@article{ZakharovaKurthsVadivasovaetal.2011, author = {Zakharova, Anna and Kurths, J{\"u}rgen and Vadivasova, Tatyana and Koseska, Aneta}, title = {Analysing dynamical behavior of cellular networks via stochastic bifurcations}, series = {PLoS one}, volume = {6}, journal = {PLoS one}, number = {5}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0019696}, pages = {12}, year = {2011}, abstract = {The dynamical structure of genetic networks determines the occurrence of various biological mechanisms, such as cellular differentiation. However, the question of how cellular diversity evolves in relation to the inherent stochasticity and intercellular communication remains still to be understood. Here, we define a concept of stochastic bifurcations suitable to investigate the dynamical structure of genetic networks, and show that under stochastic influence, the expression of given proteins of interest is defined via the probability distribution of the phase variable, representing one of the genes constituting the system. Moreover, we show that under changing stochastic conditions, the probabilities of expressing certain concentration values are different, leading to different functionality of the cells, and thus to differentiation of the cells in the various types.}, language = {en} } @article{HempelKoseskaNikoloski2013, author = {Hempel, Sabrina and Koseska, Aneta and Nikoloski, Zoran}, title = {Data-driven reconstruction of directed networks}, series = {The European physical journal : B, Condensed matter and complex systems}, volume = {86}, journal = {The European physical journal : B, Condensed matter and complex systems}, number = {6}, publisher = {Springer}, address = {New York}, issn = {1434-6028}, doi = {10.1140/epjb/e2013-31111-8}, pages = {17}, year = {2013}, abstract = {We investigate the properties of a recently introduced asymmetric association measure, called inner composition alignment (IOTA), aimed at inferring regulatory links (couplings). We show that the measure can be used to determine the direction of coupling, detect superfluous links, and to account for autoregulation. In addition, the measure can be extended to infer the type of regulation (positive or negative). The capabilities of IOTA to correctly infer couplings together with their directionality are compared against Kendall's rank correlation for time series of different lengths, particularly focussing on biological examples. We demonstrate that an extended version of the measure, bidirectional inner composition alignment (biIOTA), increases the accuracy of the network reconstruction for short time series. Finally, we discuss the applicability of the measure to infer couplings in chaotic systems.}, language = {en} } @article{KoseskaVolkovKurths2009, author = {Koseska, Aneta and Volkov, Evgenij and Kurths, J{\"u}rgen}, title = {Detuning-dependent dominance of oscillation death in globally coupled synthetic genetic oscillators}, issn = {0295-5075}, doi = {10.1209/0295-5075/85/28002}, year = {2009}, abstract = {We study dynamical regimes of globally coupled genetic relaxation oscillators in the presence of small detuning. Using bifurcation analysis, we find that under strong coupling via the slow variable, the detuning can eliminate standard oscillatory solutions in a large region of the parameter space, providing the dominance of oscillation death. This result is substantially different from previous results on oscillation quenching, where for homogeneous populations, the coexistence of oscillation death and limit cycle oscillations is always present. We propose further that this effect of detuning-dependent dominance could be a powerful regulator of genetic network's dynamics.}, language = {en} } @article{ZakharovaNikoloskiKoseska2013, author = {Zakharova, A. and Nikoloski, Zoran and Koseska, Aneta}, title = {Dimensionality reduction of bistable biological systems}, series = {Bulletin of mathematical biology : official journal of the Society for Mathematical Biology}, volume = {75}, journal = {Bulletin of mathematical biology : official journal of the Society for Mathematical Biology}, number = {3}, publisher = {Springer}, address = {New York}, issn = {0092-8240}, doi = {10.1007/s11538-013-9807-8}, pages = {373 -- 392}, year = {2013}, abstract = {Time hierarchies, arising as a result of interactions between system's components, represent a ubiquitous property of dynamical biological systems. In addition, biological systems have been attributed