Title :

Predicting Changes of Reaction Networks with Partial Kinetic Information

Author(s) :

Niehren, Joachim [Auteur]
Linking Dynamic Data [LINKS]
BioComputing
Versari, Cristian [Auteur]
BioComputing
John, Mathias [Auteur]
BioComputing
Coutte, François [Auteur]
Institut Charles Viollette (ICV) - EA 7394 [ICV]
Procédés Biologiques, Génie Enzymatique et Microbien - EA1026 [ProBioGEM]
Jacques, Philippe [Auteur]
Institut Charles Viollette (ICV) - EA 7394 [ICV]
Procédés Biologiques, Génie Enzymatique et Microbien - EA1026 [ProBioGEM]

Journal title :

BioSystems
Special Issue of CMSB 2015

Pages :

113-124

Publisher :

Elsevier

Publication date :

2016-11

ISSN :

0303-2647

English keyword(s) :

systems biology
model-based prediction
abstract interpretation
biotechnology
genetic engineering
Reaction networks
constraint solving
metabolic engineering

HAL domain(s) :

Informatique [cs]/Bio-informatique [q-bio.QM]
Informatique [cs]/Biotechnologie
Informatique [cs]/Recherche d'information [cs.IR]

English abstract : [en]

We wish to predict changes of reaction networks with partial kinetic information that lead to target changes of its steady states. The changes may be either influxes increases or decreases, reaction knockouts, or multiple ...
Show more >We wish to predict changes of reaction networks with partial kinetic information that lead to target changes of its steady states. The changes may be either influxes increases or decreases, reaction knockouts, or multiple changes of these two kinds. Our prime applications are knockout prediction tasks for metabolic and regulation networks.<p/>In a first step, we propose a formal modeling language for reaction networks with partial kinetic information. The modeling language has a graphical syntax reminiscent to Petri nets. Each reaction in a model comes with a partial de- scription of its kinetics, that is based on a similarity relation on kinetic functions that we introduce. Such partial descriptions are able to model the regulation of existing metabolic networks, for which precise kinetic knowledge is usually not available.<p/>In a second step, we develop prediction algorithms that can be applied to any reaction network modeled in our language. These algorithms perform qualitative reasoning based on abstract interpretation, by which the kinetic unknowns are abstracted away. Given a reaction network, abstract interpretation produces a finite domain constraint in a novel class. We show how to solve these finite domain constraints with an existing finite domain constraint solver, and how to interpret the solution sets as predictions of multiple reaction kockouts, that lead to a desired change of the steady states. We have implemented the prediction algorithm and integrated it into a prediction tool.</p>This journal article extends the two conference papers [1, 2] while adding a new prediction algorithm for multiple gene knockouts. An application to single gene knockout prediction for surfactin overproduction was presented in [3]. It illustrates the adequacy of the model-based predictions made by our algorithm in the wet lab.</p>Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

European Project :

Advanced Multidisciplinary Training in Molecular Bacteriology

Collections :

• Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189

Source :

Harvested from HAL