TY - JOUR A1 - Zakharova, Anna A1 - Vadivasova, Tatjana A1 - Anishchenko, Vadim S. A1 - Koseska, Aneta A1 - Kurths, Jürgen T1 - Stochastic bifurcations and coherencelike resonance in a self-sustained bistable noisy oscillator N2 - 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. Y1 - 2010 UR - http://pre.aps.org/ U6 - https://doi.org/10.1103/Physreve.81.011106 SN - 1539-3755 ER - TY - JOUR A1 - Zakharova, Anna A1 - Kurths, Jürgen A1 - Vadivasova, Tatyana A1 - Koseska, Aneta T1 - Analysing dynamical behavior of cellular networks via stochastic bifurcations JF - PLoS one N2 - 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. Y1 - 2011 U6 - https://doi.org/10.1371/journal.pone.0019696 SN - 1932-6203 VL - 6 IS - 5 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Zakharova, A. A1 - Nikoloski, Zoran A1 - Koseska, Aneta T1 - Dimensionality reduction of bistable biological systems JF - Bulletin of mathematical biology : official journal of the Society for Mathematical Biology N2 - 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. KW - Bistability KW - Time-scales hierarchy KW - Similarity transformation KW - Canonical correlation analysis KW - Dimensionality reduction Y1 - 2013 U6 - https://doi.org/10.1007/s11538-013-9807-8 SN - 0092-8240 VL - 75 IS - 3 SP - 373 EP - 392 PB - Springer CY - New York ER - TY - JOUR A1 - Winck, Flavia Vischi A1 - Arvidsson, Samuel Janne A1 - Mauricio Riano-Pachon, Diego A1 - Hempel, Sabrina A1 - Koseska, Aneta A1 - Nikoloski, Zoran A1 - Urbina Gomez, David Alejandro A1 - Rupprecht, Jens A1 - Müller-Röber, Bernd T1 - Genome-wide identification of regulatory elements and reconstruction of gene regulatory networks of the green alga chlamydomonas reinhardtii under carbon deprivation JF - PLoS one N2 - 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. Y1 - 2013 U6 - https://doi.org/10.1371/journal.pone.0079909 SN - 1932-6203 VL - 8 IS - 11 PB - PLoS CY - San Fransisco ER - TY - GEN A1 - Koseska, Aneta A1 - Zaikin, Alexey A1 - Kurths, Jürgen A1 - García-Ojalvo, Jordi T1 - Timing cellular decision making under noise via cell-cell communication N2 - Many cellular processes require decision making mechanisms, which must act reliably even in the unavoidable presence of substantial amounts of noise. However, the multistable genetic switches that underlie most decision-making processes are dominated by fluctuations that can induce random jumps between alternative cellular states. Here we show, via theoretical modeling of a population of noise-driven bistable genetic switches, that reliable timing of decision-making processes can be accomplished for large enough population sizes, as long as cells are globally coupled by chemical means. In the light of these results, we conjecture that cell proliferation, in the presence of cell-cell communication, could provide a mechanism for reliable decision making in the presence of noise, by triggering cellular transitions only when the whole cell population reaches a certain size. In other words , the summation performed by the cell population would average out the noise and reduce its detrimental impact. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 148 Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-45260 ER - TY - JOUR A1 - Koseska, Aneta A1 - Volkov, Evgenij A1 - Kurths, Jürgen T1 - Detuning-dependent dominance of oscillation death in globally coupled synthetic genetic oscillators N2 - 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. Y1 - 2009 UR - http://iopscience.iop.org/0295-5075/ U6 - https://doi.org/10.1209/0295-5075/85/28002 SN - 0295-5075 ER - TY - JOUR A1 - Koseska, Aneta A1 - Volkov, Evgenii A1 - Kurths, Jürgen T1 - Synthetic multicellular oscillatory systems controlling protein dynamics with genetic circuits JF - Physica scripta : an international journal for experimental and theoretical physics N2 - Synthetic biology is a relatively new research discipline that combines standard biology approaches with the constructive nature of engineering. Thus, recent efforts in the field of synthetic biology have given a perspective to consider cells as 'programmable matter'. Here, we address the possibility of using synthetic circuits to control protein dynamics. In particular, we show how intercellular communication and stochasticity can be used to manipulate the dynamical behavior of a population of coupled synthetic units and, in this manner, finely tune the expression of specific proteins of interest, e.g. in large bioreactors. Y1 - 2011 U6 - https://doi.org/10.1088/0031-8949/84/04/045007 SN - 0031-8949 VL - 84 IS - 4 PB - IOP Publ. Ltd. CY - Bristol ER - TY - THES A1 - Koseska, Aneta T1 - Modeling and control of synthetic gene regulatory networks Y1 - 2007 CY - Potsdam ER - TY - THES A1 - Koseska, Aneta T1 - Dynamics of biological networks : data analysis, modeling and bifurcations Y1 - 2011 CY - Potsdam ER - TY - JOUR A1 - Hempel, Stefan A1 - Koseska, Aneta A1 - Kurths, Jürgen A1 - Nikoloski, Zoran T1 - Inner composition alignment for inferring directed networks from short time series JF - Physical review letters N2 - 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. Y1 - 2011 U6 - https://doi.org/10.1103/PhysRevLett.107.054101 SN - 0031-9007 VL - 107 IS - 5 PB - American Physical Society CY - College Park ER -