Section: Research Program

Constraint Solving and Optimization

Constraint solving and optimization methods are important in our research. On the one hand, static analysis of biochemical reaction networks involves solving hard combinatorial optimization problems, for which constraint programming techniques have shown particularly successful, often beating dedicated algorithms and allowing to solve large instances from model repositories. On the other hand, parameter search and model calibration problems involve similarly solving hard continuous optimization problems, for which evolutionary algorithms, and especially the covariance matrix evolution strategy (CMA-ES ) (N. Hansen, A. Ostermeier (2001). Completely derandomized self-adaptation in evolution strategies. Evolutionary Computation, 9(2) pp. 159–195.) have been shown to provide best results in our context, for up to 100 parameters. This has been instrumental in building challenging quantitative models, gaining model-based insights, revisiting admitted assumptions, and contributing to biological knowledge (Domitille Heitzler, Guillaume Durand, Nathalie Gallay, Aurélien Rizk, Seungkirl Ahn, Jihee Kim, Jonathan D. Violin, Laurence Dupuy, Christophe Gauthier, Vincent Piketty, Pascale Crépieux, Anne Poupon, Frédérique Clément, François Fages, Robert J. Lefkowitz, Eric Reiter. Competing G protein-coupled receptor kinases balance G protein and $\beta$-arrestin signaling. Molecular Systems Biology, 8(590), 2012.) (Pauline Traynard, Céline Feillet, Sylvain Soliman, Franck Delaunay, François Fages. Model-based Investigation of the Circadian Clock and Cell Cycle Coupling in Mouse Embryonic Fibroblasts: Prediction of RevErb-alpha Up-Regulation during Mitosis. Biosystems, 149:59–69, 2016.).