TY  - GEN
A1  - Kartal, Önder
A1  - Ebenhöh, Oliver
T1  - Ground state robustness as an evolutionary design principle in signaling networks
N2  - The ability of an organism to survive depends on its capability to adapt to external conditions. In addition to metabolic versatility and efficient replication, reliable signal transduction is essential. As signaling systems are under permanent evolutionary pressure one may assume that their structure reflects certain functional properties. However, despite promising theoretical studies in recent years, the selective forces which shape signaling network topologies in general remain unclear. Here, we propose prevention of autoactivation as one possible evolutionary design principle. A generic framework for continuous kinetic models is used to derive topological implications of demanding a dynamically stable ground state in signaling systems. To this end graph theoretical methods are applied. The index of the underlying digraph is shown to be a key topological property which determines the so-called kinetic ground state (or off-state) robustness. The kinetic robustness depends solely on the composition of the subdigraph with the strongly connected components, which comprise all positive feedbacks in the network. The component with the highest index in the feedback family is shown to dominate the kinetic robustness of the whole network, whereas relative size and girth of these motifs are emphasized as important determinants of the component index. Moreover, depending on topological features, the maintenance of robustness differs when networks are faced with structural perturbations. This structural off-state robustness, defined as the average kinetic robustness of a network’s neighborhood, turns out to be useful since some structural features are neutral towards kinetic robustness, but show up to be supporting against structural perturbations. Among these are a low connectivity, a high divergence and a low path sum. All results are tested against real signaling networks obtained from databases. The analysis suggests that ground state robustness may serve as a rationale for some structural peculiarities found in intracellular signaling networks.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 130 
KW  - Complex networks
KW  - Transduction
KW  - Motifs
KW  - Cell
KW  - Organization
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44982
ER  - 
TY  - GEN
A1  - Ebenhöh, Oliver
A1  - Handorf, Thomas
T1  - Functional classification of genome-scale metabolic networks
N2  - We propose two strategies to characterize organisms with respect to their metabolic capabilities. The first, investigative, strategy describes metabolic networks in terms of their capability to utilize different carbon sources, resulting in the concept of carbon utilization spectra. In the second, predictive, approach minimal nutrient combinations are predicted from the structure of the metabolic networks, resulting in a characteristic nutrient profile. Both strategies allow for a quantification of functional properties of metabolic networks, allowing to identify groups of organisms with similar functions. We investigate whether the functional description reflects the typical environments of the corresponding organisms by dividing all species into disjoint groups based on whether they are aerotolerant and/or photosynthetic. Despite differences in the underlying concepts, both measures display some common features. Closely related organisms often display a similar functional behavior and in both cases the functional measures appear to correlate with the considered classes of environments. Carbon utilization spectra and nutrient profiles are complementary approaches toward a functional classification of organism-wide metabolic networks. Both approaches contain different information and thus yield different clusterings, which are both different from the classical taxonomy of organisms. Our results indicate that a sophisticated combination of our approaches will allow for a quantitative description reflecting the lifestyles of organisms.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 129 
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44975
ER  -