Combining State-based and Scenario-based Approaches in Modeling Biological Systems Jasmin Fisher , David Harel , E. Jane Albert Hubbard , Nir Piterman , Michael J. Stern , and Naamah Swerdlin Dept. of Computer Science and App. Math., Weizmann Institute, Rehovot 76100, Israel. Email: firstname.lastname@weizmann.ac.il Dept. of Biology, New York University, New York, NY. Email: jane.hubbard@nyu.edu Dept. of Genetics, Yale School of Medicine, New Haven, CT. Email: michael.stern@yale.edu Abstract. Biological systems have recently been shown to share many of the properties of reactive systems. This observation has led to the idea of using meth- ods devised for the construction (engineering) of complex reactive systems to the modeling (reverse-engineering) of biological systems, in order to enhance biolog- ical comprehension. Here we suggest to combine the two formal approaches used in our group — the state-based formalism of statecharts and the scenario-based formalism of live sequence charts (LSCs). We propose that biological observa- tions are better formalized in the form of LSCs, while biological mechanistic models would be more natural to specify using statecharts. Combining the two approaches would enable one to verify the proposed mechanistic models against the real data. The biological observations can be compared to the requirements in an engineered system, and the mechanistic model would be analogous to the implementation. While requirements are used to design an implementation, here the observations are used to motivate the invention of the mechanistic model. In both cases consistency of one with the other must be established, by testing or by formal verification. 1 Introduction Experimental biology is an interplay between collecting data in experiments (obser- vations), followed by analysis of the data and suggestion of a mechanistic model that would explain how the system under study works. Then, further experiments are pre- formed to test the hypothetical mechanism. Here we propose that the dichotomy be- tween theses two aspects of biology calls for separate formal methods. Recently, the resemblance between reactive systems (systems that continuously in- teract with their environment) and biological systems has been noted [Har02,KHC03]. This observation has led to the idea of using methods devised for the construction of complex reactive systems to model biological systems. The first attempt to follow this path was a modest model of T-cell activation [KHC03], which was followed by an ex- tensive animated model of T-cell behavior in the thymus [EHC02,EHC03]. At present Supported by the Dov Biegun postdoctoral fellowship. Supported in part by NIH grant F5490-01 and ISF grant 287/02. Supported by the John von-Neumann center for Verification of Reactive Systems.