@article{BaslerNikoloski2011, author = {Basler, Georg and Nikoloski, Zoran}, title = {JMassBalance - mass-balanced randomization and analysis of metabolic networks}, series = {Bioinformatics}, volume = {27}, journal = {Bioinformatics}, number = {19}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1367-4803}, doi = {10.1093/bioinformatics/btr448}, pages = {2761 -- 2762}, year = {2011}, abstract = {Analysis of biological networks requires assessing the statistical significance of network-based predictions by using a realistic null model. However, the existing network null model, switch randomization, is unsuitable for metabolic networks, as it does not include physical constraints and generates unrealistic reactions. We present JMassBalance, a tool for mass-balanced randomization and analysis of metabolic networks. The tool allows efficient generation of large sets of randomized networks under the physical constraint of mass balance. In addition, various structural properties of the original and randomized networks can be calculated, facilitating the identification of the salient properties of metabolic networks with a biologically meaningful null model.}, 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} } @article{BaslerGrimbsEbenhoehetal.2012, author = {Basler, Georg and Grimbs, Sergio and Ebenh{\"o}h, Oliver and Selbig, Joachim and Nikoloski, Zoran}, title = {Evolutionary significance of metabolic network properties}, series = {Interface : journal of the Royal Society}, volume = {9}, journal = {Interface : journal of the Royal Society}, number = {71}, publisher = {Royal Society}, address = {London}, issn = {1742-5689}, doi = {10.1098/rsif.2011.0652}, pages = {1168 -- 1176}, year = {2012}, abstract = {Complex networks have been successfully employed to represent different levels of biological systems, ranging from gene regulation to protein-protein interactions and metabolism. Network-based research has mainly focused on identifying unifying structural properties, such as small average path length, large clustering coefficient, heavy-tail degree distribution and hierarchical organization, viewed as requirements for efficient and robust system architectures. However, for biological networks, it is unclear to what extent these properties reflect the evolutionary history of the represented systems. Here, we show that the salient structural properties of six metabolic networks from all kingdoms of life may be inherently related to the evolution and functional organization of metabolism by employing network randomization under mass balance constraints. Contrary to the results from the common Markov-chain switching algorithm, our findings suggest the evolutionary importance of the small-world hypothesis as a fundamental design principle of complex networks. The approach may help us to determine the biologically meaningful properties that result from evolutionary pressure imposed on metabolism, such as the global impact of local reaction knockouts. Moreover, the approach can be applied to test to what extent novel structural properties can be used to draw biologically meaningful hypothesis or predictions from structure alone.}, language = {en} } @article{BaslerEbenhoehSelbigetal.2011, author = {Basler, Georg and Ebenhoeh, Oliver and Selbig, Joachim and Nikoloski, Zoran}, title = {Mass-balanced randomization of metabolic networks}, series = {Bioinformatics}, volume = {27}, journal = {Bioinformatics}, number = {10}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1367-4803}, doi = {10.1093/bioinformatics/btr145}, pages = {1397 -- 1403}, year = {2011}, abstract = {Motivation: Network-centered studies in systems biology attempt to integrate the topological properties of biological networks with experimental data in order to make predictions and posit hypotheses. For any topology-based prediction, it is necessary to first assess the significance of the analyzed property in a biologically meaningful context. Therefore, devising network null models, carefully tailored to the topological and biochemical constraints imposed on the network, remains an important computational problem. Results: We first review the shortcomings of the existing generic sampling scheme-switch randomization-and explain its unsuitability for application to metabolic networks. We then devise a novel polynomial-time algorithm for randomizing metabolic networks under the (bio)chemical constraint of mass balance. The tractability of our method follows from the concept of mass equivalence classes, defined on the representation of compounds in the vector space over chemical elements. We finally demonstrate the uniformity of the proposed method on seven genome-scale metabolic networks, and empirically validate the theoretical findings. The proposed method allows a biologically meaningful estimation of significance for metabolic network properties.