Computational Biology and Chemistry 71 (2017) 274–279

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Computational Biology and Chemistry

journal homepage: www.elsevier.com/locate/compbiolchem

Research Article

Solving probability reasoning based on DNA strand displacement and

probability modules$
Qiang Zhanga,b,* , Xiaobiao Wanga , Xiaojun Wanga , Changjun Zhoua
a
Key Laboratory of Advanced Design and Intelligent Computing, Ministry of Education, Dalian University, Dalian, 116622, China
b
School of Computer Science and Technology, Dalian University of Technology, Dalian, 116024, China

A R T I C L E I N F O A B S T R A C T

Article history:
Received 12 September 2017 In computation biology, DNA strand displacement technology is used to simulate the computation
Accepted 25 September 2017 process and has shown strong computing ability. Most researchers use it to solve logic problems, but it is
Available online 28 September 2017 only rarely used in probabilistic reasoning. To process probabilistic reasoning, a conditional probability
derivation model and total probability model based on DNA strand displacement were established in this
Keywords: paper. The models were assessed through the game “read your mind.” It has been shown to enable the
DNA strand displacement application of probabilistic reasoning in genetic diagnosis.
Conditional probability © 2017 Elsevier Ltd. All rights reserved.
Total probability
Probability reasoning

1. Introduction strand according to the principle of clonal selection algorithm of

Even since Adleman proposed biological computing in 1994, all
kinds of applications have gradually been put forward. As one of
the most popular types of technology in biological computing, DNA
strand displacement has been applied to various computer systems
Seelig et al. (2006), Qian and Winfree (2011), Lakin and Phillips
(2011), Boemo et al. (2015), from simple logical structures Seelig
et al. (2006), Qian and Winfree (2011) to complex chemical
reaction networks Condon et al. (2014), Zhang and Seeling (2011).
For example, in 2006, in order to realize the logic gates, Georg
Seeling et al. designed the AND, OR, and NOT gateSeelig et al.
(2006). They used single nucleotide strands as input and output.
This structural model laid the foundation for the future calculation
model. In 2013, Andrew Phillips et al. implemented and simulated
the chemical reaction network structure using DNA strand
displacement, and designed a voting system based on two-domain
strand Lakin et al. (2013). The process of DNA strand self-assembly
similar to the relationship between the antigen and antibody. In
2013, Rizki Mardian et al. designed a decision marker by using DNA
$
This paper was presented at the IDMB 2017 conference in Xi’an Medical
University on 23–24th March 2017. This paper was recommended for publication in
revised form.
* Corresponding author at: Key Laboratory of Advanced Design and Intelligent
Computing, Ministry of Education, Dalian University, Dalian, 116622, China.
E-mail address: zhangq@dlut.edu.cn (Q. Zhang).
the immune system.
The structure of network itself facilitates computation expres-
sion. The bio-molecular computation can also be used to simulate
neural networks. In 2011, Winfree et al. used the DNA strand
displacement to simulate the neural network, and they designed a
model of a four-neuron Hopfield associative memory. In 2013,
Anthony J. Genot et al. scaled down DNA circuits with competitive
neural network and simulated winner-take-all effect, it was also
proven that DNA is an exquisite substrate.
In recent years, reasoning modules were established base on
DNA strand displacement Inaki Sainz de Murieta et al. (2014), Ran
et al. (2009), Lakin et al. (2012). For example, in 2009, the logical
reasoning at the molecular level was put forward again by Shairo’s
team, who developed an enzyme-driven system to perform simple
logical deductions. In 2014, Inaki Sainz de Murieta et al. presented
a computing model based on the DNA strand displacement that
uses Bayesian inference. It has been applied to genetic diagnosis in
vitro.
The probabilistic reasoning is widely used in various applica-
tions. In 2014, Sainz de Murieta et al. implemented the conditional
probability based on DNA displacement. They used single strands
to encode the prior probabilities and double strand complexes to
encode conditional probabilities. However, in many case and
computation, the total probability must be used for getting the
result according to the probabilities reasoning.
In the paper, the modules of conditional probability and total
probability were designed based on DNA strand displacement. For

