A system-wide network reconstruction of gene regulation and metabolism in Escherichia coli.

Genome-scale metabolic models have become a fundamental tool for examining metabolic principles. However, metabolism is not solely characterized by the underlying biochemical reactions and catalyzing enzymes, but also affected by regulatory events. Since the pioneering work of Covert and co-workers as well as Shlomi and co-workers it is debated, how regulation and metabolism synergistically characterize a coherent cellular state. The first approaches started from metabolic models, which were extended by the regulation of the encoding genes of the catalyzing enzymes. By now, bioinformatics databases in principle allow addressing the challenge of integrating regulation and metabolism on a system-wide level. Collecting information from several databases we provide a network representation of the integrated gene regulatory and metabolic system for Escherichia coli, including major cellular processes, from metabolic processes via protein modification to a variety of regulatory events. Besides transcriptional regulation, we also take into account regulation of translation, enzyme activities and reactions. Our network model provides novel topological characterizations of system components based on their positions in the network. We show that network characteristics suggest a representation of the integrated system as three network domains (regulatory, metabolic and interface networks) instead of two. This new three-domain representation reveals the structural centrality of components with known high functional relevance. This integrated network can serve as a platform for understanding coherent cellular states as active subnetworks and to elucidate crossover effects between metabolism and gene regulation.

The interdependent network of gene regulation and metabolism is robust where it needs to be.

Despite being highly interdependent, the major biochemical networks of the living cell-the networks of interacting genes and of metabolic reactions, respectively-have been approached mostly as separate systems so far. Recently, a framework for interdependent networks has emerged in the context of statistical physics. In a first quantitative application of this framework to systems biology, here we study the interdependent network of gene regulation and metabolism for the model organism Escherichia coli in terms of a biologically motivated percolation model. Particularly, we approach the system's conflicting tasks of reacting rapidly to (internal and external) perturbations, while being robust to minor environmental fluctuations. Considering its response to perturbations that are localized with respect to functional criteria, we find the interdependent system to be sensitive to gene regulatory and protein-level perturbations, yet robust against metabolic changes. We expect this approach to be applicable to a range of other interdependent networks.Although networks of interacting genes and metabolic reactions are interdependent, they have largely been treated as separate systems. Here the authors apply a statistical framework for interdependent networks to E. coli, and show that it is sensitive to gene and protein perturbations but robust against metabolic changes.

The citation wake of publications detects nobel laureates' papers.

For several decades, a leading paradigm of how to quantitatively assess scientific research has been the analysis of the aggregated citation information in a set of scientific publications. Although the representation of this information as a citation network has already been coined in the 1960s, it needed the systematic indexing of scientific literature to allow for impact metrics that actually made use of this network as a whole, improving on the then prevailing metrics that were almost exclusively based on the number of direct citations. However, besides focusing on the assignment of credit, the paper citation network can also be studied in terms of the proliferation of scientific ideas. Here we introduce a simple measure based on the shortest-paths in the paper's in-component or, simply speaking, on the shape and size of the wake of a paper within the citation network. Applied to a citation network containing Physical Review publications from more than a century, our approach is able to detect seminal articles which have introduced concepts of obvious importance to the further development of physics. We observe a large fraction of papers co-authored by Nobel Prize laureates in physics among the top-ranked publications.

Motif-based success scores in coauthorship networks are highly sensitive to author name disambiguation.

Following the work of Krumov et al. [Eur. Phys. J. B 84, 535 (2011)] we revisit the question whether the usage of large citation datasets allows for the quantitative assessment of social (by means of coauthorship of publications) influence on the progression of science. Applying a more comprehensive and well-curated dataset containing the publications in the journals of the American Physical Society during the whole 20th century we find that the measure chosen in the original study, a score based on small induced subgraphs, has to be used with caution, since the obtained results are highly sensitive to the exact implementation of the author disambiguation task.