}, language = {en} } @article{ArnoldNikoloski2014, author = {Arnold, Anne and Nikoloski, Zoran}, title = {In search for an accurate model of the photosynthetic carbon metabolism}, series = {Mathematics and computers in simulation : transactions of IMACS}, volume = {96}, journal = {Mathematics and computers in simulation : transactions of IMACS}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0378-4754}, doi = {10.1016/j.matcom.2012.03.011}, pages = {171 -- 194}, year = {2014}, abstract = {The photosynthetic carbon metabolism, including the Calvin-Benson cycle, is the primary pathway in C-3-plants, producing starch and sucrose from CO2. Understanding the interplay between regulation and efficiency of this pathway requires the development of mathematical models which would explain the observed dynamics of metabolic transformations. Here, we address this question by casting the existing models of Calvin-Benson cycle and the end-product processes into an analysis framework which not only facilitates the comparison of the different models, but also allows for their ranking with respect to chosen criteria, including stability, sensitivity, robustness and/or compliance with experimental data. The importance of the photosynthetic carbon metabolism for the increase of plant biomass has resulted in many models with various levels of detail. We provide the largest compendium of 15 existing, well-investigated models together with a comprehensive classification as well as a ranking framework to determine the best-performing models for metabolic engineering and planning of in silica experiments. The classification can be additionally used, based on the model structure, as a tool to identify the models which match best the experimental design. The provided ranking is just one alternative to score models and, by changing the weighting factor, this framework also could be applied for selection of other criteria of interest.}, language = {en} } @article{AraujoNunesNesiNikoloskietal.2012, author = {Araujo, Wagner L. and Nunes-Nesi, Adriano and Nikoloski, Zoran and Sweetlove, Lee J. and Fernie, Alisdair R.}, title = {Metabolic control and regulation of the tricarboxylic acid cycle in photosynthetic and heterotrophic plant tissues}, series = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology}, volume = {35}, journal = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology}, number = {1}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0140-7791}, doi = {10.1111/j.1365-3040.2011.02332.x}, pages = {1 -- 21}, year = {2012}, abstract = {The tricarboxylic acid (TCA) cycle is a crucial component of respiratory metabolism in both photosynthetic and heterotrophic plant organs. All of the major genes of the tomato TCA cycle have been cloned recently, allowing the generation of a suite of transgenic plants in which the majority of the enzymes in the pathway are progressively decreased. Investigations of these plants have provided an almost complete view of the distribution of control in this important pathway. Our studies suggest that citrate synthase, aconitase, isocitrate dehydrogenase, succinyl CoA ligase, succinate dehydrogenase, fumarase and malate dehydrogenase have control coefficients flux for respiration of -0.4, 0.964, -0.123, 0.0008, 0.289, 0.601 and 1.76, respectively; while 2-oxoglutarate dehydrogenase is estimated to have a control coefficient of 0.786 in potato tubers. These results thus indicate that the control of this pathway is distributed among malate dehydrogenase, aconitase, fumarase, succinate dehydrogenase and 2-oxoglutarate dehydrogenase. The unusual distribution of control estimated here is consistent with specific non-cyclic flux mode and cytosolic bypasses that operate in illuminated leaves. These observations are discussed in the context of known regulatory properties of the enzymes and some illustrative examples of how the pathway responds to environmental change are given.}, language = {en} } @article{ApeltBreuerOlasetal.2017, author = {Apelt, Federico and Breuer, David and Olas, Justyna Jadwiga and Annunziata, Maria Grazia and Flis, Anna and Nikoloski, Zoran and Kragler, Friedrich and Stitt, Mark}, title = {Circadian, Carbon, and Light Control of Expansion Growth and Leaf Movement}, series = {Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants}, volume = {174}, journal = {Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants}, publisher = {American Society of Plant Physiologists}, address = {Rockville}, issn = {0032-0889}, doi = {10.1104/pp.17.00503}, pages = {1949 -- 1968}, year = {2017}, language = {en} } @article{ApeltBreuerNikoloskietal.2015, author = {Apelt, Federico and Breuer, David and Nikoloski, Zoran and Stitt, Mark and Kragler, Friedrich}, title = {Phytotyping(4D): a light-field imaging system for non-invasive and accurate monitoring of spatio-temporal plant growth}, series = {The plant journal}, volume = {82}, journal = {The plant journal}, number = {4}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0960-7412}, doi = {10.1111/tpj.12833}, pages = {693 -- 706}, year = {2015}, abstract = {Integrative studies of plant growth require spatially and temporally resolved information from high-throughput imaging systems. However, analysis and interpretation of conventional two-dimensional images is complicated by the three-dimensional nature of shoot architecture and by changes in leaf position over time, termed hyponasty. To solve this problem, Phytotyping(4D) uses a light-field