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A8 Constraint-based Modeling in Systems Biology

              

DFG Research Center MATHEON


Contents

Description

Head

Members

Funding

Duration

Publications

 

Description

Systems biology is a new area of biology that studies how the various components of a biological system (genes, RNA, proteins, ...) interact in order to perform complex biological functions. Given that biological information is typically incomplete, the idea of constraint-based modeling is to describe a biological system by a set of constraints, which characterize its possible behaviors, but in general do not allow to make a precise prediction. The classical starting point of constraint-based modeling is flux balance analysis of metabolic networks at steady state. Mathematically speaking, this involves computing a basis of the underlying polyhedral cone. Existing methods focus on pointed cones, and the metabolic networks have to be reconfigured in order to obtain this property. Within the project, we are currently developing a new method, which works on non-pointed cones, and which allows us to characterize the possible behaviors of a metabolic network in a much more compact way. While existing mathematical models in systems biology often concern metabolic networks, these cover only a small part of the activities of a cell. Equally important are signal transduction and gene regulatory networks, which have been studied much less. New mathematical approaches, based on a higher level of abstraction, seem necessary to handle these biological processes. Since quantitative biochemical information is often not available, qualitative modeling techniques like the discrete logical networks of R. Thomas become increasingly important. Within the project, we are studying different mathematical and computational problems related to the reconstruction and analysis of such networks, with special emphasis on incorporating time delays into the logical analysis of regulatory networks.

 

Head

Prof. Dr. Alexander Bockmayr

 

Members

Prof. Dr. Heike Siebert

Dr. Hannes Klarner

Dr. Lazlo David

Dr. Abdelhalim Larhlimi

 

Funding

DFG Research Center Matheon "Mathematics for key technologies"

 

Duration

04/2005-05/2010

 

Publications

Analysis of Discrete Bioregulatory Networks Using Symbolic Steady States
Heike Siebert (2009)

A new constraint-based description of the steady-state flux cone of metabolic networks
A. Larhlimi and A. Bockmayr (2009)

Dynamical and Structural Modularity of Discrete Regulatory Networks
Heike Siebert (2009)

New Concepts and Tools in Constraint-based Analysis of Metabolic Networks
A. Larhlimi (2008)

On Inner and Outer Descriptions of the Steady-State Flux Cone of a Metabolic Network
A. Larhlimi and A. Bockmayr (2008)

Temporal Constraints in the Logical Analysis of Regulatory Networks
H. Siebert and A. Bockmayr (2008)

Local Structure and Behavior of Boolean Bioregulatory Networks
H. Siebert (2008)

Deriving Behavior of Boolean Bioregulatory Networks from Subnetwork Dynamics
Heike Siebert (2008)

Constraint-based Analysis of Gene Deletion in a Metabolic Network
A. Larhlimi and A. Bockmayr (2007)

Minimal Direction Cuts in Metabolic Networks
A. Larhlimi and A. Bockmayr (2007)

Context Sensitivity in Logical Modeling with Time Delays
H. Siebert and A. Bockmayr (2007)

Relating Attractors and Singular Steady States in the Logical Analysis of Bioregulatory Networks
H. Siebert and A. Bockmayr (2007)

Incorporating Time Delays into the Logical Analysis of Gene Regulatory Networks
H. Siebert and A. Bockmayr (2006)

A New Approach to Flux Coupling Analysis of Metabolic Networks
A. Larhlimi and A. Bockmayr (2006)

Minimal Metabolic Behaviors and the Reversible Metabolic Space
A. Larhlimi and A. Bockmayr (2005)