Abstract. We present an on-the-fly abstraction technique for infinite-state continuous-time Markov chains. We consider Markov chains that are specified by a finite set of transition classes. Such models naturally represent biochemical reactions and therefore play an important role in the stochastic modeling of biological systems. We approximate the transient probability distributions at various time instances by solving a sequence of dynamically constructed abstract models, each depending on the previous one. Each abstract model is a finite Markov chain that represents the behavior of the original, infinite chain during a specific time interval. Our approach provides complete information about probability distributions, not just about individual parameters like the mean. The error of each abstraction can be computed, and the precision of the abstraction refined when desired. We implemented the algorithm and demonstrate its usefulness and efficiency on several case studies from systems biology.
We present a numerical approximation technique for the analysis of continuous-time Markov chains that describe networks of biochemical reactions and play an important role in the stochastic modeling of biological systems. Our approach is based on the construction of a stochastic hybrid model in which certain discrete random variables of the original Markov chain are approximated by continuous deterministic variables. We compute the solution of the stochastic hybrid model using a numerical algorithm that discretizes time and in each step performs a mutual update of the transient probability distribution of the discrete stochastic variables and the values of the continuous deterministic variables. We implemented the algorithm and we demonstrate its usefulness and efficiency on several case studies from systems biology.
Within systems biology there is an increasing interest in the stochastic behaviour of biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous-time Markov chain (CTMC). The uniformisation technique is an efficient method to compute probability distributions of a CTMC if the number of states is manageable. However, the size of a CTMC that represents a biochemical reaction network is usually far beyond what is feasible. In this study, the authors present an on-the-fly variant of uniformisation, where they improve the original algorithm at the cost of a small approximation error. By means of several examples, the authors show that their approach is particularly well-suited for biochemical reaction networks.
Abstract-WithinIn this paper we present an on-the-fly variant of AU, where we improve the original algorithm for AU at the cost of a small approximation error. By means of several examples, we show that our approach is particularly well-suited for biochemical reaction networks.
Abstract. We introduce bounded asynchrony, a notion of concurrency tailored to the modeling of biological cell-cell interactions. Bounded asynchrony is the result of a scheduler that bounds the number of steps that one process gets ahead of other processes; this allows the components of a system to move independently while keeping them coupled. Bounded asynchrony accurately reproduces the experimental observations made about certain cell-cell interactions: its constrained nondeterminism captures the variability observed in cells that, although equally potent, assume distinct fates. Real-life cells are not "scheduled", but we show that distributed real-time behavior can lead to component interactions that are observationally equivalent to bounded asynchrony; this provides a possible mechanistic explanation for the phenomena observed during cell fate specification.We use model checking to determine cell fates. The nondeterminism of bounded asynchrony causes state explosion during model checking, but partialorder methods are not directly applicable. We present a new algorithm that reduces the number of states that need to be explored: our optimization takes advantage of the bounded-asynchronous progress and the spatially local interactions of components that model cells. We compare our own communication-based reduction with partial-order reduction (on a restricted form of bounded asynchrony) and experiments illustrate that our algorithm leads to significant savings.
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