CSL Model Checking of Biochemical Networks

with Interval Decision Diagrams

Martin Schwarick and Monika Heiner
Department of Computer Science, Brandenburg University of Technology
Postbox 10 13 44, 03013 Cottbus, Germany
ms@informatik.tu-cottbus.de,
monika.heiner@informatik.tu-cottbus.de

Abstract. This paper presents an Interval Decision Diagram based approach to symbolic CSL model checking of Continuous Time Markov
Chains which are derived from stochastic Petri nets. Matrix-vector and
vector-matrix multiplication are the major tasks of exact analysis. We
introduce a simple, but powerful algorithm which uses explicitly the Petri
net structure and allows for parallelisation. We present results demonstrating the efficiency of our first prototype implementation when applied
to biochemical network models, specifically with increasing token numbers. Our tool currently supports CSL model checking of time-bounded
operators and the Next operator for ordinary stochastic Petri nets.

Motivation

Stochastic Petri nets are a natural way to model biochemical networks, where
token values may be interpreted as molecules or concentration levels [GHL07],
[HGD08]. Petri nets reflect explicitly the network structure, which contributes
to a better understanding of the network behaviour, and as we are going to
see supports efficiency gains otherwise not possible.
A stochastic Petri nets semantics is a Continuous Time Markov Chain (CTMC)
which can be investigated by simulative approaches, or analysed analytically by
transient and steady-state analysis [Ste94], or model checking of Continuous-time
Stochastic Logic (CSL) [ASSB00]. In this paper we concentrate on (analytic) CSL
model checking, which has been proven to be particularly useful for model validation and model-based experiment design in systems and synthetic biology: special
behavioural properties are expressed in CSL, a flexible and powerful query language, and then checked exhaustively against all behaviour the model can exhibit.
The tool of choice when applying CSL model checking of CTMCs is often
the probabilistic model checker PRISM [PNK06], which seems to represent the
current state of the art [JKO+ 08]. Stochastic Petri nets can be easily translated
into the PRISM input language as it has been done in [CDDS06], [GHL07],
[HGD08]. However, computational experiments reach pretty fast their limits, as
they always do if the famous state space explosion problem is one of the game
players.
P. Degano and R. Gorrieri (Eds.): CMSB 2009, LNBI 5688, pp. 296312, 2009.
c Springer-Verlag Berlin Heidelberg 2009
!

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PRISMs approach to cope with the problem is symbolic analysis based on

Multi Terminal Binary Decision Diagrams (MTBDD), which are basically Binary
Decision Diagrams (BDD) allowing more than two terminal nodes, each standing
for a different value. While this often works fine for technical systems resulting
into 1-bounded networks, it does not smoothly scale to the generalised bounded
case. First of all, prior knowledge of the boundedness degree of each place is
required. A place with an upper bound of k tokens is represented by !ld(k)"
MTBDD variables. This may result in an overhead in computation time and
memory. Since tokens may represent concentration levels, increasing the analysis
accuracy implies an increase of the possible number of tokens on places. Secondly,
PRISM creates an MTBDD which represents the entire CTMC with states and
transitions encoded in a matrix. Therefore it is necessary to double the number of
MTBDD variables to index rows and columns. Finally, a further drawback occurs
if the CTMC contains many different rate values, since the number of terminal
nodes in the MTBDD equals this amount. These lessons learnt from the PRISM
approach made us elaborate a new technique for symbolic CSL model checking,
specifically designed for biochemical networks with increasing token numbers.
The efficient analysis of qualitative Petri nets, provided they are bounded,
but not necessarily 1-bounded, is discussed by A. Tovchigrechko in [Tov08]. He
deploys Interval Decision Diagrams (IDD), which generalise BDDs by allowing
more than two outgoing arcs for each node, but keeping the idea of two terminal
nodes only. The developed data structures and algorithms support state space
based analysis, including model checking of Computational Tree Logic (CTL).
They do neither require a priori knowledge of the boundedness degree nor a suitable network partitioning as Kronecker-based approaches do, see e.g. [CJMS06].
The IDDs inherent compression effect often yields compact representations of
very large state spaces [HST09], see also caption of Table 2 in Section 4.
In this paper we are going to demonstrate how these IDD techniques can
be transfered and adapted to CSL model checking, which basically requires to
incorporate matrix-vector multiplication. In doing so we always bear in mind
the option of parallelised processing on nowadays standard workstations. It goes
without saying, the application of our results is not restricted to stochastic Petri
nets. Specifically we will demonstrate how PRISMs efficiency may take advantage of our pre-analysis of a networks inherent structure.

