title: Integrating quantitative knowledge into a qualitative gene regulatory network.
abstract: Despite recent improvements in molecular techniques, biological knowledge remains incomplete. Any theorizing about living systems is therefore necessarily based on the use of heterogeneous and partial information. Much current research has focused successfully on the qualitative behaviors of macromolecular networks. Nonetheless, it is not capable of taking into account available quantitative information such as time-series protein concentration variations. The present work proposes a probabilistic modeling framework that integrates both kinds of information. Average case analysis methods are used in combination with Markov chains to link qualitative information about transcriptional regulations to quantitative information about protein concentrations. The approach is illustrated by modeling the carbon starvation response in Escherichia coli. It accurately predicts the quantitative time-series evolution of several protein concentrations using only knowledge of discrete gene interactions and a small number of quantitative observations on a single protein concentration. From this, the modeling technique also derives a ranking of interactions with respect to their importance during the experiment considered. Such a classification is confirmed by the literature. Therefore, our method is principally novel in that it allows (i) a hybrid model that integrates both qualitative discrete model and quantities to be built, even using a small amount of quantitative information, (ii) new quantitative predictions to be derived, (iii) the robustness and relevance of interactions with respect to phenotypic criteria to be precisely quantified, and (iv) the key features of the model to be extracted that can be used as a guidance to design future experiments.
authors.affiliation: Computational Biology (ComBi) Group, LINA UMR 6241, Université de Nantes, Ecole des Mines de Nantes & CNRS, Nantes, France. Jeremie.Bourdon@univ-nantes.fr
authors.forename: Jérémie
authors.initials: J
authors.lastname: Bourdon
authors.forename: Damien
authors.initials: D
authors.lastname: Eveillard
authors.forename: Anne
authors.initials: A
authors.lastname: Siegel
mesh_terms: D000465:Algorithms; D002244:Carbon / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015233:Models, Statistical
chemical_list: D002244:Carbon