camera that simultaneously provides a focus image and a depth image, which contains distance information about the object surface. Our automated pipeline segments the focus images, integrates depth information to reconstruct the three-dimensional architecture, and analyses time series to provide information about the relative expansion rate, the timing of leaf appearance, hyponastic movement, and shape for individual leaves and the whole rosette. Phytotyping(4D) was calibrated and validated using discs of known sizes, and plants tilted at various orientations. Information from this analysis was integrated into the pipeline to allow error assessment during routine operation. To illustrate the utility of Phytotyping(4D), we compare diurnal changes in Arabidopsis thaliana wild-type Col-0 and the starchless pgm mutant. Compared to Col-0, pgm showed very low relative expansion rate in the second half of the night, a transiently increased relative expansion rate at the onset of light period, and smaller hyponastic movement including delayed movement after dusk, both at the level of the rosette and individual leaves. Our study introduces light-field camera systems as a tool to accurately measure morphological and growth-related features in plants. Significance Statement Phytotyping(4D) is a non-invasive and accurate imaging system that combines a 3D light-field camera with an automated pipeline, which provides validated measurements of growth, movement, and other morphological features at the rosette and single-leaf level. In a case study in which we investigated the link between starch and growth, we demonstrated that Phytotyping(4D) is a key step towards bridging the gap between phenotypic observations and the rich genetic and metabolic knowledge.}, language = {en} } @article{AnnunziataApeltCarilloetal.2017, author = {Annunziata, Maria Grazia and Apelt, Federico and Carillo, Petronia and Krause, Ursula and Feil, Regina and Mengin, Virginie and Lauxmann, Martin A. and Koehl, Karin and Nikoloski, Zoran and Stitt, Mark and Lunn, John Edward}, title = {Getting back to nature: a reality check for experiments in controlled environments}, series = {Journal of experimental botany}, volume = {68}, journal = {Journal of experimental botany}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0022-0957}, doi = {10.1093/jxb/erx220}, pages = {4463 -- 4477}, year = {2017}, abstract = {Irradiance from sunlight changes in a sinusoidal manner during the day, with irregular fluctuations due to clouds, and light-dark shifts at dawn and dusk are gradual. Experiments in controlled environments typically expose plants to constant irradiance during the day and abrupt light-dark transitions. To compare the effects on metabolism of sunlight versus artificial light regimes, Arabidopsis thaliana plants were grown in a naturally illuminated greenhouse around the vernal equinox, and in controlled environment chambers with a 12-h photoperiod and either constant or sinusoidal light profiles, using either white fluorescent tubes or light-emitting diodes (LEDs) tuned to a sunlight-like spectrum as the light source. Rosettes were sampled throughout a 24-h diurnal cycle for metabolite analysis. The diurnal metabolite profiles revealed that carbon and nitrogen metabolism differed significantly between sunlight and artificial light conditions. The variability of sunlight within and between days could be a factor underlying these differences. Pairwise comparisons of the artificial light sources (fluorescent versus LED) or the light profiles (constant versus sinusoidal) showed much smaller differences. The data indicate that energy-efficient LED lighting is an acceptable alternative to fluorescent lights, but results obtained from plants grown with either type of artificial lighting might not be representative of natural conditions.}, language = {en} } @article{AngeleskaOmranianNikoloski2021, author = {Angeleska, Angela and Omranian, Sara and Nikoloski, Zoran}, title = {Coherent network partitions}, series = {Theoretical computer science : the journal of the EATCS}, volume = {894}, journal = {Theoretical computer science : the journal of the EATCS}, publisher = {Elsevier}, address = {Amsterdam [u.a.]}, issn = {0304-3975}, doi = {10.1016/j.tcs.2021.10.002}, pages = {3 -- 11}, year = {2021}, abstract = {We continue to study coherent partitions of graphs whereby the vertex set is partitioned into subsets that induce biclique spanned subgraphs. The problem of identifying the minimum number of edges to obtain biclique spanned connected components (CNP), called the coherence number, is NP-hard even on bipartite graphs. Here, we propose a graph transformation geared towards obtaining an O (log n)-approximation algorithm for the CNP on a bipartite graph with n vertices. The transformation is inspired by a new characterization of biclique spanned subgraphs. In addition, we study coherent partitions on prime graphs, and show that finding coherent partitions reduces to the problem of finding coherent partitions in a prime graph. Therefore, these results provide future directions for approximation algorithms for the coherence number of a given graph.}, language = {en} }