References of "Selbig, Joachim"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailAlgebraic connectivity may explain the evolution of gene regulatory networks.
Nikoloski, Zoran; May, Patrick UL; Selbig, Joachim

in Journal of Theoretical Biology (2010), 267(1), 7-14

Gene expression is a result of the interplay between the structure, type, kinetics, and specificity of gene regulatory interactions, whose diversity gives rise to the variety of life forms. As the dynamic ... [more ▼]

Gene expression is a result of the interplay between the structure, type, kinetics, and specificity of gene regulatory interactions, whose diversity gives rise to the variety of life forms. As the dynamic behavior of gene regulatory networks depends on their structure, here we attempt to determine structural reasons which, despite the similarities in global network properties, may explain the large differences in organismal complexity. We demonstrate that the algebraic connectivity, the smallest non-trivial eigenvalue of the Laplacian, of the directed gene regulatory networks decreases with the increase of organismal complexity, and may therefore explain the difference between the variety of analyzed regulatory networks. In addition, our results point out that, for the species considered in this study, evolution favours decreasing concentration of strategically positioned feed forward loops, so that the network as a whole can increase the specificity towards changing environments. Moreover, contrary to the existing results, we show that the average degree, the length of the longest cascade, and the average cascade length of gene regulatory networks cannot recover the evolutionary relationships between organisms. Whereas the dynamical properties of special subnetworks are relatively well understood, there is still limited knowledge about the evolutionary reasons for the already identified design principles pertaining to these special subnetworks, underlying the global quantitative features of gene regulatory networks of different organisms. The behavior of the algebraic connectivity, which we show valid on gene regulatory networks extracted from curated databases, can serve as an additional evolutionary principle of organism-specific regulatory networks. [less ▲]

Detailed reference viewed: 108 (2 UL)
Full Text
Peer Reviewed
See detailMetabolic networks are NP-hard to reconstruct.
Nikoloski, Zoran; Grimbs, Sergio; May, Patrick UL et al

in Journal of Theoretical Biology (2008), 254(4), 807-16

High-throughput data from various omics and sequencing techniques have rendered the automated metabolic network reconstruction a highly relevant problem. Our approach reflects the inherent probabilistic ... [more ▼]

High-throughput data from various omics and sequencing techniques have rendered the automated metabolic network reconstruction a highly relevant problem. Our approach reflects the inherent probabilistic nature of the steps involved in metabolic network reconstruction. Here, the goal is to arrive at networks which combine probabilistic information with the possibility to obtain a small number of disconnected network constituents by reduction of a given preliminary probabilistic metabolic network. We define automated metabolic network reconstruction as an optimization problem on four-partite graph (nodes representing genes, enzymes, reactions, and metabolites) which integrates: (1) probabilistic information obtained from the existing process for metabolic reconstruction from a given genome, (2) connectedness of the raw metabolic network, and (3) clustering of components in the reconstructed metabolic network. The practical implications of our theoretical analysis refer to the quality of reconstructed metabolic networks and shed light on the problem of finding more efficient and effective methods for automated reconstruction. Our main contributions include: a completeness result for the defined problem, polynomial-time approximation algorithm, and an optimal polynomial-time algorithm for trees. Moreover, we exemplify our approach by the reconstruction of the sucrose biosynthesis pathway in Chlamydomonas reinhardtii. [less ▲]

Detailed reference viewed: 114 (1 UL)
Full Text
Peer Reviewed
See detailArevir: A Secure Platform for Designing Personalized Antiretroviral Therapies Against HIV
Roomp, Kirsten UL; Beerenwinkel, Niko; Sing, Tobias et al

in Leser, U.; Naumann, F.; Eckman, B. (Eds.) Data Integration in the Life Sciences (2006)

Despite the availability of antiretroviral combination therapies, success in drug treatment of HIV-infected patients is limited. One reason for therapy failure is the development of drug-resistant genetic ... [more ▼]

Despite the availability of antiretroviral combination therapies, success in drug treatment of HIV-infected patients is limited. One reason for therapy failure is the development of drug-resistant genetic variants. In principle, the viral genomic sequence provides resistance information and could thus guide the selection of an optimal drug combination. In practice however, the benefit of this procedure is impaired by (1) the difficulty in inferring the clinically relevant information from the genotype of the virus and (2) the restricted availability of this information. We have developed a secure platform for collaborative research aimed at optimizing anti-HIV therapies, called Arevir. A relational database schema was designed and implemented together with a webbased user interface. Our system provides a basis for monitoring patients, decision- support, and computational analyses. Thus, it merges clinical, diagnostic and bioinformatics efforts to exploit genomic and patient therapy data in clinical practice. [less ▲]

Detailed reference viewed: 89 (2 UL)