Reverse Engineering Time Discrete Finite Dynamical Systems: A Feasible Undertaking?

With the advent of high-throughput profiling methods, interest in reverse engineering the structure and dynamics of biochemical networks is high. Recently an algorithm for reverse engineering of biochemical networks was developed by Laubenbacher and Stigler. It is a top-down approach using time discrete dynamical systems. One of its key steps includes the choice of a term order, a technicality imposed by the use of Gröbner-bases calculations. The aim of this paper is to identify minimal requirements on data sets to be used with this algorithm and to characterize optimal data sets. We found minimal requirements on a data set based on how many terms the functions to be reverse engineered display. Furthermore, we identified optimal data sets, which we characterized using a geometric property called “general position”. Moreover, we developed a constructive method to generate optimal data sets, provided a codimensional condition is fulfilled. In addition, we present a generalization of their algorithm that does not depend on the choice of a term order. For this method we derived a formula for the probability of finding the correct model, provided the data set used is optimal. We analyzed the asymptotic behavior of the probability formula for a growing number of variables n (i.e. interacting chemicals). Unfortunately, this formula converges to zero as fast as , where and . Therefore, even if an optimal data set is used and the restrictions in using term orders are overcome, the reverse engineering problem remains unfeasible, unless prodigious amounts of data are available. Such large data sets are experimentally impossible to generate with today's technologies

Dynamic models of immune responses: what is the ideal level of detail?

<p>Abstract</p> <p>Background</p> <p>One of the goals of computational immunology is to facilitate the study of infectious diseases. Dynamic modeling is a powerful tool to integrate empirical data from independent sources, make novel predictions, and to foresee the gaps in the current knowledge. Dynamic models constructed to study the interactions between pathogens and hosts' immune responses have revealed key regulatory processes in the infection.</p> <p>Optimum complexity and dynamic modeling</p> <p>We discuss the usability of various deterministic dynamic modeling approaches to study the progression of infectious diseases. The complexity of these models is dependent on the number of components and the temporal resolution in the model. We comment on the specific use of simple and complex models in the study of the progression of infectious diseases.</p> <p>Conclusions</p> <p>Models of sub-systems or simplified immune response can be used to hypothesize phenomena of host-pathogen interactions and to estimate rates and parameters. Nevertheless, to study the pathogenesis of an infection we need to develop models describing the dynamics of the immune components involved in the progression of the disease. Incorporation of the large number and variety of immune processes involved in pathogenesis requires tradeoffs in modeling.</p