CompuGene Seminar Series – Upcoming Talks
All guests are very welcome!
June 11, 2018 – Bio Campus B1|01-052 (17:00 p.m.)
Prof. Wilhelm Huisinga (Univ. Potsdam)
“Understanding and reducing complex models of pharmacologically relevant reaction networks based on a novel input–response index”
Mathematical modeling, theoretical analysis and numerical approximation of the effective dynamical behaviour of stochastic and deterministic dynamical systems.
Design of reduced-order descriptions based on stochastic remodeling aiming at fast and reliable algorithms for complex problems.
Application to conformation dynamics of biomolecules, stochastic modeling on a cellular level, and pharmacokinetics.
A growing understanding of complex processes in biology has led to large-scale mechanistic models of pharmacologically relevant processes. These models are increasingly used to study the response of the system to a given input or stimulus, e.g., after drug administration. Understanding the input–response relationship, however, is often a challenging task due to the complexity of the interactions between its constituents as well as the size of the models. An approach that quantifies the importance of the different constituents for a given input–output relationship and allows to reduce the dynamics to its essential features is therefore highly desirable. In the talk, I present a novel state- and time-dependent quantity called the input–response index that quantifies the importance of state variables for a given input–response relationship at a particular time. It is based on the concept of time-bounded controllability and observability, and defined with respect to a reference dynamics. In application to the brown snake venom–fibrinogen (Fg) network, the input–response indices give insight into the coordinated action of specific coagulation factors and about those factors that contribute only little to the response. I demonstrate how the indices can be used to reduce large-scale models in a two-step procedure: (i) elimi- nation of states whose dynamics have only minor impact on the input–response relationship, and (ii) proper lumping of the remaining (lower order) model. In application to the brown snake venom–fibrinogen network, this resulted in a reduction from 62 to 8 state variables in the first step, and a further reduction to 5 state variables in the second step. I further illustrate that the sequence, in which a recursive algorithm eliminates and/or lumps state variables, has an impact on the final reduced model. The input–response indices are particularly suited to determine an informed sequence, since they are based on the dynamics of the original system. In summary, the novel measure of importance provides a powerful tool for analysing the complex dynamics of large-scale systems and a means for very efficient model order reduction of nonlinear systems. This is joint work with Jane Knöchel (Mathematics/Universität Potsdam/Germany) and Charlotte Kloft (Clinical Pharmacy and Biochemistry/Freie Universität Berlin/Germany).
September 5 2018
Prof. Ilka Axmann (Düsseldorf)
October 18 2018
Prof. Francois Kepes (Paris)
Prof. Torsten Waldminghaus (Marburg, Synmikro)
November 7 2018
Prof. Ulrich Gerland (TU München)