Preliminaries

Stochastic Petri Net. An ordinary stochastic Petri net SP N is a tuple

(P, T, F, V, s0 ). As usual, P denotes the set of places, T the set of transitions,
F : ((P T ) (T P )) {0, 1} the arc weight function, and s0 the initial
state (marking). The mapping V : T H, where H is the set of hazard functions, associates to each transition a function ht from H, defining a generally
state-dependent, but always exponentially distributed firing rate. We deal with
biologically interpreted stochastic Petri nets; thus we consider besides arbitrary
arithmetic functions specifically functions representing biomass action semantics
(BMA) and biolevel interpretation semantics (BLI). All these functions have in

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common that the domain is restricted to the preplaces of the corresponding

transition. For more details see [GHL07].
Continuous Time Markov Chain. The semantics of a stochastic Petri net
is a CTMC which is isomorphic to the reachability graph of the underlying
qualitative Petri net, but state transitions are labelled with firing rates. Without
t

t!

s" and s
s" are state transitions in the
loss of generality we assume, if s
CMTC, then t = t" . A CTMC is a tuple (S, R, L, s0 ), with S denoting the set of
reachable states of the underlying net, R : SS R0 the rate function, usually
represented as matrix, L : S 2AP the labelling function, and s0 the initial
state. The set AP := {pn|p P, {<, , =, *=, , >}, n N0 }{true, f alse}
of atomic propositions is defined over the set of places, which serve as integer
variables. The entry R(s, s" ) is defined as:
R(s, s ) =
"

ht (s)
0

if t T : s
s"
otherwise .

The total rate E(s) = s! S R(s, s" ) is the sum of entries of the matrix row
indexed with s. A state s with E(s) = 0 is called an absorbing state, since there
is no way to leave it when reached. The probability of a transition t enabled in
!
state s to fire (which results in state s" ) within n time units is 1 eR(s,s )n .
The transient probability (, s, ) is the probability to be in state s at time
starting from a certain probability distribution , with : S [0, 1] and
sS (s) = 1. The vector of transient probabilities for all states at time
with the initial distribution is denoted by (, ). An established technique
to compute the transient probabilities (transient analysis) of CTMCs is the uniformisation method. Its basic operation is vector-matrix multiplication which
must be done for a certain number of iterations. For more details see [Ste94].
Continuous time Stochastic Logic. CSL is the stochastic counterpart to
Computation Tree Logic (CTL). We consider CSL without the steady state
operator and time-unbounded path formulae, and define state formulae
::= a | | | | P!"p [] ,
and path formulae
::= X | U[1 ,2 ] | F[1 ,2 ] | G[1 ,2 ] ,
with a AP , '( {<, , , >}, p [0, 1], and 1 , 2 R0 1 2 2 < .
For convenience we introduce the operators F and G as short-hand notations
for the frequently used patterns true U , and (true U ).
CSL model checking of a CTMC M can be realised by transient analysis. The
basic concept is to do transient analysis for a CTMC M " which has been derived
from M by making certain states absorbing, depending on the formula to be
checked. For more details, e.g. formal semantics definition, see [BHHK00].

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299

Interval Decision Diagrams. An IDD is a rooted, directed and acyclic graph

with nodes having an arbitrary number of outgoing edges. Each edge is labelled
with a left-closed and right-open interval on N0 . The intervals of the outgoing
edges of each IDD node define a partition of N0 , inducing a total order of the
edges. There are two nodes without outgoing edges: the terminal nodes, labelled
with ONE and ZERO.
Each IDD node gets associated a variable, in our context a place of the stochastic Petri net. We assume that the variables occur in the same order on each path
from the root to a terminal node we get ordered IDDs. Furthermore we assume
that an IDD does not contain isomorphic subgraphs we get reduced ordered
IDDs. As for BDDs, the variable ordering may influence the IDD size.
We use IDDs to encode sets of states of stochastic Petri nets, see Figure 1. The
height of an IDD always equals the number of places, independently of the places
boundedness degree. IDDs grow in the breadth: a large variety of tokens on a
given place may increase the number of outgoing edges of the corresponding IDD
nodes, depending on the IDD-inherent compression effect. We consider bounded
Petri nets; thus, each IDD node for a k-bounded place has at least two outgoing
edges: [0, k+1), and [k+1, ).
A path (sequence of IDD nodes connected by edges) reaching the terminal
node ONE represents generally a set of states. We get one state by choosing
exactly one value from each of the intervals of all edges occurring along a path.
For the efficient manipulation of state sets we assume operations like , , \.
Further we assume operations for the manipulation of state sets by the firing
t
s" } represents the set of states
of transitions. F ire(S, t) := {s" |s S s
n7(p1)

[0,1)
# 0
n3(p3)

[2,3)
# 0

[1,2)
# 2
n4(p3)

[1,2)
# 0

[1,2)
# 0

t1

t4

t2

p3

t3

t5

[3,oo)
# 2

n5(p3)

[0,1)
# 0

n2(p2)

[2,oo)
# 1

[1,oo)
# 1
[0,1)
# 0

n6(p3)

