I. Caragiannis et al. (Eds.): Euro-Par 2012 Workshops, LNCS 7640, pp. 248–262, 2013. © Springer-Verlag Berlin Heidelberg 2013 Stochastic Simulation of the Coagulation Cascade: A Petri Net Based Approach Davide Castaldi 1 , Daniele Maccagnola 1 , Daniela Mari 2,3 , and Francesco Archetti 1,4 1 DISCo, University of Milan-Bicocca, Viale Sarca 336, Milan, 20126, Italy 2 IRCCS Cà Granda Ospedale Maggiore Policlinico Foundation, Via Pace 9, Milan, 20122, Italy 3 Department of Clinical Sciences and Community Health, University of Milan, 20122, Italy 4 Consorzio Milano Ricerche, Via Cozzi 53, Milan, 20126, Italy {davidefabio.castaldi,daniele.maccagnola}@disco.unimib.it, daniela.mari@unimi.it, francesco.archetti@unimib.it Abstract. In this paper we developed a Stochastic Petri Net (SPN) based model to introduce uncertainty to capture the variability of biological systems. The coagulation cascade, one of the most complex biochemical networks, has been widely analyzed in literature mostly with ordinary differential equations, outlin- ing the general behavior but without pointing out the intrinsic variability of the system. Moreover, the computer simulation allows the assessment of the reactions over a broad range of conditions and provides a useful tool for the de- velopment and management of several observational studies, potentially custo- mizable for each patient. We describe the SPN model for the Tissue Factor induced coagulation cascade, more intuitive and suitable than models hitherto appeared in the literature in terms of bioclinical manageability. The SPN has been simulated using Tau-Leaping Stochastic Simulation Algorithm, and in or- der to simulate a large number of models, to test different scenarios, we perform them using High Performance Computing. We analyze different settings for model representing the cases of “healthy” and “unhealthy” subjects, comparing their average behavior, their inter- and intra-variability in order to gain valuable biological insights. Keywords: Systems Biology, Coagulation, Stochastic Simulation, Petri Nets. 1 Introduction Petri Nets are a modeling tool widely used to represent biological systems, thanks to their intuitive graphical representation which helps to model and understand even systems with a complex structure. The graphical aspects of the Petri net are quite similar to biochemical network representation, and this gives superior communication ability to models and facilitates their design. Moreover, modelling biological systems requires to take into account uncertainty in system behaviors, due to external interferences (drugs, environment, etc), inter- variability (personal features) and intra-variability (intrinsic noise and low number of