TY - JOUR A1 - Alseekh, Saleh A1 - Tohge, Takayuki A1 - Wendenberg, Regina A1 - Scossa, Federico A1 - Omranian, Nooshin A1 - Li, Jie A1 - Kleessen, Sabrina A1 - Giavalisco, Patrick A1 - Pleban, Tzili A1 - Müller-Röber, Bernd A1 - Zamir, Dani A1 - Nikoloski, Zoran A1 - Fernie, Alisdair R. T1 - Identification and Mode of Inheritance of Quantitative Trait Loci for Secondary Metabolite Abundance in Tomato JF - The plant cell N2 - A large-scale metabolic quantitative trait loci (mQTL) analysis was performed on the well-characterized Solanum pennellii introgression lines to investigate the genomic regions associated with secondary metabolism in tomato fruit pericarp. In total, 679 mQTLs were detected across the 76 introgression lines. Heritability analyses revealed that mQTLs of secondary metabolism were less affected by environment than mQTLs of primary metabolism. Network analysis allowed us to assess the interconnectivity of primary and secondary metabolism as well as to compare and contrast their respective associations with morphological traits. Additionally, we applied a recently established real-time quantitative PCR platform to gain insight into transcriptional control mechanisms of a subset of the mQTLs, including those for hydroxycinnamates, acyl-sugar, naringenin chalcone, and a range of glycoalkaloids. Intriguingly, many of these compounds displayed a dominant-negative mode of inheritance, which is contrary to the conventional wisdom that secondary metabolite contents decreased on domestication. We additionally performed an exemplary evaluation of two candidate genes for glycolalkaloid mQTLs via the use of virus-induced gene silencing. The combined data of this study were compared with previous results on primary metabolism obtained from the same material and to other studies of natural variance of secondary metabolism. Y1 - 2015 U6 - https://doi.org/10.1105/tpc.114.132266 SN - 1040-4651 SN - 1532-298X VL - 27 IS - 3 SP - 485 EP - 512 PB - American Society of Plant Physiologists CY - Rockville ER - TY - JOUR A1 - Angeleska, Angela A1 - Nikoloski, Zoran T1 - Coherent network partitions JF - Discrete applied mathematics N2 - Graph clustering is widely applied in the analysis of cellular networks reconstructed from large-scale data or obtained from experimental evidence. Here we introduce a new type of graph clustering based on the concept of coherent partition. A coherent partition of a graph G is a partition of the vertices of G that yields only disconnected subgraphs in the complement of G. The coherence number of G is then the size of the smallest edge cut inducing a coherent partition. A coherent partition of G is optimal if the size of the inducing edge cut is the coherence number of G. Given a graph G, we study coherent partitions and the coherence number in connection to (bi)clique partitions and the (bi)clique cover number. We show that the problem of finding the coherence number is NP-hard, but is of polynomial time complexity for trees. We also discuss the relation between coherent partitions and prominent graph clustering quality measures. KW - Graph partitions KW - Network clustering KW - Coherence number KW - Coherent partition Y1 - 2019 U6 - https://doi.org/10.1016/j.dam.2019.02.048 SN - 0166-218X SN - 1872-6771 VL - 266 SP - 283 EP - 290 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Angeleska, Angela A1 - Omranian, Sara A1 - Nikoloski, Zoran T1 - Coherent network partitions BT - Characterizations with cographs and prime graphs JF - Theoretical computer science : the journal of the EATCS N2 - 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. KW - Graph partitions KW - Network clustering KW - Cographs KW - Coherent partition KW - Prime graphs Y1 - 2021 U6 - https://doi.org/10.1016/j.tcs.2021.10.002 SN - 0304-3975 VL - 894 SP - 3 EP - 11 PB - Elsevier CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Apelt, Federico A1 - Breuer, David A1 - Nikoloski, Zoran A1 - Stitt, Mark A1 - Kragler, Friedrich T1 - Phytotyping(4D): a light-field imaging system for non-invasive and accurate monitoring of spatio-temporal plant growth JF - The plant journal N2 - 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. KW - plant growth KW - hyponasty KW - 3D imaging KW - light-field camera KW - Arabidopsis thaliana KW - pgm KW - technical advance Y1 - 2015 U6 - https://doi.org/10.1111/tpj.12833 SN - 0960-7412 SN - 1365-313X VL - 82 IS - 4 SP - 693 EP - 