[0,1)
# 0

[3,4)
# 1

p2

[4,oo)
# 6

[3,4)
#5

[1,2)
# 0

[2,3)
# 1

n1(p2)
[2,oo)
# 1

p1

[2,3)
#4

[0,1)
# 0

[1,oo)
# 1

[0,1)
#0

[4,oo)
# 2

[0,2)
# 0

Fig. 1. A Petri net and the IDD, encoding its six reachable states. The path n7

0
0
n6
n2
1 represents the initial state m (p1 : 3, p2 : 0, p3 : 0). The path
1
1
1
n4
n1
1 represents the state m! (p1 : 1, p2 : 1, p3 : 1) which is reached
n7
from m by firing transition t2. Edges are labelled with intervals and additional index
data, see Section 3.1.

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obtained by firing the transition t for each state in S, and Img(S) represents
the set of all direct successor states of S. Analogously, we define RevF ire(S, t)
and P reImg(S) for backward firing. For more details see [Tov08].
While CTL model checking can be completely reduced to the manipulation of
sets of integer states, CSL model checking by transient analysis requires the (repeated) multiplication of a real-valued matrix with a real-valued vector (or vice
versa). On account of the state space explosion problem it is not worth thinking
about implementing this vector-matrix multiplication explicitly with matrix and
vector indexed by states. There is no way to avoid the explicit representation of
the vector . Actually, we need at least three (four) copies of it. Thus, the whole
problem boils down to the question: How to multiply with a matrix without
having (explicitly represented) the matrix?
In the following we present a matrix-free on-the-fly approach to realise CSL
model checking more efficiently than other tools available so far. Our tool IDDCSL computes all required data at each iteration anew from one augmented IDD
representing the reachable states of an SPN. Thus, our technique does not care
about the number of different matrix entries in the rate matrix. This is in
terms of data structures the main difference to PRISMs approach, where the
CTMCs state space S and its rate matrix R are represented symbolically by a
BDD and an MTBDD.

3
3.1

Multiplication with IDDs

Basic Algorithm

We do not use dedicated data structures to represent the CTMC as other symbolic model checkers do. All necessary information is derived from the set of
reachable states encoded as an IDD and the Petri net structure itself. However,
we do need the lexicographic index for each state in the state set, which will be
determined by each depth first search traversal of the decision diagrams. One
slight extension of the IDD is required to get these indices, which brings us to
the index-labelled IDD, LIDD for short.
Now the basic idea of our approach is simply explained. The traversal of an
IDD representing a state set S " S drives the traversal of the LIDD, representing
S. This indirect, partial traversal of the LIDD S allows to compute the index
for each state s" S " . Additionally we keep track of the index of the state
s"" , reached by firing a given transition t T in s" , assuming s" enables t. We
compute the enabling states for a transition t by ESt := SRevF ire(S, t). When
traversing an IDD, we always consider the pre- and post-conditions for the firing
of a transition t of the underlying Petri net to determine the LIDD paths of
the related target states. This idea is inspired by the fire algorithm proposed
in [Tov08]. Each traversal extracts the indices of all state transitions (matrix
entries) of the CTMC induced by the firing of a transition t. Traversing the
LIDD for all transitions controlled by their enabling states eventually extracts all
non-zero matrix entries. Thus, each iteration required for the transient analysis
means the LIDD traversal for all transitions of the Petri net.

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301

Algorithm 1. LIDD index labelling

procedure augmentIdd(states : LIdd)
augmentNode(states.root);
end procedure
function augmentNode(node : LIddN ode) int :
if node = ON E then
return 1;
end if
if node = ZERO then
return 0;
end if
count, reachable : int;
count := 0;
for 0 i < node.edges() do
edge : LIddEdge;
edge := node.edge(i);
edge.smaller = count;
reachable :=augmentNode(edge.node());
count := count + reachable edge.intervalW idth();
end for
return count;
end function

Augmentation of an IDD with index information. The required state indexing calls for an augmentation of the IDD, representing the reachable states, by
some information which allows the necessary computation. Inspired by [MC99]
we store the amount of lexicographic smaller states for each edge, which can be
reached by all its previous sibling edges. This style to organise the index information allows to keep several sets within one and the same LIDD with different sets
having different nodes as root. Algorithm 1 sketches how to derive recursively
the LIDD representing S. The generated additional index data are labelled with
a pound (#) in Figure 1.
Determining a matrix entry. We need the value (rate) of the current matrix
entry R(i, j) to multiply the rate matrix with a vector or vice versa. This rate is
determined by the hazard function of the Petri net transition which is responsible
for the state transition from the state with index i to the state with index j.
Consequently, while computing the index pair for each state transition, we have
to compute this function value, too. See Algorithm 2.
Manipulating the matrix. Please recall, model checking of time-bounded
CSL operators for a CTMC M can be reduced to the problem of applying transient analysis to M " which has been derived from M by making certain states
absorbing. For this purpose, PRISM creates a new MTBDD representing the rate
matrix of M " . In our approach this means only to call the procedure traverse
for the non-absorbing subset N ESt of the enabling states ESt of a transition
t. When A is an IDD representing the set of absorbing states, N ESt can be
computed efficiently by ESt \ A.
Model checking the X operator involves the so-called Embedded Markov
Chain (EMC). The EMC is a Discrete-time Markov Chain (DTMC), i.e. transitions are labelled with probabilities and the rate matrix R is replaced by the

