From Syntax to Semantics in Systems Biology Towards Automated Reasoning Tools

Mathematical biology has for a long time investigated the dynamics of biomolecular systems by developing numerical models involving (highly non-linear) differential equations and using tools such as Bifurcation Theory for estimating parameters [1]. Mathematical biology provides a firm ground for the numerical analysis of biological systems. However, state-of-the-art quantitative models can hardly be re-used and composed with other models in a systematic fashion, and are limited to a few tenths of variables [2]. Qualitative models of bio-molecular interactions constitute the core of nowadays cell systems biology. Interaction diagrams are the first tool used by biologists to reason about complex systems. The accumulation of knowledge on gene interaction and pathways is currently entered in databases such as KEGG[3], EcoCyc [4], etc. in the form of annotated diagrams. Tools such as BioSpice, Gepasi, GON, E-cell, etc. have been developed for making simulations based on these databases when numerical data is present. Furthermore the interoperability between databases and simulation tools is now possible with standard exchange formats such as the Systems Biology Markup Language SBML [5]. These advances give more acuity to at least three challenges for systems biology: