Incorporating time delays into the logical analysis of gene regulatory networks

Abstract. Based on the logical description of gene regulatory networks developed by R. Thomas, we introduce an enhanced modelling approach that uses timed automata. It yields a refined qualitative description of the dynamics of the system incorporating information not only on ratios of kinetic constants related to synthesis and decay, but also on the time delays occurring in the operations of the system. We demonstrate the potential of our approach by analysing an illustrative gene regulatory network of bacteriophage λ.

Integer programs and valid inequalities for planning problems

Colloque avec actes et comité de lecture. internationale.International audiencePart of the recent work in AI planning is concerned with the development of algorithms that regard planning as a combinatorial search problem. The underlying representation language is basically propositional logic. While this is adequate for many domains, it is not clear if it remains so for problems that involve numerical constraints, or optimization of complex objective functions. Moreover, the propositional representation imposes restrictions on the domain knowledge that can be utilized by these approaches. In order to address these issues, we propose moving to the more expressive language of Integer Programming (IP). We show how capacity constraints can be easily encoded into linear 0-1 inequalities and how rich forms of domain knowledge can be compactly represented and computationally exploited by IP solvers. Then we introduce a novel heuristic search method based on the linear programming relaxation. Finally, we present the results of our experiments with a classical relaxation-based IP solver and a logic-based 0-1 optimizer

A New Approach to Flux Coupling Analysis of Metabolic Networks ⋆

Abstract. Flux coupling analysis is a method to identify blocked and coupled reactions in a metabolic network at steady state. We present a new approach to flux coupling analysis, which uses a minimum set of generators of the steady state flux cone. Our method does not require to reconfigure the network by splitting reversible reactions into forward and backward reactions. By distinguishing different types of reactions (irreversible, pseudo-irreversible, fully reversible), we show that reaction coupling relationships can only hold between certain reaction types. Based on this mathematical analysis, we propose a new algorithm for flux coupling analysis.

Context Sensitivity in Logical Modeling with Time Delays

Abstract. For modeling and analyzing regulatory networks based on qualitative information and possibly additional temporal constraints, approaches using hybrid automata can be very helpful. The formalism focussed on in this paper starts from the logical description developed by R. Thomas to capture network structure and qualitative behavior of a system. Using the framework of timed automata, the analysis of the dynamics can be refined by adding a continuous time evolution. This allows for the incorporation of data on time delays associated with specific processes. In general, structural aspects such as character and strength of interactions as well as time delays are context sensitive in the sense that they depend on the current state of the system. We propose an enhancement of the approach described above, integrating both structural and temporal context sensitivity.

Geometric Constraints for the Phase Problem in X-Ray Crystallography

X-ray crystallography is one of the main methods to establish the three-dimensional structure of biological macromolecules. In an X-ray experiment, one can measure only the magnitudes of the complex Fourier coefficients of the electron density distribution under study, but not their phases. The problem of recovering the lost phases is called the phase problem. Buildingon earlier work byLunin/Urzhumtsev/Bockmayr, we extendtheir constraint-based approach to the phase problem by adding further 0-1 linear programming constraints. These constraints describe geometric properties of proteins and increase the quality of the solutions. The approach has been implemented using SCIP and CPLEX, first computational results are presented here.