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Algorithm 2. LIDD traversal

procedure traverseAllTransitions
//the following for loop can be parallelised
t : T ransition;
ESt : Idd;
for 0 <= j < SP N.transitions() do
t := SP N.getT ransition(j);
f a : F unctionArgumentSet;
ESt := S RevF ire(S, t);
traverse(t, ESt .root, S.root, S.root, 0, 0, f a);
end for
end procedure
procedure traverse(t
:
T ransition, root
:
IddN ode, src, dest
:
LIddN ode,
srcIndex, destIndex : int, f a : F unctionArgumentSet)
if root = ON E then
//e.g. vector-matrix r=v*M :
//r[srcIndex] = v[destIndex]*rf.compute(fa)
//rate is M[srcIndex][destIndex]
rate : double;
rate := t.rateF unction.compute(f a);
processData(srcIndex, destIndex, rate);
return ;
end if
p : P lace;
value, value2, srcIndex2, destIndex2 : int;
edgeIndexSrc, edgeIndexDest : int;
edgeIndexSrc, edgeIndexDest := 0;
src2, dest2 : LIddN ode;
edge : Edge;
p := src.correspondingP lace();
for 0 i < root.edges() do
edge := root.edge(i);
if edge.node() )= ZERO then
value := edge.lowerBound();
while value < edge.upperBound() do
value2 := value;
if isP reP lace(p, t) then
f a.setArgument(p, value);
end if
value2 := value + getW eight(p, t);
edgeIndexSrc := nextEdgeIndex(src, edgeIndexSrc, value);
edgeIndexDest := nextEdgeIndex(src, edgeIndexDest, value2);
src2 := src.edge(edgeIndexSrc).node();
dest2 := dest.edge(edgeIndexDest).node();
srcIndex2 := srcIndex+smallerStates(src, edgeIndexSrc, value);
destIndex2 := destIndex+smallerStates(dest, edgeIndexDest, value2);
traverse(edge.node(), src2, dest2, srcIndex2, destIndex2, f a);
value := value + 1;
end while
end if
end for
end procedure
function smallerStates(node : LIddN ode, edgeIndex, val : int) int :
smaller : int;
edge : LIddEdge;
edge : node.edge(edgeIndex);
smaller := 0;
if edgeIndex > 0 then
smaller := node.edge(edgeIndex 1).smaller;
end if
return smaller + (val edge.lowerBound()) edge.node().lastEdge().smaller;
end function

CSL Model Checking of Biochemical Networks

303

probability matrix P, where each entry (s, s" ) represents the probability of a
state transition from s to s" . The sum of each row of P is 1. The EMC Me is
derived from a CTMC M by defining P as P(s, s" ) := R(s, s" )/E(s). We assume
that the values E(s) for all states are stored in a vector. Multiplying the EMC
with a vector means to adapt Algorithm 2 by the code given in Algorithm 3.
This approach should also work for PRISMs traversal algorithm. PRISM uses
a further MTBDD to represent the EMC, for which the number of terminal nodes
and thus the overall number of nodes can explode (see Section 4).
Algorithm 3. Adaptation of Algorithm 2 to handle Embedded Markov Chains
if root = ONE then
// e.g. vector-matrix r=v*M :
// r[srcIndex] = v[destIndex]*rf.compute(fa)
// rate is M[srcIndex][destIndex]
rateEmbedded : double;
rateEmbedded := t.rateF unction.compute(f a)/E[srcIndex];
processData(srcIndex, destIndex, rateEmbedded);
return ;
end if

3.2

Optimization Techniques

In this section we sketch some optimization techniques contributing to the efficiency of our approach.
Variable Ordering. It is well known that the chosen variable order is crucial
for the size of decision diagrams and thus for the efficiency of related algorithms.
[Noa99] suggests a greedy algorithm to obtain a static variable order for Zero
Suppressed Binary Decision Diagrams which is based on heuristics exploiting the
Petri net structure. The basic idea is to create an order where related variables
are close together. Related variables are in our case places, which are directly
connected by a Petri net transition. The heuristic algorithm creates step-wise an
order , starting at the lowest IDD level and using the weight function W (p) to
determine the next place from the set of unprocessed places to be inserted in
based on the set of already processed places Q. Using the standard dot notation
to specify the set of pre- or postnodes of a given node we define W (p) by:
W (p) :=

t p |

tQ|
|t Q|

| t| + tp
|t |
| p p |

(1)

