@misc{RianoPachonKleessenNeigenfindetal.2010,
  author    = {Ria{\~n}o-Pach{\´o}n, Diego Mauricio and Kleessen, Sabrina and Neigenfind, Jost and Durek, Pawel and Weber, Elke and Engelsberger, Wolfgang R. and Walther, Dirk and Selbig, Joachim and Schulze, Waltraud X. and Kersten, Birgit},
  title     = {Proteome-wide survey of phosphorylation patterns affected by nuclear DNA polymorphisms in Arabidopsis thaliana},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1328},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43118},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431181},
  pages     = {19},
  year      = {2010},
  abstract  = {Background: Protein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets in Arabidopsis thaliana prompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites. Results: From the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86 A. thaliana proteins, among them receptor proteins were overrepresented. These results were confirmed by similar analyses of predicted phosphorylation sites in A. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected. Conclusions: We analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding loci in silico, thus constituting the largest phosphoproteomics dataset for A. thaliana available to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future.},
  language  = {en}
}
@misc{KleessenNikoloski2012,
  author    = {Kleessen, Sabrina and Nikoloski, Zoran},
  title     = {Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  number    = {852},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43112},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431128},
  pages     = {15},
  year      = {2012},
  abstract  = {Background: Flux balance analysis (FBA) together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states. Results: Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed) metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states. Conclusions: Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.},
  language  = {en}
}