@misc{HempelKoseskaNikoloskietal.2017,
  author    = {Hempel, Sabrina and Koseska, Aneta and Nikoloski, Zoran and Kurths, J{\"u}rgen},
  title     = {Unraveling gene regulatory networks from time-resolved gene expression data},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400924},
  pages     = {26},
  year      = {2017},
  abstract  = {Background: Inferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance to systems biology and bioinformatics studies. Accurate methods to address this problem can ultimately provide a deeper insight into the complexity, behavior, and functions of the underlying biological systems. However, the large number of interacting genes coupled with short and often noisy time-resolved read-outs of the system renders the reverse engineering a challenging task. Therefore, the development and assessment of methods which are computationally efficient, robust against noise, applicable to short time series data, and preferably capable of reconstructing the directionality of the regulatory interactions remains a pressing research problem with valuable applications. Results: Here we perform the largest systematic analysis of a set of similarity measures and scoring schemes within the scope of the relevance network approach which are commonly used for gene regulatory network reconstruction from time series data. In addition, we define and analyze several novel measures and schemes which are particularly suitable for short transcriptomics time series. We also compare the considered 21 measures and 6 scoring schemes according to their ability to correctly reconstruct such networks from short time series data by calculating summary statistics based on the corresponding specificity and sensitivity. Our results demonstrate that rank and symbol based measures have the highest performance in inferring regulatory interactions. In addition, the proposed scoring scheme by asymmetric weighting has shown to be valuable in reducing the number of false positive interactions. On the other hand, Granger causality as well as information-theoretic measures, frequently used in inference of regulatory networks, show low performance on the short time series analyzed in this study. Conclusions: Our study is intended to serve as a guide for choosing a particular combination of similarity measures and scoring schemes suitable for reconstruction of gene regulatory networks from short time series data. We show that further improvement of algorithms for reverse engineering can be obtained if one considers measures that are rooted in the study of symbolic dynamics or ranks, in contrast to the application of common similarity measures which do not consider the temporal character of the employed data. Moreover, we establish that the asymmetric weighting scoring scheme together with symbol based measures (for low noise level) and rank based measures (for high noise level) are the most suitable choices.},
  language  = {en}
}
@misc{KaminskiSchaubSiegeletal.2013,
  author    = {Kaminski, Roland and Schaub, Torsten and Siegel, Anne and Videla, Santiago},
  title     = {Minimal intervention strategies in logical signaling networks with ASP},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  number    = {4-5},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-41570},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-415704},
  pages     = {675 -- 690},
  year      = {2013},
  abstract  = {Proposing relevant perturbations to biological signaling networks is central to many problems in biology and medicine because it allows for enabling or disabling certain biological outcomes. In contrast to quantitative methods that permit fine-grained (kinetic) analysis, qualitative approaches allow for addressing large-scale networks. This is accomplished by more abstract representations such as logical networks. We elaborate upon such a qualitative approach aiming at the computation of minimal interventions in logical signaling networks relying on Kleene's three-valued logic and fixpoint semantics. We address this problem within answer set programming and show that it greatly outperforms previous work using dedicated algorithms.},
  language  = {en}
}
@misc{LarhlimiDavidSelbigetal.2012,
  author    = {Larhlimi, Abdelhalim and David, Laszlo and Selbig, Joachim and Bockmayr, Alexander},
  title     = {F2C2},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {921},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43243},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-432431},
  pages     = {11},
  year      = {2012},
  abstract  = {Background: Flux coupling analysis (FCA) has become a useful tool in the constraint-based analysis of genome-scale metabolic networks. FCA allows detecting dependencies between reaction fluxes of metabolic networks at steady-state. On the one hand, this can help in the curation of reconstructed metabolic networks by verifying whether the coupling between reactions is in agreement with the experimental findings. On the other hand, FCA can aid in defining intervention strategies to knock out target reactions. Results: We present a new method F2C2 for FCA, which is orders of magnitude faster than previous approaches. As a consequence, FCA of genome-scale metabolic networks can now be performed in a routine manner. Conclusions: We propose F2C2 as a fast tool for the computation of flux coupling in genome-scale metabolic networks. F2C2 is freely available for non-commercial use at https://sourceforge.net/projects/f2c2/files/.},
  language  = {en}
}