Our approach benefits from the observation that the variable orders obtained by
this algorithm usually yield small IDDs, see [Tov08], [HST09], and Section 4.
A prominent heuristics to represent matrices as MTBDDs relies on variable
orders with alternating row and column variables. Additionally, it is worthwhile
to find a good overall variable order, as we will see in Section 4. PRISM reads
models as they are, i.e. it will not change the order of modules and the variables therein contained. Using the sketched ordering algorithm when specifying

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M. Schwarick and M. Heiner

PRISM models generally speeds up the state space construction and the model
checking significantly.
Caching. As for every implementation of decision diagrams, efficiency depends
on considering redundancies. Generally, nodes on lower IDD levels will be visited
many times. Subpaths beginning in these nodes will be traversed each time anew.
Following [Par02] we set a certain layer of the LIDD and cache index and rate
information for each of its nodes for all paths to reach this node. Each time a
node of the cache layer is reached, the cache data must be retrieved only.
Our algorithm traverses the LIDD transition-wise driven by an unlabelled IDD
representing the enabling states of the transition or a non-absorbing subset of it.
Thus it is necessary to store transition-specific information for all LIDD nodes
of the cache layer. The cache data contain for each transition the index pair and
the rate function of all possible path extensions. Each visit of a cache layer node
comes with a unique index pair and a unique set of function arguments which
allow to compute all related matrix entries using the cache data. A cache datum
consists of an index pair and a rate function. Often many index pairs refer to the
same function. Thus we associate to a function a set of index pairs. In general, a
cache layer node keeps several rate function instances and their assigned index
pairs for each transition. Changing the enabling states or the rates of the CTMC,
e.g. by uniformisation, needs to reinitialise all cache data.
To use cache data requires a modification of Algorithm 2. When visiting a
cache layer node, the transition-related cache data will be processed and the
procedure traverse returns, compare Algorithm 4.
A crucial point for an implementation of this approach is to store the cache
data, in particular the index sets, as memory-saving as possible. A naive way
of doing this is to store lists of index pairs. But a closer look to the possible
values reveals that there are often consecutive pairs with a fixed step size. This
is a consequence of the fact that we obtain a huge state space by filling a Petri
net with tokens, but without changing its structure. If such sequences of consecutive index pairs exceed a critical length it is worthwhile to represent them
by a tuple (f irst rowIndex, f irst colIndex, row stepSize, col stepSize, steps).
Then, the sequence (0, 0); (5, 10); (10, 20); . . . ; (100, 200) can be encoded by the
tuple (0, 0, 5, 10, 20). An issue here is to find a suitable critical length.
Traversal for transition sets and arbitrary state sets. The basic algorithm
sketched so far requires a separate traversal for each transition of the stochastic
Petri net. An improvement is to generalise the algorithm such that it controls
the traversal of the LIDD S for a set of transitions and an IDD encoding an
arbitrary set of states S " S. Then the algorithm must treat lists of source and
target indices. The lists contain for each transition an entry holding the current
traversal data. The basic algorithm ensures that the traversal-controlling IDD
contains enabling states of a transition only. A generalization of the algorithm
must deal with disabling states, too. Our prototype tool IDD-CSL implements
the generalised algorithm.

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305

Algorithm 4. Adaptation of Algorithm 2 in order to use cache data

if cacheLayerReached() then
rate : double;
rf : RateF unction;
indices : IndexSet;
actSrcIndex, actDestIndex : int;
cd : CacheData;
cd := src.cacheData(t);
for 0 i < cd.entries() do
rf := cd.getF unction(i);
indices := cd.getIndices(i);
rate := rf.compute(f a);
for 0 j < indices.size() do
actSrcIndex := srcIndex + indices.getSrcIndex(j);
actDestIndex := destIndex + indices.getDestIndex(j);
processData(actSrcIndex, actDestIndex, rate);
end for
end for
return ;
end if

Parallelisation. Todays workstations or even standard personal computers in

an everyday secretary office tend to possess two or more processors. Thus it
is appealing to take advantage of the available multiple processors. There are
basically two approaches to divide the problem of a matrix-vector multiplication
or vice versa into smaller tasks, which can be solved concurrently.
On the one hand one could divide the Petri nets transition set and apply
the algorithm concurrently to each subset. Doing so obviously requires some
kind of synchronisation techniques. On the other hand one could partition the
state space. Applying our algorithm concurrently with forward (backward) firing
transitions with a partitioned state space means to devide the matrix row-wise
(column-wise) into submatrices and requires no synchronisation when doing a
matrix-vector (vector-matrix) multiplication, because each row (column) is considered for all transition by only one thread. When synchronisation is required
all threads get their own complete result vector and collect the results of all
other threads after each computation phase.
Although parallelisation is not the focus of this paper, we are going to indicate
its potential by presenting some related results in the following section.