switch-like properties modulating the response to various stimuli across different organisms and environmental conditions. Therefore, establishing the interplay between these features of system dynamics renders itself a challenging question of practical interest in biology. Existing methods are suitable for systems with one stable steady state employed as a well-defined reference. In such systems, the characterization of the time hierarchies has already been used for determining the components that contribute to the dynamics of biological systems. However, the application of these methods to bistable nonlinear systems is impeded due to their inherent dependence on the reference state, which in this case is no longer unique. Here, we extend the applicability of the reference-state analysis by proposing, analyzing, and applying a novel method, which allows investigation of the time hierarchies in systems exhibiting bistability. The proposed method is in turn used in identifying the components, other than reactions, which determine the systemic dynamical properties. We demonstrate that in biological systems of varying levels of complexity and spanning different biological levels, the method can be effectively employed for model simplification while ensuring preservation of qualitative dynamical properties (i.e., bistability). Finally, by establishing a connection between techniques from nonlinear dynamics and multivariate statistics, the proposed approach provides the basis for extending reference-based analysis to bistable systems.}, language = {en} } @phdthesis{Koseska2011, author = {Koseska, Aneta}, title = {Dynamics of biological networks : data analysis, modeling and bifurcations}, address = {Potsdam}, year = {2011}, language = {en} } @article{WinckArvidssonMauricioRianoPachonetal.2013, author = {Winck, Flavia Vischi and Arvidsson, Samuel Janne and Mauricio Riano-Pachon, Diego and Hempel, Sabrina and Koseska, Aneta and Nikoloski, Zoran and Urbina Gomez, David Alejandro and Rupprecht, Jens and M{\"u}ller-R{\"o}ber, Bernd}, title = {Genome-wide identification of regulatory elements and reconstruction of gene regulatory networks of the green alga chlamydomonas reinhardtii under carbon deprivation}, series = {PLoS one}, volume = {8}, journal = {PLoS one}, number = {11}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0079909}, pages = {16}, year = {2013}, abstract = {The unicellular green alga Chlamydomonas reinhardtii is a long-established model organism for studies on photosynthesis and carbon metabolism-related physiology. Under conditions of air-level carbon dioxide concentration [CO2], a carbon concentrating mechanism (CCM) is induced to facilitate cellular carbon uptake. CCM increases the availability of carbon dioxide at the site of cellular carbon fixation. To improve our understanding of the transcriptional control of the CCM, we employed FAIRE-seq (formaldehyde-assisted Isolation of Regulatory Elements, followed by deep sequencing) to determine nucleosome-depleted chromatin regions of algal cells subjected to carbon deprivation. Our FAIRE data recapitulated the positions of known regulatory elements in the promoter of the periplasmic carbonic anhydrase (Cah1) gene, which is upregulated during CCM induction, and revealed new candidate regulatory elements at a genome-wide scale. In addition, time series expression patterns of 130 transcription factor (TF) and transcription regulator (TR) genes were obtained for cells cultured under photoautotrophic condition and subjected to a shift from high to low [CO2]. Groups of co-expressed genes were identified and a putative directed gene-regulatory network underlying the CCM was reconstructed from the gene expression data using the recently developed IOTA (inner composition alignment) method. Among the candidate regulatory genes, two members of the MYB-related TF family, Lcr1 (Low-CO2 response regulator 1) and Lcr2 (Low-CO2 response regulator 2), may play an important role in down-regulating the expression of a particular set of TF and TR genes in response to low [CO2]. The results obtained provide new insights into the transcriptional control of the CCM and revealed more than 60 new candidate regulatory genes. Deep sequencing of nucleosome-depleted genomic regions indicated the presence of new, previously unknown regulatory elements in the C. reinhardtii genome. Our work can serve as a basis for future functional studies of transcriptional regulator genes and genomic regulatory elements in Chlamydomonas.