https://doi.org/10.1016/j.compbiolchem.2017.09.011
1476-9271/© 2017 Elsevier Ltd. All rights reserved.
 Q. Zhang et al. / Computational Biology and Chemistry 71 (2017) 274–279 275

reducing the complex of strand, the two-domain strand is used in

the module Cardelli (2010). All signal strands are two domains and
the double strand was only auxiliary strand. In the experiment, the
ratio of corresponding strand concentration was used to represent
the results; and all kinds of results were made possible, and
systems of more types of status were rendered possible. In order to
verify the correctness of the model, the network structure was
constructed and a module of the “read your mind” game was
prepared using the constructed probability model. The results are
shown using DNA strand displacement (DSD) software.

2. The principle of probability model and implementation

In this section, the principle of probability model and the

computational model based on DNA strand displacement reaction
are presented. Fig. 1. Encoding conditional probabilities.

2.1. Conditional probability

2.1.1. The definition of conditional probability
Sometimes considering the probability of occurrence of event
A, P(A), necessitates considering the other conditions, which is that
the proposition Q is known to occur. Here, it is commonly denoted
as P(A|Q).
Definition 1 Let (V, F, P) is a probability space, the event AF, the
event QF, and P(Q) > 0,when the proposition Q has known to occur,
the condition probability of the proposition A is defined as:
PðA \ QÞ
PðAjQÞ ¼ ð2:1Þ
PðQÞ
Formula (2.1) can be derived as following:
PðA \ QÞ ¼ PðAjQÞ  PðQÞ ð2:2Þ
Formula (2.2) can also be called the multiplication formula of
proposition probability. The two domain strands were here used to
build the model for the formula (2.2). In the logical computation,
the express way is only 0/1 or T/F. In the probability reasoning,
there is not only 0/1, but also a certain proportion of relationships.
We can control the concentration to solve the probability of
multiplication.
2.1.2. Implementation of the model
The strand displacement is used by many researchers because it
is autonomous. In the whole computation, the energy is provided
by structures themselves. The mechanism is a toehold-mediated
branch migration. The process of reaction does not need organic
sources or other motive force except DNA molecules. The strand
can be divided into a two-domain strand, a three-domain strand
and a multimedia domain strand Cardelli (2009), Soloveichik et al.
(2010). The structure of the two-domain strand is simple, invariant
and easily implemented, and it is amenable to formalization and to
mechanical verification Cardelli (2010).
In the paper, a two-domain strand was used to construct the
model. All the input and output strands were expressed using a
single strand, and the double strand served as a gate or an
intermediate auxiliary framework. Formula (2.2) showed that P
(A\Q) is produced when P(Q) and P(A|Q) are present, and its
content is related to P(A) and P(A|Q). The structure of the model is
shown in Fig. 1 (assume that the ratio of P(A)and P(A|Q) is greater
than 1).
As shown Fig. 1, the input strand <t^ A> and <t^ A_Q> (indicate
P(A) and P(A|Q) respectively) react with the auxiliary strand a1 and
a2 respectively, and produce the intermediate product strand <a
tb^> and <b tb^>; and then the intermediate strand react with
auxiliary strand a4 to produce output strand <t^ AQ>(indicate P
(A\Q)). Throughout the whole reaction, the other strands were
used for intermediate reactions of the auxiliary strand and the
recovery unit or gate.
The two input strands react with auxiliary strands in the model.
The input strands are present at different initial concentrations,
and the divided reaction was able to speed up the reaction process;
however, it also helpful to expend the model and track the reactant.
The magnitude of concentration represents the probability value.
The final output result of the multiplication formula is expressed
by controlling the concentration of the reactant.
2.2. Total probability formula
2.2.1. The definition of total probability formula
The total probability formula is an important formula in the
theory of probability. It turns a complex event probability problem
into an addition problem, which is the probability of simple events
occurring in different situations.
Definition 2 Let (V, F, P) is a probability space, A1, A2, . . . , An is