Benchmarks

In this section we present results comparing our prototype implementation IDDCSL with PRISM, and by transitivity with a couple of CSL model checking tools
on the market [JKO+ 08]. As benchmarks we consider stochastic Petri nets of the
following popular biochemical networks.
The mitogen-activated protein kinase (MAPK) cascade published in [LBS00]
and discussed as three related Petri net models in [GHL07], [HGD08]. All
initial states considered in our paper are multiples of level 4. This is the
minimal initial (integer) state respecting the ratio in the initial (real-valued)

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M. Schwarick and M. Heiner

concentrations as given in [LBS00]. Our model is structurally identical with

the MAPK cascade given on the PRISM website. The models only differ in
the names of variables, the initial state and the specified rate constants.
The RKIP inhibited ERK pathway (ERK) published in [CSK+ 03], analysed
with PRISM in [CVOG05], discussed as qualitative and continuous Petri
nets in [GH06], and as three related Petri net models in [HDG10].
The circadian clock model (CC) published in [BL00] and available as PRISM
model on the PRISM website.
For the comparison with PRISM we either use the export feature of our modelling
tool Snoopy [Sno08] (MAPK, ERK) or an available PRISM model (CC). The latter example needs capacities to enforce boundedness, which we
simulate in the Petri nets by complementary places. All models have scalable
initial states. The experiments consider biomass action (resp. biolevel interpretation) semantics, for which IDD-CSL offers the predefined BioM assAction (resp.
BioLevelInterpretation) function.
Our implementation makes use of Intels instruction set extension SSE2 which
could also speed up PRISM. In some cases the efficiency gain is about 10 percent.
Our test system is a Dell Precision workstation with 4 GB main memory and
an Intel Xeon with 4 2.83GHz running a 64bit Linux. In our computational
experiments we focus on runtime. All related figures are given in seconds.
The influence of variable order. In contrast to the modelling style in [KNP08],
our generated monolithic PRISM models consist of one module only, with a module variable for each place. The value range of the variables (boundedness degree)
and the variable order were computed by our IDD-based tool box. Table 1 illustrates the impact of the chosen variable order on PRISMs efficiency for different
levels of the MAPK cascade, and Table 2 the CTMC size for different levels computed with PRISM using a good variable order.
Table 1. Comparison of two variable orders. The table shows the time and the number
of MTBDD nodes, which PRISM needs to construct the rate matrix of the CTMC for a
good variable order,computed using formula (1), and for the plain order of the original
PRISM model, specified according to [KNP08].
levels

terminal
good order
original order
time
nodes
time
nodes
nodesa)
4
30
0.12
8,672
2.47
123,730
8
76
1.56
60,452
401.68
3,881,914
12
140
22.99
199,496
16
219
71.25
542,339
20
320
296.87
953,146
24
453
635.92
2,029,598
28
697
928.45
3,771,617
32
770
1847.60
6,015,521
a)
i.e., number of different entries in rate matrix; - exceeds the available memory;

CSL Model Checking of Biochemical Networks

307

Table 2. CTMC size for different levels computed with PRISM using a good variable
order, see Section 3.2. In principle our tool IDD-CTL allows to compute the state space
up to level 320 (2.627e+27 states ) in about 2 minutes on a standard personal computer
[HST09]. However, the transient analysis it limited to the available memory to store
the required vectors (, ) in the size of the state space.
levels

number of edgesa)

number of states

4
24,065
8
6,110,643
12
315,647,600
16
6,920,337,880
20
88,125,763,956
24
769,371,342,640
28
5,084,605,436,988
32
27,124,071,792,125
i.e., number of non-zero entries in rate matrix;

a)

206,007
78,948,888
4,958,809,056
122,381,517,819
1,689,018,298,500
15,635,976,824,982
108,065,356,604,208
597,236,499,605,178

Table 3. The formula P>0.0 [F[0,1] Raf P = 2] is true for all states for which the probability is not zero to reach a state within one time unit which satisfies Raf P = 2. For
model checking of this formula all states satisfying Raf P = 2 become absorbing; there
are 1, 083, 102 of them. The derived CTMC M ! comprises 64, 368, 742 state transitions.

b)

cl

PRISMa)
totalc)

iterd)

cl

IDD-CSL
1 thread
total
iter
440.23
170.06
158.65
110.02
93.84
79.48
84.62
75.51
84.49
75.04
90.65
81.73
100.40
91.39
127.72
118.09
253.60
243.05
692.84
676.05
1808.66 1771.00

