From the determination of complex reaction mechanisms to systems biology

This review presents several methods of determining complex chemical reaction mechanisms and their functions. One method is based on correlation functions of measured time series of concentrations of chemical species, another is on measurements of temporal responses of concentrations to various perturbations of arbitrary magnitude, the third deals with the analysis of oscillatory systems, and the fourth describes the use of genetic algorithms. All methods are applicable to chemical, biochemical, and biological reaction systems and to genetic networks. The methods depend on the design of appropriate experiments for the whole system and corresponding theories for interpretation that lead to information on the causal chemical connectivity of species, reaction pathways, reaction mechanisms, control centers in the system, and functions of the system. The first three methods require no assumption of a model or hypothesis, nor extensive calculations, unlike the interpretation of measurements made on a gene network at only one time. The methods offer advantageous approaches to systems biology.