}, language = {en} } @article{HempelKoseskaKurthsetal.2011, author = {Hempel, Stefan and Koseska, Aneta and Kurths, J{\"u}rgen and Nikoloski, Zoran}, title = {Inner composition alignment for inferring directed networks from short time series}, series = {Physical review letters}, volume = {107}, journal = {Physical review letters}, number = {5}, publisher = {American Physical Society}, address = {College Park}, issn = {0031-9007}, doi = {10.1103/PhysRevLett.107.054101}, pages = {4}, year = {2011}, abstract = {Identifying causal links (couplings) is a fundamental problem that facilitates the understanding of emerging structures in complex networks. We propose and analyze inner composition alignment-a novel, permutation-based asymmetric association measure to detect regulatory links from very short time series, currently applied to gene expression. The measure can be used to infer the direction of couplings, detect indirect (superfluous) links, and account for autoregulation. Applications to the gene regulatory network of E. coli are presented.}, language = {en} } @phdthesis{Koseska2007, author = {Koseska, Aneta}, title = {Modeling and control of synthetic gene regulatory networks}, address = {Potsdam}, pages = {viii, 82 S.}, year = {2007}, language = {en} } @article{GrimbsArnoldKoseskaetal.2011, author = {Grimbs, Sergio and Arnold, Anne and Koseska, Aneta and Kurths, J{\"u}rgen and Selbig, Joachim and Nikoloski, Zoran}, title = {Spatiotemporal dynamics of the Calvin cycle multistationarity and symmetry breaking instabilities}, series = {Biosystems : journal of biological and information processing sciences}, volume = {103}, journal = {Biosystems : journal of biological and information processing sciences}, number = {2}, publisher = {Elsevier}, address = {Oxford}, issn = {0303-2647}, doi = {10.1016/j.biosystems.2010.10.015}, pages = {212 -- 223}, year = {2011}, abstract = {The possibility of controlling the Calvin cycle has paramount implications for increasing the production of biomass. Multistationarity, as a dynamical feature of systems, is the first obvious candidate whose control could find biotechnological applications. Here we set out to resolve the debate on the multistationarity of the Calvin cycle. Unlike the existing simulation-based studies, our approach is based on a sound mathematical framework, chemical reaction network theory and algebraic geometry, which results in provable results for the investigated model of the Calvin cycle in which we embed a hierarchy of realistic kinetic laws. Our theoretical findings demonstrate that there is a possibility for multistationarity resulting from two sources, homogeneous and inhomogeneous instabilities, which partially settle the debate on multistability of the Calvin cycle. In addition, our tractable analytical treatment of the bifurcation parameters can be employed in the design of validation experiments.}, language = {en} } @article{ZakharovaVadivasovaAnishchenkoetal.2010, author = {Zakharova, Anna and Vadivasova, Tatjana and Anishchenko, Vadim S. and Koseska, Aneta and Kurths, J{\"u}rgen}, title = {Stochastic bifurcations and coherencelike resonance in a self-sustained bistable noisy oscillator}, issn = {1539-3755}, doi = {10.1103/Physreve.81.011106}, year = {2010}, abstract = {We investigate the influence of additive Gaussian white noise on two different bistable self-sustained oscillators: Duffing-Van der Pol oscillator with hard excitation and a model of a synthetic genetic oscillator. In the deterministic case, both oscillators are characterized with a coexistence of a stable limit cycle and a stable equilibrium state. We find that under the influence of noise, their dynamics can be well characterized through the concept of stochastic bifurcation, consisting in a qualitative change of the stationary amplitude distribution. For the Duffing-Van der Pol oscillator analytical results, obtained for a quasiharmonic approach, are compared with the result of direct computer simulations. In particular, we show that the dynamics is different for isochronous and anisochronous systems. Moreover, we find that the increase of noise intensity in the isochronous regime leads to a narrowing of the spectral line. This effect is similar to coherence resonance. However, in the case of anisochronous systems, this effect breaks down and a new phenomenon, anisochronous-based stochastic bifurcation occurs.}, language = {en} }