2 threads
total
iter
432.77
157.08
158.71
99.75
72.71
55.01
62.57
50.55
60.81
49.17
64.08
52.18
67.47
55.97
81.40
69.71
147.85
134.09
387.62
368.08
957.26
917.07

3
208.35
140.82
5
222.67
169.76
7
201.23
154.94
9
200.13
158.99
10
195.83
159.90
11
198.43
163.03
13
214.64
179.90
15
226.16
191.22
17
218.51
184.06
19
230.66
195.92
21
2318.86
2275.71
a)
using a good variable order, determined by the network structure, see Table 1;
b)
cache layers; c) includes time for state space construction, initialisation, computation
and determining the satisfying states; d) effective probability computation time;
65
60
55
50
45
40
35
30
25
20
1

The influence of caching. Tables 3 and 4 compare the runtime of IDD-CSL

and PRISM with different cache layers1 for the eight level version of the MAPK
cascade with biolevel interpretation semanctics. We use the flat PRISM model
with a good variable order, compare Table 1, for these experiments. We take
formulae which differ only in the specified time intervals. The interval [0, 1] in
1

In PRISM the highest cache layer is the root node layer, in IDD-CSL it is the
terminal node layer. PRISMs hybrid engine is used.

308

M. Schwarick and M. Heiner

Table 4. The formula P>0.0 [F[1,1] Raf P = 2] is true for all states for which the
probability is not zero to be at time 1 in a state which satisfies Raf P = 2 . Any path
formula F[, ] is suitable to trigger transient analysis up to time point using CSL
model checking.
PRISMa)
total

IDD-CSL
1 thread
2 threads
total
iter
total
iter
3
382.00
148.05
365.91
129.08
65
242.80
163.05
5
135.06
94.01
124.50
74.27
60
231.65
170.69
55
275.53
219.89
7
88.74
75.84
67.32
50.43
9
82.22
73.47
60.25
48.34
50
222.23
173.32
10
81.58
72.82
58.55
47.21
45
210.13
167.48
40
209.91
168.83
11
87.67
78.98
62.42
51.11
13
97.53
88.98
65.55
54.34
35
212.23
171.38
15
124.67
116.00
78.85
67.56
30
211.43
170.39
17
260.95
250.09
150.66
137.09
25
221.78
181.28
19
782.22
766.00
428.38
409.02
20
231.90
192.46
21
2128.20 2087.00 1150.41 1106.00
1
2745.47
2691.70
a)
using a good variable order, determined by the network structure, see Table 1;
cl

iter

cl

contrast to the interval [1, 1] generally results into a set of absorbing states due
to the CSL model checking algorithm [BHHK00]. A high amount of absorbing
states reduces memory consumption and run time.
The MTBDD needs 66 row and 66 column Boolean variables. The IDD needs
independently of the number of levels 22 integer variables, i.e. as many as there
are places in the Petri net model. Thus, the MTBDD hight is 132, and the IDD
hight is 22. The tables show the total processing time and the effective iteration
time for the computation of the probability vector (, 1), which requires 218
iterations for each experiment of the used formulae. The best results in terms of
total time and iteration time, depending on the used cache layer are highlighted
in bold. The last line in each table represents the case where caching is disabled.
Further results. Table 5 and 6 present results for the transient analysis using
CSL model checking for the ERK model and the circadian clock model with
biomass action semantics. We give the total run time for both tools. In general
PRISMs explicit sparse matrix engine is faster then its hybrid MTBDD engine
at the expense of a higher memory usage [JKO+ 08]. The tables show that our
tool outperforms also the sparse engine. The CTMC size affects the model checking performance. Thus, a high amount of absorbing states (which depends on
the CSL formula) may significantly speed up the model checking. Except from
choosing the engine or the number of threads, we run the tools with their default settings. Please note that changing, e.g., the cache layer would affect the
run time and the memory consumption.
We also performed experiments with the X operator; we report here of one of
them, which relates to the MAPK cascade. The formula P<0.1 [X Raf P = 2] is
true for all states for which the probability is less than 0.1 to reach in one step

CSL Model Checking of Biochemical Networks

309

Table 5. CSL-based transient analysis of ERK for several initial markings. The formula P>0.0 [F[1,1] Raf 1Star = 1] is true for all states for which the probability is not
zero to reach a state within one time unit which satisfies Raf 1Star = 1.
level

CTMC size
PRISM
states
edges
hybrid
5
1,974
12,236
0.73
10
47,047
372,372
5.52
15
368,220
3,213,408

20
1,696,618
15,609,594

25
5,723,991
54,438,930

30
15,721,464
152,964,146

time for initialisation exceeds 24 hours;

sparse
0.65
3.97

IDD-CSL
1 thread
2 threads
0.20
0.17
1.27
1.05
20.73
16.67
148.92
118.59
740.28
581.39
3,005.62
2,455.57

