In robust biological systems, wide deviations from highly controlled normal behavior may be rare, yet they may result in catastrophic complications. While in silico analysis has gained an appreciation as a tool to offer insights into systems-level properties of biological systems, analysis of such rare events provides a particularly challenging computational problem. This paper proposes an efficient stochastic simulation method to analyze rare events in biochemical systems. Our new approach can substantially increase the frequency of the rare events of interest by appropriately manipulating the underlying probability measure of the system, allowing high-precision results to be obtained with substantially fewer simulation runs than the conventional direct Monte Carlo simulation. Here, we show the algorithm of our new approach, and we apply it to the analysis of rare deviant transitions of two systems, resulting in several orders of magnitude speedup in generating high-precision estimates compared with the conventional Monte Carlo simulation.

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Even though a thorough system specification improves the quality of the design , it is not sufficient to guarantee that a system will satisfy its reliability targets. Within this paper, we present an application example of one of the activities performed in the European ESPRIT project HIDE, aiming at the creation of an integrated environment where design toolsets based on UML are augmented with modeling and analysis tools for the automatic validation of the system under design. We apply an automatic transformation from UML diagrams to Timed Petri Nets for model based dependability evaluation. It allows a designer to use UML as a front-end for the specification of both the system and the user requirements, and to evaluate dependability figures of the system since the early phases of the design, thus obtaining precious clues for design refinement. The transformation completely hides the mathematical background, thus eliminating the need for a specific expertise in abstract mathematics and the tedious remodeling of the system for mathematical analysis.

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