a finite split, and P(Ai) > 0 (i = 1, 2, . . . , n). Then for any event QiF as
follows:
X
n
PðQ i Þ ¼ PðQ j jAi ÞPðAi Þ ð2:3Þ
i¼1
The formula (2.3) is called the total probability formula.
Formula (2.3), shows that the total probability formula is a total
formula, which is a result of the sum of n conditional probability.
For this reason, the results of the conditional probability formula
must be obtained first, and then they must be put together.
2.2.2. Implement of the total probability model
In accordance with condition probability, the signal strand
structure still serves as the input signal and output signal. In the
current model, we assume n = 4, the formula is simplified as
follows:
PðQ i Þ ¼ PðA1 Q i Þ þ PðA2 Q i Þ þ PðA3 Q i Þ þ PðA4 Q i Þ ð2:4Þ
(P(A1Qi) indicates P(Qi|A1)*P(A1)) it can be implemented by the
upper conditional probability model, so are other signals. The
model is constructed as shown Fig. 2.
As shown Fig. 2, the input strand A1Q, A2Q, A3Q, and A4Q react
with the auxiliary strand a1, a2, a3, and a4 respectively, and
produce the common intermediate product strand <a t^>; and
then the product strand <a t^> and quantitative intermediate
strand <Q t^> would react with the strand a5 and finally generate
the output strand <t^ Q>. In the model, each input strand would
react with corresponding gate independently and they do not
276 Q. Zhang et al. / Computational Biology and Chemistry 71 (2017) 274–279
Fig. 2. Encoding total probability formula.
affect each other. By adjusting the concentration of the auxiliary
strand, the reaction can be controlled effectively and the
concentration of the output strand can be drawn effectively. The
concentration of output strand is the sum of the input strand. In
order to render the reaction more thorough, recycling intermediate
product equipment was added to in our model.
A two-domain strand structure was used in the current model.
The structure of each two-domain strand was simpler than that of
other multimedia domains strands. The uniform structure is
relatively easy to identify.
3. Implementation and simulation
This section introduces the read your mind game. Strand
displacement theory was used to model the game based on
probability reasoning. All possible results are expressed using the
value of probability when it is not unique. Visual DSD was used for
the experiment.
Fig. 3. (a)The process of read your mind game;(b)The relation between problems
and actions;(c)The network framework.
3.1. Read your mind game
The game involves four questions. As shown Fig. 3(a), a specific
person can be identified from a list of four possibilities using the
answers to four questions. For example, when Q3 = 0, the result is
Santiago Ramon Cajal. Of course the answer of question must be
correct. When Q1 = 0, the result is not certain, possibly Rosalind
Franklin or Claude Shannon. At this time it is not possible to judge
without enough information. Qian et al. used the DNA circuit and
neural network to implement the game in 2011. However, when
they could not confirm the single result according to given input
signal, the output is wrong. To produce a result, we will use the
principle of probability reasoning to work out this situation.
This type of situation is common in really life. When there is not
enough information, it is very hard to select the correct result. If
there is not only one result, it is often possible to express them with
probability in life. All possible answers can be shown and the
probability of each case can be established. Probability reasoning is
used in here. In the current paper, the game was modified and the
questioning process was analyzed to design network frame based
on the principle of neurons. The whole process is divided into many
small modules, which is designed from the model. The results are
shown by probability.
As shown Fig. 3(a), the process of the game is known, and the
answer to each corresponding question is controlled by the answer
to every other question. It can be seen as a mapping function
between a set of problems and actions (Fig. 3(b)). When not all
values of Q are known, we have to “guess” the result. To obtain
accurate results, the network framework shown in Fig. 3(c) was
built. At first, it was divided into four different conditions
according to the number of signals, followed by one signal, two
signals, three signals, and four signals; and then different modules
were enacted according to the specific signal value, and finally the
