@misc{LarhlimiBlachonSelbigetal.2011,
  author    = {Larhlimi, Abdelhalim and Blachon, Sylvain and Selbig, Joachim and Nikoloski, Zoran},
  title     = {Robustness of metabolic networks a review of existing definitions},
  series = {Biosystems : journal of biological and information processing sciences},
  volume    = {106},
  journal   = {Biosystems : journal of biological and information processing sciences},
  number    = {1},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0303-2647},
  doi       = {10.1016/j.biosystems.2011.06.002},
  pages     = {1 -- 8},
  year      = {2011},
  abstract  = {Describing the determinants of robustness of biological systems has become one of the central questions in systems biology. Despite the increasing research efforts, it has proven difficult to arrive at a unifying definition for this important concept. We argue that this is due to the multifaceted nature of the concept of robustness and the possibility to formally capture it at different levels of systemic formalisms (e.g, topology and dynamic behavior). Here we provide a comprehensive review of the existing definitions of robustness pertaining to metabolic networks. As kinetic approaches have been excellently reviewed elsewhere, we focus on definitions of robustness proposed within graph-theoretic and constraint-based formalisms.},
  language  = {en}
}
@article{BaslerGrimbsNikoloski2012,
  author    = {Basler, Georg and Grimbs, Sergio and Nikoloski, Zoran},
  title     = {Optimizing metabolic pathways by screening for feasible synthetic reactions},
  series = {Biosystems : journal of biological and information processing sciences},
  volume    = {109},
  journal   = {Biosystems : journal of biological and information processing sciences},
  number    = {2},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0303-2647},
  doi       = {10.1016/j.biosystems.2012.04.007},
  pages     = {186 -- 191},
  year      = {2012},
  abstract  = {Background: Reconstruction of genome-scale metabolic networks has resulted in models capable of reproducing experimentally observed biomass yield/growth rates and predicting the effect of alterations in metabolism for biotechnological applications. The existing studies rely on modifying the metabolic network of an investigated organism by removing or inserting reactions taken either from evolutionary similar organisms or from databases of biochemical reactions (e.g., KEGG). A potential disadvantage of these knowledge-driven approaches is that the result is biased towards known reactions, as such approaches do not account for the possibility of including novel enzymes, together with the reactions they catalyze. Results: Here, we explore the alternative of increasing biomass yield in three model organisms, namely Bacillus subtilis, Escherichia coil, and Hordeum vulgare, by applying small, chemically feasible network modifications. We use the predicted and experimentally confirmed growth rates of the wild-type networks as reference values and determine the effect of inserting mass-balanced, thermodynamically feasible reactions on predictions of growth rate by using flux balance analysis. Conclusions: While many replacements of existing reactions naturally lead to a decrease or complete loss of biomass production ability, in all three investigated organisms we find feasible modifications which facilitate a significant increase in this biological function. We focus on modifications with feasible chemical properties and a significant increase in biomass yield. The results demonstrate that small modifications are sufficient to substantially alter biomass yield in the three organisms. The method can be used to predict the effect of targeted modifications on the yield of any set of metabolites (e.g., ethanol), thus providing a computational framework for synthetic metabolic engineering.},
  language  = {en}
}