76
3894.72 187801.2
CPU
JAK-STAT
Pathway
133.55
CPU
t=5
PKC Pathway
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[7]
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ACKNOWLEDGEMENT
The authors would like to thank the AGEP
project of the Middle East Technical University
(Project no: BAP-08-11-2014-007) for their
support.
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