conclusion was drawn.
It is here assumed that Q = {Q1, Q2, Q3, Q4}, Y = {A, B, C, D, E}.
According to the game content in here, Q is the samples of input
signal, Y is the output signal of the sample set, E is all other cases
except given cases. When the input signal Qi is obtained, according
to the formula (2.1), the following can be determined:
PðA \ Q i Þ
PðAjQ i Þ ¼ ð3:1Þ
PðQ i Þ
PðA \ Q i Þ
PðQ i jAÞ ¼ ð3:2Þ
PðAÞ
From (3.2), the following can be determined:
PðA \ Q i Þ ¼ PðQ i jAÞPðAÞ ð3:3Þ
According to the formula (2.3), the following is true:
X
n
PðQ i Þ ¼ PðQ i jY j ÞPðY j Þ ð3:4Þ
j
Thus
PðQ i jAÞPðAÞ
PðAjQ i Þ ¼ ð3:5Þ
X
n
PðQ i jY j ÞPðY j Þ
j
The reasoning is similar for other cases.
3.2. Simulation and results
Formula (3.5) is foundation of the game process. The
computation model was designed for formula (3.5) according to
 Q. Zhang et al. / Computational Biology and Chemistry 71 (2017) 274–279
Fig. 4. (a) The result when the signal Q1 = 0; (b)The result when the signal Q2 = 0;(c) The result when the signal Q3 = 1; (d)The result when the signal Q4 = 1.
the model of conditional probability and the model of total
probability based on DNA strand displacement. The Microsoft
Visual DSD Simulator was here used to evaluate the designed
scenario Phillips and Cardelli (2009). The model was designed for
two cases, one signal and two signals. Some of the results are
shown in Figs. 4 and 5. The horizontal coordinate represents the
time, the vertical coordinate represents the concentration.
As shown in Fig. 4, when we only know the input signal Q1 = 0,
the corresponding set of probability value is got (P(A), P(C), P(E0), P
(Q1 = 0|A), P(Q1 = 0|C), P(Q1 = 0|E0)). According to the formulas
(3.3) and (3.4), we can calculate the value of the condition
probability and full probability. As shown in Fig. 4, these values
represent the strand <t^ PQ10>, <t^ PQ10A>, and <t^ PQ10C>
respectively. Their ratios are the final results. If there are two or
more answers, they can also be found. The other case is similar
when there is only one signal. Each strand represents correspond-
ing probability in Table 1 when we have only know the input signal
Q1 = 0. The concentration of output strands is an approximation.
As shown Fig. 5, when the input signal is Q1 = 0, Q3 = 1, the
corresponding probability set is P(A), P(C), P(E), P(Q1 = 0\Q3 = 1|A),
P(Q1 = 0\Q3 = 1|C), P(Q1 = 0\Q3 = 1|E).Then, the probability value
based on the formula (3.3) and (3.4) can be found. Here, two
probability values can be found. In other words, when Q1 = 0 and
Q3 = 1, the results may be A and C, and they have same probability
value. The inference of other cases is similar.
277
In the current simulation, the concentration ratio was used to
represent the probability value. The answer can be obtained even
when there is not enough information. When the input signal has
nothing to do with any of the possible results, there will be no
output. The process of probability reasoning can be applied into
many fields in the future.
4. Conclusions
In this paper, the models of conditional probability and total
probability are implemented based on DNA strand displacement.
They can be extended to the probabilistic reasoning. The entire
reaction process is completely autonomous, and enzyme free. The
“read your mind” game was used to examine the computation
capacity of the model. In the current experiment, when only one
answer or more than one answer was provided in the problem set,
the corresponding possible action may occur. The process of
computation is transformed into the network structure flow chart,
and divided into smaller framework. The models provide a means
of implementing probability reasoning based on DNA strand
displacement. It has the potential to deliver other applications of
probability. We plan to build and enhance the capacity of model so
that it can work with other network structures, such as neural
networks.
278 Q. Zhang et al. / Computational Biology and Chemistry 71 (2017) 274–279

Fig. 5. (a) The result when Q1 = 0 and Q4 = 0; (b)The result when Q1 = 0 and Q3 = 1;(c) The result when Q2 = 1 and Q3 = 1; (d)The result when Q3 = 1 and Q4 = 1.

and the Program for Liaoning Key Lab of Intelligent Information

Table 1
Relationship between the strand and the probability when the signal Q1 = 0. Processing and Network Technology in University.

Probability Corresponding stand Concentration value(nM)

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