706 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Apelt, Federico A1 - Breuer, David A1 - Olas, Justyna Jadwiga A1 - Annunziata, Maria Grazia A1 - Flis, Anna A1 - Nikoloski, Zoran A1 - Kragler, Friedrich A1 - Stitt, Mark T1 - Circadian, Carbon, and Light Control of Expansion Growth and Leaf Movement JF - Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants Y1 - 2017 U6 - https://doi.org/10.1104/pp.17.00503 SN - 0032-0889 SN - 1532-2548 VL - 174 SP - 1949 EP - 1968 PB - American Society of Plant Physiologists CY - Rockville ER - TY - JOUR A1 - Araujo, Wagner L. A1 - Nunes-Nesi, Adriano A1 - Nikoloski, Zoran A1 - Sweetlove, Lee J. A1 - Fernie, Alisdair R. T1 - Metabolic control and regulation of the tricarboxylic acid cycle in photosynthetic and heterotrophic plant tissues JF - Plant, cell & environment : cell physiology, whole-plant physiology, community physiology N2 - 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. KW - metabolic control analysis KW - metabolic regulation KW - respiration KW - Solanum lycopersicum (tomato) KW - TCA cycle Y1 - 2012 U6 - https://doi.org/10.1111/j.1365-3040.2011.02332.x SN - 0140-7791 VL - 35 IS - 1 SP - 1 EP - 21 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Arnold, Anne A1 - Nikoloski, Zoran T1 - In search for an accurate model of the photosynthetic carbon metabolism JF - Mathematics and computers in simulation : transactions of IMACS N2 - 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. KW - Calvin-Benson cycle KW - Carbon metabolism KW - Model ranking KW - Differential and algebraic equations Y1 - 2014 U6 - https://doi.org/10.1016/j.matcom.2012.03.011 SN - 0378-4754 SN - 1872-7166 VL - 96 SP - 171 EP - 194 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Arnold, Anne A1 - Nikoloski, Zoran T1 - A quantitative comparison of Calvin-Benson cycle models JF - Trends in plant science N2 - The Calvin-Benson cycle (CBC) provides the precursors for biomass synthesis necessary for plant growth. The dynamic behavior and yield of the CBC depend on the environmental conditions and regulation of the cellular state. Accurate quantitative models hold the promise of identifying the key determinants of the tightly regulated CBC function and their effects on the responses in future climates. We provide an integrative analysis of the largest compendium of existing models for photosynthetic processes. Based on the proposed ranking, our framework facilitates the discovery of best-performing models with regard to metabolomics data and of candidates for metabolic engineering. Y1 - 2011 U6 - https://doi.org/10.1016/j.tplants.2011.09.004 SN - 1360-1385 VL - 16 IS - 12 SP - 676 EP - 683 PB - Elsevier CY - London ER - TY - JOUR A1 - Basler, Georg A1 - Ebenhoeh, Oliver A1 - Selbig, Joachim A1 - Nikoloski, Zoran T1 - Mass-balanced randomization of metabolic networks JF - Bioinformatics N2 - 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. Y1 - 2011 U6 - https://doi.org/10.1093/bioinformatics/btr145 SN - 1367-4803 VL - 27 IS - 10 SP - 1397 EP - 1403 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Basler, Georg A1 - Fernie, Alisdair R. A1 - Nikoloski, Zoran T1 - Advances in metabolic flux analysis toward genome-scale profiling of higher organisms JF - Bioscience reports : communications and reviews in molecular and cellular biology N2 - Methodological and technological advances have recently paved the way for metabolic flux profiling in higher organisms, like plants. However, in comparison with omics technologies, flux profiling has yet to provide comprehensive differential flux maps at a genome-scale and in different cell types, tissues, and organs. Here we highlight the recent advances in technologies to gather metabolic labeling patterns and flux profiling approaches. We provide an opinion of how recent local flux profiling approaches can be used in conjunction with the constraint-based modeling framework to arrive at genome-scale flux maps. In addition, we point at approaches which use metabolomics data without introduction of label to predict either non-steady state fluxes in a time-series experiment or flux changes in different experimental scenarios. The combination of these developments allows an experimentally feasible approach for flux-based large-scale systems biology studies. Y1 - 2018 U6 - https://doi.org/10.1042/BSR20170224 SN - 0144-8463 SN - 1573-4935 VL - 38 PB - Portland Press (London) CY - London ER -