Table 6. CSL-based transient analysis of the circadian clock for several initial markings. The formula P>0.0 [F[1,1] a = 1] is true for all states for which the probability is
not zero to reach a state within one time unit which satisfies a = 1.
level

CTMC size
PRISM
states
edges
hybrid
sparse
5
31,104
290,160
3.90
2.36
10
644,204
6,766,320
122.55
64.94
15
4,194,304
45,972,480
1,090.44
570.43
20
16,336,404
183,032,640
5,569.65
2,835.89
25
47,525,504
539,650,800

30
114,516,604 1,312,110,960

exceeds the physical memory; time for initialisation exceeds

IDD-CSL
1 thread
2 threads
1.76
1.16
44.65
26.10
466.47
312.83
2,471.70
1684.96
8,595.37
6,027.33
26,085.95
17,314.66
24 hours;

a state which satisfies Raf P = 2. To represent the Embedded Markov Chain

PRISM creates an MTBDD which comprises 48, 149, 682 nodes, among which
are 217, 974 terminal nodes. The model checking takes 201.09 seconds including
state space construction and initialization. IDD-CSL requires five seconds.
The figures speak for themselves. The gap between PRISM and IDD-CSL gets
larger with increasing amount of levels (tokens, boundedness degree). Our data
structure is less sensitive to increasing the amount of levels, and does not care
about the amount of different matrix entries in the rate matrix.

Technicalities

The tool is implemented in C++ , re-using our IDD-based CTL model checking
implementation IDD-CTL [HST09] and the GNU MB Bignum Library (GMP).
The parsing of CSL formulae has been generated by the lexical analyser and
parser generator f lex and bison. For parallelisation we use the POSIX pthread
library. The tool comes as an all-inclusive binary (statically linked libraries) for
our development and reference test system Linux. Versions for Windows and
Mac/OS are in preparation.

310

M. Schwarick and M. Heiner

The Petri net models have been constructed using Snoopy [Sno08], [HRS08], a
tool to design and animate or simulate hierarchical graphs, among them stochastic Petri nets as used in this paper. Snoopy provides export to various analysis
tools, recently complemented by PRISM, as well as import and export of the
Systems Biology Markup Language (SBML).
The tools are available at www-dssz.informatik.tu-cottbus.de, free of charge
for scientific purposes. At the same web site you find also the Petri net examples
(in Snoopy, APNN, and PRISM syntax), which we used as benchmarks in the
preceding section. Thus, all reported computational experiments can be easily
repeated.

Conclusions

We have presented a new tool for symbolic CSL model checking of ordinary
stochastic Petri nets. We combine approved heuristics with an innovative approach to represent symbolically a CTMCs rate matrix by Interval Decision
Diagrams. We accept potentially higher computational costs in favour of smaller
data structures. The models have to be bounded, however, no a priori knowledge
of the precise boundedness degree is required. Likewise, we do not depend on a
suitable partitioning as Kronecker-based approaches do. A crucial point for the
tools performance are the algorithms exploiting knowledge of the network structure. The implementation benefits in particular from the chosen static variable
order which also increases PRISMs performance significantly.
In total we gave the results of more than 100 computational experiments. The
presented benchmarks show that our data structure used for the symbolic state
space representation is relatively insensitive to increasing token numbers. The
IDD hight is completely defined by the number of variables. The IDD breadth
may increase with increasing token numbers, but this depends on the IDD compression effect. Our approach is not sensitive at all to an increasing amount of
different entries in the rate matrix. In summary this means that we are able to
do transient analysis for any SPN for which we can construct the state space,
provided we have enough memory to keep the vectors . Using our IDD-CSL
prototype we are now able to compute CSL properties, which were formerly not
amenable to analytic model checking, for examples see [GHL07], [HGD08].
We are working on improvements of the sketched optimisation techniques, in
particular the parallelisation. Furthermore we are going to support non-ordinary
stochastic Petri nets and full CSL model checking. Thus, iterative solving of
homogenous linear equation systems will be realised. For the time being we
model capacities of places by introducing complementary places, which does its
job, but blows up the models (e.g., our circadian clock model) and prohibits
the use of predefined functions as BioM assAction. To avoid such restrictions
and eventually improve performance and memory consumption, we are going to
support extended arc types, including the inhibitor arcs.
There are other stochastic Petri net tools, offering numeric analysis techniques
as transient analysis which is the key to CSL model checking, e.g. SMART

CSL Model Checking of Biochemical Networks

311

[CJMS06] and M
obius [PCS07]. We will also compare our tool with them, including technical networks in a representative benchmark suite as well.
Acknowledgements. We appreciate the support by the PRISM tool, which
we use in our back-to-back testing process as golden prototype.
Snoopys export to PRISM has been implemented by Fei Liu, who is funded
by the FMER (BMBF), funding number 0315449H. The export offers various
variable ordering options for comparison and teaching purposes.

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